JP2866301B2 - Dialysis probe - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention is used, for example, when a chemical substance which is inserted into a living tissue such as a brain tissue and exists in an extracellular liquid space in a minute region of the living tissue is sampled by a dialysis principle. It relates to a dialysis probe.

[0002]

2. Description of the Related Art Various substances in living tissues, for example, substances necessary for cell metabolism and signal substances for transmitting biological information (hormones such as insulin and estrogen, transmitting substances released from nerve endings, etc.). To measure,
Conventionally, a method disclosed in Japanese Patent Publication No. 3-16861 has been proposed.

[0003] This measurement method uses a dialysis probe having the following configuration.

As shown in FIGS. 4 and 5, the dialysis probe has a tubular dialysis membrane 41 having a sealed distal end, and extends through the inside of the dialysis membrane 41 to a position near the distal end thereof. And a conduit 43 having an opening near the base end of the dialysis membrane 41 so that a flow of perfusate is formed inside the dialysis membrane 41 by the conduits 42 and 43. The dialysis membrane 41 is
It is surrounded and supported by a mounting tool 44 having higher rigidity, and is partially exposed.

According to this method, the chemical substance present in the extracellular fluid space outside the dialysis membrane 41 is extracted into the perfusion fluid flowing through the dialysis membrane 41 through the dialysis membrane 41, and Collecting the inside and analyzing it reveals what the chemical is. Since the technique using the dialysis principle does not directly inject the perfusate into the living tissue, there is an advantage that the living tissue is not seriously damaged. Furthermore, since the dialysis probe is reinforced by the mounting tool 44, the dialysis membrane 41 can be supported by the mounting tool 44 when the dialysis probe is inserted into a predetermined position.

[0006]

However, in the dialysis probe shown in FIG. 4, it is necessary to produce a partly exposed mounting tool 44 and provide the dialysis membrane 41 on the exposed part.
There is a disadvantage that the production is difficult and the cost is high. Further, in this dialysis probe, there is a limit in reducing the outer diameter of the mounting tool 44. For example, it is difficult to reduce the outer diameter to 400 μm or less.

In the dialysis probe shown in FIG. 5, since the base of the dialysis membrane 41 is covered with the mounting tool 44, the outer diameter of the mounting tool 44 is also smaller than the outer diameter of the dialysis membrane 41 in this dialysis probe. The dialysis membrane 41 and the attachment 4
A step 45 is formed between the step 45 and the step 4. Therefore, there is a disadvantage that the living tissue is damaged when the dialysis probe having such a configuration is inserted into the living tissue.

The present invention has been made in order to solve the above-mentioned drawbacks, and an object of the present invention is to reduce the outer diameter of a living tissue so that it can be inserted into the living tissue without damaging it. It is to provide a dialysis probe which can be used. Another object of the present invention is to provide a dialysis probe that does not cause a step between the dialysis membrane and the mounting tool and does not damage the living tissue when inserted into the living tissue.

[0009]

According to the present invention, there is provided a dialysis probe comprising a tubular dialysis membrane 1 whose tip is sealed,
An extension tube disposed at the base end of the dialysis membrane and the extension tube disposed between the base end of the dialysis membrane and the distal end of the extension tube. A fixed connection pipe, a supply pipe for supplying a perfusion solution into a space formed by the dialysis membrane, the connection pipe and the extension pipe, and a supply pipe for returning the perfusion solution in the space to a measurement device. And a return pipe, whereby the object is achieved.

[0010]

The connecting tube is arranged between the base end of the dialysis membrane and the distal end of the extension tube inside the dialysis membrane and the extension tube, and is fixed to both tubes with an adhesive. Can be approximately the same as the outer diameter of Therefore, it is possible to form the extension tube with an outer diameter as small as possible. Furthermore, since the dialysis membrane is supported by the extension pipe and the connecting pipe, deformation and the like of the dialysis membrane are suppressed.

[0011]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be specifically described below based on embodiments.

As shown in FIG. 1, a dialysis probe 1 includes an extension tube 11, a dialysis membrane 12 attached to a distal end of the extension tube 11, and a connection portion between the extension tube 11 and the dialysis membrane 12. The inserted connecting pipe 13, the extension pipe 11, and the connecting pipe 1
A supply tube 15 inserted into a space 14 formed by the dialysis membrane 12 and the dialysis membrane 12 for supplying a perfusate, and a return tube 1 for returning the perfusate in the space 14 to the measuring device.
And 6.

The extension tube 11 is formed of a tube member having a higher rigidity than the dialysis membrane 12, and can be formed of, for example, a quartz tube whose outer surface is coated with polyimide.
Its outer diameter can be 300 μm or less.

The connection pipe 13 is also formed of a pipe member having a higher rigidity than the dialysis membrane 12 like the extension pipe 11, and can be formed of, for example, a stainless steel pipe. The outer diameter of the connecting pipe 13 can be changed according to the diameter of the extension pipe 11 to be used, and can be, for example, 120 to 180 μm. The connecting pipe 13 is adhered to the inner surfaces of the extension pipe 11 and the dialysis membrane 12 with an adhesive 10 such as an epoxy adhesive.

The tip of the dialysis membrane 12 is closed by a lid member 17 made of an adhesive or a resin. The outer diameter of the dialysis membrane 12 can be substantially the same as the outer diameter of the extension tube 11,
Its outer diameter can be from 100 to 300 μm, particularly preferably from 200 to 300 μm.

A supply pipe 15 provided in the space 14
Has an opening near the distal end of the dialysis membrane 12, and the distal end of the return pipe 16 has an opening near the base end of the extension pipe 11 in the space 14. And at least the space 1 inside the dialysis membrane 12
A flow of perfusate is formed in 4.

A connecting pipe 18 is fixed to the base end of the extension pipe 11 with an adhesive 29. The connection tube 18 can be formed of a quartz tube whose outer surface is coated with polyimide or the like.

A fixing member 20 formed of an acrylic resin or the like is fixed around the connection pipe 18.
A filling member 22 formed of a vinyl chloride resin or the like is loaded therein. Then, the connecting pipe 18 and the fixing member 2
A resin 19 such as an epoxy resin is embedded in 0,
The bases of the supply pipe 15 and the return pipe 16 are fixed to a resin 19. A stainless steel pipe 21 is provided so as to surround the bases of the supply pipe 15 and the return pipe 16.

Next, a method for measuring a substance in a living tissue, for example, a brain of a laboratory animal using the dialysis probe 1 having the above-described configuration will be described.

<Experimental Example 1> First, a hole is made in the skull, and the dialysis probe 1 shown in FIG. 1 is inserted into an appropriate place in the brain through the hole. Then, the dialysis probe 1 is fixed with cement or the like. The supply pipe 15 and the return pipe 16 of the dialysis probe 1 are connected to a dialysis device.

Since the distal end of the supply pipe 15 is arranged near the distal end of the dialysis membrane 12, the perfusate supplied from the supply pipe 15 reaches the distal end of the dialysis probe 1, and then the perfusate is supplied. It flows between the pipe 15 and the inner surface of the dialysis membrane 12 to the opening of the return pipe 16. Thus, dialysis is performed by the dialysis membrane 12 when the perfusate flows through the space 14. Then, the perfusate returned through the return pipe 16 is guided to a measuring device, and the substance contained in the liquid is measured.

<Experimental Example 2> FIG. 2 shows a guide cannula 2 used for inserting the dialysis probe 1 into a living tissue.
FIG. 3 is a cross-sectional view of a cap nut 3 used for fixing the guide cannula 2 to a tissue.

The guide cannula 2 is a long guide tube 2
4 is formed by fixing a cylindrical fixing portion 25 to the base portion with an adhesive 28 or the like. The proximal end of the guide tube 24 is curved outward, and the distal end of the guide tube 24 is a through-hole 2 provided in the fixing portion 25.
6 is in contact with the outer peripheral surface. A screw groove 27 is formed on the outer peripheral surface of the fixing portion 25. The guide tube 24 can be formed of a stainless steel tube or the like, and the fixing portion 25 can be formed of a molded product such as an acrylic resin.

The cap nut 3 is formed of a Teflon resin or the like, has an insertion hole 30 formed therein, and has a screw groove 32 formed on the inner surface of the outer peripheral portion 31 so as to be screwable with the screw groove 27 of the fixing portion 25. I have.

Next, a method of fixing the dialysis probe 1 to a living tissue using the guide cannula 2 and the cap nut 3 having the above-described configuration will be described.

As shown in Example 1, a hole is made in the skull, and then the guide cannula 2 is inserted through the hole into a proper position in the brain, and then the dialysis probe 1 shown in FIG.
Is inserted into the guide tube 24 of the guide cannula 2, and the dialysis membrane 12 of the dialysis probe 1 is inserted into the guide tube 24.
Exposed from the tip of Here, the fixing member 20 of the dialysis probe 1 is disposed in contact with the fixing portion 25 of the guide cannula 2.

Next, the screw groove 32 of the cap nut 3 will be described.
Is screwed into the screw groove 27 of the guide cannula 2 to fix the dialysis probe 1 to the guide cannula 2. Thereafter, as in the first embodiment, the perfusate supplied from the supply pipe 15 reaches the distal end of the dialysis probe 1 and dialysis is performed on the dialysis membrane 12, and the perfusate passes through the return pipe 16 to the measurement device. The measurement is performed by being guided.

The number of supply pipes 15 and return pipes 16 in the dialysis membrane 12 is not limited to one, and may be more. In any case, the perfusate may be kept flowing inside the membrane involved in dialysis. Further, the dialysis probe of the present invention is particularly useful for dialysis of brain tissue, but is not limited to dialysis of brain tissue but can be applied to dialysis of various living tissues.

The dialysis probe of the present invention can be used not only for studying living tissues of small experimental animals but also for clinical examinations and treatments, not to mention large experimental animals. For example, it is used to measure various metabolites and transmitters to monitor the state of the brain after cranial trauma. With the right isotope,
Various brain functions can be tracked. Tumor metabolism can also be examined to make a basic diagnosis of the tumor. Cytoxin (cytotoxic)
In dialysis, dialysis can also be used to monitor the amount of cytoxin reaching the tumor and the amount of cytoxin received by normal tissue. Cytoxin can also be administered locally by reverse dialysis.

As in basic research, in clinical practice, the dialysis method can be used to examine the penetration of drugs into the brain and other tissues. Dialysis can be used for organs other than the brain.

In other words, in the study of liver function, in the study of muscle metabolism and cardiac metabolism during and before and after surgery, in the case of tumor puncture for diagnosis and treatment, and also in pursuit of body fluid status and metabolism subcutaneously and in organs. It can also be used for a number of intensive treatments. It can also be inserted into a blood vessel to continuously monitor the condition of blood without the need to collect blood from the patient. The dialysis probe can also be used for various cell cultures, in vitro experiments such as sampling metabolites in fermentation vessels. The dialysate is transferred to a chemical laboratory for analysis or connected directly to a suitable measuring device.

[0032]

According to the present invention, chemical substances which are inserted into a living tissue such as a brain tissue and are present in the extracellular liquid space of a minute region of the living tissue can be analyzed by the dialysis principle. Since the outer diameter of the membrane and the outer diameter of the extension tube can be made the same, the outer diameter of the extension tube can be made as small as possible, and further, there is no step between the extension tube and the dialysis membrane. Therefore, when inserting the dialysis probe into the living tissue, the tissue is not damaged by the probe.

Further, by forming the extension pipe and the connecting pipe with a pipe member having higher rigidity than the dialysis membrane, the dialysis membrane can be supported by the connecting pipe from the inside, and the dialysis membrane can be suppressed from being deformed. Further, since the exposed area of the dialysis membrane can be regulated by the extension tube, the dispersion of the measurement can be reduced.

[Brief description of the drawings]

FIG. 1 is an enlarged sectional view of one embodiment of a dialysis probe of the present invention.

FIG. 2 is an enlarged cross-sectional view of a guide cannula used for fixing the dialysis probe of FIG. 1 to a living tissue.

3 is an enlarged sectional view of a cap nut used to fix the dialysis probe of FIG. 1 to the guide cannula of FIG. 2;

FIG. 4 is an enlarged sectional view of a conventional dialysis probe.

FIG. 5 is an enlarged sectional view of another conventional dialysis probe.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Dialysis probe 2 Guide cannula 3 Cap nut 10 Adhesive 11 Extension tube 12 Dialysis membrane 13 Connection tube 14 Space part 15 Supply tube 16 Return tube

Claims (4)

(57) [Claims] 1. A tubular dialysis membrane having a sealed distal end portion, an extension tube disposed at a proximal end portion of the dialysis membrane, and a portion between a proximal end portion of the dialysis membrane and a distal end portion of the extension tube. Supplying a perfusate into a space formed by the dialysis membrane, the connection tube and the extension tube, the connection tube being disposed inside the dialysis membrane and the extension tube and fixed to both tubes by an adhesive; A dialysis probe, comprising: a supply pipe for performing the measurement, and a return pipe for returning the perfusate in the space to the measurement device. 2. The extension pipe and the connection pipe are formed of a pipe member having higher rigidity than the dialysis membrane.
A dialysis probe according to item 1. 3. The dialysis probe according to claim 1, wherein the connecting pipe is formed of a stainless steel pipe. 4. The extension tube has an outer diameter of 200 μm to 300 μm.
The dialysis probe according to claim 1, 2 or 3, which has a diameter of µm.