JP6430281B2 - Sample preparation system - Google Patents

Description

  The present invention relates to a sample preparation system.

  The properties of pharmaceuticals are mainly solid (tablet or powder) and liquid, and powdered pharmaceuticals are administered as they are, or after dissolving or dissolving and diluting. In a state where the solid is dissolved in the liquid, since it is easily affected by the outside such as light and temperature, a quick dispensing operation is required.

  In particular, anticancer drugs with strong side effects are expected to be more effective and reduce side effects when administered in the type, amount, and timing according to the patient's symptoms. It is done as a part. With the spread of tailor-made medicine in the future, it is expected that the need for dispensing operations to dissolve solids will increase.

  In recent years, as anticancer agents, solid pharmaceuticals having a large molecular weight such as protein and difficult to dissolve in liquids are increasing. Generally, it is dissolved in a liquid such as a physiological saline solution or an infusion preparation by a batch operation using a stirring blade, a stirring bar, ultrasonic stirring, shaking or the like. However, in the case of protein, it is known that solution foaming is likely to occur and concentration unevenness is likely to occur. Since a foamed pharmaceutical solution cannot be used as an intravenous infusion or injection, it is necessary to wait until the foaming disappears after a while or to crush the bubbles one by one with the tip of an injection needle. Become.

  Various developments and studies have been made so far on solid dissolution methods that prevent foaming and are less likely to cause uneven density.

  For example, Patent Document 1 describes a method of supplying a liquid to a solid at a fixed position on a fine channel and dissolving it in a device having the fine channel.

JP 2008-128907 A

  However, as in the technique described in Patent Document 1, in a device having a fine flow path, when a liquid is supplied and dissolved with respect to a solid at a fixed position on the fine flow path, the solid is in an aggregated state. If it is, it will dissolve from the surroundings, and the center will not dissolve easily. Further, if a fine channel corresponding to a residence time sufficient for the solid to dissolve is provided, the fine channel becomes longer and the pressure loss becomes higher.

  An object of the present invention is to efficiently obtain a solution in which a solid sample, a gas sample, or a liquid sample is uniformly dissolved in a liquid sample. For example, a pharmaceutical solution in which a solid sample is uniformly dissolved with little foaming is prepared and provided.

  In order to achieve the above object, for example, a sample preparation system for dissolving a solid sample, a gas sample, or a liquid sample with respect to a liquid sample, the flow path through which the liquid sample flows, and the solid sample or gas sample with respect to the liquid sample Alternatively, a dissolution device having an introduction part for introducing a liquid sample, and a region in which the liquid sample flows toward the introduction part in the flow path, the solid sample, the gas sample, or the liquid sample is introduced by the introduction part. When the flow area of the liquid sample is an outflow section, the liquid sample flowing through the outflow section has a circulation channel for introducing the liquid sample into the inflow section, and a solution state measurement section that measures the solution state of the liquid sample in the outflow section. Then, based on the measurement result of the solution state by the solution state measurement unit, the time during which the liquid sample flowing through the outflow part stays in the circulation channel is changed.

According to the present invention, it is possible to efficiently obtain a solution in which a solid sample, a gas sample, or a liquid sample is uniformly dissolved in a liquid sample.

It is a block diagram of the sample preparation system by Example 1 of this invention. 1 is a perspective view of a melting device 101. FIG. The change with respect to the linear velocity of the gas which pumps a solid pharmaceutical, when the internal diameter of the solid pharmaceutical holding | maintenance part 102 is 2 mm is shown. The change with respect to the linear velocity of the gas which pumps a solid pharmaceutical in the case where the internal diameter of the solid pharmaceutical holding | maintenance part 102 is 1.5 mm is shown. It is the figure which showed a mode that the solid pharmaceutical in case the linear velocity of gas is relatively small melt | dissolves in a liquid. It is the figure which showed a mode that the solid pharmaceutical in the case where the linear velocity of gas is comparatively large melt | dissolves in a liquid. In a present Example, when the solution state of a solid pharmaceutical is measured with an optical system, it is the figure which showed the change with respect to the elapsed time of the light absorbency of a pharmaceutical solution. It is a flowchart at the time of utilizing the system of a present Example. It is a figure of the sample preparation system by Example 2 of this invention. It is a figure of the sample preparation system by Example 3 of this invention. It is a figure of the sample preparation system by Example 4 of this invention. It is a figure of the sample preparation system by Example 5 of this invention.

  Hereinafter, embodiments of the present invention will be described with reference to FIGS.

  Hereinafter, the first embodiment of the present invention will be described with reference to FIGS.

  FIG. 1 is a configuration diagram of a sample preparation system according to Embodiment 1 of the present invention.

  In this embodiment, a case where a solid drug is introduced into a solution sample will be described as an example.

  1 includes a dissolution device 101, a liquid container 103, a solid introduction unit 104, a pump 106, a valve 107, a solution container 108, a circulation channel 109, a pump 110, a valve 111, a solution state measurement unit 112, and a control device. 113. The dissolution device 101 has a solid pharmaceutical product holding part 102 and a flow path 105. The detailed configuration of the melting device 101 will be described later with reference to FIG.

  The dissolution device 101 is a unit that dissolves a solid pharmaceutical in a liquid such as physiological saline or an infusion preparation. However, in this embodiment, the solid introduction part 104 and the flow path 105 need not be unitized.

  The liquid container 103 holds a liquid to be introduced into the dissolution device 101, and the solution is introduced into the dissolution device 101 via the pump 106 and the valve 11. The solution introduced into the dissolution device 101 flows through the flow path 105 and the solid medicine is introduced from the solid introduction part 104 for introducing the solid medicine. The solid introduction unit 104 pumps a solid sample by conveying a gas to the solid. The solution into which the solid drug is introduced flows through the flow path 105 and is led out from the dissolution device 101. The solution into which the solid medicine flowing through the flow path 105 is introduced measures the state of the solution using the solution state measuring unit 112.

  The derived solution is introduced into the circulation channel 109. The circulation channel 109 is a channel for retaining a solution (pharmaceutical solution) in which a solid drug is dissolved through the dissolution device 101, and the liquid sample flows toward the solid introduction part 104 in the channel 105. When the region is an inflow portion and the region in which the liquid sample into which the solid sample is introduced by the introduction portion is the outflow portion, the flow path is a channel for introducing the liquid sample flowing through the outflow portion into the inflow portion.

  A switching valve 107 is provided in the circulation channel 109, and can be switched between the case where the liquid sample is circulated and retained in the circulation channel 109 and the case where the liquid sample is allowed to flow to the drug solution container 108 for obtaining the drug solution. . Specifically, how the solution is circulated and retained in the circulation channel 109 will be described with reference to FIG.

  The control device 113 can control the pump 106, the valve 111, the pump 110, the valve 107, and the solution state measuring unit 112.

  Note that this embodiment can be applied not only to dissolving a solid sample in a liquid sample but also to dissolving a liquid sample and a gas sample. As a liquid sample, for example, the present invention can also be applied to a case where a liquid medicine having high viscosity is dissolved in a liquid. Moreover, it is applicable also when it becomes a suspension which a solid pharmaceutical dissolves in a liquid without dissolving.

  FIG. 2 is a perspective view of the melting device 101.

  The dissolution device 101 includes a solid introduction part connection part 201, a solid medicine holding part 102, circulation flow path connection parts 202 and 203, a flow path 105, and solution state measurement windows 204 and 205.

  The circulation channel 109 is connected to the circulation channel connection unit 202, and the pharmaceutical solution is introduced into the channel 105. The solid introduction part 104 is connected to the solid introduction part connection part 201, and the solid medicine is introduced by the solid introduction part 104 via the solid introduction part connection part 201 and the solid medicine holding part 102. The solution flowing through the flow path 105 is measured inline by the solution state measuring unit 112 via the solution state measuring windows 204 and 205. The circulation channel connection unit 203 is connected to the circulation channel 109, and the pharmaceutical solution is discharged through the channel 109.

  In the solution state measurement windows 204 and 205, the transparency can be increased and the solution state can be measured in-line as close to the flow path 105 as possible, and the solution state can be accurately measured without contacting the liquid. The solution state measurement windows 204 and 205 are preferably made of a transparent material.

  Here, the liquid stored in the liquid solution 103 is introduced by the pump 106, and the pharmaceutical solution is circulated through the circulation channel 109 by the pump 110. The liquid feeding means is, for example, a syringe pump, a manual syringe, a tube pump, A plunger pump, a diaphragm pump, a screw pump, etc. can be used. Moreover, the liquid feeding means using a water head difference may be used.

  In addition, the solid medicine is introduced by the solid introduction unit 104, and the introduction means may be a gas pressure feed, a gas delivery, a powder injection pump, a gravity difference, or the like.

  In addition, the material of the dissolution device 101 and the circulation channel 109 can be appropriately changed according to the type of the solid pharmaceutical and the liquid as long as they do not adversely affect the pharmaceutical solution. For example, stainless steel, silicon, gold, glass, hastelloy, ceramic, silicon resin, cycloolefin polymer, cycloolefin copolymer, polyethylene, polycarbonate, polypropylene, acrylic resin, fluorine resin, and the like can be used. Further, a glass lining, a metal surface coated with nickel, gold, or the like, or a silicon surface oxidized may be used which has improved corrosion resistance.

  However, from the viewpoint of tailor-made medical care, it is desirable that the dissolution device 101 having the liquid contact portion and the circulation channel 109 are disposable and the material is resin. The materials of the melting device 101 and the circulation channel 109 do not need to be the same, and the melting device 101 may also be composed of a plurality of materials, and can be appropriately changed according to workability, measurement method, and the like. it can.

  In addition, when the representative length of the channel diameter of the channel 105 and the circulation channel 109 in the dissolution device 101 is set to several mm or less, the effect of the micro field can be obtained when the solid pharmaceutical is dissolved. Here, the micro field means a micro space, and by reducing the size, the micro field is rapidly mixed by the effect of molecular diffusion, and the ratio of the surface area to the space area is increased. That is, in the micro field, the contact surface area between the solid drug and the liquid increases, so that the dissolution rate can be increased, and the dissolved solid drug diffuses quickly into the liquid, reducing the concentration unevenness and making the solution state uniform. be able to.

  The flow path shape of the dissolution device 101 may be Y-shaped or a shape having a plurality of solid drug holding parts 102 as long as a solid drug is introduced into the liquid. Also good.

  The solution state measurement unit 112 may be anything as long as it can determine a non-uniform solution state such as density unevenness, and includes an optical method, a capacitance method, an ultrasonic method, an image method, and the like. In the image system, the non-uniform state of the solution is determined not by the concentration but by image analysis.

  FIG. 3A shows a change in the amount of solid medicine introduced with respect to the linear velocity of the gas for pumping the solid medicine when the internal diameter of the solid medicine holding portion 102 is 2 mm.

  FIG. 3B shows a change in the amount of the solid drug introduced with respect to the linear velocity of the gas for pumping the solid drug when the inner diameter of the solid drug holding unit 102 is 1.5 mm.

  As shown in FIG. 3A and FIG. 3B, it can be seen that the solid drug introduction amount has a double peak with respect to the linear velocity of the gas for pumping the solid drug, regardless of the inner diameter of the solid drug holding unit 102.

  FIG. 4A is a diagram illustrating a state in which a solid drug dissolves in a liquid when the linear velocity of the gas is relatively small, and FIG. 4B illustrates a solid drug when the linear velocity of the gas is relatively large. It is the figure which showed a mode that it melt | dissolves in the liquid.

  As shown in FIG. 4A, in the case where the liquid 402 is flowing in the direction of the arrow 404, if the gas linear velocity is low, only the solid pharmaceutical 401 is introduced into the liquid (pharmaceutical solution) 402 in the flow path 105. Dissolve immediately in the liquid (pharmaceutical solution) 402. The gas 403 is discharged together at a certain timing. Thus, the concentration of the solid medicine 401 in the liquid becomes high.

  On the other hand, as shown in FIG. 4B, when the liquid 402 is flowing in the direction of the arrow 404 and the linear velocity of the gas is high, the solid medicine 401 is dispersedly introduced into the gas 403. . In the flow path 105, the gas 403 and the liquid (pharmaceutical solution) 402 in which the solid medicine 401 is dispersed form a slag flow that flows alternately. In each slag gas and each slag liquid, a circulating flow 405 is generated as indicated by an arrow. Since the solid medicine 401 is supplied to the slag interface according to the concentration gradient of the solid medicine 401 by this circulating flow 405 (arrow 406), the dissolution efficiency of the solid medicine 401 is improved.

  In each dissolution pattern of FIG. 4A and FIG. 4B, because there is an optimum gas linear velocity at which the amount of solid pharmaceutical agent introduced becomes maximum due to the physical properties of the solid pharmaceutical agent, as shown in FIG. 3A and FIG. It can be said that there is a double peak with respect to the linear velocity of the gas for pumping.

  FIG. 5 is a diagram showing a change in the absorbance of the pharmaceutical solution with respect to the elapsed time when the solution state (concentration) of the solid pharmaceutical is measured by an optical method in the present example.

  As shown in FIG. 5, when the linear velocity of the gas is high to some extent, a slag flow in which the gas 403 and the liquid (pharmaceutical solution) 402 alternately flow is formed in the flow path 105. Since absorption intensity is low in gas and absorption intensity is high in liquid (pharmaceutical solution) 402, as shown in FIG. 5, portions with low absorbance and high portions alternately appear with respect to the elapsed time. Further, the absorbance of the liquid (pharmaceutical solution) changes depending on the solution state (concentration) of the solid pharmaceutical.

  Therefore, by observing the time variation of the absorbance of the pharmaceutical solution at short time intervals, it is possible to determine the dispersion (concentration unevenness) of the solution state of the solid pharmaceutical agent, and by looking at the time variation of the absorbance of the pharmaceutical solution at a long time interval, The convergence of the solution state of the pharmaceutical product (target solution state) can be determined. The flow path of this example is a so-called micro flow path with a small diameter. However, due to the effect of the micro field, the dissolved solid medicine quickly diffuses into the liquid, and concentration unevenness in the radial direction of the flow path ( Such a determination can be made because it is difficult for a variation in the dissolved state to occur. From the in-line measurement result of the solution state, it is possible to determine the time for staying in the dissolution device and the circulation channel, that is, the time for the solid pharmaceutical to dissolve in the liquid. Details will be described later with reference to FIG.

  In addition, when the influence of an electrical noise enters into the measured light absorbency, you may measure the value which performed the time average for every short unit time. In that case, depending on the set value of the unit time, a value obtained by averaging the portion having a small absorbance due to the gas and the portion having a large absorbance due to the solution with respect to the elapsed time is measured. However, particularly when using a microchannel, the small and large portions of the absorbance appear with good reproducibility, so even when measuring the averaged value, the same as when considering only the large portion of the absorbance By observing the time variation of the absorbance of the drug solution at short time intervals, it is possible to determine the dispersion (concentration unevenness) of the solution of the solid drug, and by looking at the time variation of the absorbance of the drug solution at a long time interval, The convergence of the dissolved state (target solution state) can be determined. However, when determining the convergence, it is necessary to consider that the absorbance is measured to be smaller due to the influence of the gas than when the absorbance of only the solution is measured.

  In addition, the solution state can be determined at least in units of slag liquid in the flow path 105. However, since the introduction of solid pharmaceuticals may not be uniform continuously, two or more slag liquids may be combined into one slag liquid. It is desirable to judge as a unit. However, since a slag flow flows while a trace amount of liquid or pharmaceutical solution remains on the wall surfaces of the flow channel 105 and the circulation flow channel 109, as the pharmaceutical solution circulates in the circulation flow channel, each slag liquid is circulated. It can be said that the difference in solution state will be eliminated.

  FIG. 6 is a flowchart when the system of this embodiment is used.

  First, the solid medicine holding part 102 in the dissolution device 101 is filled with the solid medicine (step 601).

  Next, introduction of the liquid into the flow path 105 of the dissolution device 101 is started (step 602). Here, steps 601 and 602 may be performed simultaneously or in reverse order.

  Then, the solid medicine is introduced into the liquid in the channel 105 (step 603), and mixed and dissolved in the channel (step 604).

  The solution state measuring unit 112 determines whether the solution state is uniform (step 605). If the solid medicine is not uniformly dissolved (NO in step 605), the medicine solution is introduced into the circulation channel 109 ( Step 606), mixing and dissolving in the flow path.

  If the solid drug is dissolved uniformly, the process proceeds to step 607. In step 607, the solution state is determined by the solution state measuring unit 112 (step 607).

  The solution state is determined, and compared with the solution state (target solution state) obtained when the whole amount of the solid pharmaceutical agent is introduced, if there is an unintroduced solid pharmaceutical agent (step 608), the solution is circulated. It introduces to the path 109 (step 606). Further, the solid medicine is introduced into the liquid in the channel 105 and mixed and dissolved in the channel 105 (step 603).

  On the other hand, when the whole amount of the solid pharmaceutical is introduced (step 608), a pharmaceutical solution is obtained (step 610).

  In step 607, the comparison is made with the solution state (target solution state) obtained when the entire amount of the solid drug is introduced. For this purpose, a calibration curve representing the relationship between the solution state (concentration) and the absorbance in advance is used. It is necessary to acquire. Note that the method for obtaining the calibration curve for the solution state is not limited to the optical method based on absorbance, and includes, for example, an optical method based on transmittance, an electrostatic capacity method, an ultrasonic method, and an image method.

  In addition, in the case where it is not compared with the solution state (target solution state) obtained when the entire amount of the solid drug is introduced, it is partially introduced even though the solid drug remains in the dissolution device. Since the solid pharmaceutical is uniformly dissolved, a pharmaceutical solution is obtained (step 610), and the concentration of the solution may become smaller than the intended value.

  As described above, according to the first embodiment of the present invention, based on the in-line measurement result of the solution state in the dissolution device 101, the time and number of stays in the dissolution device 101 and the circulation channel 109 are changed. Thus, it is possible to efficiently prepare and provide a pharmaceutical solution in which a solid pharmaceutical is uniformly dissolved. For example, when the flow path 105 after the solid introduction part is lengthened in order to make the dissolved state uniform, the pressure loss due to the length of the flow path increases, and a uniform solution can be obtained efficiently. I can't. On the other hand, in this embodiment, since the solution is circulated through the circulation passage 109 having a predetermined passage distance and the dissolution treatment is performed by the dissolution device 101, pressure loss or the like does not occur compared to the above method. A uniform solution can be obtained efficiently.

  Hereinafter, a second embodiment of the present invention will be described with reference to FIG.

  FIG. 7 is a diagram of a sample preparation system according to Embodiment 2 of the present invention.

  With reference to FIG. 1 and FIG. 2, only the structure which has a change from Example 1 is shown below. The sample preparation system of FIG. 7 eliminates the solution state measurement windows 204 and 205 from the dissolution device 101 of FIG. 2, and the solution state measurement unit 112 measures the solution state in the circulation channel 109 in-line. The solution state measurement unit 112 may be anything as long as it can determine the solution state unevenness, and includes an optical method, a capacitance method, an ultrasonic method, an image method, and the like. By adopting this configuration, even when the melting device 101 is replaced, the replacement work can be simplified.

  Hereinafter, a third embodiment of the present invention will be described with reference to FIG.

  FIG. 8 is a diagram of a sample preparation system according to Example 3 of the present invention. With reference to FIG. 1, only the configuration changed from the first embodiment is shown below.

  The sample preparation system of FIG. 8 is provided with a solid drug introduction amount measuring unit 801 with respect to the solid drug holding unit 102 of FIG. Then, with respect to the measurement result 802 by the solid drug introduction amount measuring unit 801, the control device 113 performs pump control and feedback 114, valve control and feedback 115, pump control and feedback 116, valve control and feedback 117. By doing so, a predetermined amount of solid pharmaceutical can be introduced. The solid drug introduction amount measuring unit 801 may be anything as long as the remaining amount of the solid drug in the solid drug holding unit 102 is known. When the solid introduction unit 104 is pumped, the pressure method or the image method in the solid drug holding unit 102 is used. and so on.

  With this configuration, since the introduction amount of the solid drug is measured, the entire amount of the solid drug can be more reliably introduced.

  Hereinafter, the fourth embodiment of the present invention will be described with reference to FIG.

  FIG. 9 is a diagram of a sample preparation system according to Example 4 of the present invention. With reference to FIG. 1, only the configuration changed from the first embodiment is shown below.

  The sample preparation system of FIG. 9 removes the gas in the circulation channel 109 by providing an exhaust valve 901 in the middle of the circulation channel 109 of FIG. Here, the exhaust valve 901 is provided on the upstream side of the pump 110, but may be provided on the downstream side of the pump 110. However, particularly when a pump that cannot transfer gas and liquid simultaneously is used as the pump 110, the exhaust valve 901 is provided to remove the gas in the circulation flow path 109, thereby causing trouble due to the inclusion of gas in the liquid. Therefore, the exhaust valve 901 is preferably provided on the upstream side of the pump 110.

  By providing the exhaust valve 901 to remove the gas in the circulation channel 109, the solid drug is not continuously and uniformly introduced, and the amount of the solid drug introduced into each slag liquid in the channel 105 is reduced. Even when they are different, a plurality of slag liquids can be combined into one slag liquid, so that the solution state can be made uniform faster. Further, by controlling the exhaust valve and feedback 902 by the control device 113, it is possible to collect only the slag liquid having a large variation in solution state (concentration unevenness).

  Furthermore, when it takes a long time to introduce the solid pharmaceutical, a considerable amount of gas is introduced into the circulation flow path 109, so that the internal pressure in the system increases. If the internal pressure becomes too high, the circulation channel connecting portions 202 and 203 may be disconnected, or the circulation channel 109 may be damaged. However, by providing the exhaust valve 901 and removing the gas in the circulation flow path 109, it is possible to prevent the internal pressure in the system from increasing.

  Further, as described in the second embodiment, the solution state measurement windows 204 and 205 are eliminated from the dissolution device 101, and the solution state measurement unit 112 is provided on the downstream side of the exhaust valve 901 and the upstream side of the dissolution device 101. Then, the gas is removed by the exhaust valve 901, and the liquid in which a plurality of slag liquids are combined into one slag can be measured in-line. In the solution state measuring unit 112, the portion having a small absorbance due to gas is reduced, so that the solution state can be determined more easily. However, when it is determined that the solid pharmaceutical is uniformly dissolved and the entire amount of the solid pharmaceutical is dissolved, and the pharmaceutical solution is obtained by switching the valve 107, the pharmaceutical solution is transferred from the solution state measuring unit 112 to the valve 107. It is necessary to switch the valve 107 in consideration of the time difference to reach.

  As described above, in the fourth embodiment of the present invention, as in the first to third embodiments, the residence time in the dissolution device and the circulation channel is changed based on the measurement result of the solution state measured in-line. By doing so, a pharmaceutical solution in which a solid pharmaceutical is uniformly dissolved can be efficiently prepared and provided. Furthermore, by combining a plurality of slag liquids into one slag liquid, the solution state can be homogenized more quickly.

  Hereinafter, the fifth embodiment of the present invention will be described with reference to FIG.

  FIG. 10 is a diagram of a sample preparation system according to Example 5 of the present invention. With reference to FIG. 1, only the configuration changed from the embodiment is shown below.

  The sample preparation system of FIG. 10 is provided with a buffer container 1001 in the middle of the circulation channel 109 of FIG. 1, and once the solution is discharged into the buffer container 1001 and only the solution is sucked therefrom by the pump 110, The gas in 109 is removed. As the buffer container 1001, a sealed pressure container capable of adjusting the internal pressure, a container having an open top, or the like can be used. Further, the buffer container 1001 and the drug solution container 108 can be used together, and the solution obtained in the buffer container 1001 can be used as a drug solution.

  Here, the buffer container 1001 is provided on the upstream side of the pump 110, but may be provided on the downstream side of the pump 110. However, especially when a pump that cannot transfer gas and liquid at the same time is used as the pump 110, troubles due to inclusion of gas in the liquid by removing the gas in the circulation channel 109 by providing the buffer container 1001. Therefore, the buffer container 1001 is preferably provided on the upstream side of the pump 110.

  When the buffer container 1001 is provided, the gas can be removed more reliably than when the exhaust valve 901 is provided. Therefore, a plurality of slag liquids can be combined into one liquid that does not contain gas. It is also possible to prevent the internal pressure in the system from increasing.

  Further, similarly to the fourth embodiment, the solution state measurement windows 204 and 205 are eliminated from the dissolution device 101, and the solution state measurement unit 112 is provided on the downstream side of the buffer container 1001 and the upstream side of the dissolution device 101, thereby providing a buffer. Gas is removed by the container 1001, and a liquid not containing gas can be measured in-line. In the solution state measuring unit 112, since there is almost no portion where the absorbance due to gas is small, the solution state can be determined more easily. However, when it is determined that the solid pharmaceutical is uniformly dissolved and the entire amount of the solid pharmaceutical is dissolved, and the pharmaceutical solution is obtained by switching the valve 107, the pharmaceutical solution is transferred from the solution state measuring unit 112 to the valve 107. It is necessary to switch the valve 107 in consideration of the time difference to reach.

As described above, in the fifth embodiment of the present invention, as in the first to fourth embodiments, the residence time in the dissolution device and the circulation channel is changed based on the measurement result of the solution state measured in-line. By doing so, a pharmaceutical solution in which a solid pharmaceutical is uniformly dissolved can be efficiently prepared and provided. Furthermore, the solution state can be made uniform more quickly by combining a plurality of slag liquids into one liquid that does not contain gas.

  DESCRIPTION OF SYMBOLS 101 ... Dissolution device, 102 ... Solid pharmaceutical holding part, 103 ... Liquid container, 104 ... Solid introduction means, 105 ... Channel, 106 ... Pump, 107 ... Valve, 108 ... Pharmaceutical solution container, 109 ... Circulation channel, 110 ... Pump, 111 ... Valve, 112 ... Solution state measuring means, 113 ... Control device, 114 ... Pump control and feedback, 115 ... Valve control and feedback, 116 ... Pump control and feedback, 117 ... Valve control and feedback, 118: In-line measurement result by solution state measuring means, 201 ... Solid introduction means connecting portion, 202, 203 ... Circulating flow path connecting portion, 204, 205 ... Solution state measuring window, 401 ... Solid medicine, 402 ... Liquid (pharmaceutical solution) 403 ... Gas 404 ... Flow direction 405 ... Circulating flow 406 ... Flow body pharmaceuticals, 801 ... solid pharmaceutical introduction amount measuring means 802 ... solid pharmaceutical introduction amount measuring means by the measurement result, 901 ... exhaust valves, 902 ... control and feedback of the exhaust valves, 1001 ... buffer container

Claims (9)

A sample preparation system for dissolving a solid sample, a gas sample, or a liquid sample with respect to a liquid sample,
A flow path through which the liquid sample flows;
A dissolution device having an introduction part for introducing a solid sample, a gas sample, or a liquid sample into the liquid sample;
In the flow channel, when the region in which the liquid sample flows toward the introduction portion is an inflow portion, and the region in which the liquid sample into which the solid sample, the gas sample, or the liquid sample is introduced by the introduction portion is an outflow portion,
A circulation channel for introducing the liquid sample flowing through the outflow portion into the inflow portion;
A solution state measuring unit that measures the solution state of the liquid sample in the outflow part,
A sample preparation system characterized in that, based on the measurement result of the solution state by the solution state measurement unit, the time during which the liquid sample flowing through the outflow part stays in the circulation channel is changed.   By changing the number of times that the liquid sample flowing through the outflow part is introduced into the inflow part via the circulation circuit, the time during which the liquid sample circulates in the dissolution device and the circulation channel is changed. The sample preparation system according to claim 1.   The sample preparation system according to claim 1, wherein the solution state measurement unit measures the solution state in the dissolution device in-line. A solid introduction amount measurement unit for measuring the remaining amount of the sample remaining in the introduction unit is provided,
2. The sample preparation according to claim 1, wherein the time or number of times of circulation in the dissolution device and the circulation channel is changed according to the remaining amount of the sample measured by the solid introduction amount measurement unit. system.   The sample preparation system according to claim 1, wherein the solution state measurement unit is an optical system.   The sample preparation system according to claim 1, wherein the flow path has a fine flow path.   The sample preparation system according to claim 1, wherein the circulation channel is provided with an exhaust valve for removing gas contained in the liquid flowing in the circulation channel. The circulation channel is provided with a buffer container capable of storing the liquid flowing in the circulation channel, and only the solution stored in the buffer container is sucked by a pump and the solution sucked into the circulation channel is introduced. sample preparation system according to claim 1, characterized in that to. The sample preparation system according to claim 1, wherein the liquid sample obtained by dissolving the solid sample, the gas sample, or the liquid sample with respect to the liquid sample is a pharmaceutical product.