JP3354652B2 - Chemical solution administration device - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid medicine administration device for administering a liquid medicine into a living body.

[0002]

2. Description of the Related Art At present, for unresectable malignant tumors,
Chemotherapy is performed by administration of anticancer drugs.However, systemic administration causes side effects such as cardiac, hepatic and renal toxicity and bone marrow suppression.Therefore, there are significant restrictions on the concentration, dosage, and duration of anticancer drugs. The concentration of the drug in tumor tissue is low,
Insufficient therapeutic results have been obtained.

[0003] As a method of minimizing side effects caused by systemic administration of an anticancer drug, arterial infusion therapy of an anticancer drug combined with blood adsorption has been attempted. In this method, an anticancer drug is injected from a catheter inserted into an artery near a tumor-bearing organ (for example, when the tumor-bearing organ is the bladder, bilateral internal iliac arteries just above the bifurcation of the superior vesical artery). Blood is removed from the vein, the components of the anticancer agent are removed from the blood, and the blood is returned to the cubital vein.

However, even in this method, since blood containing an anticancer drug flows in a range from the superior vesical artery to the inferior vena cava, a problem of side effects also arises, and the above disadvantages have not been solved.

[0005]

SUMMARY OF THE INVENTION An object of the present invention is to provide a drug solution administration device which can obtain a sufficient drug effect while preventing side effects associated with in vivo administration of a drug.

[0006]

This and other objects are attained by the present invention which is defined below as (1). In addition, the following (2)-
(16) is preferred.

(1) A drug solution administration device for administering a drug solution to a target site in a living body and recovering the drug solution, wherein at least one first device inserted near the upstream side of the target site in the blood flow direction. A circulatory circuit including a catheter and at least one second catheter inserted in the vicinity of the blood flow downstream side of the target site, and in the middle of the circulatory circuit via the first catheter, A drug solution supply port for supplying a drug solution to a site, a pump for generating a circulating flow in the circulation circuit, and a gas exchanger are provided, and the oxygenated blood containing the drug solution is supplied only to the target site. Characteristic drug administration device.

(2) The liquid medicine administration device according to the above (1), wherein an expandable and contractible expandable body is provided at a distal end portion of the first catheter.

(3) The first catheter has a catheter main body having a double tube structure composed of an outer tube and an inner tube, and a lumen of the inner tube forms a part of the circulation circuit. The drug solution administration device according to (2), wherein a space formed between the inner tube and the outer tube communicates with the inside of the expansion body.

(4) The medicinal-solution administration device according to any one of (1) to (3), wherein an expandable and contractible expandable body is provided at a distal end of the second catheter.

(5) The second catheter has a catheter main body having a double tube structure composed of an outer tube and an inner tube, and the lumen of the inner tube forms a part of the circulation circuit. The drug solution administration device according to (4), wherein a space formed between the inner tube and the outer tube communicates with the inside of the expansion body.

(6) The medicinal-solution administration device according to any one of (1) to (5), including a plurality of the second catheters.

(7) The chemical solution according to any one of (1) to (4), wherein a hub is attached to a base end of the first catheter, and the chemical solution supply port is formed in the hub. Dosing device.

(8) The liquid medicine administration device according to any one of (1) to (7), wherein a heating means for heating the liquid circulating in the middle of the circulation circuit is provided.

(9) The liquid medicine administration device according to the above (8), wherein the heating means is provided upstream of the gas exchanger.

(10) The drug solution administration device according to any one of (1) to (9), wherein the gas exchanger is a hollow fiber membrane oxygenator.

(11) The drug solution administration device according to any one of (1) to (10), wherein an antithrombotic material is provided in a portion of the circulating circuit that comes into contact with blood.

(12) The drug solution administration device according to any one of (1) to (11), further comprising a drug solution removing means for removing components of the drug solution from the liquid flowing in the circulation circuit.

(13) The chemical liquid administration device according to the above (12), further comprising a bypass flow path bypassing a part of the circulation circuit, wherein the chemical liquid removing means is provided in the middle of the bypass flow path.

(14) The liquid medicine administration device according to the above (13), further comprising flow path switching means for selectively flowing a part of the circulation circuit and the bypass flow path.

(15) The above-mentioned chemical solution removing means comprises a column filled with an adsorbent.
The drug solution administration device according to any of 4).

(16) The liquid medicine administration device according to any one of the above (1) to (15), wherein the liquid medicine is an anticancer agent.

[0023]

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a perspective view of a liquid medicine administration device according to the present invention.

FIG. 1 is a circuit diagram schematically showing a configuration example of a drug solution administration device of the present invention. The drug solution administration device 1A shown in FIG. 1 locally administers a drug solution (anticancer agent) to a tumor-bearing organ 100 in a living body, and has a blood circulation circuit 2. This circulation circuit 2 has a first catheter 3 and a second catheter 5.

The first catheter 3 is preferably inserted percutaneously, for example, from the femoral artery.
Is located near the tumor-bearing organ.

The second catheter 5 is preferably inserted percutaneously, for example, from a femoral vein.
It is located in a target site in the living body, that is, in the vicinity of the tumor-bearing organ of the vein 102 from the tumor-bearing organ 100.

FIG. 2 is a longitudinal sectional view showing a configuration example of the first catheter. As shown in the figure, the first catheter 3 has a catheter main body 31 having a double tube structure composed of an outer tube 32 and an inner tube 33.

The outer tube 32 and the inner tube 33 are each made of a flexible resin or elastomer. Examples of the constituent materials include polyolefins such as polyethylene and polypropylene, polyesters such as polyethylene terephthalate (PET) and polybutylene terephthalate (PBT), polyvinyl chloride, ethylene-vinyl acetate copolymer (EVA), and polyamide. , Polytetrafluoroethylene, polyurethane, silicone rubber, polyamide elastomer, polyester elastomer, polystyrene elastomer, and polyolefin elastomer.

It is also preferable that at least the outer surface of the outer tube 32 and / or at least the inner surface of the inner tube 33 are made of an antithrombotic material. As the antithrombotic material, for example, an antithrombotic polymer having a microphase-separated structure, in particular, a urethane type such as a segmented polyurethane, a fluorine-containing segmented polyurethane, a polyvinyl chloride-polyurethane block copolymer, and a segmented polyamide ( Japanese Patent Application No. 01-314924, Japanese Patent Application No. 02-7435
Various block copolymers such as an amide type such as described in No. 7), an ester type such as a polyhydroxyethyl methacrylate-polystyrene block copolymer, and a polyether-polyester block copolymer. Among them, urethane-based, amide-based or styrene-based ones are particularly preferable in terms of appropriate flexibility, high antithrombotic properties, and the like, and further, segmented polyurethane, segmented polyamide, and polyhydroxyethyl methacrylate-
Polystyrene block copolymers are preferred. When such a material is used, the microphase separation structure formed on the surface of the material exhibits excellent antithrombotic properties (particularly, suppression of platelet adhesion).

In addition, an anti-thrombotic material such as a layer containing an antithrombotic material such as heparin, prostaglandin, urokinase, arginine derivative or the like is formed on the outer surface of the outer tube 32 and / or the inner surface of the inner tube 33. A thrombotic treatment may be performed.

On the distal end side (left side in FIG. 2) of the catheter body 31, an inner tube 33 projects a predetermined length from the distal end of the outer tube 32, and both ends of a cylindrical expandable body (balloon) 36 , Outer peripheral surface of the distal end portion of outer tube 32 and inner tube 3
3 is hermetically fixed to the outer peripheral surface of the distal end. Inner tube 33
The flow path 35 formed in the inner lumen constitutes a part of the circulation circuit 2 and is released to the distal end of the catheter body 31. In addition, a flow path 34 formed in a space between the inner pipe 33 and the outer pipe communicates with the inside of the expansion body 36.

The expandable body 36 is expandable and contractible by a change in internal pressure. For example, various elastic materials such as silicone rubber, latex rubber, polyurethane, polyamide elastomer, polyester elastomer, polystyrene elastomer and polyolefin elastomer,
Or a thin film made of a polyolefin such as soft polyvinyl chloride, polybutadiene, polyethylene, polypropylene, ethylene-vinyl acetate copolymer (EVA), or a polyester such as polyethylene terephthalate (PET) or polybutylene terephthalate (PBT). ing. Further, at least the outer surface of the expansion body 36 is
It may be composed of an antithrombotic material as described above or may have been subjected to an antithrombotic treatment.

When the working fluid is supplied into the expansion body 36 through the flow path 34, as shown in FIG. 1, the expansion body 36 is expanded and the distal end of the first catheter 3 is inserted. It closely adheres to the inner wall of the blood vessel (the artery near the upstream of the blood flow of the cancer-bearing organ 100), and blocks the blood flow. Thus, even if blood containing a drug solution is jetted from the distal end of the first catheter 3, the drug solution component is prevented from leaking into the artery beyond the dilator 36. The working fluid supplied into the expansion body 36 includes, for example, a gas such as air and a liquid such as water.

On the outer peripheral surface of the inner tube 33 in the expansion body 36, a marker 37 made of a substance having X-ray
Is installed. Thus, for example, when the first catheter 3 is inserted into a blood vessel, the position of the distal end of the first catheter 3 can be confirmed under fluoroscopy. Examples of the marker 37 include a ring-shaped member fitted on the outer periphery of the inner tube 33, and examples of the constituent material thereof include metals such as gold, platinum, tungsten, and alloys containing these.

A hub 4 that is gripped when the first catheter 2 is inserted into a blood vessel or the like is mounted on the proximal end side (the right side in FIG. 2) of the first catheter 3.
A front space 41 and a rear space 42 are formed inside the hub 4, while an inner tube 33 protrudes from the base end of the outer tube 32 by a predetermined length on the base end side of the catheter body 31. The base end of the outer tube 32 is in the front space 41 in the hub 4,
The proximal ends of the inner tubes 33 are air-tightly connected to the rear spaces 42 in the hub 4 respectively. In this case, the front space 41 and the rear space 42 are shielded by the inner pipe 33.

A rear space 42 is provided at the base end of the hub 4.
The distal end of the tube 13 is connected in a liquid-tight manner so as to communicate with the tube. The hub 4 is formed with two branch portions 43 and 45. The lumen of the tubular branch portion 43 formed on the distal end side (front) of the hub 4 communicates with the front space 41. A working fluid supply port 44 whose inner peripheral surface is tapered is formed at an end of the branch portion 43. For example, the distal end of a syringe (not shown) filled with the working fluid as described above is connected to the working fluid supply port 44, and the plunger of the syringe is pressed to divide the working fluid in the syringe. Inside the part 43, the front space 41 and the flow path 3
4 and sequentially supplied into the expansion body 36, and the expansion body 36 expands. On the other hand, when the plunger of the syringe is withdrawn, the working fluid in the expansion body 36 flows through the flow path 34 and the front space 4.
1 and the inside of the branch portion 43 are sequentially collected in the syringe, and the expanded body 36 contracts.

The tubular branch 45 formed on the base end side (rear side) of the hub 4 has a lumen communicating with the rear space 42. A chemical supply port 46 having an inner peripheral surface tapered is formed at an end of the branch portion 45. For example, the tip of a syringe (not shown) filled with a drug solution such as an anticancer drug is connected to the drug solution supply port 46, and the plunger of the syringe is pressed, so that the drug solution in the syringe is removed from the branch portion 45. Is supplied to the rear space 42 and mixed with blood flowing from the proximal end side of the hub 4 via the tube 13. The blood mixed with the chemical is ejected from the distal end of the first catheter 3 through the flow path 34.

The second catheter 5 has the same configuration as the first catheter 3 described above. The hub 6 connected to the proximal end of the second catheter 5 has the same configuration as the above-described hub 4 except that the hub 6 does not have the drug solution supply port 46.

Also in the second catheter 5, as shown in FIG. 1, an expandable body (balloon) 56 is expanded to insert a blood vessel (cancer-bearing organ 1) into which the distal end of the second catheter 5 is inserted.
(00), close to the inner wall of the vein near the downstream side of the blood flow, and cut off the blood flow. Thereby, the blood containing the drug solution flowing from the cancer-bearing organ 100 can be sucked and collected from the distal end of the second catheter 3 while the blood containing the drug solution flowing from the cancer-bearing organ 100 is blocked by the expandable body 56. Leakage into the vein 102 is prevented.

In the configuration shown in FIG. 1, the first catheter 3 and the second
Although 6 and 56 are provided, in the present invention, one or both of the first catheter 3 and the second catheter 5 may not have an expansion body. However, in the present invention, the cancer-bearing organ (target site) 100
The second catheter 5 downstream of the blood flow is preferably a catheter with an expandable body. As a result, almost all of the drug solution administered to the tumor-bearing organ 100 can be collected downstream of the blood flow without leaking into the vein 102 and diffusing.

One end of a flexible tube 10 is connected to the rear end of the hub 6, and the other end of the tube 10 is connected to the suction side of the pump 7. One end of a flexible tube 11 is connected to the discharge side of the pump 7, and the other end of the tube 11 is connected to a blood inlet 88 a of the heat exchanger 8 as a heating unit. One end of a flexible tube 12 is connected to the blood outlet 88b of the heat exchanger 8, and the other end of the tube 12 is connected to a blood inlet 98a of the oxygenator 9 as a gas exchanger. . One end of a flexible tube 13 is connected to the blood outlet 98 b of the oxygenator 9, and the other end of the tube 13 is connected to the rear end of the hub 4.

The first and second catheters 3 and 5, hubs 4 and 6, pump 7, heat exchanger 8 and artificial lung 9 as described above
The tubes 10 to 13 constitute the circulation circuit 2.

In the present invention, a plurality of second catheters 5 may be provided. For example, when a plurality of veins are provided on the downstream side of the blood flow of the tumor-bearing organ 100, the second catheter 5 is inserted into each of the veins, and the blood containing the anticancer drug is collected. Can be more reliably prevented. In such a case, the hub 6 is attached to the proximal end of each second catheter 5.
Is mounted, and tubes connected to the rear ends of the hubs 6 are joined together by, for example, a branch connector and connected to the suction side of the pump 7. Similarly, a plurality of first catheters 3 may be provided.

The pump 7 generates a circulating flow in the circulating circuit 2, and examples thereof include a roller pump and a centrifugal pump. In addition, it is preferable to use a roller pump in that the priming amount is small and the stability of the ejection amount is excellent.

The discharge amount of the pump 7 is not particularly limited, and is preferably adjusted appropriately so as to obtain an appropriate blood flow rate according to the target site (target organ).

The installation position of the pump 7 in the circulation circuit 2 is not particularly limited, and may be, for example, between a heat exchanger 8 and the artificial lung 9 described later or between the artificial lung 9 and the hub 4. .

FIG. 3 is a sectional front view showing an example of the configuration of the heat exchanger 8. As shown in the figure, the heat exchanger 8 has a casing 81, and the inside of the casing 81 is formed by a pair of partition walls 82 and 83, a heat medium inflow space 84 and a blood storage space 85.
And a heat medium outflow space 86.

In the blood storage space 85, both ends are provided with partitions 82, 8.
A number of metal tubes 87 buried and fixed in 3 are installed in parallel, and both ends of each metal tube 87 open to a heat medium inflow space 84 and a heat medium outflow space 86, respectively.
Thus, the heat medium inflow space 84 and the heat medium outflow space 86
Communicate with each other via each metal tube 87. The metal tube 87 is made of a metal material having a high thermal conductivity, such as copper, stainless steel, aluminum, and titanium.

A blood inlet 88a and a blood outlet 88b communicating with the blood storage space 85 are formed on both opposing side surfaces of the casing 81, respectively. Further, a heat medium inlet 89 a communicating with the heat medium inflow space 84 and a heat medium outlet 89 b communicating with the heat medium outflow space 86 are formed on the lower surface and the upper surface of the casing 81, respectively.

The casing 81 may be made of, for example, polycarbonate, acrylic resin, polyethylene terephthalate, polyethylene, polypropylene, polystyrene, polyvinyl chloride, acryl-styrene copolymer,
An acryl-butadiene-styrene copolymer can be exemplified.

As a constituent material of the partition walls 82 and 83, a high-potential polymer potting material such as polyurethane, silicone, and epoxy resin can be used.

The blood sent from the tube 11 flows into the blood storage space 85 through the blood inlet 88a, and the metal tube 8
2 through the gap between the casings 7 and between the casing 81 and the metal tube 87, and flows out of the casing 81 from the blood outlet 88b.

On the other hand, when a heat medium is supplied to the heat medium inflow space 84 from the heat medium inflow port 89a, the heat medium flows into the heat medium outflow space 86 through the inner cavities of the metal tubes 87, and the heat medium flow It is discharged out of the casing 81 from the outlet 89b. When the heat medium passes through each metal tube 87, heat is exchanged between the blood and the heat medium via the tube wall of the metal tube 87, and the blood flowing in the blood storage space 85 is heated.

The heat medium used for the heat exchanger 8 can be, for example, water, alcohol, or the like, and the temperature thereof is preferably one that can heat blood to about 37 to 42 ° C.

It is known that cancer cells are susceptible to heat. By installing such a heat exchanger 8 in the circulation circuit 2 and heating the circulating blood, the cancer cells in the cancer-bearing organ 100 are heated. Can enhance the antitumor effect of the anticancer agent acting on the antitumor agent.
When the anticancer agent to be administered has an action mechanism of the alkylating agent, the activity of the circulating blood is increased by heating the circulating blood, and the antitumor effect can be further enhanced.

The arrangement of the heat exchanger 8 in the circulation circuit 2 is not particularly limited, but it is preferable that the heat exchanger 8 is installed upstream of the artificial lung 9 described later. In the circulation circuit 2, after heating the blood and performing gas exchange,
This is because the generation of air bubbles in blood can be more effectively prevented.

FIG. 4 is a sectional front view showing an example of the configuration of the oxygenator (gas exchanger) 9. The artificial lung 9 shown in the figure is a hollow fiber membrane-type artificial lung, and includes a cylindrical main body 911 and funnel-shaped gas flow path forming members 912 and 913 mounted on both ends of the cylindrical main body 911, respectively. Housing 9
One.

At the center of the housing 91, a large number (for example, 5000 to 80000) of hollow fiber membranes 97 are spaced apart from each other in parallel along the longitudinal direction of the housing 91. Both ends of each hollow fiber membrane 97 are liquid-tightly supported and fixed at both ends of the cylindrical main body 911 by the support members 92 and 93 in a state where the respective end openings are not closed.

Inside the housing 91, both support members 92, 9
3, the gas inflow space 94, the blood storage space 95, and the gas outflow space 96 are partitioned, and the gas inflow space 94 and the gas outflow space 96 communicate with each other through the lumen of each hollow fiber membrane 97.

The cylindrical main body 911 has a narrowed portion 914 having the smallest inner diameter at the center in the longitudinal direction, and has a structure in which the diameter is increased toward both ends. Therefore, the bundle of the hollow fiber membranes 97 stored in the cylindrical main body 911 is narrowed down by the narrowing portion 914, and the filling rate of the hollow fiber membranes 97 is the highest.

A blood inlet 98 communicating with the blood storage space 95 is provided at the upper part and the lower part of the cylindrical main body 911 in the figure, respectively.
a and a blood outlet 98b are formed. In this case, the blood inlet 98a and the blood outlet 98b are preferably formed so as to protrude toward the tangential direction of the inner circumference of the cylindrical main body 911, respectively.

The gas flow path forming members 912 and 91
A gas inlet 99a communicating with the gas inflow space 94 and a gas outlet 99b communicating with the gas outflow space 96 are formed at the top of the nozzle 3 respectively. For example, a gas containing oxygen is supplied to the gas inlet 99a.

The cylindrical body 911 and the gas flow path forming member 9
As the constituent materials of 12, 913, the same materials as those of the casing 81 described above can be used. The support members 92 and 93 are formed, for example, by pouring the above-described polymer potting material into both ends of the cylindrical main body 911 by a centrifugal injection method and curing the same.

The hollow fiber membrane 97 may be either a dense membrane (for example, made of silicone rubber) or a porous membrane, but is preferably a porous membrane made of polypropylene or cellulose diacetate.

The effective membrane area of the artificial lung 9 is not particularly limited, but is preferably about 0.1 to 9.0 m ² , more preferably about 0.6 to 6.5 m ² .

The blood sent from the tube 12 flows into the blood storage space 95 from the blood inlet 98a, and the gap between the hollow fiber membranes 97 is formed along the longitudinal direction of the housing 91 (from the upper side to the lower side in FIG. 4). Flow), blood outlet 98
b flows out of the housing 91.

On the other hand, when an oxygen-containing gas is supplied to the gas inflow space 94 from the gas inflow port 99a, this gas flows into the gas outflow space 96 through the inner cavity of each hollow fiber membrane 97, and flows from the gas outflow port 99b. It is discharged out of the housing 91. In the blood storage space 95, while the blood flows through the gap between the hollow fiber membranes 97, the oxygen-containing gas flows through the lumen of the hollow fiber membrane 97 through a number of pores formed on the surface of each hollow fiber membrane 97. And gas exchange is performed, that is, oxygenation and decarbonation are performed.

By arranging the artificial lung 9 in the circulation circuit 2 as described above, it is possible to prevent the tumor-bearing organ 100 from being deprived of oxygen during blood circulation and to maintain its activity. In addition, an increase in the oxygen partial pressure in the circulating blood promotes a medicinal effect, particularly an antitumor effect when an anticancer agent is administered (an additive antitumor effect with NH ₂ of the anticancer agent is obtained).

Furthermore, some cancer cells contain oxygen and some have no oxygen. The latter is known to be about three times more resistant to radiation than the former. When used in combination, the oxygen partial pressure in the circulating blood is increased by the artificial lung 9 and the abundance of anoxic cancer cells in the tumor-bearing organ 100 is reduced, thereby weakening the resistance to radiation and reducing its therapeutic effect. Can be improved.

The artificial lung 9 may be used so that blood flows in the lumen of each hollow fiber membrane 97 and gas flows outside the hollow fiber membrane 97. Further, the oxygenator is not limited to the hollow fiber membrane oxygenator as shown in the figure, but may be a flat membrane type, for example.

In the present invention, the heat exchanger 8 and the artificial lung 9 may be connected and integrated.
It is also possible to use a heat and gas exchanger capable of simultaneously performing heat exchange and gas exchange as described in the specification of No. 9961. Thereby, the priming amount of the circulation circuit 2 can be further reduced.

As the constituent materials of the tubes 10 to 13, the same materials as those of the outer tube 32 and the inner tube 33 described above can be used. In addition, each tube 10
At least the inner surface of 13 may be composed of an antithrombotic material as described above or may have been subjected to an antithrombotic treatment. The same applies to at least portions of the hubs 4, 6, the pump 7, the heat exchanger 8, and the artificial lung 9 that come into contact with blood.

The total priming amount of the circulation circuit 2 configured as described above can be set relatively small, for example, about 100 to 1000 ml, particularly about 200 to 500 ml.

Next, an example of how to use the drug solution administration device 1A shown in FIG. 1 will be described. The administration of the drug solution by the drug solution administration device 1A is performed according to the following procedure.

[1] Insertion of First Catheter The first catheter 3 to which the hub 4 is attached is percutaneously inserted from the femoral artery using a sheath by, for example, Seldinger method, and the hub is inserted under fluoroscopy. 4, an operation that appropriately combines advance / retreat (insertion / removal) of the first catheter 3, rotation, and advance / retreat of a guide wire (not shown) inserted into the flow path 35 from the rear end of the hub 4 is performed. While selecting the bifurcation of the blood vessel, the tip of the first catheter 3 is placed in the cancer-bearing organ 10.
It is inserted until it reaches the vicinity of the tumor-bearing organ of the artery 101 reaching 0.

[2] Insertion of Second Catheter The second catheter 5 with the hub 6 attached thereto is inserted from the femoral vein in the same manner as the first catheter 3, and the hub 6 is grasped under fluoroscopy. Then, an operation that appropriately combines advance / retreat (insertion / removal) of the second catheter 5, rotation, and advance / retreat of a guide wire (not shown) inserted from the rear end of the hub 6 is performed while selecting a branch of a blood vessel. Then, the second catheter 5 is inserted until the distal end of the second catheter 5 reaches the vicinity of the tumor-bearing organ of the vein 102 from the tumor-bearing organ 100.

[3] Assembling and priming of circulation circuit Tubes 13 and 10 are connected to hubs 4 and 6, respectively, to constitute circulation circuit 2 shown in FIG. Prior to the connection of the tubes 13 and 10, the inside of the flow path 35 of the first catheter 3 and the second catheter 5 is primed with a priming solution such as saline or blood (for example, patient's own blood). deep. Tube 1
Priming is similarly performed in the circuit from 0 to the tube 13 (the lower part in FIG. 1).

[4] Expansion of Expansion Body The plunger of a syringe (not shown) connected to the working fluid supply port 44 of the hub 4 is pressed to transfer the working fluid in the syringe through the flow path 34. It is sent into the expansion body 36 installed in one catheter 3 and the expansion body 36 is expanded. Similarly, the plunger of a syringe (not shown) connected to the working fluid supply port 64 of the hub 6 is pressed to push the working fluid in the syringe to the expansion body 56 installed in the second catheter 5. And the expansion body 56 is expanded. Thus, blood flow is blocked before and after the tumor-bearing organ 100. During the circulation of blood, which will be described later, the expanded state of the expansion bodies 36 and 56 is maintained.

[5] Blood Circulation The pump 7 is operated to generate blood circulation in the circulation circuit 2, and the plunger of a syringe (not shown) connected to the chemical solution supply port 46 of the hub 4 is pressed to operate. The anticancer drug (medical solution) in the syringe is injected and mixed into the circulating blood. When the blood circulation is in a steady state, the blood containing the anticancer agent discharged from the pump 7 is supplied to the tube 1.
1 to the heat exchanger 8 where, for example, 38 to
It is heated to 42 ° C., and then supplied to the oxygenator 9 via the tube 12, where oxygenation and decarbonation are performed,
Furthermore, the gas is ejected from the distal end opening of the first catheter 3 through the tube 13, the hub 4, and the flow path 35 of the first catheter 3 sequentially, and is supplied to the cancer-bearing organ 100. The cancer-bearing organ 100 exhibits an anticancer effect due to the drug effect of the anticancer agent.
The blood containing the anticancer drug that has passed through the cancer-bearing organ 100 is suctioned and collected from the distal end opening of the second catheter 5, and sequentially passes through the inner tube flow path, the hub 6 and the tube 10, and the pump 7.
And returned to circulation again. It should be noted that such blood circulation can be performed continuously for a predetermined time or intermittently a plurality of times.

As described above, in the present invention, after the blood containing the anticancer agent is supplied to the tumor-bearing organ 100 by the circulation circuit 2,
Collecting this blood and performing blood circulation again,
Furthermore, by performing blood circulation in a state where the blood flow around the cancer-bearing organ 100 is blocked by the expansion bodies 36 and 56, the anticancer drug component leaks out of the circulation circuit 2 and diffuses throughout the body via blood vessels. Therefore, even if a large amount of a high-concentration anticancer drug is administered, there is no problem of side effects due to systemic diffusion, and excellent drug efficacy can be obtained. In addition, as described above, since the priming amount of the circulation circuit 2 is relatively small, a high concentration can be obtained even if the injection amount of the anticancer agent into the circulation circuit 2 is small.

[6] Removal of anticancer drug Blood containing the above anticancer drug is circulated for a predetermined time,
When the treatment with the anticancer agent is completed, the inside of the circulating circuit 2 is replaced with the priming liquid or blood not containing the anticancer agent (for example, patient's own blood), and the circulation of the circulating circuit 2 is performed for a predetermined time by the operation of the pump 7. As a result, the portion between the dilated bodies 36 and 56 including the tumor-bearing organ 100 is replaced with the priming solution or blood not containing an anticancer agent, so that the first and second catheters are extracted in the following step [8]. In this case, there is no problem of side effects due to diffusion of the residual anticancer drug in this portion. In addition, the circulation circuit 2
Injection of the priming solution or the like into the inside can be performed, for example, from the chemical solution supply port 46 of the hub 4.

[7] Contraction of Expanded Body The plunger of the syringe connected to the working fluid supply port 44 of the hub 4 is pulled, and the working fluid in the expanded body 36 installed in the first catheter 3 flows through the flow path 34. The syringe 36 is sucked into the syringe and collected, and the expansion body 36 is contracted.

Similarly, the plunger of the syringe connected to the working fluid supply port 64 of the hub 6 is pulled, and the second
The working fluid in the expansion body 56 installed in the catheter 5 is sucked into the syringe and collected, and the expansion body 56 is contracted.

[8] Removal of first and second catheters The first catheter 3 and the second catheter 5 are extracted from the artery 101 and the vein 102, respectively.

FIG. 5 is a circuit diagram schematically showing a configuration example of the drug solution administration device of the present invention. The drug administration device 1B shown in the figure has a drug removal means for removing components of an anticancer drug from blood flowing in the circulation circuit 2. Hereinafter, the configuration of the drug administration device 1B is different from that of the drug administration device 1A. The points will be described.

In the drug solution administration device 1B, three tubes 13a, 13b and 1
3c is installed. One end of the tube 13a is connected to the blood outlet 98b of the oxygenator 9, and the other end of the tube 13a and one end of the tube 13b are connected to the first port 141 and the second port 141 of the three-way cock 14 as the flow path switching means, respectively. It is connected to port 142. The other end of the tube 13b and one end of the tube 13c are connected via a T-shaped branch connector 15, and
The other end of 3c is connected to the base end of hub 4.

One end of a tube 16 is connected to the third port 143 of the three-way cock 14.
It is connected to a blood inlet 20 of a chemical liquid removing means 18 described later. Further, one end of a tube 17 is connected to the blood outlet 21 of the drug solution removing means 18, and the other end of the tube 17 is connected to a branch end of the branch connector 15.

Tubes 16 and 17 and chemical liquid removing means 1
8, a part of the circulation circuit 2, ie, the tube 13b
Is formed.

The three-way cock 14 is configured to be able to select the communication between the first port 141 and the second port 142 and the communication between the first port 141 and the third port 143 by the rotation of the lever 144. I have. When the former is selected, the blood from the tube 13a flows to the tube 13b, and when the latter is selected, the blood from the tube 13a flows to the tube 17, that is, the bypass flow path.

FIG. 6 is a cross-sectional front view showing an example of the configuration of the chemical solution removing means in the chemical solution administration device 1B. As shown in the figure, the chemical liquid removing means 18 is provided with a cylindrical column body 191.
And funnel-shaped lids 192 and 1 attached to both ends thereof
93 and a column 19.

At the tops of the lids 192 and 193, a blood inlet 20 and a blood outlet 21 are formed, respectively. The blood inlet 20 and the blood outlet 21 have ends of tubes 16 and 17, respectively. It is connected.

The openings at both ends of the column main body 191 are provided with support members (filters) 22 for fixing the granular adsorbent 24.
And 23 respectively. The support members 22 and 23 are formed of, for example, a mesh, and have a large number of pores formed so that blood can pass therethrough but the adsorbent 24 cannot pass through. The space surrounded by the column body 191 and the support members 22 and 23 is filled with an adsorbent 24 made of, for example, activated carbon.

The conditions such as the type, particle size, and filling amount of the adsorbent 24 are appropriately selected according to the type and amount of the chemical to be removed. As the adsorbent 24, any material can be used as long as it can remove the chemical component mixed in the blood. The adsorbent 24 is not limited to a porous granular material such as the activated carbon, and may be an ion exchange resin such as an ion exchange resin. A body can also be used, and the form may be any form such as a fiber form or a film form.

In such a chemical solution removing means 18, the blood containing the anticancer drug sent from the tube 16 flows from the blood inlet 20 into the space surrounded by the lid 192 and the support member 22, and then the support member 22 After passing through the column body 191, the anticancer agent component is adsorbed and removed by contact with the adsorbent 24. The blood from which the anticancer drug component has been removed passes through the support member 22 and the lid 193 and the support member 23.
And flows out of the column 19 through the blood outlet 21.

Next, an example of how to use the drug solution administration device 1B shown in FIG. 5 will be described. In the drug solution administration device 1B,
First, steps similar to the above [1] to [5] are performed. In this case, in the step [3], the inside of the bypass channel is also primed with a priming liquid or the like. In step [5], the first port 141 and the second port 142 are communicated with each other by rotating the lever 144, and blood from the tube 13a is selectively flown to the tube 13b.

Next, while continuing the blood circulation, the lever 14
The rotation of the first port 141 and the third port 1
43, and the blood from the tube 13a flows selectively to the bypass channel. Thus, the anticancer drug component in the blood is removed by the drug solution removing means 18 provided in the middle of the bypass flow path as described above, and this blood is removed from the tube 17, the branch connector 15, the tube 13c, the hub 4, and the It is supplied to the tumor-bearing organ 100 through the channel 35 of one catheter 3 sequentially.

When the blood circulation passing through the liquid medicine removing means 18 is performed for a predetermined time, the portion between the expansion bodies 36 and 56 including the tumor-bearing organ 100 is replaced with blood containing no anticancer drug. Therefore, when the first and second catheters are extracted, there is no problem of side effects due to diffusion of the remaining anticancer drug in this portion.

When performing blood circulation through the bypass channel, the heat exchanger 8 and the artificial lung 9 may be in an inactive state. Thereafter, the same steps as in [7] and [8] are performed.

In such a drug solution administration device 1B, it is not necessary to replace the inside of the circulation circuit 2 with the priming solution or blood as in the above step [6], and the operation is easy.
There is an advantage that consumption of blood and the like can be reduced. In addition,
In the drug solution administration device 1B, the flow path switching means is not limited to the three-way cock 14 as shown in the drawing, and is configured to selectively close the tube 13b and the tube 16 by a tube clamping device such as a clamp. May be used.

The bypass flow path that bypasses a part of the circulation circuit 2 bypasses the artificial lung 9 (the flow switching means is provided in the middle of the tube 12) or the artificial lung 9 and the heat exchanger 8. Bypass (Tube 1
1). Since the ratio of the priming amount of the artificial lung 9 and the heat exchanger 8 to the priming amount of the entire circulating circuit 2 is large, by adopting such a configuration, the amount of blood for removing the anticancer agent in the chemical solution removing means 18 is significantly reduced. However, the removal of the anticancer agent can be performed quickly and efficiently.

As described above, the liquid medicine administration device of the present invention has been described with respect to the configuration examples shown in the respective drawings, but the present invention is not limited to these. For example, the chemical solution supply port is not limited to the case where the chemical solution supply port is formed in the hub 4.
It can be provided at an arbitrary position in the range from the hub 6 of the circulation circuit 2 to the tube 13 (the range not including the first and second catheters), such as in the middle of 3.

The heating means may be a heating element such as an electric heater (particularly having a temperature control means) installed in the middle of the circulation circuit.

The first catheter 3 and the second catheter 5 are not limited to those inserted / removed each time a drug solution is administered. For example, Japanese Patent Application Nos. 01-505694 and 01-505694.
It may be a subcutaneously implantable catheter as described in the specification such as 171499. The drug solution administered by the drug solution administration device of the present invention is not limited to an anticancer drug.

[0104]

As described above, according to the drug solution administration device of the present invention, a circulation circuit for locally administering a drug solution to a target site in a living body and thereafter collecting the drug solution passing through the target site. Therefore, there is no possibility that the drug solution diffuses into the normal tissue and causes side effects. Therefore, the concentration of the drug solution,
Sufficient pharmacological effects can be obtained without being restricted by the dose, timing and frequency of administration.

Particularly, when the drug solution to be administered is an anticancer drug,
The antitumor effect can be enhanced by adding oxygen with a gas exchanger or heating with a heating means. Further, since the circulating circuit in the drug solution administration device of the present invention has a relatively small priming amount, even if the injection amount of the drug solution is small,
At a target site in a living body, a high concentration can be obtained,
Demonstrates excellent medicinal effects.

[Brief description of the drawings]

FIG. 1 is a circuit configuration diagram schematically showing a configuration example of a drug solution administration device of the present invention.

FIG. 2 is a longitudinal sectional view showing a configuration example of a first catheter according to the present invention.

FIG. 3 is a sectional front view showing a configuration example of a heating means (heat exchanger) in the present invention.

FIG. 4 is a cross-sectional front view showing a configuration example of a gas exchanger (artificial lung) according to the present invention.

FIG. 5 is a circuit configuration diagram schematically showing another configuration example of the drug solution administration device of the present invention.

FIG. 6 is a cross-sectional front view showing a configuration example of a drug solution removing unit in the drug solution administration device shown in FIG.

[Explanation of symbols]

 Reference Signs List 1A, 1B Drug solution administration device 2 Circulation circuit 3 First catheter 31 Catheter body 32 Outer tube 33 Inner tube 34, 35 Flow path 36 Expansion body 37 Marker 4 Hub 41 Front space 42 Back space 43 Branch portion 44 Working fluid supply port 45 Branch 46 Chemical solution supply port 5 Second catheter 56 Expansion body 6 Hub 64 Working fluid supply port 7 Pump 8 Heat exchanger 81 Casing 82, 83 Partition wall 84 Heat medium inflow space 85 Blood storage space 86 Heat medium outflow space 87 Metal tube 88a Blood inlet 88b Blood outlet 89a Heat medium inlet 89b Heat medium outlet 9 Artificial lung 91 Housing 911 Cylindrical body 912, 913 Gas flow path forming member 914 Narrowing portion 92, 93 Support member 94 Gas inflow space 95 Blood storage space 96 Gas outflow space 97 Hollow fiber membrane 98a Blood inlet 98b Blood outflow 99a Gas inlet 99b Gas outlet 10, 11, 12, 13 Tube 13a, 13b, 13c Tube 14 Three-way stopcock 141 First port 142 Second port 143 Third port 144 Lever 15 Branch connector 16, 17 Tube 18 Chemical removal Means 19 Column 191 Column main body 192, 193 Lid 20 Blood inlet 21 Blood outlet 22, 23 Support member 24 Adsorbent 100 Cancer-bearing organ 101 Artery 102 Vein

──────────────────────────────────────────────────続 き Continued on the front page (58) Field surveyed (Int.Cl. ⁷ , DB name) A61M 1/14-1/36 A61M 25/00-31/00 A61B 17/00

Claims (8)

(57) [Claims] 1. A drug administration device for administering a drug solution to a target site in a living body and recovering the drug solution, wherein at least one first catheter inserted near a blood flow upstream side of the target site. And a circulatory circuit including at least one second catheter inserted in the vicinity of the blood flow downstream side of the target portion. The target portion is provided in the middle of the circulatory circuit via the first catheter. A chemical solution supply port for supplying a chemical solution to the pump, a pump for generating a circulating flow in the circulation circuit, and a gas exchanger are provided, and oxygenated blood containing the chemical solution is supplied only to the target site. Drug administration device. 2. The method according to claim 1, wherein at least one of the first catheter and the second catheter has an expanded portion at its distal end.
The drug solution administration device according to claim 1, wherein a contractible expansion body is provided. 3. At least one of the first catheter and the second catheter has a catheter main body having a double tube structure composed of an outer tube and an inner tube, and the lumen of the inner tube is provided in the circulation circuit. The liquid medicine administration device according to claim 2, wherein a space formed between the inner tube and the outer tube communicates with the inside of the expansion body. 4. The liquid medicine administration device according to claim 1, comprising a plurality of the second catheters. 5. The liquid medicine administration device according to claim 1, wherein a heating means for heating the liquid circulating in the middle of the circulation circuit is provided. 6. The drug solution administration device according to claim 1, further comprising a drug solution removing unit for removing a component of the drug solution from a liquid flowing in the circulation circuit. 7. A bypass flow path, comprising: a bypass flow path bypassing a part of the circulation circuit; and flow path switching means for selectively flowing a part of the circulation circuit and the bypass flow path. 7. The liquid medicine administration device according to claim 6, wherein the liquid medicine removing means is provided in the middle of the step. 8. The liquid medicine administration device according to claim 1, wherein the liquid medicine is an anticancer agent.