JP2007114172A - Apparatus for measuring diffusion of percutaneously absorptive drug - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an apparatus for measuring the diffusion of a percutaneously absorptive drug capable of easily measuring diffusion properties (percutaneous absorbability) of the percutaneous absorptive drug over a long time. <P>SOLUTION: The apparatus for measuring the diffusion of percutaneously absorptive drug comprises a cell for measuring the diffusion of percutaneously absorptive drug; a receptor solution supply device for supplying a receptor solution for the diffusion measuring cell; a rotator housed in the diffusion measuring cell; a thermostatic chamber for housing the diffusion measuring cell; a rotating device arranged below the thermostatic chamber for rotating the rotator; and a receptor solution preparative isolation device for preparatively isolating and storing a chemical solution diffused in a receptor solution from a percutaneously absorptive drug. The thermostatic chamber is made of a metal block in which a recession part or a through hole for housing the diffusion measuring cell is formed and in which a temperature regulating device is installed. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a diffusion measurement device for measuring a state in which a drug of a transdermally absorbable preparation permeates and diffuses through the skin.

In general, Franz cells have been used as a device for measuring the speed at which a specific substance is absorbed by a certain membrane and moves from one side of the membrane to the other.
A Franz cell sandwiches a membrane between an upper container and a lower container, supplies a substance to be measured to the upper container, supplies a receptor liquid to the lower container, and after a predetermined time, determines the concentration of the substance to be measured in the receptor liquid. It is a device that measures the diffusion rate by measuring.

  However, when a transdermal absorption preparation such as nitroglycerin tape, ISDN tape, indomethacin gel, prednisolone ointment, etc. is applied to the human body, the state in which the drug contained in the percutaneous absorption preparation is absorbed by the human body is grasped over time. It is an essential requirement for treatment, but the above-mentioned Franz cell alone could not measure the change over time in the diffusion rate of the drug over a long period of time.

  In order to measure the diffusion state of the substance to be measured over time, a diffusion cell that is a Franz-type cell shown in FIG. FIG. 8 is a schematic cross-sectional view showing an example of a proposed diffusion cell.

  In the figure, 100 is a cylindrical container body having a flange at the upper end, and 200 is an upper container having a cylindrical shape and having a flange at the lower end. Around the container main body 100, a jacket 101 having a heat retaining liquid inlet 102 near the lower end and a heat retaining liquid outlet 103 near the upper end is installed. In addition, a receptor liquid injection port 104 communicates with the vicinity of the lower end of the container body 100, and a sample collection part 105 for collecting a sample is installed in a branch shape in the middle part of the container body 100. A sample collection tube 300 is inserted into the sample collection unit 105 so that the tip thereof reaches the approximate center of the container body 100.

  In order to measure the diffusion state of the substance to be measured over time in the diffusion cell, first, the rotor 400 is supplied into the container body 100, and the membrane 500 is formed by the flange of the container body 100 and the flange of the upper container 200. Hold it. Next, the receptor liquid is injected from the receptor liquid injection port 104 to fill the container body 100, and the rotor 400 is rotated to stir the receptor liquid.

Further, a heat retaining medium heated to a predetermined temperature is injected from the heat retaining liquid inlet 102 into the jacket 101, and a measurement target substance is supplied onto the membrane 500 on the upper container 200 side. Then, a predetermined amount of the receptor liquid is injected from the receptor liquid inlet 104 every predetermined time, and the receptor liquid in which the substance to be measured is diffused overflows from the sample collection tube 300, and the obtained sample liquid is measured. The concentration of the target substance is measured, and the diffusion state is measured over time (for example, see Patent Document 1).
US Pat. No. 5,198,109

  The diffusion cell can measure the diffusion state of the substance to be measured over time. However, when measuring the diffusion of the drug contained in the transabsorbable preparation into the human body, it is necessary to measure for a long time over one to several days while maintaining the receptor liquid at a predetermined temperature. The receptor liquid in the container body 100 is maintained at a predetermined temperature by always injecting a heat-retaining medium heated to a predetermined temperature from the heat-retaining liquid inlet 102 into the jacket 101 and circulating during measurement. It was cumbersome and difficult to maintain the temperature of the receptor liquid at a constant temperature for 1 to several days by injecting and circulating the heated heat-retaining medium into the jacket 101.

  It is also possible to measure by immersing the diffusion cell without the jacket 101 in a constant-temperature water tank, but if the measurement is performed for a long time, the water in the constant-temperature water tank evaporates and is difficult to manage. In general, since the internal volume of the container body 100 is a small cell of 3 to 10 ml, it is difficult to measure stably for a long time by standing in a constant temperature water tank.

  An object of the present invention is to provide a diffusion measuring device for a percutaneously absorbable preparation that can easily measure the diffusibility (percutaneous absorbability) of the percutaneously absorbable preparation over a long period of time in view of the above drawbacks.

  A diffusion measurement device for a transdermal absorption preparation according to the present invention includes a diffusion measurement cell for a transdermal absorption preparation, a receptor liquid supply device for supplying a receptor liquid to the diffusion measurement cell, a rotor accommodated in the diffusion measurement cell, A thermostatic chamber for storing the diffusion measurement cell, a rotating device for rotating the rotor, and a receptor liquid sorting device for separating and storing the drug solution diffused from the transdermal absorption preparation to the receptor liquid. The receptor liquid supply device and the receptor liquid injection path of the diffusion measurement cell are communicated by a receptor liquid supply tube, and the receptor liquid discharge path of the diffusion measurement cell and the receptor liquid sorting device are communicated by a receptor liquid discharge tube. The thermostatic chamber is made up of a metal block in which a recess or a through-hole for accommodating the diffusion measurement cell is formed and a temperature control device is installed. I am characterized in.

  As the diffusion measurement cell of the transdermal absorption preparation, any diffusion measurement cell conventionally used as a diffusion measurement cell can be used. For example, the diffusion cell shown in FIG. Since the diffusion measurement cell is housed in a thermostat and maintained at a predetermined temperature, a diffusion cell in which the jacket 101 is not installed in the diffusion cell can be used.

  However, when measuring the diffusion rate of the drug of the transdermal absorption preparation using the diffusion cell, the transdermal absorption preparation and the skin are sandwiched between the upper surface of the container body 100 so that the skin is on the receptor chamber side. Since the receptor liquid is injected from the lower end of the container body 100 to fill the container body 100, air bubbles remain on the lower surface of the skin, and the contact area between the skin and the receptor liquid is not constant, and accurate data cannot be obtained. It was. Moreover, it was very difficult to remove the bubbles, and a long time was required. Therefore, a lot of labor and time are required for the measurement, and it was difficult to perform a large number of measurements.

  Therefore, a diffusion measurement cell having a structure in which bubbles do not remain between the skin and the receptor liquid when the receptor liquid is injected into the receptor chamber is preferable, and an opening for installing the skin and the percutaneous absorption preparation is provided in the middle part of the side wall. A cell body in which a receptor chamber for filling a receptor liquid is formed, and a lid for fixing the skin and the percutaneously absorbable preparation to the opening. A diffusion measurement cell in which a receptor liquid discharge path communicating with the outside of the cell and a receptor liquid injection path communicating with the outside of the cell main body from the vicinity of the lower end of the side wall of the receptor chamber are preferable.

  When measuring with the above diffusion measurement cell, the diffusivity of the percutaneous absorption preparation is measured, so the diffusion measurement cell is placed in a constant temperature bath at the same temperature as the body temperature of the person, animal, etc. to which the percutaneous absorption preparation is applied. Since it is necessary to stand up and it is preferable to perform many measurements at the same time, the shape of the cell body is preferably a substantially cubic or rectangular parallelepiped.

  The lid is not particularly limited as long as it can fix the skin and the percutaneous absorption preparation to the opening, but since the skin and the percutaneous absorption preparation are soft, they can be securely fixed without being deformed into the opening. In order to do this, it preferably comprises a holding member for holding the skin and the transdermally absorbable preparation in the opening, and a lid body for pressing and fixing the holding member to the opening.

  Further, in order to easily and surely press and fix the holding member to the opening by the lid body, the lid body is preferably made to be screwable with the side wall of the cell body.

  The cell body and lid (lid body and holding member) may be formed of any conventionally known material used for diffusion measurement cells. Thermoplastic resins such as methyl methacrylate resin and polycarbonate resin are preferred. This thermoplastic resin preferably does not substantially contain a compound that can be eluted in the receptor liquid.

  The cell body is preferably formed of a transparent thermoplastic resin so that the receptor chamber, receptor liquid discharge path and receptor liquid injection path can be seen from the outside.

  The shape of the receptor chamber is not particularly limited, but it is preferable to be agitated so that the drug to be measured in the receptor liquid is uniform. The upper part of the receptor chamber is gradually directed toward the receptor liquid discharge path. It is preferable that it is made into a trumpet shape so as to be thin.

  In addition, an opening for installing the skin and the transdermally absorbable preparation is formed in the intermediate portion of the side wall of the receptor chamber. The shape of the opening is not particularly limited, and examples thereof include a circle, an ellipse, and a quadrangle.

  The skin is not particularly limited as long as it is a skin that has been conventionally used for measuring the diffusibility of a transdermally absorbable preparation. For example, human skin, rat, mouse, miniature pig, monkey, snake, rabbit, Examples include animal skin such as guinea pigs, artificial skin, dialysis membranes, and silicon membranes.

  In order to form a receptor chamber, a receptor liquid discharge path, and a receptor liquid injection path in the cell body, a method of drilling a recess for the receptor chamber, receptor liquid discharge path and receptor liquid injection path in the cell body and embedding necessary portions Is preferably formed.

  When measuring with the above diffusion measurement cell, since the diffusibility of the transdermally absorbable preparation is measured, it is necessary to install the diffusion measurement cell in a thermostatic bath at a temperature substantially the same as the human body temperature. The openings of the discharge channel and the receptor liquid injection channel are preferably opened on the upper wall of the cell body.

  In the device for measuring the diffusion of a percutaneously absorbable preparation of the present invention, in order to supply the receptor fluid to the diffusion measurement cell (receptor chamber), the receptor fluid supply device and the receptor fluid injection path of the diffusion measurement cell are the receptor fluid supply tube. In addition, in order to supply the receptor liquid in the diffusion measurement cell (receptor chamber) to the receptor liquid sorting device, the receptor liquid discharge path of the diffusion measurement cell and the receptor liquid sorting device are connected to the receptor liquid discharge tube. It is communicated by.

  It is preferable that the receptor liquid discharge path, the receptor liquid discharge tube, and the receptor liquid injection path and the receptor liquid injection tube are connected easily and reliably in a liquid-tight manner. It is preferable that a threaded groove is cut and a connecting member is installed at the end of the receptor liquid discharge tube or receptor liquid injection tube, and the connecting member is watertightly screwable.

  When the inner diameter of the receptor fluid discharge tube and the receptor fluid injection tube is increased, the drug diffused from the percutaneous absorption preparation into the receptor fluid in the receptor chamber diffuses into the receptor fluid in the tube, and the measurement accuracy is reduced. In general, it is 0.2 to 5 mm, preferably 0.5 to 2 mm.

  In addition, when the length of the tube for discharging the receptor liquid is increased, a large amount of the receptor liquid is infused into the receptor chamber when the receptor liquid in which the drug of the percutaneous absorption preparation is diffused is measured by infusion into the receptor liquid sorting device. It is necessary to reduce the concentration of the receptor solution drug in the receptor chamber and decrease the measurement accuracy. Therefore, the shorter one is preferable, generally 20 to 100 cm, and preferably 30 to 50 cm.

  The receptor liquid supply device is not particularly limited as long as it is a device that supplies the receptor liquid to the diffusion measurement cell. However, when measuring, it is necessary to supply a predetermined amount of the receptor liquid every predetermined time. The liquid supply device includes a receptor liquid storage container and a pump capable of transporting a predetermined amount of receptor liquid. The receptor liquid storage container and the pump are communicated by an infusion tube, and the pump is communicated by a receptor liquid supply tube. It is preferable.

  Moreover, in the diffusion measurement apparatus for transdermally absorbable preparations of the present invention, it is preferable that a large number of measurements can be performed at the same time. Therefore, one receptor liquid supply apparatus and one diffusion measurement cell are connected, and a plurality of diffusion measurement cells are installed. Preferably it is done.

  The receptor fluid sorting device is a device for sorting and storing the receptor fluid at different times in order to measure the concentration of the drug diffused in the receptor fluid. Any device having the same function as the fraction collector in principle can be used.

  In the receptor liquid sorting apparatus, the receptor liquid in which the transdermal drug agent that has been transfused is diffused is stored in a sample cell of the receptor liquid sorting apparatus, and then a device for measuring the concentration (for example, high performance liquid chromatography). Graph (HPLC), gas chromatograph, etc.).

  For example, a sample cell in which a receptor liquid into which a drug of a transdermal absorption drug that has been infused has been separated is collected is placed in an HPLC sample holder, and the drug concentration is measured by HPLC.

  The thermostat is made of a metal block in which a recess or a through-hole for accommodating the diffusion measurement cell is formed and a temperature control device is installed.

  The metal block may be a lump of metal or may be a block formed by laminating metal plates. As the metal, for example, any metal such as iron, stainless steel, and aluminum can be used. However, a metal that is lightweight, excellent in formability, and excellent in rust prevention is preferable, and aluminum is preferably used.

The shape of the recess or the through hole is not particularly limited. However, since the diffusion measurement cell is accommodated and held at a predetermined temperature, the substantially same shape as the diffusion measurement cell is preferable so that the diffusion measurement cell can be closely accommodated. When the shape of the diffusion measuring cell is substantially a cube or a rectangular parallelepiped, a rectangular tube is preferable.
It is preferable that a large number of recesses or through-holes are formed so that diffusion measurement of a large number of transdermal preparations can be performed.

  Further, the temperature control device is not particularly limited, and any conventionally known temperature control device can be used. For example, a heating device such as a planar heater or a linear heater installed in or around a metal block and connected thereto. And a temperature control device comprising a temperature controller such as a thermostat.

  Another example of the temperature control device is a temperature control device including a pipe installed in or around a metal block and a circulation device for circulating a liquid medium such as water or oil at a predetermined temperature through the pipe.

  The rotating device is a device that is installed under a thermostatic chamber and rotates a rotor housed in the diffusion measurement cell, and any conventionally known rotating device can be used. In the case where a plurality of recesses or through holes are formed for storing the diffusion measurement cells formed in the thermostatic bath, the diffusion measurement cells are stored in the respective recesses or through holes. A rotating device is preferably installed so as to correspond to the through-hole, and a rotating device in which a plurality of rotating devices generally called 6-stir stirrers, 12-stir stirrers and the like are integrally installed is preferable.

  Next, a method for measuring the diffusion of the drug in the transdermal absorption preparation using the diffusion measurement cell with the diffusion measurement apparatus for the transdermal absorption preparation of the present invention will be described.

  First, the rotor is housed in the receptor chamber, the diffusion measurement cell is placed with the opening facing upward, and the skin and percutaneous absorption preparation are placed so as to close the opening, and the skin is placed on the receptor chamber side. It fixes to an opening part with a cover so that it may become.

  If the transdermal preparation is in the form of an adhesive tape, it may be applied directly to the skin, but if it has gel-like or ointment-like fluidity, it is preferably applied and applied to a sheet substrate such as a synthetic resin sheet. .

  If the lid consists of a lid body and a holding member, place the skin and the transdermal absorption preparation so as to close the opening, place the holding member on it, temporarily fix the skin and the transdermal absorption preparation, Next, the lid body is pressed and fixed. In addition, after temporarily fixing the skin and the percutaneous absorption preparation to the holding member, the holding member on which the skin and the percutaneous absorption preparation are temporarily fixed is placed so as to close the opening with the skin and the percutaneous absorption preparation. You may press and fix with a main body. In this case, even if the lid body is screwed to the side wall of the cell body, the skin and the transdermally absorbable preparation are temporarily fixed by the holding member, so that they are not twisted or wrinkled.

  Next, the diffusion measurement cell is accommodated in the concave portion or the through hole of the metal block of the thermostatic bath so that the skin and the transdermal absorption preparation are vertically oriented, and the receptor liquid is filled in the receptor chamber. That is, the diffusion measurement cell is accommodated in the concave portion or the through hole of the metal block of the thermostat so that the upper wall of the cell body is on the top. In order to fill the receptor chamber with the receptor solution, it is preferable to supply the receptor solution by a pump, particularly for simultaneous measurement using many diffusion cells.

  Before storing the diffusion measurement cell in the thermostatic chamber, the receptor liquid supply device and the receptor liquid injection path of the diffusion measurement cell are connected by a receptor liquid supply tube, and the receptor liquid discharge path of the diffusion measurement cell and the receptor liquid separation are connected. It is preferable that the apparatus is communicated with a receptor liquid discharge tube.

  Since the skin and the transdermally absorbable preparation are installed vertically, bubbles do not adhere to the skin surface when the receptor liquid is filled. For example, even if air bubbles adhere to the skin surface, the air bubbles can be easily removed by vibrating the diffusion measurement cell.

  Next, the receptor liquid is maintained at a predetermined temperature in the thermostatic chamber, and the rotor is rotated to diffuse the drug from the percutaneous absorption preparation into the receptor liquid. Since the diffusion rate of the drug in the percutaneously absorbable preparation is measured, it is preferable that the receptor liquid is kept substantially the same as the body temperature of the subject to which the percutaneously absorbable preparation is applied. The rotor also stirs the receptor fluid in the receptor chamber to make the drug concentration in the receptor fluid uniform. The rotation of the rotor is generally rotated by a rotating device installed under the receptor chamber (diffusion measurement cell, thermostat).

  Then, at a predetermined time (generally 1 to 4 hours), the receptor fluid is infused into the receptor chamber, whereby the receptor fluid in which the drug of the percutaneous absorption preparation is diffused is infused into the receptor fluid fractionation device. The receptor fluid that has been infused by the collecting device is collected and stored in the sample cell.

When injecting the receptor fluid into the receptor chamber for measurement, the receptor fluid initially remaining in the receptor fluid discharge tube is infused, so that the amount of receptor fluid infused into the receptor chamber is reduced. If the receptor fluid in the receptor chamber is not infused and the amount increases, the concentration of the receptor fluid in the receptor chamber diminishes and the measurement accuracy decreases, so the amount of receptor fluid infused into the receptor chamber for one measurement is 0.05-2.0 cm < ³ > is preferable, More preferably, it is 0.1-1.0 cm < ³ >.

  In addition, when the receptor fluid is infused into the receptor fluid separator and dispensed into the sample cell, the fluid that is first fed from the receptor fluid discharge tube to the sample cell is the fluid that was present in the tube. It is not a liquid having a concentration in the receptor chamber. Therefore, it is necessary to dispense the liquid after first discarding the liquid corresponding to the total volume of the receptor liquid discharge tube into the sample cell.

  The configuration of the diffusion measurement device for the transdermally absorbable preparation of the present invention is as described above, and it is not necessary to use water as a heating medium of the thermostatic bath, and since it does not evaporate during measurement, management is easy. The diffusivity (percutaneous absorbability) of the transdermally absorbable preparation can be easily measured over a long period of time.

  Next, a diffusion measuring device for a transdermally absorbable preparation of the present invention will be described with reference to the drawings. FIG. 1 is a schematic diagram showing an example of a diffusion measuring device for a transdermally absorbable preparation of the present invention. FIG. 2 (a) is a plan view showing an example of a thermostatic bath, and FIG. 2 (b) is a cross-sectional view taken along the line AA in FIG. 2 (b). FIG. 3 is a longitudinal sectional view showing an example of the cell body, and FIG. 4 is a sectional view taken along the line BB in FIG.

  FIG. 5 is a longitudinal sectional view showing an example of a state in which the skin and the transdermal absorption preparation are installed in the opening of the diffusion measurement cell, and FIG. 6 is a sectional view taken along the line CC in FIG. FIG. 7 (a) is a front view showing an example of the holding member, FIG. 7 (b) is a rear view, and FIG. 7 (c) is a side view.

  In FIG. 1, reference numeral 3 denotes a receptor liquid supply device. The receptor liquid supply device 3 includes a receptor liquid storage container 31 and a pump 33 capable of transporting a predetermined amount of receptor liquid. The receptor liquid storage container 31 and the pump 33 are infusion tubes. The pump 33 is in communication with the receptor liquid supply tube 7. The receptor liquid storage container 31 stores a receptor liquid 34.

  Reference numeral 4 denotes a thermostatic bath, which is electrically connected to the temperature controller 45 and maintained at a predetermined temperature. Reference numeral 1 denotes a substantially rectangular parallelepiped diffusion measurement cell which is housed in a rectangular tube-shaped through-hole of the thermostat 4 and is kept at a predetermined temperature by the thermostat 4.

  Reference numeral 5 denotes a rotating device installed on the lower side of the thermostatic chamber 4, and the rotor 2 in the receptor chamber is rotatably installed. When a plurality of diffusion measurement cells 1 are installed and a plurality of concentration measurements are performed at the same time, a rotating device (for example, a 12 stirrer) capable of rotating the plurality of rotors 2 at the same time is used.

  The receptor liquid injection path 13 of the diffusion measurement cell 1 and the pump 33 are communicated with each other by a receptor liquid injection tube 7. The receptor liquid discharge path 12 of the diffusion measurement cell 1 and the receptor liquid sorting device 6 are connected to a receptor liquid discharge tube 8. It is communicated by.

  In FIG. 2, reference numeral 42 denotes an aluminum block in which four rectangular tube-shaped through holes 43 are formed, and a planar heating element 44 is wound around the aluminum block. Reference numeral 41 denotes a rectangular tube-shaped heat insulating box made of a vinyl chloride resin plate, in which three aluminum blocks 42 are installed in the heat insulating box 41, and the planar heating element 44 is electrically connected to the temperature controller 45 to keep the temperature constant. A tank 4 is formed.

  3 and 4, reference numeral 10 denotes a substantially rectangular parallelepiped cell body made of a transparent vinyl chloride resin. The cell body 10 is formed with a receptor chamber 11 for filling the receptor liquid. The receptor chamber 11 has a flat bottom and a cylindrical shape. The upper portion of the receptor chamber 11 has a trumpet shape so that the receptor chamber 11 becomes gradually thinner. A receptor liquid discharge passage 12 is communicated with the tip of the receptor chamber 11. The receptor liquid discharge path 12 is opened in the upper wall of the cell body 10, the vicinity of the opening is expanded, and a screw groove 121 is cut.

  A receptor liquid injection path 13 is communicated with the vicinity of the lower end of the side wall of the receptor chamber 11, the other end of the receptor liquid injection path 13 is opened in the upper wall of the cell body 1, and the vicinity of the opening is expanded. The screw groove 131 is cut.

  Reference numeral 14 denotes a substantially circular recess for fixing the lid body 21, which is formed from the side wall of the cell body 11 toward the receptor chamber 11, and a screw groove 141 is cut in the side wall of the recess 14. In the middle part of the side wall of the receptor chamber 11, an opening 15 for installing the skin and the transdermally absorbable preparation is bored toward the recess 14. Reference numeral 16 denotes an anti-rotation pin for the holding member 22 erected on the bottom of the recess 14.

  In FIGS. 5 and 6, reference numeral 20 denotes a lid, and the lid 20 includes a lid body 21 and a holding member 22. As shown in FIG. 7, the holding member 22 is a plate-like body 221 having a substantially circular shape when viewed from the front, and the size thereof is substantially the same as that of the concave portion 14 so that the holding member 22 can be fitted into the concave portion 14. The plate-like body 221 has a through-hole 223 having a shape substantially the same as that of the opening 15 concentrically formed in the center thereof, and a convex portion 222 is formed concentrically around the lid body 21. Yes.

  The lid body 21 is a cylindrical body having a screw groove 211 cut around the lid body 21, and a convex portion 212 that can be fitted into the through hole 223 of the holding member 22 and a convex portion 222 of the holding member 22 are fitted at the front end portion thereof. Convex portions 214 that can be fitted into the concave portions 213 and the concave portions around the convex portions 222 of the holding member 22 are formed concentrically in order from the central portion in the circumferential direction.

  The skin and percutaneous absorption preparation 9 are fixed by screwing the screw groove 211 of the lid main body 21 into the screw groove 141 of the recess 14 after the opening 15 is closed and temporarily fixed by the holding member 22.

  A receptor liquid injection tube 7 has a connecting member 71 connected to the tip thereof, and a screw groove 72 is cut around the connecting member 71. By screwing the connecting member 71 into a screw groove 131 cut in the vicinity of the opening of the receptor liquid injection path 13, the receptor liquid injection tube 7 and the receptor liquid injection path 13 are communicated in a watertight manner.

  Reference numeral 8 denotes a receptor liquid discharge tube. A connecting member 81 is connected to the tip of the tube, and a screw groove 82 is cut around the connecting member 81. By screwing the connecting member 81 into a screw groove 121 cut in the vicinity of the opening of the receptor liquid discharge passage 12, the receptor liquid discharge tube 8 and the receptor liquid discharge passage 12 are communicated in a watertight manner. Reference numeral 2 denotes a rotor supplied to the receptor chamber 11.

  In order to measure the concentration of the drug diffused from the transdermally absorbable preparation into the receptor liquid, first, as shown in FIGS. 5 and 6, the skin and the percutaneously absorbable preparation 9 are installed in the diffusion measuring cell 1, and FIG. As shown, the cell body 10 is housed in the through-hole 43 of the thermostat 4 so that the upper wall of the cell body 10 is on the top (so that the skin and the transdermal absorption preparation 9 are oriented vertically). Next, the pump 32 is operated, the receptor liquid 34 in the receptor liquid storage container 31 is infused into the receptor chamber 11, the receptor chamber 11 is filled with the receptor liquid, and the rotor 2 is rotated to percutaneously stir the receptor liquid. The drug in the absorption preparation is diffused into the receptor fluid. Then, every predetermined time, the pump 32 is operated, a predetermined amount of the receptor liquid in the receptor liquid storage container 31 is infused into the receptor chamber 11, the receptor extruded from the receptor chamber 11 and supplied to the receptor liquid sorting device 6. Dispense and store liquid in sample cell.

  It is a schematic diagram which shows an example of the spreading | diffusion measuring apparatus of this invention.   (A) is a top view which shows an example of a thermostat, (b) is AA sectional drawing in (a).   It is a longitudinal cross-sectional view which shows an example of a cell main body.   It is BB sectional drawing in FIG.   It is a longitudinal cross-sectional view which shows an example of the state which installed the skin and the transdermal absorption preparation in the opening part of a spreading | diffusion measurement cell.   It is CC sectional drawing in FIG.   (A) is a front view which shows an example of a holding member, (b) is a rear view, (c) is a side view.   It is a cross-sectional schematic diagram which shows an example of the conventional diffusion cell.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Diffusion measurement cell 2 Rotor 3 Receptor liquid supply apparatus 4 Constant temperature bath 5 Rotating apparatus 6 Receptor liquid sorting apparatus 7 Receptor liquid injection tube 8 Receptor liquid discharge tube 9 Skin and transdermal absorption preparation 10 Cell body 11 Receptor chamber 12 Receptor liquid discharge path 13 Receptor liquid injection path 14 Recess 15 Opening 16 Anti-rotation pin 20 Lid body 21 Lid body 22 Holding member 31 Receptor liquid storage container 32 Ring liquid tube 33 Pump 34 Receptor liquid 41 Insulation box 42 Aluminum block 43 Through Hole 44 Surface heater 45 Temperature controller

Claims (10)

  Diffusion measurement cell for percutaneous absorption preparation, receptor liquid supply device for supplying receptor liquid to diffusion measurement cell, rotor housed in diffusion measurement cell, constant temperature bath for storing diffusion measurement cell, under constant temperature bath And a receptor liquid separator for separating and storing a drug solution diffused into a receptor liquid from a percutaneous absorption preparation and a receptor for rotating the rotor. The liquid injection path is connected with the receptor liquid supply tube, the receptor liquid discharge path of the diffusion measurement cell and the receptor liquid sorting device are connected with the receptor liquid discharge tube, and the thermostatic chamber is for storing the diffusion measurement cell. The diffusion measurement of a transdermally absorbable preparation characterized by comprising a metal block in which a recess or a through hole is formed and a temperature control device is installed Apparatus.   The diffusion measuring apparatus for a percutaneous absorption preparation according to claim 1, wherein a plurality of recesses or through holes are formed.   A diffusion measurement cell for a transdermal absorption preparation has a cell body having a receptor chamber for filling a receptor liquid, having an opening for placing the skin and the percutaneous absorption preparation in the middle part of the side wall; It consists of a lid for fixing the percutaneously absorbable preparation to the opening. The cell body is connected to the cell body from the upper part of the receptor chamber and from the vicinity of the lower end of the side wall of the receptor chamber. A diffusion measuring device for a percutaneous absorption preparation according to claim 1, wherein a receptor liquid injection path communicating with the outside of the percutaneous absorption preparation is formed.   The diffusion measuring device for a percutaneous absorption preparation according to claim 3, wherein the cell body is substantially a cube or a rectangular parallelepiped.   The transcutaneous body according to claim 3, wherein the lid comprises a holding member for holding the skin and the transdermally absorbable preparation in the opening, and a lid main body for pressing and fixing the holding member to the opening. Absorption preparation diffusion measurement device.   6. The diffusion measurement apparatus for a transdermal absorption preparation according to claim 5, wherein the lid body is screwable with the side wall of the cell body.   4. The apparatus for measuring the diffusion of a percutaneous absorption preparation according to claim 3, wherein the openings of the receptor liquid discharge path and the receptor liquid injection path are opened in the upper wall of the cell body.   Screw holes are cut in the openings of the receptor liquid discharge path and the receptor liquid injection path, and the connection member installed at the end of the receptor liquid discharge tube or the receptor liquid injection tube can be screwed in a watertight manner. A diffusion measuring cell for a transdermally absorbable preparation according to claim 3, wherein the cell is a diffusion measuring cell.   The receptor liquid supply device comprises a receptor liquid storage container and a pump capable of transporting a predetermined amount of receptor liquid. The receptor liquid storage container and the pump are communicated with an infusion tube, and the pump is communicated with a receptor liquid supply tube. The apparatus for measuring diffusion of a transdermally absorbable preparation according to claim 1, wherein   The diffusion measurement device for a percutaneous absorption preparation according to claim 1, wherein one receptor liquid supply device and one diffusion measurement cell are communicated, and there are a plurality of diffusion measurement cells.

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