JP2650932B2 - Catheter device for treating tumors in the body - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to a device for treating a disease or immunodeficiency, and more particularly to a device for treating a tumor present in a patient.

BACKGROUND OF THE INVENTION In the treatment of solid tumors, chemotherapeutic agents have been injected into arteries. This is a one-way, unidirectional process in which the drug passes through the tumor via the arterial side of the body. The first disadvantage of this method is that the toxic element circulates through the tissues and organs of the whole body, so that the dosage of the drug and / or the action time of the drug required to obtain the dosing effect are secured. That is not possible. That is, the current method of treating a solid tumor using a chemotherapeutic agent has attenuated the effect of the harmful chemotherapeutic agent leaking to other parts of the human body.

Normal blood flow originates in the heart, flows through arteries, and flows from capillaries to veins. The walls of the postcapillary venules, capillaries, and sinusoids are the exchange vessels, which serve as exchange sites between the blood and the tissue fluid that bathes the cells. The venules and veins that are larger than the vessels contain a system of reservoirs for pooling blood. These are large-volume, low-pressure vessels through which blood flow is returned to the right side of the heart.

Under normal conditions, the endothelial cells that form the lining of the vascular network fall and regenerate at very slow rates by themselves.
w) Folkman describes “tumor neovascularization” (Scientific
In a book entitled "American, June, 1976 (p. 71)," when it is necessary to heal a wound or impart an immune effect, a part of the vascular system However, new blood vessels always return after a short period of time and regenerative activity subsides to its previous low state. " The cells are required to obtain immunity to heal the wound and grow rapidly. However, such growth is maintained only as needed. Thereafter, the regenerative activity is likely to return to its previous state.

Blood circulation to solid tumors occurs in a similar manner, flowing from arteries through capillaries to veins. However, in the local area between the exchange vessel and the large venule, the flow direction changes abruptly. Folkman explains what's going on: "When a malignant tumor emits a chemical message, endothelial cell proliferation occurs rapidly near the tumor. Capillaries emerge from the side walls of the venules and extend long into thin tubes. And gather at one point on the tumor from all directions. "Since tumor blood vessels have such characteristics, many sideways (VV sideways) connecting veins are formed, and these sideways (shunts) are formed. ) Are the physical elements underlying the process of retrograde perfusion. The significance of the VV bypass in treating tumors is described below.

The normal kinetic pressure in the tumor vasculature is based on the change in velocity of the blood flowing from the capillaries to the venous system, which is related to the cross-sectional area (V ₁ × A ₁ = V ₂ ×
A ₂ : where the subscripts 1 and 2 represent capillaries and veins, respectively). That is, the pressure drop in these VV paths is caused by a change in the flow velocity when blood flows out of the capillaries. Tumor vascular flow is weakened in this way,
2 to 15 percent of the blood flow of the surrounding tissue. The circulation thus weakened is identified as the vasculature of the cancer. Blood may pass through the VV route (probability)
Is much lower than when passing through the normal vasculature.
Thus, even if an attempt is made to add a chemotherapeutic agent to a tumor, the likelihood that the agent will spread to other parts of the human body is much greater than if the agent reaches the tumor.

The problem of the circulation of toxic elements through the system by chemotherapy remains an obstacle to providing therapeutic treatment for cancer. In 1961, Stehlin et al. Reported that escaping and circulating chemotherapeutic agents through the system was "one of the most significant limitations in providing effective perfusion to certain areas of the human body." Thought. Most recently, in March 1981, the Journal of the American Medical Association (Jour
nal of the American Medical Association)
And related articles by Chuang. These editorials deal with chemoembolizatio
n), which describes "a method that combines injecting a chemotherapeutic agent into an artery and blocking the blood flow to the tumor by clogging the artery." This method has a longer survival rate, but is dose-limited due to systemic toxic effects. Similarly, Fewer, Wilson, and Lewis argue that "there is no change in the amount returned to the venous system, resulting in the inability of the toxic agent to move through the body and maintain the time required for the drug to act." Has been stated. Dosage is another critical factor in cancer chemotherapy. By continuing to increase the dose of tumor treatment, the response rate (response
There is some evidence that rate increases. This can be recognized in studies of bone marrow tissue transplantation, isolated infusion or local perfusion. Nevertheless,
Arterial perfusion and infusion revealed that delivering drugs to solid tumors with the artery as the first route was the only advantage over intravenous infusion (IV infusion). Subsequent toxicity issues remain.

[Means for Solving the Problems] Tissue and organ toxicity and dosage are important factors in the treatment of solid tumors. However, the previous technology did not take into account the following two factors, so no results were obtained. One of them is typically the V-
V bypass, another one is the outflow from the tumor.
The key to effective perfusion is the integral use of the tumor vasculature and the control of its outflow. Retrograde perfusion according to the present invention provides a mechanism to achieve these two objectives.

Illustrating the invention, the present invention provides two coaxial catheters having a wide range of maneuverability, as well as pumps, filters, analyzers, and a method for regulating and monitoring the outflow from a tumor. Other suitable means are provided. The first step is to take an arteriogram, from which a graphic representation of the inner loop in the bloodstream is obtained, which vessels preferentially enter the tumor, i.e. Helps determine thick veins. The perfusion process begins by retrograde insertion of two coaxial catheters through the external vein and into the preferential drainage of a solid tumor. One catheter is deployed at the entry point for the chemotherapeutic agent and forms a passage to the VV bypass. The second or suction catheter is at the end,
That is, on the distal side, the catheter has the necessary inhalation capacity to contain the therapeutic agent, arterial blood flow, venous and lymphatic drainage, and the preferred drainage.
Next, both catheters are placed in place and retrograde emboli is controlled to prevent leakage in critical areas of the vasculature. The treating physician can make the necessary corrections or adjustments during the treatment due to changes in cross-sectional area, reduced circulation, and other factors specific to the tumor vasculature.

The coaxial catheter placed within the preferential drainage of the tumor as described above creates a third in vivo space in addition to the first (cellular) in vivo space and the second (cellular space space) in vivo space. . This is a difference from the conventional method. Within a predetermined area within the organ selected for perfusion, a connection to an external monitoring system is formed, thereby forming a feedback loop.
The monitoring system includes pressure, concentration, temperature, time, and other variables that ensure that system toxicity is avoided,
Monitor variables to ensure that proper dosages are maintained, variables to ensure that organ integrity is not violated, and the like. When the drug is delivered by the arteries and passes through a solid tumor, the drug reacts with at least one, or preferably all three, of the human body, the tumor, and the consumed drug itself to produce an organism. Transformation. next,
The drug is guided out of the body via a suction catheter, filtered by a suitable filter means and analyzed by an analyzer. This process is repeated as many times as necessary to reach a predetermined steady state. Thus, the treatment technique of the present invention allows clinicians to utilize retrograde perfusion as a component of the tumor vasculature. Clinicians can interact with the drug and the tumor and know what interactions can occur. That is, it serves as a monitor of tumor growth, and the homeostasis of the tumor (home
ostatic inertia can be interrupted, creating a feedback system that allows for virtually unlimited interaction.

The present invention has three features that are commonly lacking in conventional treatment methods. First, conventional methods cannot change the basic pattern of blood flow in a tumor. Second,
With conventional methods, the formed cancer cells persist and cannot prevent the homeostasis of the tumor. Finally, the ability to interact with tumors using conventional methods has prevented control of the flow pattern, and thus the action of drugs, which is a critical issue in effective treatment of cancer. Time, dosage, priority drainage, leak factors, and toxicity levels could not be controlled.

One advantage of this method is that it provides a shunt between the veins, i.e., a VV bypass, and the vascular flow passing through the VV bypass is no longer treated as a substrate limiting process. . The physical structure of the tumor vasculature is one limiting factor in delivering chemotherapeutic agents. Since they are located beyond the precapillary sphincter and the capillary bed, the VV shunt can be perfused exclusively randomly by this method, and the concentration, duration of drug action, or, in effect, the biological efficacy of chemotherapy Sex is random. In the case of retrograde perfusion, the reduction in circulating volume through the tumor need no longer be taken into account. The reason is that this new method allows the clinician to deliver the chemotherapeutic agent through the loop created in the tumor vasculature at the pressure needed to push the flow backwards. When a loop is created, the leak site is sealed off, preventing toxin flow through the system and ensuring that the appropriate level of chemotherapeutic agent reaches the tumor.

The second advantage of retrograde perfusion is that it is possible to recognize the progress of tumors in need, and that malignant traits in vascular tumors grow at a constant rate. According to Folkman, tumor progression may be due to a rapid increase in cell division caused by angiogenesis. When cells proliferate for more than a period of time, they first metastasize and invade surrounding tissues, and eventually appear as ascites cells in the abdominal cavity. The method of the present invention allows the clinician to selectively intervene at the appropriate time and to reduce the dosage, concentration, pressure, time of drug action, and the occurrence of hemangiomas, since the differences in the stage of tumor progression can be recognized by the method of the present invention. Other factors that effectively suppress tumor growth can be treated in an appropriate combination.

Response curves for chemotherapeutic dosages are well known, and the higher the drug dose, the steeper the curve.
At present, the response to dosing is based on three criteria:
Judgment by shrinkage of tumor mass, increase in number of survivors or biopsy. A third advantage of retroperfusion is that biopsy methods can be used to evaluate the optimal conditions of a steep dosing response curve. By accurately tracking the response curve, any and all means can be taken to eliminate the deviation points that represent tumor growth and reduced patient survival.

Another advantage of the method of the present invention is that the tumor can be substantially separated from the human body. Separating the tumor from the human body provides several advantages, in several respects, such as: The immune system is raised. The passage of the chemotherapeutic agent is no longer a single route, for example, only perfusion of the artery. Chemotherapeutic agents are in constant contact in hemangiomas, which is particularly useful when using radiosensitizers. The radioactive slurry can be more easily delivered from the catheter device. The dose of a chemotherapeutic agent can be calculated according to the extent of the tumor, rather than by the effect of toxicity on tissue or organ systems. In addition, a catheter having a common axis can be used as a means for hyperalimentation, that is, a transvenous hypercaloric infusion, which can lead a patient to a favorable condition.

The greatest advantage of the retrograde perfusion according to the present invention is that it can be used not only for delivering a chemotherapeutic agent but also for various other procedures.

(Embodiment) According to the present invention, a human body can be treated using a catheter device C (FIGS. 1 and 6) having two balloons and having the same axis. The catheter C is used to perform retroperfusion of the human body, and a drug is injected into a patient's venous system in a direction opposite to a normal blood flow. The infused drug perfuses through the venous system into a part of the body being treated.

In an embodiment, the catheter device C is used to inject a therapeutic agent, for example, a chemotherapeutic agent, and to retrograde the solid tumor. At this time, variables such as concentration, duration of action of the drug, and toxicity of the system are controlled. As described below, the catheter device C can be used to reverse perfuse an active agent, such as an enzyme, a catalyst, or an immunological agent.

During the treatment according to the invention, the response or response from the patient is determined by using two coaxial balloon catheters (14, 16), a computerized axial tomography (CAT) scanner (10) (FIG. 1) and a video. Observed and monitored by the monitor (12). The double balloon coaxial catheters (14) and (16) according to the present invention comprise an inner tube or infusion catheter (18) (FIG. 6), and an inflatable balloon (22) near the end (20) of the catheter. ), Which is used to seal the patient's vein at the site where the catheter (18) is located. The structure of the catheters (14) and (16) is shown in FIG.
In order to further clarify the features, the illustration is somewhat simplified. An infusion catheter (18) is inserted to allow the therapeutic agent to flow through the blood vessels to the part of the body being treated. Catheter (18) as usually done
At its end (20), a guide wire (24) is provided to assist in insertion and movement of the patient to a desired location within the venous system. Guide wire (24)
Is collected after the catheter (18) is placed in the proper position.

The driving force for the infusion catheter (18) is the catheter (1
8) provided by a manual pump injector (26) with push and pull capacity for insertion and withdrawal. The catheter (18) contributes to creating a feedback loop of the flow from the tumor vessels to the outside of the human body and allows to control the concentration, pressure, temperature and time of the delivered therapeutic agent. In this way, toxicity of the system is avoided, appropriate dosages are maintained, and organ integrity is not violated. The infusion catheter (18) further comprises an open passage (25) at its end (20), which forms an inlet for the therapeutic solution delivered from the manual pump (26) to the patient's blood vessel. The infusion catheter (18) includes a second passageway or lumen (30) used for either infusion or aspiration purposes.
It has. A port (33) is provided in the area surrounded by the inflatable balloon (22), and the balloon (22) can be inflated as needed to seal the vein and direct the flow of the chemotherapeutic agent. I'm trying to do it. Inside the catheter (18) is an inflatable balloon (22)
A port (31) serving as an inlet to a rear port (30) is formed so that a liquid can be injected or extracted from a vein by a push / pull operation of a manual pump injector (32).

The port (34) formed in the suction catheter (35)
As described below, a manual pump for collecting partially or completely consumed drug after the chemotherapeutic drug is delivered in reverse (36)
It is intended to be collected inside. The infusion catheter (18) is coaxially disposed inside the suction catheter (35), and the suction catheter (35) is for transporting the collected drug to a manual pump (36) for collection outside the body. The liquid in the manual pump (36) is sent to a suitable filter and filtered. The filtered, non-toxic chemotherapeutic agent is reinjected, if necessary, into the vein via port (25), thereby providing a continuous feedback loop of flow, which is essential for controlling the above variables. Can be maintained.

The second catheter (35) of the present invention also has a balloon (3
8) wherein the balloon is inflatable in the patient's vein through the port (40), thereby sealing the vein and allowing the chemotherapeutic to flow to other parts of the patient. Can be blocked. A port (42) is formed in the catheter (35) and provides an inlet to a lumen or passageway (44) for fluid communication with a manual pump injector (46). Manual pump injector (46)
Contains filtered, non-toxic fluid that circulates through port (42) and is returned to the venous system and the right side of the heart.

The catheters (18) and (35) are joined at a T-joint or side arm (47) and have a common axis. Similarly, the liquid passages leading to the manual pumps (26) and (32) are branched, and separated so that the liquids are not mixed by the side arms (48a). On the other hand, the liquid passages to the manual pumps (36) and (46) are branched at the side arms (48b), and each liquid is separated and distinguished. The manual pumps (26) and (36) are each provided with a tee member (49a) controlled by a lever (49b) and having a sample port (49c).

The process of retroperfusion according to the present invention is performed as follows. First, the tumor vasculature is formed, for example, in a tumor (52) in the kidney (54) by the reference numeral (50) (FIG. 3) using a dye or the like based on a conventional arterial image. Mark the system and create a map of the selected site. In this arterial image, the tumor is marked in red and the position of the tumor blood vessel (52) and the preferential drainage path (56) can be known using this as a guide. By using the scanner (10), images of the tumor blood vessels (52) and priority drainage (56) are displayed on the video monitor (12). After the above preliminary treatment, the catheters (18) (35) are placed in the vasculature.

The coaxial catheters (18) and (35) enter the left renal vein (60) (FIG. 3) via the left femoral vein (58) to gain access to an organ such as the left kidney (54) (FIG. 2). To steer the coaxial catheters (18) (35) so that they are held in place, an image on a video screen (12) and a guide wire (24) are used. Guide wire (2
4) guides the catheter (18) through the left femoral vein (58) to a suitable location in the left renal vein (60). Priority drainage is performed at this location, and the suction catheter (35) can collect effluent from the tumor. Once the inhalation catheter (35) is in place, a guidewire (2
4) is withdrawn from inside the inhalation catheter (35), leaving the catheter (35) in its place. Following the same procedure, a second catheter, the infusion catheter (18), is placed at the selected location for perfusion to the kidney.

FIG. 4 shows a number of tributaries (6
The right lung (62) with 4) is shown. Catheter (1
8) Because (35) has extensive maneuverability, it can be repositioned as many times as needed and where needed in the vasculature of the lungs or other organs. When the catheter is in place, if desired, the selected vessel can be retrograde to separate a particular venous flow path. To accomplish this step, the microencapsulated drug can be selectively injected into a branch of a blood vessel that is to be excluded from the perfusion process. The microencapsulated drug may be naturally degraded or recoverable. The microencapsulated drug forms a third in vivo space and separates the VV bypass ahead of the tumor to be treated. In this way, the infusion of the drug into the vein prevents the chemotherapeutic agent from leaking to other parts of the body and helps direct the flow of the drug. After the balloons (22) and (38) of the catheters (18) and (35) are inflated (FIG. 5) and the emboli (emboli) are in place, before performing the actual perfusion with a chemotherapeutic agent, A perfusion simulation is performed to check for leaks or other problems in the system. After all factors have been taken into account and the necessary adjustments have been made, retrograde perfusion is initiated. This is done by forcing a chemotherapeutic agent upstream of the vein (50) by means of a manual pump injector (26), and via a VV bypass, the inflation of the catheter (18) (35). Balloon (22) (38)
And the path formed by the embossments.

It should be noted here that retroperfusion occurs over a substantial range of distances across organs or sites of the body part of the patient to be treated. The reason for using different codes for the balloons used in the present invention is that the balloon (22) and the balloon (38) have a certain distance from each other to ensure that the drug flows through the tumor vasculature. In order to clarify that they are placed in

The injection amount of the chemotherapeutic agent into the tumor vasculature by the injector (26) and the suction amount by the injector (36)
It is maintained at an equal value so that no liquid flows back into the arterial flow (FIG. 5). In general, many parallel V-
The V bypass is selectively formed, forming a passage for the drug through the tumor. Since the injection volume and the suction volume are made equal, there is no need to make embossed. However, embossing is effective if needed.

The first feedback loop or passage of the therapeutic agent through the third in vivo space is formed by the chemotherapeutic agent being drawn back from the port (34) into the interior of the suction catheter (35) by a manual pump injector (36). . The chemotherapeutic agent is further filtered and then repeatedly re-injected into the tumor vessel via the injector (26) and port (25). The drug thereby has a maximal effect on the tumor and a minimal effect on the human body. The feedback loop as described above is repeated as many times as necessary until a necessary flow balance and a predetermined steadiness are obtained.

The formation of the second feedback loop involves forcibly injecting a drug such as a chemotherapeutic agent upstream into the vein (50) by a manual pump injector (26), passing the catheter through the VV bypass, (18) by pushing along the path formed by the inflated balloons (22) (38) of (35) towards the manual pump injector (36). The injector (36) acts to withdraw the drug from the port (34) for analysis and filtration. The filtered fluid is then pumped by a manual pump (46) through the lumen (44) and port (42) to the venous system and the right side of the heart. The second feedback loop can stimulate the human body as an excellent means of hyper-alimentation because the filtered fluid can be recirculated to other parts of the human body. On the other hand, the other feedback loop acts on the tumor.

In this way, a third in vivo space is created by separating the tumor load from the human body, allowing the clinician to interact with the tumor as desired. Since the present invention can perform control in this way, it is possible to execute two feedback loops at the same time and repeat as many times as possible until both loops reach a predetermined stable state. In order to perform the perfusion described here, two feedback loop systems were used, but this is not limited to the treatment of solid tumors, but as a means of hyperalimentation to make patients healthy, and lack of immunity The present invention is also applied as a means for supplying an immunizing or activating agent to a human body.

It should also be appreciated that, depending on the situation, a single catheter can be used for retrograde perfusion. In these cases,
Port (25) serves as an injection point in front of balloon (22), while port (31) serves as a suction or extraction port. As described above, the injection volume and the extraction volume are kept equal.

The foregoing description of the invention has been presented by way of example, and various modifications may be made in size, shape, material, or other details of the structures shown, without departing from the spirit of the invention.

[Brief description of the drawings]

FIG. 1 is a view showing a situation in which a patient is undergoing treatment, FIG. 2 is a view schematically showing a renal treatment method according to the present invention, FIG. 3 is an enlarged view of the kidney shown in FIG. FIG. 5 is an enlarged view of a lung receiving treatment according to the present invention; FIG. 5 is a view showing a catheter of the present invention positioned in a tortuous tumor vasculature;
FIG. 6 is a perspective view showing a double balloon coaxial catheter according to the present invention. (10) CAT scanner, (12) Video monitor (14) (16) Double-balloon coaxial catheter (18) Infusion catheter (35) Suction catheter (22) (38) Balloon, (30) ... Tube hole (26) (32) (36) (46) ... Manual pump injector (31) (33) (34) (40) (42) ... Port

Claims (5)

(57) [Claims] 1. A catheter device for treating a tumor in a patient's body using a chemotherapeutic agent, comprising: (a) (1) a suction port (44) having a port (34) at a front end; And (2) an infusion catheter (18) having an infusion tube (30) extending beyond the suction tube hole (44) and having a port (25) at its tip. A catheter means (14) (16) for installation near a tumor site in a patient's vein, and (b) a catheter means provided between the suction catheter (35) and the infusion catheter (18). Inflatable infusion seal means (38) provided; and (c) an inflation provided in said catheter means to seal the flow in the patient's vein at a location past said suction catheter (35). Possible suction sealing means (22)
(D) attached to one end of an infusion catheter (18) so that the chemotherapeutic agent can be delivered to the tumor, and for injecting the chemotherapeutic agent into the patient's vein through the infusion tube (30). Means (26); (e) said suction port (44) attached to one end of a suction catheter (35) after the chemotherapeutic agent has passed through the tumor;
Means (36) for collecting a chemotherapeutic agent from the container; and (f) a suction port (44) at a position opposite to the port (34) with respect to the injection sealing means (38). A means (46) for communicating with the formed port (42) through a lumen (44) and for supplying the liquid which has been withdrawn and processed as required by the means for collection (36) to the venous system; A catheter device for treating a tumor in a body, which is constituted. 2. The catheter device according to claim 1, further comprising means for analyzing the collected chemotherapeutic agent. 3. The catheter device according to claim 1, further comprising means for filtering the collected chemotherapeutic agent. 4. The catheter device according to claim 3, further comprising means for reinjecting the filtered chemotherapeutic agent into a patient's vein. 5. The catheter device according to claim 1, further comprising means for maintaining the amount of collection at the suction lumen substantially equal to the amount of injection at the catheter means for injection. .