WO2015093274A1

WO2015093274A1 - Substance administration catheter

Info

Publication number: WO2015093274A1
Application number: PCT/JP2014/081772
Authority: WO
Inventors: 朋香栗田
Original assignee: テルモ株式会社
Priority date: 2013-12-16
Filing date: 2014-12-01
Publication date: 2015-06-25

Abstract

A substance administration catheter (10) comprises an inner tube (20) which delivers a first substance, and an outer tube (30) which delivers a second substance. The inner tube (20) is positioned in the outer tube (30) in the leading end side of the outer tube (30). The leading end part (31) of the outer tube (30) is fixed to and closed off by the outer face (21) of the inner tube (20). A communicating part (22) whereby the inside of the outer tube (30) and the inside of the inner tube (20) communicate is formed on the leading end side of the inner tube (20). A substance administration catheter is thus provided whereby it is possible, when internally administering the first substance and the second substance, to discharge both substances in a desirable mixed state while suppressing a reaction among the substances or other phenomena, by sufficiently mixing the substances immediately prior to discharge.

Description

Substance administration catheter

The present invention relates to a substance administration catheter for mixing and administering a first substance and a second substance in the body.

In recent years, for malignant glioma (glioblastoma, anaplastic astrocytoma, etc.), in addition to surgical therapy and radiation therapy, various therapies such as chemotherapy, immunotherapy, gene therapy, molecular target therapy, etc. Attempts have been made to improve the outcome of malignant brain tumors, including glioma. However, the most malignant glioblastoma has a low 5-year survival rate of about 7% and still has the poorest prognosis among all cancers.

The basis of treatment for malignant glioblastoma is as much as possible removal of the tumor by surgery. However, because the brain performs various functions depending on the region, it is often impossible to remove the tumor sufficiently. In particular, in malignant glioblastoma, since tumor cells infiltrate the surrounding brain tissue, total excision at the tissue level is impossible. Therefore, radiotherapy and chemotherapy are indispensable as postoperative adjuvant therapy to improve the treatment outcome of malignant glioblastoma.

Despite the proven effectiveness of chemotherapy for malignant glioma, the therapeutic effect is still not sufficient. In brain tumors, when a therapeutic drug is administered intravenously, the therapeutic drug is permeated through the blood brain barrier (BBB), so there is an inherent problem of permeability, and applicable drugs are limited. . Furthermore, even if BBB permeability is obtained, the drug dosage is limited due to concerns about side effects to the whole body caused by the drug, and an effective drug concentration cannot be ensured at the tumor site.

A convection-enhanced delivery (CED) method has been devised as a new drug administration method for overcoming the problems of chemotherapy for malignant glioma as described above. The CED method is local chemotherapy in which a drug is actively infused from a catheter placed stereotaxically in the brain parenchyma using a microinfusion pump. In the conventional local administration technique to the central nervous system, the distribution of the drug depends on the diffusion of the substance, whether it is intracavitary administration to the tumor excision cavity or a local chemotherapeutic agent placed in the brain. The diffusion of substances is defined by concentration gradients and tissue properties, and even a low-molecular compound with good diffusivity is considered to have a range of only a few millimeters due to absorption and metabolism in capillaries. This is inadequate for 80-90% of malignant glioma recurrences occurring within 2 cm of the initial lesion. On the other hand, in the CED method, the pressure gradient during the injection is maintained to induce a bulk flow between the cerebral layers to enhance the diffusion of the injected substance. Therefore, compared with the conventional local administration method, the drug can be distributed more uniformly and at a high concentration over a wide range. In addition, the distribution of the drug in the brain can be controlled by the injection volume and the injection speed, and it is possible to reduce the dose compared to the systemic administration by vein, so that systemic side effects can be suppressed to a level where there is no problem. Is possible. There are a wide variety of drugs that can be administered by the CED method, and various drugs have been tried in rat brain tumor transplantation models, and their effectiveness has been reported. Because of these advantages, the CED method is expected as a method for treating not only brain tumors but also Parkinson's disease, Alzheimer's disease, epilepsy and the like.

課題 One of the issues in the widespread clinical application of the CED method is drug backflow that occurs along the outer surface of a catheter placed in the brain. Once the drug flows backward and leaks into the brain surface, sulcus, or excision space, it becomes difficult to maintain the pressure gradient, and further diffusion cannot be expected. To avoid drug regurgitation, in many studies, the catheter diameter in the CED method is small and the drug infusion rate is very slow, 0.5-10 μl / min. As a result, in order to reach a therapeutically effective amount, administration for a long time is unavoidable, and in some cases, infusion over several days is required.

However, for example, when it is desired to administer a plurality of drugs at the same time, it takes a long time until the mixed drug is supplied to the catheter and then released from the catheter. Undesirable phenomena may occur, such as formulation changes such as drug crystallization.

In addition, a polymer solution containing a drug and a two-liquid mixed polymer that gels or solidifies by mixing two liquids having fluidity may be administered into a living tissue and used as a local drug delivery system (DDS). . When such a polymer solution is administered into a living tissue, if it takes a long time to be released after the polymer solution is supplied to the catheter, the polymers mixed in the catheter react with each other and become non-flowable. This is not preferable because the flow path is blocked. In addition, when used as a DDS, if the polymer solution is not sufficiently mixed, the cross-linking rate at the reaction point of each polymer decreases, and the interstitial cavity of the living tissue before the polymer solution changes to a non-flowable state. In addition to being easily diffused, it is difficult to obtain a gel having a necessary function, and there is a possibility that a sufficient therapeutic effect cannot be obtained.

As a medical instrument capable of mixing two different substances immediately before administration, for example, Patent Document 1 discloses that two flow paths for distributing different drugs become one flow path at a junction near the front end. A catheter capable of discharging a mixed medicine from an opening is described.
Further, in Patent Document 2, by providing a mixing element in which two different liquids merge and a pouring part into which a mixing member for mixing them is inserted, the mixed solution can be discharged from the opening at the tip. Medical instruments are described.

Japanese Patent No. 2744911 JP 2013-27599 A

The catheter described in Patent Document 1 has a structure in which the second flow path merges from the one direction with respect to the first flow path, so that the substances supplied from the respective flow paths are not sufficiently mixed. There is a possibility of being discharged as it is. In particular, a liquid having a relatively high viscosity such as a solution of a two-component mixed polymer that gels or solidifies by mixing two components when a slow and continuous administration such as the CED method is required. When administered, mixing tends to be inadequate.

The medical instrument described in Patent Document 2 enables efficient mixing by providing a mixing element including a mixing member having a characteristic structure, but the mixing is performed inside a thin tube such as a catheter. Creating a complex structure such as a member involves manufacturing difficulties. In addition, the flexibility of the distal end of the catheter may be reduced and the biological tissue may be damaged.

The present invention has been made in view of the circumstances described above, and when both the first substance and the second substance are administered into the body, the two substances are mixed immediately before ejection and sufficiently mixed. It is an object of the present invention to provide a substance administration catheter capable of discharging both substances in a desired mixed state while suppressing phenomena such as reaction between them.

In order to solve the above-mentioned problems, the present invention provides a substance administration catheter for mixing and administering a first substance and a second substance in the body, the first tube for feeding the first substance, A second tube for feeding two substances, wherein the first tube is disposed in the second tube on a distal end side of the second tube, and a distal end portion of the second tube is disposed on the first tube. It is fixed to the outer surface of the first tube and is closed, and a communication portion for communicating the inside of the second tube and the inside of the first tube is formed on the tip side of the first tube.

According to such a configuration, the first substance passing through the first tube and the second substance passing through the second tube are mixed until reaching the region where the communicating portion located on the distal end side of the substance administration catheter is formed. The second substance in the second tube flows into the first tube from the periphery of the first tube through the communicating portion immediately before being discharged from the substance administration catheter, and merges with the first substance. To mix well. For this reason, in the substance administration catheter, it is possible to ensure a mixed state of substances desirable for administration while suppressing phenomena such as reaction between the two substances mixed and compounding changes such as substance crystallization.

Further, the present invention is characterized in that the communication part is a spiral cut.

According to such a configuration, since the second substance is spirally sent to the first substance and merges, turbulence is generated in the mixing region where both substances are mixed and mixing is promoted, and both substances are discharged. Immediately before, it is possible to mix and discharge more effectively.
In addition, the communication part by cutting is in a state in which the communication part is opened and the second substance is pushed out when the second substance in the second tube is pressurized. And the second substance can be reduced in contact with each other. This is convenient for performing a procedure of filling the first substance and the second substance to the tip of the substance administration catheter (priming operation), for example, inserting the substance administration catheter into the brain parenchyma.

Further, the present invention is characterized in that an axial length of a region where the communication portion is formed is 0.5 to 50 mm.

According to such a configuration, the necessary mixing state of the first substance and the second substance can be further ensured by setting the axial length of the region where the communication part is formed to 0.5 mm or more. . In addition, by setting the axial length of the region where the communication portion is formed to be 50 mm or less, the first substance and the second substance are mixed before reaching the tip of the substance administration catheter, for example, the reaction between the two substances. It is possible to prevent the material from becoming a gel.

Further, the present invention is characterized in that the first tube protrudes from the distal end portion of the second tube to the axial distal end side by 0.1 to 30 mm.

According to such a configuration, the distal end of the substance administration catheter can be thinned by protruding the first tube from the distal end portion of the second tube to the distal end side in the axial direction by 0.1 mm or more, and the material can be produced without resistance without damaging the tissue. The administration catheter can be inserted into the body, and the tip portion of the second tube forming the step portion between the first tube and the second tube is a mixed substance of the first substance and the second substance along the outer surface of the substance administration catheter. Suppresses backflow. Further, by setting the protruding amount of the first tube from the distal end portion of the second tube to the axial distal end side to be 30 mm or less, for example, both the first substance and the second substance are disposed inside the protruding portion of the first tube. It is possible to further prevent gelation due to the above reaction.

Further, the present invention is characterized in that a distal end of the region where the communication portion is formed is located on the proximal end side in the axial direction of 1 to 20 mm from the distal end portion of the second tube.

According to such a configuration, the distal end portion of the second tube is moved to the proximal end side of the first tube by positioning the distal end of the region where the communication portion is formed at least 1 mm from the distal end portion of the second tube in the axial direction proximal end side. It can be easily and reliably fixed to the outer surface of the first tube without being applied to the communication portion. Further, by setting the position of the distal end of the region where the communication portion is formed to a position of 20 mm or less from the distal end portion of the second tube to the axially proximal end side, the first substance and the second substance are placed in the substance administration catheter. It can be further prevented that they are mixed before reaching the tip and become, for example, gelled due to the reaction between the two substances.

The present invention is also characterized in that it is used for increased convection delivery of a substance to a tumor.

According to such a configuration, it is possible to mix the first substance and the second substance such as a drug through the substance administration catheter and administer them to the target site near the tumor by the convection increasing delivery method.

The present invention is also characterized in that it is used for increased convection delivery of substances to the brain.

According to such a configuration, it is possible to mix the first substance and the second substance such as a drug through the substance administration catheter and administer them to the target site in the brain parenchyma by the convection increasing delivery method.

According to the present invention, when the first substance and the second substance are administered into the body, these two substances are mixed well immediately before discharge, thereby suppressing a phenomenon such as a reaction between the two substances. A substance administration catheter capable of discharging both substances in a desired mixed state can be provided.

It is a figure showing composition of a substance administration system to which a substance administration catheter concerning one embodiment of the present invention was applied. It is an enlarged view which shows the principal part of the substance administration system shown by FIG. It is an enlarged view which shows the front end side vicinity of a substance administration catheter in a partial cross section. FIG. 4 is an enlarged view showing a part of the vicinity of the distal end side of the substance administration catheter during a pressurizing operation by a microinfusion pump. It is an enlarged view which shows the front end side vicinity of the substance administration catheter which concerns on other embodiment of this invention in a partial cross section. It is an enlarged view which shows the front end side vicinity of the substance administration catheter which concerns on other embodiment of this invention in a partial cross section. It is an enlarged view which shows the front end side vicinity of the substance administration catheter which concerns on other embodiment of this invention in a partial cross section.

Embodiments of the present invention will be described in detail with reference to the drawings as appropriate.
Note that, in the drawings shown below, the same members or corresponding members are denoted by the same reference numerals, and redundant description is omitted as appropriate. In addition, the size and shape of the member may be schematically represented by being modified or exaggerated for convenience of explanation.

FIG. 1 is a diagram showing a configuration of a substance administration system 100 to which a substance administration catheter 10 according to an embodiment of the present invention is applied. In the present embodiment, a case will be described in which the substance administration system 100 is used for continuous delivery of a substance into a living tissue, in particular, for increased convection delivery of a therapeutic substance into the brain parenchyma.

As shown in FIG. 1, a substance administration system 100 includes a substance administration catheter 10 that is a tubular body having an insertion portion 11 introduced into a living tissue such as a brain parenchyma (inside the body) on the distal end side, and the substance administration catheter 10 inside. And a substance supply device 50 for supplying the substance toward the head.

The substance administration catheter 10 according to this embodiment is used to mix and administer a first substance and a second substance in the body. The substance to be supplied for administration into the body is here a therapeutic substance, and a liquid such as a liquid (liquid drug) containing a drug is used. Note that in this specification, a liquid as a substance for supply includes a sol-like substance having fluidity.

The substance supply device 50 includes a first syringe 60, a second syringe 70, and a microinjection pump 80. The first syringe 60 has a first delivery port 61 through which the first substance for supply is housed and the first substance is delivered. Further, the second syringe 70 has a second delivery port 71 through which the second substance for supply is housed and the second substance is delivered. The microinjection pump 80 can simultaneously pump the first substance in the first syringe 60 and the second substance in the second syringe 70 from the first delivery port 61 and the second delivery port 71, respectively.

FIG. 2 is an enlarged view showing a main part of the substance administration system 100 shown in FIG. In the following, “tip” refers to the end on the side to be inserted into the body, and “base” refers to the opposite side of the “tip”, that is, the end on the substance supply device 50 side.
As shown in FIG. 2, the base end of the first liquid delivery tube 62 is connected to the first delivery port 61 of the first syringe 60. The proximal end of the second liquid delivery tube 72 is connected to the second delivery port 71 of the second syringe 70.

The substance administration catheter 10 includes an inner tube (first tube) 20 that sends a first substance and an outer tube (second tube) 30 that sends a second substance. The distal end of the first liquid feeding tube 62 is connected to the hub 41 attached to the proximal end of the inner tube 20. The distal end of the second liquid feeding tube 72 is connected to the hub 42 attached to the proximal end of the outer tube 30.

The distal end side of the inner tube 20 of the substance administration catheter 10 is inserted into the outer tube 30 through a hole 32 formed in the side surface of the outer tube 30. A space between the inner surface of the hole 32 in the outer tube 30 and the outer surface of the inner tube 20 is fixed and sealed with an adhesive, a heat shrinkable tube, or the like.

FIG. 3 is an enlarged view showing the vicinity of the distal end side of the substance administration catheter 10 with a partial cross section. In FIG. 3, for convenience of explanation, the inner tube 20 is shown in a side view and the outer tube 30 is shown in a sectional view (the same applies to FIGS. 4 to 7).

As shown in FIG. 3, the inner tube 20 is disposed in the outer tube 30 on the distal end side of the outer tube 30 (see also FIG. 2). Further, the distal end portion 31 of the outer tube 30 is fixed to the outer surface 21 which is the outer peripheral surface of the inner tube 20 with an adhesive, a heat shrinkable tube, or the like, and is closed. In the present embodiment, the distal end portion 31 of the outer tube 30 has a planar shape perpendicular to the axial direction.

At the tip end side of the inner tube 20, a communication part 22 that connects the inside of the outer tube 30 and the inside of the inner tube 20 is formed. Therefore, the first substance sent through the inner pipe 20 and the second substance sent through the outer pipe 30 join and mix inside the inner pipe 20 corresponding to the region where the communication part 22 is formed. A mixed region 23 is formed. The inner tube 20 has a discharge port 24 opened at the tip of the inner tube 20, so that both the first substance and the second substance mixed in the mixing region 23 are discharged from the discharge port 24. It has become.

The outer diameter of the outer tube 30 and the outer diameter of the inner tube 20 are appropriately selected in consideration of the subject into which the substance administration catheter 10 is inserted, the mixing ratio of the first substance to the second substance to be administered, the viscosity, and the like. can do. For example, when the substance administration catheter 10 is used for administration to the brain parenchyma, the outer diameter of the outer tube 30 is preferably 0.1 to 3 mm, and the outer diameter of the inner tube 20 is preferably 0.05 to 2.5 mm.

In addition, the method of adhering and closing the distal end portion 31 of the outer tube 30 to the outer surface 21 of the inner tube 20 is not limited to the above-described adhesion, and is, for example, a method of bonding by pressure bonding or heat. Also good. Further, a method of covering another outer tube 30 such as a heat-shrinkable tube on the radially outer side in the vicinity of the distal end portion 31 of the outer tube 30 so that the outer tube 30 is closely attached to or fused to the inner tube 20 by the heat shrinkage of the heat-shrinkable tube. May be used.

The communication part 22 is a spiral cut (slit) in this embodiment. Specifically, the communication portion 22 can be formed by making a spiral cut with a blade having a thin blade such as a cutter knife, a laser, or the like with respect to the inner tube 20. As will be described later, the communication part 22 is opened by the pressure of the second substance in the outer pipe 30 during the pressurizing operation by the microinjection pump 80 (see FIG. 1), and the second substance in the outer pipe 30 passes through the communication part 22. Therefore, the width (slit width) of the communication portion 22 when the pressurizing operation is stopped is arbitrary and may be almost zero. Here, the communication portion 22 is a single continuous spiral cut, but is not limited thereto, and may be a plurality of spiral cuts such as a double spiral. .

The helical pitch in the communication part 22 is optimized depending on the types of the first substance and the second substance to be mixed, but is preferably 0.1 to 15 mm, more preferably 0.5 to 5 mm. By making the pitch of the helix more than the lower limit value, the strength and rigidity of the inner tube 20 can be further ensured. In addition, by setting the spiral pitch to be equal to or less than the upper limit value, the second substance can be more uniformly joined to the first substance in the circumferential direction and mixed.

The region where the communication portion 22 is formed, that is, the axial length L1 of the mixing region 23 is optimized depending on the types of the first substance and the second substance to be mixed, but is preferably 0.5 to 50 mm, more preferably 0.5 to 30 mm. By setting the axial length L1 of the mixing region 23 to be equal to or greater than the lower limit value, the first substance and the second substance are appropriately mixed, and the necessary mixing state can be further ensured. In addition, by setting the axial length L1 of the mixing region 23 to be equal to or less than the upper limit value, the first substance and the second substance are mixed before reaching the distal end of the substance administration catheter 10, for example, the reaction between the two substances. It is possible to prevent the material from becoming a gel.

The inner tube 20 protrudes from the distal end portion 31 of the outer tube 30 to the distal end side in the axial direction by 0.1 to 30 mm. By setting the protruding amount L2 of the inner tube 20 from the distal end portion 31 of the outer tube 30 to the axial distal end side to be 0.1 mm or more, the distal end of the substance administration catheter 10 can be made thinner, and the substance can be more resistant without damaging the tissue. The administration catheter 10 can be inserted into the body, and the distal end portion 31 of the outer tube 30 forming a stepped portion between the inner tube 20 and the outer tube 30 is formed along the outer surface of the substance administration catheter 10 with the first substance and the second substance. This prevents the mixed substance from flowing back. In addition, by setting the protruding amount L2 to 30 mm or less, it is possible to further prevent the gel from being formed in the protruding portion of the first tube due to the reaction between the first substance and the second substance. However, it is possible to adopt a configuration in which the inner tube 20 is not protruded from the distal end portion 31 of the outer tube 30 toward the distal end side in the axial direction.

The region where the communication part 22 is formed, that is, the distal end of the mixing region 23 is located 1 to 20 mm axially proximal from the distal end 31 of the outer tube 30. By setting the distance L3 from the distal end portion 31 of the outer tube 30 to the distal end of the mixing region 23 toward the proximal end side in the axial direction to 1 mm or more, the distal end portion 31 of the outer tube 30 becomes the communication portion 22 of the inner tube 20. Without this, it can be easily and reliably fixed to the outer surface 21 of the inner tube 20. In addition, by setting the distance L3 to 20 mm or less, the first substance and the second substance are mixed before reaching the distal end of the substance administration catheter 10, and for example, the gel is formed into a gel by the reaction between the two substances. Can be prevented.

The outer tube 30 and the inner tube 20 are made of a flexible material, and for example, polyurethane elastomer, polyamide elastomer, polyester elastomer, polyvinyl chloride, silicone elastomer, and the like can be suitably applied. Furthermore, although what combined 2 or more types of these (a polymer alloy, a polymer blend, a laminated body, etc.) is mentioned, it is not limited to these.

The substance administration catheter 10 may be provided with one or a plurality of lumens separately from the flow path for administering the substance. These lumens are used for the purpose of introducing a stylet or a guide wire, for example, when the substance administration catheter 10 is inserted into the body. It is also possible to use the inner tube 20 for introducing a stylet or a guide wire.

In addition, the substance administration catheter 10 may include a marker or a coating for imparting radiopacity or MRI visibility. Thereby, the substance administration catheter 10 can be visually recognized by an image diagnostic apparatus such as an X-ray fluoroscope, X-ray CT, and MRI, and the insertion position of the substance administration catheter 10 in the body can be confirmed. For example, in the case of a coating or radiopaque line, the exact position of the catheter within the living tissue can be known by providing it at the tip of the entire catheter or at least the portion inserted into the living tissue. . Further, in the case of a gold marker or the like, it is provided on the outer surface of the inner tube 20 (for example, near L2) near the tip or the outer tube 30 in order to grasp the position of the tip of the substance administration catheter 10 in the living tissue. it can. This not only prevents damage to brain tissue due to movement of the substance administration catheter 10 during substance administration, administration to unnecessary sites, infections, etc., but also insertion of the substance administration catheter 10 and administration of therapeutic substances. This is also very useful in that it can be used together with real-time monitoring technology. Real-time monitoring technology is an important technology for accurately and safely implementing the CED method. In addition, it is also possible to confirm the insertion length into the living tissue by installing contrasting markers at regular intervals.

Examples of the first substance and the second substance include anticancer agents, more specifically, alkylating agents such as nimustine, ranimustine, and temozolomide, platinum preparations such as cisplatin, oxaliplatin, and dahaplatin, sulfazine, methotrexate, fluorouracil, fructocin, azathioprine Antimetabolite such as pentostatin, topoisomerase inhibitor such as irinotecan, doxorubicin, levofloxacin, microtubule depolymerization inhibitor such as paclitaxel, dotaxel, antitumor antibiotics such as doxorubicin, epirubicin, bleomycin, imatinib, gefitinib, sunitinib Molecular target drugs such as cetuximab, trastuzumab, and the like, but are not limited thereto.

Next, a method for using the substance administration catheter 10 configured as described above will be described with reference to FIGS.
First, an operator such as a doctor connects the first liquid feeding tube 62 connected to the first syringe 60 to the first hub 41 and the second liquid feeding tube 72 connected to the second syringe 70 to the first liquid feeding tube 72. 2 Connect to the hub 42.
Subsequently, a priming operation is performed. By the operation of the microinjection pump 80, the first substance is supplied from the first syringe 60 to the first liquid feeding tube 62 and flows into the inner tube 20, and the second substance is fed from the second syringe 70 to the second liquid feeding tube 72. To flow into the outer tube 30. The microinjection pump 80 is stopped when the administration substance is filled up to the tips of the inner tube 20 and the outer tube 30 through the first liquid feeding tube 62 and the second liquid feeding tube 72. Thereby, since the discharge substance is filled up to the discharge port 24, air can be prevented from entering the brain via the substance administration catheter 10. In addition, when a 1st substance and a 2nd substance are gelatinized by mixing, operation after priming mentioned later is performed immediately.

The operator inserts the insertion portion 11 on the distal end side of the substance administration catheter 10 into a target site such as the vicinity of the brain tumor. At this time, a scale (depth scale from the catheter tip) may be provided on the outer surface of the outer tube 30 of the catheter 10 by printing or the like so that the insertion depth can be visually confirmed. If the first and

second hubs

41 and 42 have three-way stopcocks or check valves, the first and second hubs are placed after the insertion portion 11 of the primed substance administration catheter 10 is placed in the living tissue. The

liquid feeding tubes

62 and 72 may be connected to the first and

second hubs

41 and 42, respectively.

Then, by operating the microinjection pump 80, the first substance and the second substance are administered to a target site such as in the vicinity of the brain tumor via the substance administration catheter 10 placed in the living tissue.

FIG. 4 is an enlarged view showing, in partial cross section, the vicinity of the distal end side of the substance administration catheter 10 during the pressurizing operation by the microinfusion pump 80.
As shown in FIG. 4, in the substance administration catheter 10, the first substance that has flowed into the inner tube 20 is sent in the direction A in FIG. 4 toward the distal end side in the axial direction through the inside of the inner tube 20. The second substance that has flowed into the outer tube 30 passes through the space between the inner surface of the outer tube 30 and the outer surface of the inner tube 20, and is sent in the direction B in FIG. Here, the outer tube 30 has a distal end portion 31 closed, while the inner tube 20 has a communication portion 22 with the outer tube 30 on the distal end side, and is opposed to the communication portion 22 and has an inner tube. A mixing region 23 is formed inside 20. For this reason, the second substance flowing in the outer tube 30 flows into the inner tube 20 from the periphery of the inner tube 20 through the communication portion 22 in the direction C in FIG. 4 and mixes in the inner tube 20. And mixed with the first substance.

At this time, since the distal end portion 31 of the outer tube 30 is fixed to the outer surface 21 of the inner tube 20 and is closed, the inner pressure of the outer tube 30 (the pressure of the second substance) rises, and the second portion in the outer tube 30 increases. The substance passes through the communication part 22 while expanding the opening area of the communication part 22 formed in the inner pipe 20 as shown in FIG. 4, and is pushed out and flows into the inner pipe 20.

The first substance and the second substance mixed in the mixing region 23 in the inner tube 20 pass through the discharge port 24 at the tip of the inner tube 20 and are directed to a target site (treatment site) at a predetermined injection amount and injection rate. Is emitted in the direction D in FIG. Therefore, the first substance such as the drug and the second substance can be mixed through the substance administration catheter 10 and can be administered to a target site such as the vicinity of the tumor in the brain parenchyma by the convection increasing delivery method.

As described above, the substance administration catheter 10 according to the present embodiment includes the inner tube 20 that sends the first substance and the outer tube 30 that sends the second substance, and the inner tube 20 is located at the distal end side of the outer tube 30. Arranged in the outer tube 30, the distal end portion 31 of the outer tube 30 is fixed and closed to the outer surface 21 of the inner tube 20, and the inner tube 20 and the inner tube are disposed on the distal end side of the inner tube 20. A communication portion 22 that communicates with the inside of the communication device 20 is formed.

Therefore, according to the present embodiment, the first substance passing through the inner tube 20 and the second substance passing through the outer tube 30 reach a region where the communication portion 22 located on the distal end side of the substance administration catheter 10 is formed. The second substance in the outer tube 30 flows into the inner tube 20 from the periphery of the inner tube 20 through the communicating portion 22 immediately before being discharged from the substance administration catheter 10 without being mixed. Mix well with one substance. For this reason, in the substance administration catheter 10, it is possible to ensure a mixed state of substances desirable for administration while suppressing phenomena such as a reaction between the mixed substances and a change in the composition such as crystallization of the substances.
That is, when the first substance and the second substance are administered into the body, both these substances are desirable while mixing both of these substances immediately before discharge and sufficiently suppressing the reaction between the two substances. The substance administration catheter 10 that can be discharged in a mixed state can be provided.

In the present embodiment, the communication portion 22 is a spiral cut. According to such a configuration, since the second substance is spirally sent to the first substance and merges, turbulence is generated in the mixing region 23 where both substances are mixed, and the mixing is promoted. Immediately before discharge, it is possible to mix and discharge more effectively. In addition, the communication part 22 by cutting is in a state where the communication part 22 is opened and the second substance is pushed out when the second substance in the outer tube 30 is pressurized by the microinjection pump 80. The chance that the first substance and the second substance come into contact with each other in the stopped state can be reduced. This is advantageous in performing a procedure for filling the substance administration catheter 10 to the tip of the substance administration catheter 10 (priming operation) and inserting the substance administration catheter 10 into the brain parenchyma.

Next, with reference to FIGS. 5 to 7, another embodiment of the present invention will be described with a focus on the differences from the embodiment shown in FIGS. 1 to 4, and a description of the common points will be given. Omitted.

FIG. 5 is an enlarged view showing a portion of the vicinity of the distal end side of the substance administration catheter 10a according to another embodiment of the present invention in a partial cross section.
As shown in FIG. 5, the substance administration catheter 10a differs from the distal end portion 31 shown in FIG. 3 in that the distal end portion 31a of the outer tube 30a has a tapered shape that tapers toward the distal end side. According to such a configuration, in addition to being able to achieve the same functions and effects as the embodiment shown in FIGS. 1 to 4, the tip of the substance administration catheter 10a can be made smoother and thinner, and the tissue can be further improved. The substance administration catheter 10a can be inserted into the body without resistance without being damaged.

FIG. 6 is an enlarged view showing, in partial cross section, the vicinity of the distal end side of the substance administration catheter 10b according to still another embodiment of the present invention.
As shown in FIG. 6, the substance administration catheter 10b differs from the communication part 22 shown in FIG. 3 in that the communication part 22a is a plurality of cuts (slits) perpendicular to the axial direction. The communicating portion 22a is formed in an axial direction having a predetermined depth smaller than the outer diameter of the inner tube 20a by a blade or a laser having a thin blade such as a cutter knife with respect to the outer surface (cylindrical wall portion) of the inner tube 20a. It can be formed by making a plurality of vertical cuts evenly. In addition, when providing a cut | incision in the outer surface of the inner tube | pipe 20a, it is not limited to the cut | disconnection perpendicular | vertical to the axial direction of the inner tube | pipe 20a. For example, a plurality of cuts parallel to the axial direction of the inner tube 20a may be created evenly with respect to the outer surface of the inner tube 20a.

FIG. 7 is an enlarged view showing, in partial cross section, the vicinity of the distal end side of the substance administration catheter 10c according to still another embodiment of the present invention.
As shown in FIG. 7, the substance administration catheter 10c is different from the communication part 22 shown in FIG. 3 in that the communication part 22b is a plurality of holes (for example, circular holes) communicating between the inside and the outside of the inner tube 20b. A plurality of communication portions 22b are equally arranged with respect to the outer surface (cylindrical wall portion) of the inner tube 20b.

Even when the first substance and the second substance are administered into the body using the

substance administration catheters

10b and 10c shown in FIGS. 6 and 7, the two substances are sufficiently mixed immediately before ejection. It is possible to discharge both substances in a desirable mixed state while suppressing a phenomenon such as a reaction between the two substances.

In the

substance administration catheters

10, 10a to 10c shown in FIGS. 3 to 7, the

inner tubes

20, 20a and 20b are coaxially arranged in the

outer tubes

30 and 30a, but the

inner tubes

20, 20a and 20b are arranged coaxially. May be arranged not on the same axis as the

outer tubes

30 and 30a but on the inner surface side of the

outer tubes

30 and 30a.

As mentioned above, although this invention was demonstrated based on embodiment, this invention is not limited to the structure described in the said embodiment, The combination thru | or selecting suitably the structure described in the said embodiment is included. The configuration can be changed as appropriate without departing from the spirit of the invention. In addition, a part of the configuration of the embodiment can be added, deleted, and replaced.

For example, in the above-described embodiment, the substance administration catheter is inserted into the brain parenchyma, which is a non-luminal region that is not a biological lumen (blood vessel, vessel, ureter, etc.), and delivers a therapeutic substance. The subject into which the substance administration catheter is inserted is not limited to the brain parenchyma, and may be delivered to living tissue in a non-luminal region other than the brain, such as the liver, pancreas, gallbladder, breast, uterus, and large intestine. Alternatively, the substance administration catheter may be inserted into a biological lumen such as a blood vessel, a vascular vessel, or a ureter to deliver the substance to a predetermined position in the lumen region.

In the substance administration catheter according to the above-described embodiment, the first substance and the second substance, which are therapeutic substances, are mixed. However, both substances to be mixed are not limited to the therapeutic substances. There is no particular limitation as long as it is a substance that can be mixed, such as an agent and a therapeutic substance, a contrast medium and physiological saline, or a therapeutic substance and physiological saline. Further, the two substances to be mixed may be two liquids before mixing of the two-liquid mixed polymer that is gelled or solidified by mixing the two liquids having fluidity. The transition of the two-component mixed polymer to the non-flowable state is achieved by forming a network structure in which polymer chains are three-dimensionally cross-linked by physical interaction or chemical bonding. One or both of the two liquids may or may not contain a therapeutic substance. The two liquids used in the two-liquid mixed polymer are not particularly limited. For example, one of the two liquids can be a cross-linking agent or a pH adjuster and the other can be a polymer that is cross-linked by a cross-linking agent or a pH adjuster. Alternatively, the two liquids used in the two-liquid mixed polymer may be, for example, a polymer that has a reactive site in each and crosslinks by mixing.

Examples of materials constituting such a polymer include general natural or synthetic polymers, copolymers, biological polymers, hydrogels, and composite materials thereof. Specifically, fibrin adhesive, collagen, hyaluronic acid, chitosan, gelatin, alginate, starch, sugar, cellulose, polylactic acid, polyglycolic acid, polyε-caprolactam, polyethylene glycol, polyacrylic acid, polymethacrylic acid, Preferred examples include polyacrylamide, polymethacrylamide, polydimethylmethacrylamide, cyanoacrylate, and derivatives thereof. These materials may be used alone or in combination of two or more. These materials may be chemically copolymerized into polymers. Further, some chemical modification may be applied to each polymer chain for solidification or gelation in a living tissue.

By using a substance administration catheter for administration of the two-component mixed polymer, the two components used in the two-component mixed polymer are not mixed until immediately before administration, so that it is difficult to transfer to a non-flowable state in the substance-administering catheter. Road blockage can be suppressed. In addition, since the polymer solution can be sufficiently mixed, it becomes difficult for the polymer solution to diffuse into the interstitial space of the living tissue before administration before the polymer solution changes to a non-flowable state. A gel having the functions necessary for proper mixing can be obtained.

By mixing a drug as a therapeutic substance with a gelled or solidified polymer and administering it to a living tissue, a medical material containing the drug can be easily prepared, and the drug can be gradually released using it as a reservoir. is there. This, as a local drug delivery system (DDS), avoids continuous administration and frequent administration of the drug, and reduces side effects and improves the therapeutic effect by keeping the drug concentration constant. In addition, a polymer containing cells (and cell growth factors), not a drug as a therapeutic substance, can be used as a scaffold for tissue regeneration by being administered to a defect to form a medical material. .

10, 10a, 10b, 10c

Substance administration catheter

20, 20a, 20b Inner tube (first tube)
21

outer surface

22, 22a,

22b communicating part

30, 30a outer pipe (second tube)
31, 31a Tip

Claims

A substance administration catheter for mixing and administering a first substance and a second substance in the body,
A first tube for delivering the first substance;
A second tube for feeding the second substance,
The first tube is disposed in the second tube on the distal end side of the second tube,
The distal end portion of the second tube is fixed and closed on the outer surface of the first tube,
A substance administration catheter, characterized in that a communicating portion for communicating the inside of the second tube and the inside of the first tube is formed on the distal end side of the first tube.
The substance administration catheter according to claim 1, wherein the communication part is a spiral cut.
The substance administration catheter according to claim 1, wherein an axial length of a region where the communication part is formed is 0.5 to 50 mm.
The substance administration catheter according to claim 1, wherein the first tube protrudes from the distal end of the second tube to the distal end in the axial direction by 0.1 to 30 mm.
2. The substance administration catheter according to claim 1, wherein the distal end of the region where the communication portion is formed is located on the proximal end side in the axial direction of 1 to 20 mm from the distal end portion of the second tube.
The substance administration catheter according to claim 1, which is used for increased convection delivery of a substance to a tumor.
The substance administration catheter according to any one of claims 1 to 6, wherein the substance administration catheter is used for increased convection delivery of a substance to the brain.