JP6418711B2 - Permeability test equipment - Google Patents

Description

  The present invention relates to a permeability test apparatus for measuring the permeability and diffusibility of a sample. For example, the permeability for measuring a state in which a drug of a percutaneous absorption preparation as a sample permeates and diffuses through a skin as a permeable membrane. It relates to a test apparatus.

In research fields such as pharmaceuticals and cosmetics, a state where a sample such as a drug to be studied permeates and diffuses through the skin as a permeable membrane is measured, and whether or not its efficacy / effect can be expected is verified and evaluated. A permeability test apparatus is used as an apparatus for testing the permeation and diffusion state that is the basis of this verification and evaluation.
Generally, Franz cells are used as the permeability test apparatus. This Franz cell sandwiches a permeable membrane such as skin between an upper container and a lower container, supplies a sample such as a drug as a substance to be measured to the upper container, supplies a receptor liquid to the lower container, It is an apparatus for measuring the diffusion rate by measuring the concentration of the drug or the like in the receptor liquid after time.

In the Franz cell, as known from the past, only one sample can be tested per test, so that it takes a lot of time to test many samples.
In order to solve this problem, Patent Document 1 proposes a permeability test apparatus having a plurality of wells (also referred to as an upper container and a lower container or a cell, hereinafter referred to as a cell).
This permeation test device has multiple cells (upper container and lower container), so the permeability of many samples can be tested in parallel. Can be verified.

JP 2008-271895 A

By the way, in the permeability test apparatus described in Patent Document 1, a plate provided with a plurality of cells capable of receiving a receiver liquid is used.
However, the number of cells formed on the plate is predetermined. Therefore, in the test, when the number of samples exceeds the number of cells provided on the plate, the test cannot be performed at once, and there is a technical problem that the samples must be divided and tested.

On the other hand, when the number of samples is small, there is a technical problem in that handling is inconvenient because a plate larger than necessary must be used even though the number of cells used is small.
As described above, the plate of the conventional permeability test apparatus has a technical problem that the number of cells cannot be changed according to the number of samples.

  Furthermore, preparing a large number of plates with different numbers of cells in advance and using one of the many plates according to the number of samples raises a new technical problem that increases the manufacturing cost of the plate. It is.

  The present invention has been made to solve the above technical problem, and an object of the present invention is to provide a permeability test apparatus that can vary the number of cells according to the number of samples.

In the permeability test apparatus according to the present invention, a permeable membrane is accommodated in the interior, and the interior is divided into an upper space and a lower space by the permeable membrane, and further a donor liquid is accommodated in the upper space and in the lower space. A cell unit containing a receiver liquid, and a cell base configured to detachably hold a plurality of cell units set in advance, the cell base being set in advance An arbitrary number of the cell units within the number range are mounted, and the cell unit is formed at the upper part, the donor cell part having a plurality of donor chambers, the receiver cell part formed at the lower part, the donor cell part and the receiver cell part And a coupling means for integrating the donor cell portion and the receiver cell portion with a permeable membrane sandwiched between them. Provided with a spring that biases the bar toward the receiver cell part, and when the coupling means integrates the donor cell part and the receiver cell part, the tip of the donor chamber is urged by the spring and the permeable membrane. It is characterized in that in contact.

In this way, any number of the cell units within a preset number range can be detachably attached to the cell base, so that the cell can be selected according to the number of samples of drugs or the like for which a permeability test is performed. The number of units can be varied.
In addition, since a plurality of the same cell units are used, they can be manufactured at low cost.

Here, the cell base, are formed in a frame shape, openings penetrated is formed at the central portion, the lower portion of the front SL cell unit, inserted through the opening of the cell-based, the bottom surface of the cell unit It is desirable that the bottom surface of the cell base is flush with the same surface.
In this way, the lower part of the cell unit is inserted through the opening of the cell base so that the bottom surface of the cell unit and the bottom surface of the cell base are flush with each other. In such a case, the temperature of the cell unit can be suitably adjusted.

Each of the donor chambers has a cylindrical shape, and the receiver cell section closes the plurality of cylindrical receiver chambers, two through holes formed in the bottom surface of each receiver chamber, and the through holes. A stopper, and through the one through hole, the needle of the syringe is inserted into the stopper from outside the bottom surface of the receiver chamber to fill the receiver chamber with the receiver liquid through the through hole, Alternatively, it is desirable to remove the air in the receiver chamber when the receiver liquid in the receiver chamber is collected and filled through another through hole .
Since it is comprised in this way, a receiver liquid can be filled into a receiver chamber from the exterior of a cell unit, or a receiver liquid can be collect | recovered from a receiver chamber.

In addition, the cell base includes a concave portion formed on the upper surface, into which the cell unit is fitted, and a pipe for circulating hot water provided therein, and the cell unit has a donor cell portion formed on the upper portion, A cell main body portion having a receiver cell portion formed at a lower portion thereof, and a convex portion formed at a lower portion of the cell main body portion, wherein the convex portion of the cell unit is fitted in the concave portion of the cell base. It is desirable that it be formed.
Thus, since the convex part of the said cell unit is formed so that it may fit in the recessed part of the said cell base, it can attach or detach easily. Moreover, since the pipe which circulates the warm water for temperature control is provided in the cell base, the several cell units (cell main-body part) mounted in a cell base can be temperature-controlled equally.

The donor cell portion of the cell main body portion is a space having a circular cross section, a permeable membrane is disposed in the donor cell portion, the receiver cell portion of the cell main body portion is a space having a circular cross section, and its lower surface is made of sapphire glass. Further, a receiver liquid supply pipe for supplying receiver liquid to the receiver cell section and a receiver liquid outlet pipe for extracting the receiver liquid in the receiver cell section are connected to the side surface of the cell main body section. It is desirable that
Thus, since the lower surface of the receiver cell portion is closed by the closing member made of sapphire glass, the heat conductivity is good and the temperature can be adjusted well.
Further, a receiver liquid supply pipe for supplying receiver liquid to the receiver cell section and a receiver liquid outlet pipe for extracting the receiver liquid in the receiver cell section are connected to the side surface of the cell main body section. Data can be collected over time, and permeability data with time can be obtained.

The receiver liquid supplied from the receiver liquid supply pipe is supplied into the receiver cell section near the lower surface of the permeable membrane, and the receiver liquid derived from the receiver liquid outlet pipe is derived from the receiver cell section near the lower surface of the permeable membrane. It is desirable that
Thus, since the receiver liquid is supplied to the vicinity of the lower surface of the permeable membrane and derived from the vicinity of the lower surface of the permeable membrane, the air staying in the vicinity of the lower surface of the permeable membrane (air mixed in the receiver cell portion) can be discharged. .

In addition, a support member that supports the permeable membrane is provided on an upper surface of the permeable membrane in the donor cell portion, and the support member includes a ring portion formed in a ring shape, a connecting portion that connects the ring portions in a radial direction, and a donor It is desirable to provide a space part through which the liquid flows.
Thus, by providing the support member, it is possible to suppress the occurrence of twisting or wrinkling of the permeable membrane.

In addition, a cell unit in which a permeable membrane is accommodated in the interior, the interior is divided into an upper space and a lower space by the permeable membrane, a donor liquid is accommodated in the upper space, and a receiver liquid is accommodated in the lower space; A cell base configured to detachably hold the plurality of cell units, and the cell base is mounted with an arbitrary number of cell units within a preset number range. The cell base comprises a recess formed on the upper surface, into which the cell unit is fitted, and a pipe provided inside for circulating hot water. A cell main body portion formed with a receiver cell portion at a lower portion and a convex portion formed at a lower portion of the cell main body portion, so that the convex portion of the cell unit fits into the concave portion of the cell base. Formed, the donor cell part of the cell body part is a space with a circular cross section, a permeable membrane is arranged in the donor cell part, the receiver cell part of the cell body part is a space with a circular cross section, and its lower surface is made of sapphire glass Is closed by a closing member, and further, a receiver liquid supply pipe for supplying the receiver liquid to the receiver cell part and a receiver liquid outlet pipe for extracting the receiver liquid in the receiver cell part are connected to the side surface of the cell main body part, The receiver liquid supplied from the receiver liquid supply pipe is supplied into the receiver cell part near the lower surface of the permeable membrane, and the receiver liquid derived from the receiver liquid outlet pipe is derived from the receiver cell part near the lower surface of the permeable film, Support members for supporting the permeable membrane are provided on the upper and lower surfaces of the permeable membrane in the donor cell portion, and each of the support members is made of a conductive material. A ring portion formed in a ring shape, and a connecting portion connecting the ring portion in a radial direction, and a space portion donor liquid is circulated, said respective support member is preferably used as an electrode.
Thus, by adding a function as an electrode to the support member, it is possible to suppress the occurrence of twisting or wrinkling of the sample and to measure the resistance value and the like.

According to the present invention, it is possible to obtain a permeability test apparatus that can vary the number of cells according to the number of samples.

FIG. 1 is a plan view showing a first embodiment of a permeability test apparatus according to the present invention. FIG. 2 is a side view showing a state in which the permeability test apparatus shown in FIG. 1 is placed on a shaker. FIG. 3 is a plan view of the cell unit of the permeability test apparatus shown in FIG. FIG. 4 is a partial cross section of the cell unit shown in FIG. FIG. 5 is a plan view of a donor cell portion constituting the upper portion of the cell unit shown in FIG. 6 is a partial cross-sectional view of the donor cell portion shown in FIG. FIG. 7 is a plan view of a receiver cell unit that forms the lower part of the cell unit. FIG. 8 is a partial cross-sectional view of the receiver cell portion shown in FIG. FIG. 9 is a partial cross-sectional view showing a case where a stirring chain is provided in the donor chamber. FIG. 10 is a plan view showing a second embodiment of the permeability test apparatus according to the present invention. FIG. 11 is a front view showing a state in which the permeability test apparatus shown in FIG. 10 is placed on a shaker. FIG. 12 is a side view showing a state where the permeability test apparatus shown in FIG. 11 is placed on a shaker. FIG. 13 is an exploded cross-sectional view of the cell unit. 14 is a cross-sectional view of the cell unit shown in FIG. FIG. 15 is a cross-sectional view showing an example in which a support member is provided inside the cell unit shown in FIG. 16 is a cross-sectional view showing an example in which a support member having an electrode function is provided inside the cell unit shown in FIG. FIG. 17 is a schematic configuration diagram illustrating a relationship between the permeability test apparatus and the fraction collector according to the second embodiment.

A first embodiment of a permeability test apparatus according to the present invention will be described with reference to FIGS.
As shown in FIG. 1, a cell unit 2 having a permeable membrane disposed therein and a cell base 2 to which the cell unit 2 is detachably attached are provided. In FIG. 1, four cell units 2 are detachably attached to one cell base 3. Further, twelve cells 2a are formed in one cell unit 2.

As shown in FIGS. 1 and 2, the cell base 3 is formed in a frame shape, and an opening 3 b is formed in the center of the cell base 3. A positioning pin is provided on the upper surface of the frame-shaped portion 3 a of the cell base 3. 3c is provided.
The cell unit 2 is mounted on the cell base 3 by fitting the positioning pin 3 c into a positioning hole 2 b provided in the cell unit 2. At this time, the lower portion of the cell unit 2 is inserted through the opening 3b of the cell base 3, so that the bottom surface of the cell unit 2 and the bottom surface of the cell base 3 are flush with each other.
Therefore, the opening 3b and the positioning pin 3c of the cell base 3 are formed so as to detachably hold the plurality of cell units 2 set in advance.

Since it is comprised in this way, the said cell unit 2 can be attached on the cell base 3 as needed. That is, an arbitrary number of the cell units 2 within a preset number range can be attached to the cell base 3.
In the permeability test apparatus 1 shown in FIG. 1, 1 to 5 cell units 2 can be selected and used. That is, the number of cells (number of cell units) corresponding to the number of cells to be used can be selected and used from among 12, 24, 36, and 48 cells.

As shown in FIG. 2, the permeability test apparatus 1 is placed on a temperature control plate 4 a provided in the shaker 4.
The temperature control plate 5a is provided with positioning pins 4b, and the positioning pins 4b are fitted into positioning holes 3d provided in the cell base 3, whereby the cell base 3 is placed on the temperature control plate 4a. It is attached.

  When the cell unit 2 is mounted on the cell base 3, as described above, the bottom surface of the cell unit 2 and the bottom surface of the cell base 3 are flush with each other. Therefore, when the cell base 3 is placed on the temperature control plate 4a provided in the shaker 4, the bottom surface of the cell unit 2 is in contact with the temperature control plate 4a, and the cell unit 2 is suitably temperature controlled. The

  Next, the cell unit 2 will be described with reference to FIGS. 3 is a plan view of the cell unit, FIG. 4 is a partial cross-sectional view of the cell unit shown in FIG. 3, FIG. 5 is a plan view of a donor cell portion constituting the upper part of the cell unit, and FIG. 5 is a partial sectional view of the donor cell portion shown in FIG. 5, FIG. 7 is a plan view of the receiver cell portion constituting the lower part of the cell unit 2, and FIG. 8 is a partial sectional view of the receiver cell portion shown in FIG. FIG.

  As shown in FIG. 3, the cell unit 2 includes a donor cell unit 21 that forms the upper part of the cell unit 2 and a receiver cell unit 22 that forms the lower part of the cell unit 2. Can be integrated by the coupling means 23.

First, the donor cell part 21 is demonstrated based on FIG. 5, FIG.
The donor cell portion 21 includes a cylindrical donor chamber 21a constituting the upper portion of the cell 2a, a sleeve holder 21b having a through hole 21b1 through which the donor chamber 21a is inserted, and a support 21d through the sleeve holder 21b. And a sleeve guide 21c disposed below.

Further, at both ends of the sleeve holder 21b, cutout portions 21b2 which are a part of the coupling means 23 used when the donor cell portion 21 and the receiver cell portion 22 are integrated are provided.
The sleeve guide 21c guides the donor chamber 21a to move up and down due to vibration by the shaker 4, and a through hole 21c1 through which the donor chamber 21a is inserted is formed.

The donor chamber 21a is supplied with a donor liquid, and a cylindrical space 21a1 is formed therein to store the donor liquid.
A flange 21a2 is formed on the lower outer peripheral surface of the donor chamber 21a. The flange portion 21a2 is formed to have a diameter larger than the diameter of the through hole 21c1 of the sleeve guide 21c.
A spring 21e is provided on the upper surface of the flange 21a2 and the lower surface of the sleeve holder 21b, and the donor chamber 21a is urged toward the sleeve guide 21c by the spring 21e.
As a result, when the donor cell portion 21 and the receiver cell portion 22 are not integrated, the flange portion 21a2 is locked to the upper surface of the sleeve guide 21c.

Next, the receiver cell unit 22 will be described with reference to FIGS.
The receiver cell part 22 is formed at both ends of the receiver cell main body part 22a and a receiver cell main body part 22a in which a plurality of cylindrical receiver chambers 22c forming the lower part of the cell 2a are formed. A locking portion 22b that constitutes a part of the coupling means 23 is provided.
As shown in FIG. 8, the receiver cell body 22a is formed such that the portion where the receiver chamber 22a is formed is thick and the portion where the locking portion 22b is provided is thin. . That is, the lower part of the receiver chamber 22a is formed in a shape protruding downward from the receiver cell body 22a.

Further, two small-diameter through holes 22c1 are formed on the bottom surface of each receiver chamber 22c. A plug 22d made of urethane, for example, is provided on the lower surface of the through hole 22c1 to close the through hole 22c1. The stopper 22d is in close contact with the through hole 22c1 and is closed by a pressing member 22e attached to the receiver cell main body 22a.
The holding member 22e has a through hole 22e1 at a position corresponding to the through hole 22c1.
Accordingly, by inserting a needle such as a syringe from the bottom surface side of the receiver cell main body 22a through the through hole 22e1 and piercing the plug 22d, the receiver chamber 22c is filled with the receiver liquid and the receiver chamber 22c. Collect the receiver fluid etc. from the inside.

  Further, as shown in FIG. 8, the locking portion 22b includes a support 22b1 provided on the upper surface of both ends of the receiver cell body 22a, and a lever 22b3 pivotally supported on the upper end of the support 22b1. And a knob 22b2 provided at the end of the lever 22b3.

In addition, positioning pins 21f are formed on the upper surfaces of both end portions of the receiver cell main body 22a.
This positioning pin 21f fits into the positioning hole 21c2 of the donor cell portion 21 when the donor cell portion 21 is placed on the receiver cell portion 22, and positions the donor cell portion 21 and the receiver cell portion 22.

In addition, positioning holes 22g into which the positioning pins 3c of the cell base 3 are fitted are formed on the lower surfaces of both ends of the receiver cell main body 22a (lower positions where the positioning pins 22f are formed).
Thus, since the positioning hole 22g is formed in the lower surface of the both ends of the receiver cell body 22a (the lower position where the positioning pin 22f is formed), the cell unit 2 is placed at a predetermined position of the cell base 3. Can be placed.
Note that positioning pins 3c corresponding to the number of cell units 2 are provided on the cell base 3 in order to position a plurality of cell units 2 (four cell units 2 in FIG. 1).

  Further, as shown in FIG. 4, a stirring ball 6 is accommodated in the receiver chamber 22c. The stirring sphere 6 stirs the receiver liquid in the receiver chamber 22 c by receiving the vibration of the shaker 4. The stirring sphere 6 does not necessarily need to be stored, but it is preferable to store the stirring ball 6 in order to make the receiver liquid uniform.

Moreover, as shown in FIG. 9, it is preferable to accommodate the stirring chain 8 in the donor chamber 21a.
The stirring chain 8 is preferably attached to the lower surface of the lid 7 that closes the donor chamber 21a, and is suspended in the donor chamber 21a.
The stirring chain 8 stirs the donor liquid in the donor chamber 21a by receiving the vibration of the shaker 4. The stirring chain 8 does not necessarily need to be stored, but it is preferable to store the stirring chain 8 to make the donor liquid uniform. In addition, it is preferable to provide the stirring chain 8 with a plurality of ball portions 8a because the stirring function is further improved.

In order to set the permeability test apparatus 1 configured as described above, first, a cell unit 2 corresponding to the number of samples is prepared.
As shown in FIG. 4, the stirring sphere 6 is accommodated in the receiver chamber 22 c of the prepared cell unit 2.

Further, a permeable membrane 5 such as a human skin, an artificial skin, or an animal skin such as a guinea pig is placed on the receiver cell portion 22. As the permeable membrane 5, one cell unit 2 uses one skin.
That is, without setting the permeable membrane 5 for each cell 2a, by setting one permeable membrane 5 on the receiver cell section 22, the permeable membrane 5 is set simultaneously for a plurality of cells 2a. (In this embodiment, the permeable membrane 5 can be set to 12 cells 2a simultaneously).

Then, the donor cell portion 21 is placed on the receiver cell portion 22 (on the permeable membrane 5), and the positioning pin 22 of the receiver cell portion 22 is fitted into the positioning hole 21c2 of the donor cell portion 21 for positioning. .
Thereafter, the knob portion 22b2 is held and the lever 22b3 of the locking portion 22b which is the coupling means 23 is rotated.
By this rotation, the lever 22b3 enters the notch 21b2 which is a part of the coupling means 23. 2 and 4, the knob portion 22b2 presses the donor cell portion 21 (the upper surface of the sleeve holder 21b), and the donor cell portion 21 and the receiver cell portion 22 are integrated.

At this time, the tip of the donor chamber 21a protruding downward from the sleeve guide 21c contacts the permeable membrane 5 (the upper end of the receiver chamber 22c).
Further, since the donor cell portion 21 (sleeve holder 21b) is pressed and moved downward by the knob portion 22b2, the donor chamber 21a resists the repulsive force of the spring 21e, while the sleeve holder 21b, the sleeve guide. It moves relatively upward while being guided by 21c.

Therefore, the donor chamber 21a is pressed against the permeable membrane 5 (receiver chamber 22c) and is not fixed to the sleeve holder 21b and the sleeve guide 21c, and is in a so-called floating state.
Thus, since the donor chamber 21a is fixed in a so-called floating state, even when subjected to vibration from the shaker 4, it can maintain a close contact state with the permeable membrane 5 (receiver chamber 22c), Liquid leakage can be suppressed.

Then, through the receiver chamber 22c of the required cell unit 2 (cell 2a), using a syringe (not shown), the through hole 22e1 is inserted from the bottom surface side of the receiver cell main body portion 22a, and is inserted into the plug 22d. The receiver liquid is filled through the hole 22c1.
After filling, the syringe (not shown) is pulled out. However, when the stopper 22d is made of a material such as urethane, the hole created by the needle of the syringe is closed, so that the occurrence of liquid leakage is suppressed. Is done.

  Note that two through holes 22e1 are formed in the bottom surface of the receiver chamber 22c. One is used for filling the receiver liquid as described above, and the other is used for filling the receiver chamber 22c. Used to evacuate the air inside.

The prepared cell unit 2 filled with the receiver liquid is placed at a predetermined position of the cell base 3. The cell unit 2 is attached to the cell base 3 by fitting the positioning pins 3 c on the cell base 3 into the positioning holes 22 g of the cell unit 2.
At this time, for example, when the two cell units 2 are attached to the cell base 3 on which the four cell units 2 can be placed, it is preferable to attach the cell base 3 to the center portion.

Further, the cell base 3 is placed on a temperature control plate 4a provided in the shaker 4, as shown in FIG.
The cell base 3 is mounted on the temperature adjustment plate 4a by fitting the positioning pins 4b of the temperature adjustment plate 4a into the positioning holes 3d provided in the cell base 3.
Thereafter, the donor liquid is supplied into the donor chamber 21a, and the receiver liquid is recovered from the receiver chamber 22c after a predetermined time at a predetermined temperature.

Similar to the filling of the receiver liquid, the recovery is performed by inserting the through hole 22e1 from the bottom surface side of the receiver cell main body 22a and piercing the stopper 22d by using a syringe. Alternatively, the donor cell unit 21 may be removed from the cell unit 2 and the receiver liquid may be recovered from above the receiver chamber 22c.
And the density | concentration (transmittance) of a sample in the receiver liquid collect | recovered from each receiver chamber 22c is measured.

  The permeability test apparatus 1 configured as described above is detachable from the cell base 2, so that the cell unit 2 can be used as needed, and the handling is convenient. Yes, it can be done inexpensively.

Next, a second embodiment of the permeability test apparatus according to the present invention will be described with reference to FIGS.
As shown in FIGS. 10 and 11, the permeability test apparatus 101 includes a cell unit 102 in which a permeable membrane 5 is disposed, and a cell base 103 to which the cell unit 102 is detachably attached. .
In FIG. 10, twelve cell units 102 are detachably attached to one cell base 103.

In the first embodiment described above, one cell unit 2 is composed of a plurality of cells (a plurality of donor cell units 21 and receiver cell units 22). In this second embodiment, one cell unit 2 The cell unit 102 is different in that it is composed of one cell (one donor cell part and one receiver cell part).
In the first embodiment described above, the donor liquid is supplied into the donor chamber 21a and the receiver liquid is collected from the receiver chamber 22c after a predetermined time has elapsed. The embodiment is different in that the receiver liquid is collected from the receiver cell portion with time.

As shown in FIG. 12, a plurality of recesses 103a corresponding to the shape of the cell unit 102 are formed on the upper surface of the cell base 103, and the cell unit 102 is formed to be fitted therewith.
That is, the cell unit 102 is detachably attached to the cell base 103 by fitting into the recess 103a.

As shown in FIG. 10, penetrating positioning holes 103 b are formed above and below the both sides of the cell base 3.
The temperature control plate 4a is provided with positioning pins 4b, and the positioning pins 4b are fitted into positioning holes 103b provided in the cell base 3, whereby the cell base 103 is placed on the temperature control plate 4a. It is attached.

  As described above, when the cell base 103 is mounted on the temperature control plate 4a by using the positioning pins 4b of the temperature control plate 4a in the first embodiment, the shaker 4 has the first function. Both the permeability tester of the embodiment and the permeability tester of the second embodiment can be used.

At this time, in the second embodiment, since one cell unit 102 is composed of one cell, if a number of cell units 102 (cells) are formed so as to be mounted on the cell base 103, the cell The base 103 is increased in size.
As a result, as shown in FIG. 12, the cell base 103 becomes larger than the temperature control plate 4a of the shaker 4, and the cell unit 102 outside the temperature control plate 4a cannot be temperature controlled.

For this reason, a pipe (not shown) for circulating hot water is provided inside the region where the recess 103a of the cell base 103 is formed (the central region of the cell base 103), and the temperature of the cell base 103 itself is controlled. It is configured as follows. A pipe (not shown) for circulating hot water may be formed inside the entire area of the cell base 103.
By controlling the temperature of the cell base 103, the temperature of the cell unit 102 located outside the temperature control plate 4a can be controlled.
10 and 11, reference numeral 103 c is a supply port for introducing hot water into the pipe, and reference numeral 103 d is a discharge port for introducing hot water into the pipe.

In the second embodiment, as described above, the cell unit 102 can be mounted on the cell base 103 as necessary. In the permeability test apparatus 1 shown in FIG. 10, an arbitrary number of 1 to 12 cell units 102 can be selected.
Moreover, since the cell unit 102 is detachably attached to the cell base 103 by fitting into the concave portion 103a, the cell unit 102 can be attached and used as necessary, and handling is convenient. Manufacturing costs can also be reduced.

  Next, the cell unit 102 will be described with reference to FIGS. 13 is an exploded sectional view of the cell unit 102, and FIG. 14 is a sectional view of the cell unit 102 shown in FIG.

  As shown in FIG. 13, the cell unit 102 is connected to a cell body 102a having a donor cell portion 102A formed in the upper portion and a receiver cell portion 102B formed in the lower portion, and a side surface of the cell body portion 102a. A receiver liquid supply pipe 102b for supplying the receiver liquid 102b to the receiver cell section 102B, a receiver liquid outlet pipe 102c for extracting the receiver liquid in the receiver cell section 102B, and a donor chamber 102d attached to the upper portion of the cell main body 102a. ing.

Further, the cell main body portion 102a will be described. The receiver cell portion 102B is a space having a circular cross section, and the lower surface thereof is closed by a closing member 102f made of sapphire glass via a packing 102e.
The closing member 102f is attached to the cell main body 102a by screwing the lock screw 102g into the cell main body 102a.

The lower part 102o of the cell body part 102a in which the packing 102e, the closing member 102f, and the locking screw 102g are accommodated protrudes from the cell body part 102a part where the receiver cell part 102B is formed, and is formed as a so-called columnar convex part. Has been.
The cell unit 102 is detachably attached to the cell base 103 by fitting the lower portion 102o of the cell main body 102a into the recess 103a of the cell base 103.

When the cell unit 102 is detachably attached to the cell base 103, the lower part 102o of the cell main body 102a comes into contact with the recessed portion 103a of the temperature-controlled cell base 103 to transfer heat.
At this time, since the closing member 102f made of sapphire glass is used, good heat transfer efficiency can be obtained.

The donor cell portion 102A is a space having a circular cross section, and a permeable membrane 5 such as human skin, artificial skin, or skin of an animal such as guinea pig is placed in the donor cell portion 102A.
The permeable membrane 5 is fixed to the cell body 102a by attaching the donor chamber 102d to the cell body 102a via the spacer 102h.
By placing the permeable membrane 5 on the bottom surface of the donor chamber 102d, the inside of the cell main body 102a is divided into a donor cell portion 102A and a receiver cell portion 102B.

The donor chamber 102d is supplied with a donor liquid, and a cylindrical space is formed therein to store the donor liquid.
The donor chamber 102d is attached to the cell main body 102a by a lever 102i formed on the cell main body 102a so as to be rotatable around one end, and a spring that presses the donor chamber 102d against the cell main body 102a by the lever 102i. This is done by using the clamp 102j.

  That is, as shown in FIG. 10, the spring clamp 102j is formed with a slit 102k that enters when the lever 102i rotates. The spring clamp 102j portion where the slit 102k is formed is curved in an arc shape. A pressing member 102l is provided at the tip of the lever 102i.

  As a result, the lever 102i enters the slit 102k, and the pressing member 102l presses the spring clamp 102j, whereby the donor chamber 102d is pressed toward the cell main body 102a and is fixed to the cell main body 102a.

Further, the cell main body 102a is provided with a supply path 102m for supplying the receiver liquid and a lead-out path 102n for leading the receiver liquid. The supply path 102m and the lead-out path 102n for leading the receiver liquid are formed above the receiver cell unit 102B (near the lower surface of the permeable membrane 5).
Thus, since the supply path 102m and the lead-out path 102n for leading the receiver liquid are formed above the receiver cell part 102B (near the lower surface of the permeable membrane 5), air is mixed into the receiver cell part 102B. Even in this case, the receiver liquid is supplied from the receiver liquid supply pipe 102b and the receiver liquid is led out from the receiver liquid lead-out pipe 102c so that the mixed air is discharged to the outside and the receiver cell unit 102B is filled with the receiver liquid. Can do.

  In addition, as shown in FIG. 14, the stirring ball 6 is accommodated in the receiver cell part 102B. The stirring sphere 6 stirs the receiver liquid in the receiver cell portion 102B by receiving the vibration of the shaker 4. The stirring sphere 6 does not necessarily need to be stored, but it is preferable to store the stirring ball 6 in order to make the receiver liquid uniform.

In addition, as shown in FIG. 15, a spacer 102h and a donor chamber 102d may be attached to the cell main body 102a via a support member 104 on the upper surface of the permeable membrane 5.
The support member 104 includes a ring part 104a formed in a ring shape, a connecting part 104b that connects the ring part 104a in the radial direction, and a space part 104c through which the donor liquid flows.
As described above, since the supply path 102m and the lead-out path 102n for leading the receiver liquid are formed above the receiver cell portion 102B (near the lower surface of the permeable film 5), the receiver liquid hits the permeable film 5 and is twisted. In some cases, it may be deformed or curved. In order to suppress the deformation, a support member 104 is provided.

Further, as shown in FIG. 16, a spacer 102h and a donor chamber 102i may be attached to the cell main body 102a via support members 105 and 106 on the upper and lower surfaces of the skin 5, respectively. Note that FIG. 16 is a cross-sectional view that differs in the direction of 90 degrees from FIGS.
The support members 105 and 106 have the same configuration, and ring portions 105a and 106a formed in a ring shape, connecting portions 105b and 106b that connect the ring portions 105a and 106a in a radial direction, and a donor liquid circulate. Space portions 105c and 106c.
However, unlike the support member 104 described above, the support members 105 and 106 are made of a conductive material.

  The support members 105 and 106 are connected to an electric resistance meter 107. That is, the support members 105 and 106 have a function as an electrode in addition to the function of supporting the permeable membrane 5. As a result, the resistance value before and after flowing through the skin of the donor liquid can be measured.

In the permeability testing apparatus 1 configured as described above, first, as shown in FIG. 14, the lower surface of the receiver cell portion 102B of the cell unit 102 is closed with a closing member 102f, and the permeable membrane 5 is covered with the cell unit 102. And set the donor chamber 102d using the spring clamp 102j.
Further, the receiver liquid supply pipe 102 b and the receiver liquid outlet pipe 102 c are connected to the cell unit 102.

Then, the cell unit 102 is attached to the cell base 3 by fitting the convex portion 102 o of the cell unit 102 into the concave portion 103 a of the cell base 3. The cell base 3 is placed on a temperature control plate 4 a provided in the shaker 4.
Thereafter, the receiver liquid is supplied into the receiver cell from the receiver liquid supply pipe 102b, and the donor liquid is supplied into the donor cell portion 102A.

In the second embodiment, the receiver liquid in the receiver cell unit 102B can be derived from the receiver liquid outlet tube 102c over time. The receiver liquid led out from the receiver liquid lead-out pipe 102c is collected and stored by the fraction collector.
Subsequently, it is used for the apparatus for density | concentration measurement (for example, high performance liquid chromatograph (HPLC)), and permeability is measured with time.

  Here, as shown in FIG. 17, the shaker 4 is provided with a nozzle 107 that discharges the receiver liquid led out from the receiver liquid lead-out pipe 102c, and the shaker 4 is attached to the fraction collector 108, thereby receiving the receiver liquid lead-out pipe. It is preferable to shorten the distance between 102c and the nozzle 107.

In FIG. 17, reference numeral 109 denotes a reagent bottle in which receiver liquid is stored, and reference numeral 110 denotes a tube pump for supplying the receiver liquid to the cell unit 102.
Reference numeral 111 denotes a hot tub for warming the reagent bottle 109, and the hot water in the hot tub is connected to the cell base 103 and used for temperature control of the cell base 103.
The sample S collected and stored by the fraction collector 108 may be transported to an apparatus for concentration measurement (for example, high performance liquid chromatograph (HPLC)) by an automatic machine such as a robot. good.

DESCRIPTION OF SYMBOLS 1 Permeability test apparatus 2 Cell unit 3 Cell base 3a Frame-shaped part 3b Opening part 5 Permeation film 21 Donor cell part 21a Donor chamber 22 Receiver cell part 22c Receiver chamber 22c1 Through-hole 22d Plug 23 Coupling means 101 Permeability test apparatus 102 Cell unit 102A Donor cell part 102B Receiver cell part 102a Cell body part 102b Receiver liquid supply pipe 102c Receiver liquid outlet pipe 102d Donor chamber 102f Closure member 102i Lever 102j Spring clamp 102m Supply path 102n Lead path 102o Lower part of the cell body (convex part)
103 cell base 103a recess 103c hot water supply port 103d hot water discharge port 104 support member 105 support member 106 support member

Claims (8)

A cell unit in which a permeable membrane is housed, the interior is divided into an upper space and a lower space by the permeable membrane, further a donor liquid is housed in the upper space, and a receiver liquid is housed in the lower space;
A cell base configured to detachably hold a plurality of preset cell units; and
Wherein the cell base, be any transparently testing apparatus for mounting the cell unit number within the number range set in advance,
The cell unit is formed in an upper part, a donor cell part having a plurality of donor chambers, a receiver cell part formed in the lower part, and a state in which a permeable membrane is sandwiched between the donor cell part and the receiver cell part, A coupling means for integrating the donor cell portion and the receiver cell portion,
The donor cell portion includes a spring that biases each donor chamber toward the receiver cell portion,
When the coupling means integrates the donor cell portion and the receiver cell portion, the distal end portion of the donor chamber is in contact with the permeable membrane while being biased by the spring. Sex test equipment. The cell base is formed in a frame shape, and an opening is formed in the central portion thereof.
Lower pre SL cell unit, inserted through the opening of the cell-based, permeability testing apparatus of claim 1, wherein the bottom surface and the cell base of the bottom surface of the cell unit is made in the same plane. Each of the donor chambers is cylindrical
The receiver cell unit includes a plurality of cylindrical receiver chambers, two through holes formed in the bottom surface of each receiver chamber, and a plug that closes the through holes,
Fill the receiver chamber with the receiver liquid by piercing the stopper with the needle of the syringe from the outside of the bottom surface of the receiver chamber through one through hole , or collect the receiver liquid in the receiver chamber ,
The permeability test apparatus according to claim 2 , wherein the air in the receiver chamber is evacuated when filling through another through hole . The cell base includes a recess formed on the upper surface, into which the cell unit is fitted, and a pipe provided inside for circulating hot water,
The cell unit includes a cell body portion in which a donor cell portion is formed in an upper portion and a receiver cell portion is formed in a lower portion, and a convex portion formed in a lower portion of the cell body portion,
The permeability test apparatus according to claim 1, wherein the convex portion of the cell unit is formed to fit into the concave portion of the cell base. The donor cell part of the cell body part is a space having a circular cross section, and a permeable membrane is disposed in the donor cell part,
The receiver cell part of the cell body part is a space having a circular cross section, and the lower surface thereof is closed by a closing member made of sapphire glass,
Furthermore, a receiver liquid supply pipe for supplying receiver liquid to the receiver cell section and a receiver liquid outlet pipe for extracting the receiver liquid in the receiver cell section are connected to the side surface of the cell main body section. The permeability test apparatus according to claim 4.   The receiver liquid supplied from the receiver liquid supply pipe is supplied into the receiver cell section near the lower surface of the permeable membrane, and the receiver liquid derived from the receiver liquid outlet pipe is derived from the receiver cell section near the lower surface of the permeable membrane. The permeability test apparatus according to claim 5. Provided on the upper surface of the permeable membrane in the donor cell portion, a support member that supports the permeable membrane,
7. The transmission according to claim 6, wherein the support member includes a ring portion formed in a ring shape, a connecting portion that connects the ring portions in a radial direction, and a space portion through which the donor liquid flows. Sex test equipment. A cell unit in which a permeable membrane is housed, the interior is divided into an upper space and a lower space by the permeable membrane, further a donor liquid is housed in the upper space, and a receiver liquid is housed in the lower space;
A cell base configured to detachably hold a plurality of preset cell units; and
A permeability test apparatus for mounting an arbitrary number of the cell units within a preset number range on the cell base,
The cell base includes a recess formed on the upper surface, into which the cell unit is fitted, and a pipe provided inside for circulating hot water,
The cell unit includes a cell body portion in which a donor cell portion is formed in an upper portion and a receiver cell portion is formed in a lower portion, and a convex portion formed in a lower portion of the cell body portion,
The convex part of the cell unit is formed to fit into the concave part of the cell base,
The donor cell part of the cell body part is a space having a circular cross section, and a permeable membrane is disposed in the donor cell part ,
The receiver cell part of the cell body part is a space having a circular cross section, and the lower surface thereof is closed by a closing member made of sapphire glass,
Furthermore, a receiver liquid supply pipe for supplying receiver liquid to the receiver cell section and a receiver liquid outlet pipe for deriving the receiver liquid in the receiver cell section are connected to the side surface of the cell main body section,
The receiver liquid supplied from the receiver liquid supply pipe is supplied into the receiver cell part near the lower surface of the permeable membrane, and the receiver liquid derived from the receiver liquid outlet pipe is derived from the receiver cell part near the lower surface of the permeable film,
Provided on the upper and lower surfaces of the permeable membrane in the donor cell portion with a support member that supports the permeable membrane,
Each of the support members is made of a conductive material, and includes a ring portion formed in a ring shape, a connecting portion that connects the ring portions in the radial direction, and a space portion through which the donor liquid circulates. , transparently testing apparatus, characterized in that it is used as an electrode.

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