JP2014030572A - Carcinostatic administration device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an intraperitoneal carcinostatic administration device that selectively applies a load of a carcinostatic to a target organ and reduces a side effect of the carcinostatic on a normal cell, and provide an intraperitoneal carcinostatic administration method using the device.SOLUTION: An intraperitoneal carcinostatic administration device comprises means for: injecting a liquid chemical containing a carcinostatic injected from a liquid chemical supply port 1a into a peritoneal cavity 6 via a catheter 2 for injection retained in the peritoneal cavity 6; after injecting the carcinostatic-containing liquid chemical into the peritoneal cavity 6, discharging the carcinostatic liquid chemical in the peritoneal cavity from a used-chemical discharge port 4 after a lapse of time that is preliminarily assumed on the basis of a prior inspection and is required for the carcinostatic liquid chemical to arrive at a cancer cell of a target organ; using a liquid feeding pump 5 of the cleaning liquid container to inject a cleaning liquid injected from the liquid chemical supply port 1a into the peritoneal cavity 6 via the catheter 2 for injection retained in the peritoneal cavity; and removing the carcinostatic liquid chemical remaining in the peritoneal cavity 6 from the used-chemical discharge port 4 with the cleaning liquid.

Description

  The present invention relates to an anticancer agent administration device used for intraperitoneal chemotherapy in which a drug containing an anticancer agent is injected intraperitoneally, and an anticancer agent administration method using the device.

In general, when cancer treatment is performed with an anticancer agent, a method of administration via a vein is widely known.
However, when an anticancer drug is administered via a vein, if an effective amount of the anticancer drug reaches an organ containing cancer cells (hereinafter referred to as a target organ), the anticancer drug is administered to the whole body according to the blood flow. Since cancer drugs are distributed, there is a problem that their side effects affect normal cells throughout the body. Therefore, if you try to administer the necessary amount of anticancer drug to the affected area, it will result in systemic critical symptoms, so the dosage of anticancer drug is unavoidable and limited to an acceptable dosage that the patient can withstand systemic administration Is done. Then, after a few weeks when the side effects of the anticancer drug are attenuated and the patient's physical strength is restored, treatment is repeated again.
Apart from molecularly targeted anticancer drugs that selectively load anticancer drugs onto target cancer cells, anticancer drugs are not sufficiently selective for intravenous or oral administration of anticancer drugs. It has the disadvantage of causing side effects on normal cells and degrading the patient's physical strength.
This drawback is due to the low proportion of the amount of drug reaching the target organ out of the total dose of drug.
In the case of a peritoneal disseminated tumor, intraperitoneal administration of an anticancer agent is known through a reservoir placed subcutaneously in the abdominal wall (see Non-Patent Document 1).
In this case, the ratio of the amount of the drug that reaches the target organ is high in the total amount of drug administered, but the anticancer drug solution in the abdominal cavity is absorbed into the body and diffused to a long-distance organ for a long time. There is a drawback that side effects of cancer drugs occur in distant organs.
The present inventor has previously applied for a patent regarding a catheter for intraperitoneal administration of a drug solution, but there was no consideration for problems associated with intraperitoneal administration of an anticancer agent at that time (see Patent Document 1).

Japanese Patent Laid-Open No. 10-5342 Japanese Patent No. 4882054

"Cancer and Chemotherapy", 2011, 38, 12, p2084-2086

  The present invention provides an intraperitoneal anticancer drug administration device that selectively loads an anticancer drug on a target organ and reduces side effects of the anticancer drug on normal cells, and an intraperitoneal anticancer drug using the device. The purpose is to provide a method for administering a cancer drug.

When the anticancer drug is indirectly administered into the abdominal cavity close to the target organ, the inventor of the present invention is able to reduce the total dose of the drug compared to intravenous administration in which the anticancer drug is distributed throughout the body. Focusing on the significant improvement in the proportion of the drug that reaches the target organ, first administer an anticancer drug into the peritoneal cavity, and then the anticancer drug is in the nearby target organ cancer cells If the excess anticancer drug present in the abdominal cavity is quickly removed after reaching the target, the side effects of the anticancer drug on the target organ and other organs close to the abdominal cavity to which the anticancer drug is administered can be reduced. Thus, the present invention has been completed which reduces the side effects of anticancer agents on normal cells.
In peritoneal dialysis, co-occurrence of peritoneal sclerosis, fibrosis, mesothelial cell detachment, adhesion, intestinal obstruction and the like has been reported due to glucose-modified products such as glyoxal and methylglyoxal contained in the dialysate. Since intraperitoneal chemotherapy contains components that are more cytotoxic than peritoneal dialysis fluid, it is likely that similar symptoms have progressed. By utilizing the knowledge obtained in the improvement study of peritoneal dialysis therapy in the present invention (see Japanese Patent No. 4882054), washing with a washing solution added with a side effect reducing agent, ultrafiltration using an osmotic pressure gradient was utilized. We succeeded in improving edema and promoting the discharge of residual anticancer drugs.
Furthermore, after removing the extra anticancer agent in the abdominal cavity, injecting a diluent and / or an anticancer agent side effect reducing agent to reduce the side effect of the anticancer agent and high osmotic pressure in the abdominal cavity The present invention has been completed to reduce the side effects of anticancer agents by circulating dialysate and discharging excess anticancer agents remaining in the vicinity of the abdominal cavity.
That is, the present invention
(1) A device having a circulation circuit that communicates with a used drug solution outlet by a plastic tube after passing through a drug solution supply port, an infusion catheter placed in the abdominal cavity, and a discharge catheter placed in the abdominal cavity, It has a chemical solution container connection circuit in which an anticancer drug solution container and a cleaning solution container are connected to the chemical solution supply port, and a liquid feed pump is attached to the outer periphery of the outlet tube of each container of the chemical solution container connection circuit. The anti-cancer drug is injected into the abdominal cavity via an injection catheter placed in the abdominal cavity with a liquid-feeding pump in the drug solution container containing the anti-cancer agent. After injecting the drug solution containing the drug into the abdominal cavity, the anticancer drug solution in the abdominal cavity has been used after the time that the anticancer drug solution that has been assumed based on the preliminary examination reaches the cancer cells of the target organ has elapsed. Chemical discharge The solution remaining in the abdominal cavity is injected into the abdominal cavity via an injection catheter placed in the abdominal cavity by a liquid feeding pump of the cleaning liquid container, and injected into the abdominal cavity. An intraperitoneal anticancer drug administration device comprising means for removing the cancer drug solution from the used chemical solution discharge port together with the washing solution;
(2) A dilution water container or an anticancer drug side effect reducing agent container is further connected to the chemical liquid supply port as another chemical liquid container, and a liquid feed pump is attached to the outer periphery of the tube at the outlet of the other chemical liquid container. After the anti-cancer drug solution remaining in the abdominal cavity is removed from the used chemical solution discharge port together with the cleaning solution, the diluted water or anti-cancer injected from the drug solution supply port by the liquid feeding pump of the other chemical solution container An intraperitoneal anticancer drug administration device according to item (1), characterized by comprising means for injecting an agent side effect reducing agent into the abdominal cavity via an injection catheter placed in the abdominal cavity;
(3) The osmotic pressure dialysis container as another chemical solution container is further connected to the chemical solution supply port, and a liquid feed pump is attached to the outer periphery of the tube at the outlet of the other chemical solution container, and remains in the abdominal cavity. After removing the anticancer drug solution from the used chemical solution outlet with the cleaning solution,
The high osmotic pressure dialysate is returned to the used chemical solution discharge port via the chemical solution supply port, the infusion catheter placed in the abdominal cavity, and the discharge catheter placed in the abdominal cavity by the liquid feeding pump of the other chemical solution container. The intraperitoneal anticancer drug administration device according to (1) or (2), characterized by having means for continuously circulating the hyperosmotic dialysate in the circulation circuit after filling the circuit ,
(4) In the intraperitoneal anticancer drug administration device according to any one of (1) to (3), between or around the target organ and the abdominal cavity wall is heated or irradiated with ultrasonic waves or electromagnetic waves In the intraperitoneal anticancer drug administration device characterized by comprising means, and in the intraperitoneal anticancer drug administration device according to any one of (5) (1) to (4), all drug solutions An intraperitoneal anticancer drug administration device characterized by having an adapter that can be connected aseptically to an intraperitoneal catheter in a circuit in which containers are integrally connected in advance,
Is to provide.

The present invention reduces the side effects of anticancer agents on normal cells other than cancer cells of the target organ, thereby speeding up the recovery of the patient's physical strength after a single administration and shortening the cycle until the next administration By doing so, the cancer suppression effect is synergistically improved.
By adding an alleviating agent that counteracts the cytotoxic effect of the anticancer agent to the washing solution, degeneration and damage of the peritoneum can be prevented and long-term transperitoneal medication can be performed.

It is a figure which shows an example of the path | route in use of this invention apparatus.

  The intraperitoneal anticancer drug administration device of the present invention is, for example, as shown in FIG. 1, an infusion catheter 2 in which a chemical solution supplied to the chemical solution supply ports 1a, 1b, 1c is placed in the abdominal cavity, and placed in the abdominal cavity. The anti-cancer drug solution container a, the cleaning solution container b, and the anti-cancer drug supply port 1a, 1b, 1c are connected to the discharged discharge catheter 3 and the used drug solution discharge port 4 by a plastic tube. A chemical solution container connection circuit to which a drug side effect reducing agent chemical solution container c is connected is provided. And the liquid feeding pump 5 is attached to the outer periphery of the plastic tube of the discharge part of each container, This plastic tube is connected with the circulation circuit.

In the mode of item (1) of the present invention, when the anticancer drug is administered by the intraperitoneal anticancer drug administration device of FIG. 1, the used chemical liquid discharge port 4 is opened, and the chemical liquid supply port is opened. Close the passage.
Then, only the liquid feeding pump 5a of the anticancer drug solution container a is driven, and 1 to 2 liters of the anticancer drug solution is injected into the abdominal cavity 6 via the injection catheter 2, and the liquid supply pump 5a is stopped. To do. Immediately after the injection, the anticancer drug solution preliminarily assumed reaches the cancer cells of the target organ. It is discharged by (not described). Next, the liquid feeding pump 5b of the washing liquid container b is driven to inject the washing liquid into the abdominal cavity via the injection catheter 2 placed in the abdominal cavity, and the anticancer drug solution remaining in the abdominal cavity is injected. It is removed together with the cleaning liquid from the used chemical liquid outlet 4. Thereby, the side effect by the anticancer agent in the abdominal cavity after the time when the anticancer drug solution reaches the cancer cells of the target organ can be stopped. The cleaning liquid used in the present invention is an aqueous solution or emulsion containing a solvent, an electrolyte salt and an additive used in an anticancer drug solution, and the reaction of the anticancer drug as a side effect reducing agent of the anticancer drug. Depending on sex, agents known as antioxidants (eg, sodium thiosulfate), antibodies, receptors, antagonists can be used.

  In the mode of item (2) of the present invention, after the washing of item (1) is completed, only the liquid feeding pump 5c of the drug solution container c of the anticancer drug side effect reducing agent of FIG. The side effect reducing agent is injected into the abdominal cavity 6 via the infusion catheter 2 placed in the abdominal cavity 6. The anticancer agent side effect reducing agent injected into the abdominal cavity 6 prevents the side effects of the anticancer agent on the abdominal cavity and normal organs close to the abdominal cavity. The anticancer agent side effect reducing agent is discharged from the used drug solution outlet 4 after being retained in the abdominal cavity for about 5 to 20 minutes.

In the form of the above-described figure, a circuit in which the anticancer drug solution container a and the cleaning solution container b and the anticancer drug side effect reducing agent drug solution container c are connected is shown, but the apparatus of the present invention is limited to this configuration. It includes a combination of a dialysate container supply circuit, an additional pump, a filter, a heater, a three-way stopcock at a branched portion, a thermometer, an osmometer, an electromagnetic wave irradiation device, and the like.
By applying physical stimulation such as warming, ultrasound, and electromagnetic waves only to the local area from the abdominal cavity to the target organ, the diffusion and penetration of the anticancer drug is superior to the target organ compared to other parts. Proceed to. The timing of applying the physical stimulation can be selected from the initial stage of injection of the anticancer drug solution into the abdominal cavity, the latter half of the injection, or after discharge and before the injection of the washing solution.

For example, the aspect of item (3) of the present invention is an invention that reduces the cytotoxic effect of an anticancer agent on peritoneal tissue using a hyperosmotic dialysate.
That is, after removal of the anticancer agent by the washing liquid of the aspect of (1), the infusion catheter 2 in which the high osmotic pressure dialysate is placed in the abdominal cavity by the liquid feeding pump 5c of the high osmotic pressure dialysate container c. Then, after injecting into the circuit circulating to the used drug solution outlet 4 via the discharge catheter 3 placed in the abdominal cavity, the high osmotic pressure dialysate is continuously discharged to the circuit by the liquid feed pump 5c. The drive of the high osmotic pressure dialysate pump continues for 30 minutes to several hours. As a result, edema (excessive extracellular fluid) in the body is guided into the abdominal cavity through the peritoneum by the high osmotic pressure of the dialysate and the osmotic pressure gradient between the extracellular fluid in the body (ultrafiltration). Along with this ultrafiltration phenomenon, residual anticancer agents and catabolic reaction products are discharged out of the body. At this time, the volume obtained by adding the volume of the body fluid containing the anticancer drug absorbed in the high osmotic pressure dialysate in the abdominal cavity to the volume of the liquid discharged by the liquid feeding pump of the hyperosmotic pressure dialysate container has been used. It is discharged from the chemical solution outlet.

  As the high osmotic pressure dialysate used in the present invention, for example, a dialysate used for peritoneal dialysis, that is, an aqueous solution in which glucose is added to sodium, potassium, magnesium chloride, sulfate, bicarbonate or the like is used. can do.

  The above-mentioned treatment is usually performed for several hours to several tens of hours by attaching a disposable circuit to a device installed in a medical facility when a patient is hospitalized or hospitalized for one night. 3 and 3 and the connecting portions (adapter) 2d and 3d at the distal end of the catheter are sealed to prevent invasion of pathogens from the outside.

As a method for predicting the time required for the anticancer drug solution of the present invention to reach the target organ, and more accurately expressing the time taken to penetrate the surface membrane of the target organ and into the cancer cell, PET ( Various methods such as positron emission tomography and SPECT (single photon emission tomography) are conceivable. For example, a method of assuming the time to reach the target organ using PET can be used.
The method using PET is similar to the anticancer drug using the intraperitoneal anticancer drug administration device of the present invention while placing the patient to be injected with the anticancer drug on the PET measuring table and observing the PET image. A contrast medium solution (positron emission isotope labeling) showing the permeation ability of is injected into the abdominal cavity. And by PET image, the time until the (proton radioisotope labeling) contrast agent reaches the target organ and penetrates into cancer cells in the organ is measured, Suppose.
Since the peritoneal permeability may increase after the start of this treatment, it is desirable to periodically perform a peritoneal permeability test to correct the estimated time to reach the cancer cells of the target organ.

  The liquid feeding pump used in the present invention is attached to the outer periphery of the tube, and any type of pump can be used as long as the liquid flowing in the tube does not touch the outside air and cause pathogenic bacteria to be mixed. For example, it is possible to use a sliding pump that slides across a tube used for hemodialysis or infusion and sends out a liquid.

The advantage of supplying the anticancer drug solution container of the present invention (usually a soft plastic bag) to the treatment site as a kit integrated with a circulation circuit tube in advance is that mounting and removing procedures are unnecessary, and drug selection mistakes, concentrated stock solutions These include avoiding accidents during dilution work and ensuring the safety of treatment personnel without touching powerful drugs.
By injecting an anticancer drug solution into the abdominal cavity with the device of the present invention, efficient dosing for organ cancers such as prostate, bladder, uterus, ovary, etc. located near the abdominal cavity can be performed.

  The present invention can be used in the industrial field of manufacturing an intraperitoneal anticancer drug administration device.

DESCRIPTION OF SYMBOLS 1a, 1b, 1c Chemical solution supply port 2 Injection catheter 2d Injection catheter adapter 3 Discharge catheter 3d Discharge catheter adapter 4 Used chemical solution discharge port 5a, 5b, 5c Infusion pump 6 Abdominal cavity a Anticancer drug solution container b Cleaning liquid container c Anticancer drug side effect reducing drug liquid container

Claims (5)

  A device having a circulation circuit that communicates with a used chemical solution discharge port by a plastic tube after passing through a drug solution supply port, an infusion catheter placed in the abdominal cavity, and a discharge catheter placed in the abdominal cavity, the drug solution supply port A chemical solution container connection circuit to which an anticancer drug solution container and a cleaning solution container are connected, and a liquid feed pump is attached to the outer periphery of the tube of the outlet of each container of the chemical solution connection circuit. Contains the anticancer drug by injecting the drug solution containing the anticancer drug injected from the drug solution supply port into the abdominal cavity via the injection catheter placed in the abdominal cavity with the liquid supply pump of the drug solution container After the intraperitoneal injection of the drug solution to be performed, the anticancer drug solution in the abdominal cavity is used after the time until the anticancer drug solution that has been assumed based on the preliminary examination reaches the cancer cells of the target organ has elapsed. From The anticancer agent remaining in the abdominal cavity is injected into the abdominal cavity via an injection catheter placed in the abdominal cavity by a liquid feeding pump of the cleaning liquid container An intraperitoneal anticancer drug administration device comprising means for removing a chemical solution together with a cleaning solution from a used chemical solution outlet.   Further, a dilution water container or an anticancer agent side effect reducing agent container is further connected to the drug solution supply port as another drug solution container, and a liquid feed pump is attached to the outer periphery of the tube at the outlet of the other drug solution container. After removing the anticancer drug solution remaining in the chamber together with the cleaning solution from the used chemical solution discharge port, diluting water or anticancer drug side effects alleviated from the drug solution supply port by the liquid feeding pump of the other chemical solution container The intraperitoneal anticancer agent administration device according to claim 1, further comprising means for injecting the agent into the abdominal cavity via an injection catheter placed in the abdominal cavity. A high osmotic pressure dialysis container as another chemical solution container is further connected to the chemical solution supply port, and a liquid feed pump is attached to the outer periphery of the outlet tube of the other chemical solution container, so that the anti-cancer remaining in the abdominal cavity After removing the chemical solution together with the cleaning solution from the used chemical solution outlet,
The high osmotic pressure dialysate is returned to the used chemical solution discharge port via the chemical solution supply port, the infusion catheter placed in the abdominal cavity, and the discharge catheter placed in the abdominal cavity by the liquid feeding pump of the other chemical solution container. The intraperitoneal anticancer drug administration device according to claim 1 or 2, further comprising means for continuously circulating the hyperosmotic dialysate in the circulation circuit after filling the circuit.   The intraperitoneal anticancer drug administration device according to any one of claims 1 to 3, further comprising a means for heating or irradiating ultrasonic waves or electromagnetic waves between and around the target organ and the abdominal wall. An intraperitoneal anticancer drug administration device.   The intraperitoneal anticancer drug administration device according to any one of claims 1 to 4, comprising an adapter capable of aseptically connecting to an intraperitoneal indwelling catheter in a circuit in which all drug solution containers are integrally connected in advance. An intraperitoneal anticancer drug administration device.

Images