JP2019077627A - Drug dissolving apparatus and drug dissolving method - Google Patents

Abstract

To provide drug dissolving apparatus that can prepare a solution having a predetermined concentration by improving the dissolution rate of a solid drug into a solvent, and to provide drug dissolution methods.SOLUTION: Provided is a drug dissolution apparatus 1 comprising a circulation dissolution means having a circulation piping 30 for circulatively supplying a mixture of a drug 32 and a drug 34 discharged from a drug container 14 by supplying the drug 32 to the drug container 14 containing the drug 34, further to the drug container 14, and in which the supply of the solvent 32 to the drug container 14 is started, in a state where the drug 34 in the drug container 14 can flow toward the supply port of the solvent 32 to the drug container 14 and the discharge port of the mixture from the medicine container 14 which are in communication with the circulation piping 30.SELECTED DRAWING: Figure 1

Description

  The present invention is mainly used for preparation of a dialysate used for artificial dialysis, and a drug dissolving apparatus for dissolving and adjusting a drug such as a powder or granular solid dialysis agent to a predetermined concentration, and a drug dissolving method About.

  A dialysis agent is a drug for producing a dialysate. The dialysate is used to remove the waste of body fluid instead of the function originally performed by the kidney by hemodialysis, hemofiltration, peritoneal dialysis, etc., and in some cases, to supplement the necessary components in the blood. It is an aqueous solution having a close electrolyte composition.

  Current dialysis agents generally include sodium chloride, potassium chloride, magnesium chloride, calcium chloride, glucose, and pH adjuster (eg, acetic acid and sodium acetate), which are electrolyte components including sodium ion and potassium ion. Or a mixture thereof or a "dialysis agent A agent" containing citric acid and sodium citrate etc.) and a "dialysis agent B agent" containing sodium hydrogen carbonate.

  There are two types of dialysis agents: liquid type and solid type. The liquid-type dialysis agent is mostly occupied by water, and the weight and volume increase, so the burden of carrying work on dialysis medical workers becomes large, and the storage space also becomes large. Therefore, in recent years, when using a dialysate, a solid type dialysate which is introduced into an automatic drug dissolving apparatus and dissolved in water to prepare a dialysate is rapidly spreading.

  In Patent Document 1, a drug dissolution apparatus which arranges and transports a plurality of containers on a turntable, connects a circulation pipe to a drug container at a predetermined position, supplies a drug and a solvent to a dissolution tank through the solvent in the drug container. Has been proposed.

  Further, in Patent Document 2, the downstream end of the circulation pipe and the upstream end of the discharge pipe can be communicated in a fluid-tight manner to the spout provided at the bag opening of the drug storage bag, and the drug storage bag is started after the solvent pump is started to be driven. After the time has passed for the body to be filled with the drug and the solvent, the bag holder is inverted, and the drug storage bag is converted from the upward posture to the downward posture while continuing to supply the solvent into the drug storage bag. Thus, a drug dissolving apparatus has been proposed which deflates the drug storage bag while flowing in the solvent and discharging the drug and the solvent.

  The conventional drug dissolving apparatus is a drug dissolving apparatus of a dissolving method in which the drug is dissolved in the container while the inside of the container containing the drug is filled with the solvent, and when the drug is a highly cohesive substance, the solvent The drug that has been soaked in may cause aggregation, which may reduce the dissolution rate. Therefore, the conventional drug dissolution apparatus leaves room for improvement in the rate of dissolution in a solvent.

JP-A-5-146487 Patent No. 5445850 gazette

  An object of the present invention is to provide a drug dissolving apparatus capable of preparing a solution having a predetermined concentration by improving the dissolution rate of a solid drug in a solvent and providing a drug dissolving method.

  The present invention is a drug dissolving apparatus for preparing a solution by dissolving a solid drug with a solvent, wherein the solvent is supplied to a drug container containing the drug, and the drug is discharged from the drug container. The apparatus further comprises a circulating dissolution means having a circulation pipe for circulating and supplying a mixed liquid of the medicine and the solvent to the medicine container, and the supply port of the solvent to the medicine container in communication with the circulation pipe, and the medicine It is a medicine dissolution apparatus in which supply of the solvent to the medicine container is started in a state where the medicine in the medicine container can flow toward the discharge port of the mixed liquid from the container.

  In the drug dissolving apparatus, a circulation pipe connection port having the supply port and the discharge port is connected to an opening of the drug container, and the flow path in the drug container is directed toward the supply port and the discharge port. It is preferable that the supply of the solvent to the drug container is started while the drug can flow.

  In the drug dissolution apparatus, preferably, the supply of the solvent to the drug container is started in a flowable state by gravity action.

  The drug dissolution apparatus can be suitably applied when the drug contains a component having a pseudocrystal polymorph.

  The present invention is a drug dissolving method for preparing a solution by dissolving a solid drug with a solvent, and supplying a solvent to a drug container containing the drug through a circulation pipe, from the drug container A supply port of the solvent to the drug container, which further includes a circulating dissolving step of circulating a solution containing the drug and the solvent discharged and circulatingly supplying the drug container for circulation and dissolution; In the drug dissolution method, the supply of the solvent to the drug container is started in a state where the drug in the drug container can flow toward the discharge port of the mixed liquid from the drug container.

  In the drug dissolution method, a circulation pipe connection port having the supply port and the discharge port is connected to an opening of the drug container, and the flow path in the drug container is directed toward the supply port and the discharge port. It is preferable to start supply of the solvent to the drug container in a state where the drug can flow.

  In the drug dissolution method, preferably, the supply of the solvent to the drug container is started in a flowable state by gravity action.

  The drug dissolution method can be suitably applied when the drug contains a component having pseudocrystal polymorph.

  Further, the present invention is a drug dissolving device control program for preparing a solution by dissolving a solid drug with a solvent, wherein the drug dissolving device stores the drug through the circulation pipe in the drug container. The drug container further comprising: a circulating dissolution step of supplying a solvent and circulatingly supplying a mixed solution of the drug and the solvent discharged from the drug container to the drug container for circulation and dissolving. Starting supply of the solvent to the medicine container in a state where the medicine in the medicine container can flow toward the supply port of the solvent and the discharge port of the mixed liquid from the medicine container A drug dissolver control program that performs the method.

  In the drug dissolution apparatus control program, it is preferable to execute a method in which the supply of the solvent to the drug container is started in a flowable state by gravity action.

  According to the present invention, it is possible to provide a drug dissolving apparatus and a drug dissolving method capable of preparing a solution having a predetermined concentration by improving the dissolution rate of a solid drug in a solvent.

It is a schematic block diagram which shows an example of the chemical | medical agent melt | dissolution apparatus which concerns on embodiment of this invention. It is a schematic diagram showing an example of the dissolution method by the medicine dissolution device concerning an embodiment of the present invention. It is a schematic diagram showing an example of the dissolution method by the medicine dissolution device concerning an embodiment of the present invention. It is a schematic diagram showing an example of the dissolution method by the medicine dissolution device concerning an embodiment of the present invention. It is the schematic which shows the other example of the medicine container in embodiment of this invention, and circulation piping connection port.

  Embodiments of the present invention will be described below. The present embodiment is an example for implementing the present invention, and the present invention is not limited to the present embodiment.

  An outline of an example of a drug dissolution apparatus according to an embodiment of the present invention is shown in FIG. 1, and the configuration thereof will be described. The drug dissolving apparatus 1 shown in FIG. 1 is an apparatus for dissolving a drug 34 with a solvent 32 to prepare a solution, which supplies the solvent 32 to the drug container 14 containing the drug 34, and from the drug container 14. The liquid mixture of the discharged medicine 34 and the solvent 32 is further circularly supplied to the medicine container 14 for circulation and dissolution, and a circulation dissolution means having a circulation pipe 30 (pipe 16, pipe 18 and pipe 20) is provided. The drug dissolution apparatus 1 further includes, for example, a dissolution tank 10 capable of containing a predetermined amount of solvent 32 or a mixed solution of a circulated drug 34 and a solvent 32 as circulation dissolution means, and a solvent 32 through circulation piping 30 or A circulation pump 12 for circulating a mixture of the drug 34 and the solvent 32 may be provided.

  In the drug dissolving apparatus 1, a drug container 14 containing a drug 34 (for example, a dialysis agent) to be a solute dissolved in the solvent 32 is attached to the drug dissolving apparatus 1. The circulation discharge port of the dissolution tank 10 and the suction port of the circulation pump 12 are connected by a pipe 20, the discharge port of the circulation pump 12 and the drug container 14 are connected by a pipe 16, and the solvent in the dissolution tank 10 is Reference numeral 32 is fed to the piping 20 and piping 16 by the circulation pump 12 so that it can be supplied into the medicine container 14. The drug container 14 and the inlet of the dissolving tank 10 are connected by a pipe 18 so that the mixed liquid containing the drug 34 and the solvent 32 in the drug container 14 can be discharged into the dissolving tank 10 through the pipe 18. Thus, the liquid mixture containing the drug 34 and the solvent 32 is circulated in the order of the drug container 14, the pipe 18, the dissolving tank 10, the pipe 20, the circulation pump 12, the pipe 16, and the drug container 14. .

  A circulation pipe connection port 22 is connected to the mouth of the medicine container 14. A connecting mechanism that operates to connect with the mouth of the medicine container 14 to the circulation piping connection port 22 and a posture of the medicine container 14 while supporting the medicine container 14 after being connected with the mouth of the medicine container 14 For example, a posture changing mechanism is provided which operates so as to change the state where the mouth of the medicine container 14 is upward (upright state) to the state where the mouth of the medicine container 14 is downward (upside down). The circulation pipe connection port 22 is connected, for example, to one end of the pipe 16, and is connected to a supply port for supplying the solvent 32 or the mixed liquid into the medicine container 14, and to one end of the pipe 18. The supply port and the discharge port can communicate with the inside of the medicine container 14 in a liquid tight state.

  A branch pipe 36 is connected to the discharge port of the dissolution tank 10, and the branch pipe 36 is connected to a dialysate supply device such as a multi-party dialysate supply device (not shown) via the discharge valve 26. May be In addition, the pipe 16 is provided with a densitometer 28 comprising a conductivity meter or the like as a chemical liquid concentration measuring means, and the concentration meter 28 determines whether the concentration of the chemical liquid (mixed liquid) flowing in the circulation pipe 30 has reached a predetermined value. It may be configured such that it can be determined whether or not the drug 34 is sufficiently dissolved by the solvent 32, that is, whether or not preparation of the drug solution is completed. The connection position of the branch pipe 36 may not necessarily be the discharge port of the dissolution tank 10, or may be an intermediate portion of the circulation pipe 30, and is not particularly limited. The installation position of the concentration meter 28 may be in the middle of the circulation pipe 30, and is not particularly limited, but may be the dissolution tank 10.

  The drug dissolution apparatus 1 may include a control device 24 as a control means. The control device 24 is connected to the circulation pipe connection port 22 and the circulation pump 12 by electrical connection or the like, and the control of the circulation pipe connection port 22 and the circulation pump 12 is enabled based on a signal from the control device 24. Further, the control device 24 is connected to the concentration meter 28 by electrical connection or the like, and the drive control of the circulation pipe connection port 22 and the circulation pump 12 is possible based on the signal from the control device 24 based on the measurement value of the concentration meter 28. It may be done. The connection and support of the medicine container 14 by the circulation pipe connection port 22, the operation of changing the posture of the medicine container 14, and the driving of the circulation pump 12 will be described later.

  Next, the medicine container 14 will be described.

  The drug container 14 is made of, for example, a synthetic resin such as polyethylene, and has a bottle shape. The drug container 14 has, for example, a main body portion and a mouth portion, and the main body portion is formed, for example, in a cylindrical shape with a bottom, and the mouth portion is, for example, an opening and a tapered portion (tilted) And when the mouth portion of the medicine container 14 and the circulation pipe connection port 22 are connected, a tapered mouth portion is formed so as to surround the circulation pipe connection port 22. When the opening of the medicine container 14 is horizontal, the angle between the horizontal surface and the taper is smaller than the collapse angle of the medicine 34 contained in the medicine container 14 when the opening of the medicine container 14 is horizontal. Preferably, it is set to a large angle shape.

  The drug 34 contained in the drug container 14 is, for example, a carbohydrate component (eg, glucose), an electrolyte component (eg, sodium chloride, potassium chloride, magnesium chloride, calcium chloride), a pH adjuster (eg, anhydrous sodium acetate) Glacial acetic acid), an alkalized component (for example, sodium hydrogen carbonate) and the like are in the form of powder or granules, etc., and a predetermined amount is accommodated in the medicine container 14. In order to store the medicine 34 in the medicine container 14, for example, the medicine 34 is put in from the mouth of the medicine container 14, and a lid material made of a synthetic resin such as polyethylene is welded to the mouth of the medicine container 14 It may be sealed by the method of As a result, when the medicine 34 is stored in the medicine container 14, the medicine 34 in the inside is hardly denatured, so storage, transportation and the like are easy.

  Among the components to be the raw material of the dialysis agent are components having pseudocrystal polymorphs such as hydrate and anhydride (eg, glucose, calcium chloride, magnesium chloride, sodium acetate). When an aggregate of substances having pseudocrystal polymorphs is brought into contact with a solvent such as water and allowed to stand still for a certain period of time, substances having pseudocrystal polymorphs may adhere to each other to form aggregates. Since the aggregates have a small contact area with a solvent (eg, water), if the aggregates are generated during the dissolution operation of the drug, it may take a lot of time to completely dissolve the drug.

  Next, the method of dissolving the drug 34 in the drug dissolving apparatus 1 will be described. First, as shown in FIG. 2, the dissolution tank 10 contains a predetermined amount of a solvent (for example, water) 32 for dissolving the drug 34 (specifically, for example, the amount of the drug 34 stored in the drug container 14 When the solution is dissolved in the solvent 32, the amount of the solution component suitable for use as a chemical solution is stored in advance, the discharge valve 26 is closed, and the solvent 32 in the dissolution tank 10 is circulated. It is made to flow into the suction port of the pump 12.

  For example, the connection mechanism of the circulation pipe connection port 22 is drive-controlled by the control device 24, and the mouth of the medicine container 14 and the circulation pipe connection port 22 are connected in a state where the port faces upwards (upright state) Let After the mouth of the medicine container 14 and the circulation pipe connection port 22 are connected, for example, the posture changing mechanism of the circulation pipe connection port 22 is driven and controlled by the control device 24, and as shown in FIG. It is operated while supporting the medicine container 14 of the circulation pipe connection port 22 so that the part is directed downward (inverted state).

  Next, as shown in FIG. 4, the supply port of the solvent 32 to the drug container 14 and the drug container 14 communicated with the circulation pipe 30 in a state where the mouth of the drug container 14 faces downward (inverted state). The medicine 34 in the medicine container 14 can flow toward the circulation pipe connection port 22 having the mixed liquid discharge port from the above (the state where the drug 34 is concentrated on the circulation pipe connection port 22), Supply of the solvent 32 to the container 14 (dissolution operation) is started (circulation dissolution step). For example, after the mouth of the medicine container 14 is directed downward, the circulation pump 12 is driven and controlled by, for example, the controller 24, and the solvent 32 in the dissolution tank 10 is circulated by the circulation pump 12 through the piping 20 and the piping 16. Supplied to At this time, the circulation pump 12 is set so that, for example, the solvent 32 is delivered at a pressure (for example, a pressure of 100 kPa or less) that can withstand the drug container 14 without bursting.

  When the solvent 32 is supplied into the drug container 14, the drug in the vicinity of the mouth of the drug 34 in the drug container 14 is moved to the dissolving tank 10 together with the solvent 32 through the pipe 18. Then, if the drug 34 in the vicinity of the mouth in the drug container 14 is moved, the middle and upper part of the drug container 14 away from the mouth in the drug container 14 are the inner wall surface of the main body of the drug container 14 and the tapered portion. Along the inner wall surface, it is fluidly moved to the vicinity of the circulation pipe connection port 22 supplying the solvent 32, and is moved to the dissolution tank 10 together with the solvent 32 through the pipe 18.

  The dissolution operation is performed in a state where the medicine 34 in the medicine container 14 can flow (the medicine 34 as a solute is concentrated on the circulation pipe connection port 22) toward the supply port and the discharge port of the circulation pipe connection port 22. By being started, the drug 34 is supplied to the pipe 18 immediately after coming into contact with the solvent 32, so that the generation of aggregates or the amount of aggregates and the size of the aggregates are suppressed, and the dissolution rate in the solvent is increased. Improve. By starting the dissolving operation in a state in which the drug 34 in the drug container 14 can flow (a state in which the drug 34 as a solute is concentrated on the circulation pipe connection port 22), the pipe 18 is in a state where the concentration of the drug 34 is high. , And circulated through the dissolution tank 10 and the circulation pipe 30, so that the dissolution rate in the solvent is improved.

  Then, in the drug dissolving apparatus 1, the liquid mixture of the drug 34 and the solvent 32 is circulated in the dissolving tank 10 and the circulation pipe 30 of the drug dissolving apparatus 1 by continuing driving of the circulation pump 12, and the drug 34 is the solvent 32. The solution is sufficiently dissolved to prepare a drug solution of a predetermined concentration.

  As described above, in the drug dissolving apparatus and the drug dissolving method according to the embodiment of the present invention, the mixed solution of the drug 34 and the solvent 32 is supplied to the dissolving tank 10 through the closed circulation circuit in a high concentration slurry state. 34 can obtain many contact opportunities with the solvent 32. Therefore, the dissolution rate of the solid drug in the solvent can be improved, and in a short time, the solid drug can be dissolved in the solvent and adjusted to a predetermined concentration.

  In addition, since the drug 34 in the drug container 14 is moved to the dissolution tank 10 together with the solvent 32 through the pipe 18 immediately after coming into contact with the solvent 32, this is a case where the drug 34 contains a component having pseudocrystal polymorphism. Even if the group of substances having pseudocrystal polymorphs is contacted with water, it can reduce the chance of standing still for a certain period of time, and the occurrence of aggregates and the amount of aggregates even if aggregates are generated. And the size of aggregates can be suppressed, and the dissolution rate in the solvent is improved.

  As a state in which the drug 34 in the drug container 14 can flow toward the supply port of the solvent 32 to the drug container 14 and the discharge port of the mixed liquid from the drug container 14 in communication with the circulation piping 30, an external force is It is preferable that the drug 34 in the drug container 14 be in a flowable state by the action of gravity because it may not be given. The state in which the drug 34 in the drug container 14 can flow toward the supply port and the discharge port includes a flowable state by a solvent, a flowable state by compressed air, and a flowable state by gravity action. There are a flowable state by vibration, a flowable state by impact, and a flowable state by rotational movement. State that the mouth of the medicine container 14 to which the circulation pipe connection port 22 is connected is directed downward (inverted state), in which the medicine 34 in the medicine container 14 can flow by gravity action toward the supply port and the discharge port Although I mentioned as an example, it is not limited to this. For example, the supply port of the solvent 32 to the drug container 14 and the discharge port of the mixed liquid from the drug container 14 are provided on the side surface of the taper portion of the drug container 14 having a tapered shape that narrows from the body to the bottom. To start the dissolving operation in a state where the mouth of the medicine container 14 faces upward (in an upright state), the bottom of the medicine container 14 having a tapered shape which is tapered to narrow from the main body toward the bottom. The supply port of the solvent 32 to the drug container 14 and the discharge port of the mixed liquid from the drug container 14 are provided, and the dissolution operation is started in a state where the port of the drug container 14 faces upward (upright state) Methods etc.

  The state in which the mouth of the medicine container 14 faces downward means that the inclination of the taper of the mouth does not fall below the horizontal plane when the medicine container 14 is tilted. In addition to the case where the opening surface is in the horizontal state, the case where the opening surface of the mouth of the medicine container 14 is inclined, for example, 10 degrees to 60 degrees with respect to the horizontal plane is included.

  The shape of the medicine container 14 is capable of containing the medicine 34, and when the supply of the solvent 32 into the medicine container 14 is started, the medicine 34 accommodated therein is directed toward the supply port and the discharge port of the solvent 32. There is no particular limitation as long as it can flow. The shape of the drug container 14 is capable of containing the drug 34, and when the supply of the solvent 32 into the drug container 14 is started, the drug 34 contained therein is supplied with an outlet and an outlet for the solvent 32 by gravity. It is preferable that it is a shape which can flow toward. The medicine container 14 is, for example, a container having a bottomed, for example, a cylindrically formed main body, and a mouth provided with an opening. The medicine container 14 preferably has a bottomed body, for example, a cylindrically formed main body, and an opening, and a mouth including a tapered portion (inclined portion) which is inclined to narrow from the main body toward the opening. And a container. The tapered portion (inclined portion) may be inclined in a plane or in a curved shape. It is preferable that the inner wall surface of the drug container 14 does not have an uneven portion (for example, an uneven portion having a height of 100 μm or more).

  When the opening of the medicine container 14 is horizontal, the angle between the horizontal surface and the taper is smaller than the collapse angle of the medicine 34 contained in the medicine container 14 when the opening of the medicine container 14 is horizontal. The angle is preferably set to a large angle, and more preferably set to the repose angle of the medicine 34 or more. As a result, when the solvent 32 is supplied to the drug container 14 with the mouth of the drug container 14 facing downward (inverted state), the drug 34 is broken along the tapered portion toward the discharge port in order And the mixture of the drug 34 and the solvent 32 is transferred to the dissolution tank 10 almost without interruption.

  In the present specification, "repose angle" and "collapse angle" are piled up with one another to form peaks when the powder is dropped gently from a certain height toward one point. The angle formed by the slope of the mountain and the horizontal plane is called "rest angle", and the angle formed by the slope of the mountain and the horizontal plane broken by giving a certain impact is called "collapse angle".

  Specifically, when the opening of the medicine container 14 is horizontal, the angle formed by the horizontal plane and the taper is preferably 10 degrees to 60 degrees. It is preferable to set in the range, more preferably, in the range of 15 degrees to 55 degrees, and further preferably, in the range of 20 degrees to 50 degrees. If this angle exceeds 60 degrees, the height of the medicine container 14 may be long, and if it is less than 10 degrees, the medicine 34 may be difficult to flow by gravity.

  The circulation pipe connection port 22 is connected, for example, to one end of the pipe 16, and is connected to a supply port for supplying the solvent 32 or the mixed liquid into the medicine container 14, and to one end of the pipe 18. The supply port and the discharge port can communicate with the inside of the medicine container 14 in a liquid tight state. The supply port and the discharge port may be disposed at a position where the medicine 34 flows and concentrates, and for example, as shown in FIGS. As shown in 5, it may be opposed. In the example of FIG. 5, for example, the circulation pipe connection port 22 is connected to one end of the pipe 18 and has a discharge port for discharging the mixed liquid from the inside of the medicine container 14. One end of the pipe 16 is inserted, for example, from the bottom of the drug container 14 and is connected to a supply pipe 38 having a supply port for supplying the solvent 32 or the mixture into the drug container 14. It extends to the vicinity so as to face the discharge port of the pipe connection port 22. In this case, the supply of the solvent to the medicine container 14 may be started in a state where the medicine 34 can flow toward the supply port at the tip of the supply pipe 38 and the discharge port of the circulation pipe connection port 22.

  After the circulation pump 12 is operated with the mouth of the medicine container 14 facing downward and the medicine 34 near the mouth in the medicine container 14 is moved to the dissolution tank 10 to some extent, the solvent 32 is in the medicine container 14 In the filled state, even if the pendulum operation is performed so that the mouth of the medicine container 14 turns downward (inverted state) and upward (upright state) alternately, or the medicine container 14 is vibrated or circulated and dissolved. Good.

  After confirming that the dissolving operation has been properly completed by the concentration of the chemical solution reaching a predetermined concentration by the concentration meter 28 such as a conductivity meter, the circulation pump 12 is stopped by the control device 24, for example. The circulation pump 12 may be stopped based on a signal from the controller 24 based on the measurement value of the densitometer 28. The drug solution in the drug container 14 is transferred into the dissolution tank 10, the discharge valve 26 is opened, and the drug solution is supplied through the branch pipe 36 to a dialysis fluid supply device such as a multi-party dialysate supply device.

  The drug dissolving apparatus and drug dissolving method according to the present embodiment are mainly used for preparation of a dialysate used for artificial dialysis, and dissolve and adjust drugs such as powdered or granular solid dialysis agents to a predetermined concentration. It is for.

  The drug dissolving apparatus and the drug dissolving method according to the present embodiment are particularly useful for drugs containing a component having pseudocrystal polymorphism such as hydrate and anhydrate (eg, glucose, calcium chloride, magnesium chloride, sodium acetate) It can be suitably applied to dissolution.

  The dissolution tank 10 can be sealed, can contain a predetermined amount of solvent 32, or a mixed solution of drug 34 and solvent 32, and can dissolve drug 34 with solvent 32 to prepare a drug solution. Well, there is no particular restriction. The dissolution tank 10 may be equipped with a stirring device having a stirring blade or the like for stirring the solvent 32 in the dissolution tank 10 or a mixture of the drug 34 and the solvent 32. If circulation pipe 30 can accommodate a predetermined amount of solvent 32 or a mixed solution of drug 34 and solvent 32 and can dissolve drug 34 with solvent 32 to prepare a drug solution, dissolution tank 10 It can be omitted.

  The circulation pipe 30 is not particularly limited as long as the solvent 32, or a liquid mixture of the drug 34 and the solvent 32 can flow, and there is no particular limitation, for example, resin made of resin of inner diameter 55 mm to 〜25 mm, metal, etc. Piping is used.

  The concentration meter 28 which is a chemical liquid concentration measuring means is not particularly limited as long as it can measure the concentration of the drug 34 in the mixture of the drug 34 and the solvent 32, but there is no particular limitation. Ultrasonic densitometer, refractometer, spectrophotometer and the like.

  The circulation pipe connection port 22 has, for example, a cylindrical shape such as a cylindrical shape made of a resin material having rigidity, a metal material or the like.

  The connection mechanism provided in the circulation pipe connection port 22 may be any mechanism that operates to connect the circulation pipe connection port 22 with the mouth of the medicine container 14, and is not particularly limited. In the connection mechanism, for example, a drive unit is connected to the circulation pipe connection port 22, and the drive unit is driven based on a drive signal from the control device 24, for example, and circulates to the mouth of the medicine container 14 installed. The pipe connection port 22 is configured to be fitted and connected. A space between the mouth of the medicine container 14 and the fitting portion of the circulation pipe connection port 22 is sealed by, for example, a sealing member or the like.

  The posture changing mechanism provided in the circulation piping connection port 22 is a state in which the mouth of the medicine container 14 faces downward from the state where the mouth of the medicine container 14 faces upward (the upright state) There is no particular limitation as long as the mechanism operates to change to the inverted state). In the posture changing mechanism, for example, a rotational drive unit such as a motor is connected to the circulation pipe connection port 22, and the rotational drive unit is driven based on a drive signal from the control device 24, for example, to change the posture of the medicine container 14. It is configured to be able to. The medicine container 14 may be attached to the medicine dissolving apparatus 1 in a state where the mouth of the medicine container 14 faces downward (inverted state). In this case, the drug dissolution apparatus 1 may not include the posture change mechanism. The tapered portion of the medicine container 14 need not be provided at the mouth, and may be, for example, at the bottom of the main body of the medicine container 14 (opposite the opening (the medicine filling port)).

  The control device 24 is configured to include a control element such as a CPU, and has a function of controlling the circulation pump 12, the concentration meter 28, the connection mechanism of the circulation pipe connection port 22, the attitude change mechanism, and the like.

  The drug dissolution apparatus 1 may further include at least one of a storage unit, a user interface, an input unit, and the like. The storage unit includes, for example, storage devices such as a semiconductor memory, a hard disk, and an optical disk device, and can store and hold electronic information such as programs and data processed by the control device 24. The user interface is configured to include a monitor, a touch panel, and the like, and is used to receive an instruction or the like from the user to the control device 24 or to present information to the user. The input unit is configured to include a keyboard, a mouse, a touch panel, and the like, and is used to obtain various information used for processing from the user. When the user interface includes an input unit such as a touch panel, the input unit may not be provided.

  The drug 34 is a solid drug, for example, in the form of powder or granules. The drug 34 is, for example, a dialysis agent containing at least one of an electrolyte component, a pH adjuster, a carbohydrate component, and an alkalized component.

  Examples of the electrolyte component include sodium chloride, potassium chloride, magnesium chloride, calcium chloride and the like.

  Examples of pH adjusters include organic solid acids such as citric acid anhydride, malic acid, lactic acid, fumaric acid, succinic acid and malonic acid, citrates such as sodium citrate, and acetates such as sodium acetate and sodium diacetate , Lactates such as sodium lactate, malates such as sodium malate, fumarates such as sodium fumarate, succinates such as sodium succinate, organic acid salts such as malonic acid such as sodium malonate, etc. It can be mentioned. Among these, preferred as a pH adjuster are citric acid monohydrate, sodium citrate anhydride, sodium citrate dihydrate, acetic acid, sodium diacetate, sodium acetate anhydride in addition to citric acid anhydride It is.

  Examples of the sugar component include glucose such as anhydrous crystalline glucose and the like.

  As an alkalization component, sodium hydrogencarbonate (sodium bicarbonate) etc. are mentioned, for example.

  The solvent 32 is, for example, water.

  The amount of the solvent 32 used, that is, the amount of the solvent 32 stored in advance in the dissolution tank 10 is, for example, a solution component suitable as a drug solution when the amount of the drug 34 stored in the drug container 14 is dissolved in the solvent 32 The amount may be set so as to obtain the concentration.

  The temperature of the solvent may be, for example, in the range of 10 ° C to 50 ° C.

  The flow rate of the solvent 32 supplied into the drug container 14 at the start of the operation of the drug dissolving apparatus 1, that is, at the start of the operation of the circulation pump 12 is such that the drug in the vicinity of the mouth of the drug 34 in the drug container There is no particular limitation as long as the flow rate can be moved to the dissolution tank 10 together with the solvent 32 through the above, and for example, it may be in the range of 5 liters / minute to 40 liters / minute.

  Each step of the drug dissolution method according to the present embodiment is converted into a computer-processable drug dissolver control program, and stored and held in a storage unit or the like. The control device 24 of the drug dissolution apparatus 1 reads out the drug dissolution apparatus control program stored in the storage unit or the like, and the drug dissolution apparatus 1 executes each step of the drug dissolution method according to the present embodiment.

  A drug dissolution apparatus control program according to an embodiment of the present invention is a drug dissolution apparatus control program for preparing a solution by dissolving a solid type drug with a solvent, the medicine dissolution apparatus comprising: A solvent is supplied to a drug container containing a drug, and a mixed solution of the drug and the solvent discharged from the drug container is further circulatingly supplied to the drug container to circulate and dissolve, and the circulating solution step is included. To the drug container in a state where the drug in the drug container can flow toward the supply port of the solvent to the drug container and the discharge port of the mixed liquid from the drug container in communication with a pipe And a program for executing the method of starting the supply of the solvent.

  Hereinafter, the present invention will be described in more detail by way of examples and comparative examples, but the present invention is not limited to the following examples.

Example 1
[sample]
As a drug, a sample in which 2.4 kg of anhydrous crystalline glucose (the amount by which the drug is 80% of the internal volume of the container) was enclosed in a drug container (internal volume 4 L) was used. As a medicine container, a container having a cylindrical main body with a bottom and a mouth provided with a taper and an opening was used. The tapered portion of the drug container was inclined in a plane, and when the opening of the drug container was horizontal, a drug container in which the angle between the horizontal surface and the tapered portion was 36 degrees was used. The angle of repose of anhydrous crystalline glucose is 33 degrees, the collapse angle is 31 degrees. The powder is made to fall gently toward one point from a height of 160 mm, stacked on top of each other to form a mountain, and the angle between this mountain slope and the horizontal plane is defined as the angle of repose. The impact angle of 17N was given three times, and the slope of the collapsed mountain and the horizontal plane was defined as the collapse angle.

[Experimental device]
As shown in FIG. 2, a circulation pump (flow rate: 29 L / min), a drug container, and a dissolution tank (containing 10.3 L of pure water (reverse osmosis membrane treated water) at 25 ° C. as a solvent) are connected by circulation piping. The experimental apparatus of the dissolution method was used in which reverse osmosis membrane treated water was supplied from the dissolution tank into the drug container, and a mixed solution of drug and solvent was supplied from the inside of the drug container to the dissolution tank (circulating dissolution). State that the mouth of the medicine container faces downward (inverted state), using the circulation pipe connection port for connecting the drug container and the circulation pipe, and connecting the supply port and the discharge port on the plane at the circulation pipe connection port The drug was placed at a position where it would flow and concentrate by gravity. As the circulation pipe, a silicon resin pipe having an inner diameter of 15 mm was used.

[experimental method]
The above sample (drug container) is connected to the above experimental apparatus, and the following dissolution operation (1) (Example 1), dissolution operation (2) (Comparative Example 1) or dissolution operation (3) (Comparative Example 2) respectively The device was turned on and the weight of the remaining drug was measured if it did not dissolve within 240 seconds of operation and time for the drug to dissolve and the circulation pump was turned on. Three experiments were performed for each dissolution operation. The results are shown in Table 1.
Dissolution operation (1): The circulation pump is operated with the mouth of the medicine container facing downward (inverted state), and circulation dissolution dissolution operation (2): state where the mouth of the medicine container faces upward (standing state) 10 seconds after the circulation pump is operated, and with the water filled in the medicine container 10 seconds after the circulation pump is operated, the mouth is downward (inverted) for 20 seconds, and upward (upright) for 13 seconds Circulating dissolution Dissolution operation (3): The circulation pump is operated with the mouth of the medicine container facing upward while operating the pendulum so that the direction of the mouth changes alternately.

  In the dissolution operation (1) of Example 1, in all three experiments, the drug (anhydrous crystalline glucose) dissolves within 30 seconds after operating the circulating pump, and neither generation of aggregation nor dissolution residue is visually observed The In the dissolution operation (2) of Comparative Example 1 and the dissolution operation (3) of Comparative Example 2, the drug did not dissolve even in 240 seconds after the operation of the circulation pump in all three experiments, and the generation of aggregates and dissolution The rest was seen. In the dissolution operation (3) of Comparative Example 2 which is considered to be the most disadvantageous operation for the dissolution of the drug, the amount of undissolved matter is larger than that of the dissolution operation (2) of Comparative Example 1.

  In the dissolution operation (2) of Comparative Example 1, the circulation pump is operated with the mouth of the medicine container facing upward, and after the solvent is filled in the medicine container, pendulum operation is performed. It is considered that the agent which has been in contact for a while is in a stationary state for a while, and the drug immersed in the solvent aggregates and the dissolution rate in the solvent decreases.

  Thus, by the dissolution operation (1) of Example 1, it was possible to improve the dissolution rate of the solid drug in the solvent and prepare a solution of a predetermined concentration.

  Reference Signs List 1 drug dissolving apparatus, 10 dissolving tank, 12 circulating pumps, 14 drug containers, 16, 18, 20 pipes, 22 circulating pipe connection ports, 24 controllers, 26 discharge valves, 28 concentration meter, 30 circulating pipes, 32 solvents, 34 Drug, 36 branch piping, 38 supply piping.

Claims (8)

A drug dissolving apparatus for dissolving a solid drug with a solvent to prepare a solution,
A solvent is supplied to a drug container in which the drug is stored, and a circulating solution means having a circulation pipe for circulating and supplying a mixed solution of the drug and the solvent discharged from the drug container to the drug container is further provided. ,
The drug in a state in which the drug in the drug container can flow toward the supply port of the solvent to the drug container and the discharge port of the mixed liquid from the drug container in communication with the circulation pipe. A drug dissolving apparatus characterized in that the supply of the solvent to the container is started. The drug dissolving apparatus according to claim 1, wherein
A circulation pipe connection port having the supply port and the discharge port is connected to the mouth of the drug container, and the medicine in the drug container can flow toward the supply port and the discharge port. The drug dissolving apparatus, wherein the supply of the solvent to the drug container is started. The drug dissolving apparatus according to claim 1 or 2, wherein
A drug dissolving apparatus characterized in that supply of the solvent to the drug container is started in a flowable state by gravity action. A drug dissolving method for preparing a solution by dissolving a solid drug with a solvent, wherein
A solvent is supplied to a drug container containing the drug through a circulation pipe, and a mixed solution of the drug and the solvent discharged from the drug container is further circulatingly supplied to the drug container to circulate and dissolve it. Including
The drug in a state in which the drug in the drug container can flow toward the supply port of the solvent to the drug container and the discharge port of the mixed liquid from the drug container in communication with the circulation pipe. A drug dissolving method comprising starting supply of the solvent to a container. The drug dissolution method according to claim 4, wherein
A circulation pipe connection port having the supply port and the discharge port is connected to the mouth of the drug container, and the medicine in the drug container can flow toward the supply port and the discharge port. Starting the supply of the solvent to the drug container. The drug dissolution method according to claim 4 or 5, wherein
A drug dissolution method characterized in that supply of the solvent to the drug container is started in a flowable state by gravity action. A drug dissolution apparatus control program for preparing a solution by dissolving a solid drug with a solvent, the program comprising:
In the drug dissolution device,
A solvent is supplied to a drug container containing the drug through a circulation pipe, and a mixed solution of the drug and the solvent discharged from the drug container is further circulatingly supplied to the drug container to circulate and dissolve it. Including
The drug in a state in which the drug in the drug container can flow toward the supply port of the solvent to the drug container and the discharge port of the mixed liquid from the drug container in communication with the circulation pipe. A drug dissolution apparatus control program, which executes a method of starting supply of the solvent to a container. The drug dissolution apparatus control program according to claim 7, which is
A drug dissolving device control program, which executes a method of starting supply of the solvent to the drug container in a flowable state by gravity action.

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