JP2017158671A - Dosing method - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a dosing method that can penetrate a tumor tissue and the like with drug solution quickly.SOLUTION: The dosing method includes: inserting a nozzle 9 into a tumor tissue 15; injecting a pulse flow of drug solution 4 from the nozzle 9 into the tumor tissue 15; and, after injecting the pulse flow, injecting a continuous flow of the drug solution 4 into the tumor tissue 15.SELECTED DRAWING: Figure 7

Description

  The present invention relates to a dosing method.

  When tumor tissue or inflamed tissue is formed in the body (for example, in the brain), a method of surgically removing these tissues (surgical operation) is performed. At this time, in order not to damage the nerves and blood vessels, the tumor tissue around the nerves and blood vessels may not be completely removed or intentionally removed. For this reason, there is a case in which a chemical solution is permeated into a tumor tissue that could not be removed by a surgical method, and treatment or removal of the tumor tissue or the like is performed. In addition, referring to the size and location of tumor tissue or the like, if there is a high risk of damaging nerves or blood vessels in surgical operation, chemotherapy may be performed without performing surgical operation.

  Patent Document 1 discloses a method of penetrating a drug solution into a tumor tissue or the like. According to this, a tube called a cannula or catheter was inserted into a tumor tissue or the like, and a drug solution was administered from the tube to the tumor tissue or the like. This method is called a convection augmented delivery method. Hereinafter, the discharge port of the cannula and the catheter is referred to as a nozzle.

Special table 2009-507531

  Tumor tissues and the like are often hard tissues compared to normal tissues. For this reason, a chemical | medical solution does not osmose | permeate tumor tissue etc. compared with a normal tissue. Therefore, in consideration of the penetration rate of the drug solution into the tumor tissue or the like, the injection rate of the drug solution was very low, 0.5 to 10 μl / min, so that the supply amount does not exceed the penetration rate. Therefore, it took a long time to administer the drug solution when performing chemotherapy. The treatment was a physical burden because the patient had to be rested during the drug administration. For this reason, there has been a demand for a dosing method capable of rapidly infiltrating a drug solution into a tumor tissue or the like.

  The present invention has been made to solve the above-described problems, and can be realized as the following forms or application examples.

[Application Example 1]
A dosing method according to this application example, which includes inserting a nozzle into a tissue and injecting a pulse flow of a drug solution from the nozzle into the tissue.

  According to this application example, the nozzle is inserted into the tissue. Then, a pulse flow of the chemical solution is ejected from the nozzle to the tissue. The pulse flow is a fluid in which the pressure fluctuation of the chemical solution is repeated. High pressure is repeatedly applied to the tissue by jetting the pulsed flow. As a result, the tissue is softened, and a gap through which the chemical solution flows between the cells of the tissue is formed. The tissue can be softened, or a gap can be formed between the cells of the tissue to allow the drug solution to flow, so that the drug solution can quickly penetrate into the tissue.

  Furthermore, a liquid pool is formed in the tissue. The area where the liquid reservoir of the chemical solution contacts the tissue is wider than the area where the nozzle contacts the tissue. And when a chemical | medical solution osmose | permeates a structure | tissue, the one where the contact area of a chemical | medical solution and a structure | tissue is large will infiltrate early. Therefore, the chemical solution can be quickly infiltrated into the tissue.

[Application Example 2]
In the dosing method according to the application example described above, a continuous flow of the drug solution is jetted onto the tissue after jetting the pulse flow.

  According to this application example, after the tissue is softened and a liquid pool of the chemical solution is formed, a continuous flow of the chemical solution is jetted onto the tissue. After the tissue is softened and the liquid reservoir of the chemical liquid is formed, the chemical liquid easily penetrates into the tissue, so that the continuous flow of the chemical liquid penetrates quickly into the tissue. In addition, the pulse flow mainly penetrates the chemical solution in the injection direction, but the chemical solution penetrates radially by changing the pulse flow to a continuous flow. Therefore, when the tissue lump has a shape close to a sphere, the chemical solution can be quickly infiltrated into the entire tissue by spraying with a continuous flow.

FIG. 2 is a block diagram illustrating a configuration of a liquid ejecting apparatus according to the first embodiment. The principal part enlarged view which shows the structure of an injection pipe. The flowchart of a medication method. The schematic diagram for demonstrating the administration method. The schematic diagram for demonstrating the administration method. The schematic diagram for demonstrating the administration method. The schematic diagram for demonstrating the administration method. FIG. 6 is a block diagram illustrating a configuration of a liquid ejecting apparatus according to a second embodiment. The schematic diagram for demonstrating the administration method.

Hereinafter, embodiments will be described with reference to the drawings.
In addition, each member in each drawing is illustrated with a different scale for each member in order to make the size recognizable on each drawing.

(First embodiment)
In the present embodiment, a characteristic example of a liquid ejecting apparatus and a dosing method for administering to a tumor tissue using the liquid ejecting apparatus will be described with reference to the drawings. Hereinafter, embodiments will be described with reference to the drawings. In addition, each member in each drawing is illustrated with a different scale for each member in order to make the size recognizable on each drawing.

  FIG. 1 is a block diagram illustrating a configuration of the liquid ejecting apparatus. The liquid ejecting apparatus 1 according to this embodiment is a medical device used in a medical institution, and has a function of dispensing a drug solution to an affected part by ejecting a fluid to the affected part. It can also be used for medication to animals other than humans.

  As shown in FIG. 1, the liquid ejecting apparatus 1 includes a pump 2. The pump 2 can be a syringe-type pump or a tube pump. In the case of a syringe type, it is preferable to install a device for supplying fluid into the syringe. Thereby, the liquid ejecting apparatus 1 can be continuously driven.

  A water inlet pipe 2 a is installed in the pump 2, and one end of the water inlet pipe 2 a is connected to the water storage tank 3. The water tank 3 contains a chemical solution 4. The drug solution 4 contains, for example, a therapeutic substance that reduces tumor tissue. Examples of therapeutic substances 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, and pentostatin. Antimetabolite, irinotecan, doxorubicin, levofloxacin and other topoisomerase inhibitors, paclitaxel, dotaxel and other microtubule depolymerization inhibitors, doxorubicin, epirubicin, bleomycin and other antitumor antibiotics, imatinib, gefitinib, sunitinib, cetuximab Molecular target drugs such as, but not limited to. In addition, a single type or concentration of the chemical solution may be used, and a plurality of types may be used, such as appropriately replacing in the course of medication.

  The pump 2 is connected to the pulsation imparting unit 6 via the tube 5. The pulsation imparting unit 6 has a function of turning the fluid passing therethrough into a pulse flow. The pulsation imparting unit 6 is provided with an ejection pipe 8 through a tube 7. A nozzle 9 that ejects fluid is installed at one end of the ejection pipe 8.

  A room through which the chemical solution 4 passes is installed in the pulsation imparting unit 6. The chemical solution 4 enters this room from the tube 5 and flows from this room toward the tube 7. A diaphragm is installed on one surface of the room, and a piezoelectric element is installed on the diaphragm. Then, the piezoelectric element vibrates the diaphragm. The drive voltage applied to the piezoelectric element repeats on (maximum voltage) and off (0 V) at a high frequency of 300 Hz, for example. Thereby, expansion and reduction of the volume of the room are repeated. Then, pulsation is given to the fluid. The fluid pushed out of the room is ejected as a pulse flow from the nozzle 9 at the tip of the ejection tube 8.

  The injection of a pulse flow means that the flow rate or the flow rate is injected with fluctuations, and is not limited to repeating the injection and stop of the fluid. That is, various injection forms such as a form in which the injection is completely interrupted between injections and a form in which a low-pressure flow exists between the injections are included.

  The liquid ejecting apparatus 1 includes a control device 10, and the control device 10 controls the operation of the liquid ejecting apparatus 1. The pulsation imparting unit 6 and the pump 2 are connected to the control device 10 by a cable 10a. The control device 10 is provided with an injection switch 11, a changeover switch 12, and the like. The ejection switch 11 is a switch for switching between ejection and non-ejection of fluid from the nozzle 9. The injection switch 11 is a switch operated by the surgeon stepping on the foot. The changeover switch 12 is a switch that switches between driving and non-driving of the pulsation imparting unit 6. The changeover switch 12 can switch the chemical liquid 4 ejected from the nozzle 9 to either a pulse flow or a continuous flow.

  The surgeon turns on the injection switch 11. The pump 2 is activated, and the pump 2 causes the chemical solution 4 to flow from the water storage tank 3 to the pulsation imparting unit 6. When the surgeon selects the pulse flow with the changeover switch 12, the drug solution 4 that has reached the pulsation imparting unit 6 is applied with a pulsed pulsation by the pulsation imparting unit 6. A pulsed pulsating flow is called a pulse flow. The chemical solution 4 that has passed through the pulsation imparting unit 6 passes through the injection pipe 8 and is injected from the nozzle 9. Since the chemical solution 4 passing through the nozzle 9 has a pulse flow, it is jetted by a pulse flow. The injection tube 8 has a tubular shape centered on the nozzle 9. A pulse flow of the chemical liquid 4 is ejected from the nozzle 9.

  When the surgeon selects the continuous flow with the changeover switch 12, the drug solution 4 that has reached the pulsation imparting unit 6 is not subjected to pulsed pulsation by the pulsation imparting unit 6. The chemical solution 4 that has passed through the pulsation imparting unit 6 passes through the injection pipe 8 and is injected from the nozzle 9. Since the chemical | medical solution 4 which passes the nozzle 9 becomes a continuous flow, it is a continuous flow injection. The injection tube 8 has a tubular shape centered on the nozzle 9. A continuous flow of the chemical solution 4 is ejected from the nozzle 9. The continuous flow refers to a flow with small pressure fluctuation.

  FIG. 2 is an enlarged view of a main part showing the structure of the injection pipe. As shown in FIG. 2, a cylindrical needle 13 is installed at the end of the injection tube 8. The tip of the needle 13 is a nozzle 9. The needle 13 is a tube thinner than the injection tube 8, and can be inserted into the tumor tissue with a small force. The operator holds the ejection tube 8 with a finger and inserts the needle 13 into the tumor tissue. Note that the shape of the needle 13 is not limited to this, and may be bent, have a step, or be cut at an angle according to the usage situation. Further, the position and the number of nozzles can be appropriately changed as long as the chemical liquid is ejected.

  Next, a method for administering the drug solution 4 to the tumor tissue using the liquid ejecting apparatus 1 described above will be described with reference to FIGS. FIG. 3 is a flowchart of the dosing method, and FIGS. 4 to 7 are schematic diagrams for explaining the dosing method. In the flowchart of FIG. 3, step S1 corresponds to a nozzle installation step, and is a step of inserting the nozzle 9 into the tumor tissue. Next, the process proceeds to step S2. Step S2 is a pulse flow injection process. This step is a step of injecting a pulse flow of the drug solution 4 from the nozzle 9 to the tumor tissue. Next, the process proceeds to step S3. Step S3 is a continuous flow injection process. This step is a step of injecting a continuous flow of the drug solution 4 to the tumor tissue. Next, the process proceeds to step S4. Step S4 is a nozzle removal process. This step is a step of removing the nozzle 9 from the tumor tissue. The process of administering the drug solution 4 to the tumor tissue is completed by the above process. In addition, treatments such as craniotomy and craniotomy not described are appropriately performed.

  Next, the dosing method will be described in detail with reference to FIGS. 4 to 7 in association with the steps shown in FIG. 4 and 5 are diagrams corresponding to the nozzle installation step of step S1. As shown in FIG. 4, a tumor tissue 15 as a tissue is formed in the brain of the patient 14. An anesthetic is preliminarily administered to the patient 14, and the patient 14 is less likely to feel pain. The operator recognizes the position of the tumor tissue 15 in advance using an inspection apparatus. The surgeon grasps the ejection tube 8 and inserts the nozzle 9 into the tumor tissue 15. Next, the surgeon applies the adhesive tape 16 to fix the tube 7 to the patient 14.

  As shown in FIG. 5, patient 14 has tumor tissue 15 in normal tissue 17. Then, the operator inserts the needle 13 so that the nozzle 9 is positioned in the tumor tissue 15.

  FIG. 6 is a diagram corresponding to the pulse flow injection process of step S2. In step S <b> 2, the surgeon operates the changeover switch 12 to drive the pulsation imparting unit 6. Then, as shown in FIG. 6, the liquid ejecting apparatus 1 ejects a pulse flow of the drug solution 4 from the nozzle 9 to the tumor tissue 15. Since a high pressure is repeatedly applied to the tumor tissue 15 in the pulse flow, the tumor tissue 15 is softened. Since the tumor tissue 15 is softened, the drug solution 4 can be quickly penetrated into the tumor tissue 15.

  Furthermore, in the tumor tissue 15, a liquid reservoir 18 in which the drug solution 4 is accumulated between cells is formed. The area where the liquid reservoir 18 of the drug solution 4 contacts the tumor tissue 15 is wider than the area where the tip of the nozzle 9 contacts the tumor tissue 15. And when the chemical | medical solution 4 osmose | permeates the tumor tissue 15, the one where the contact area of the chemical | medical solution 4 and the tumor tissue 15 is wide infiltrates early. Therefore, the medicinal solution 4 can be quickly penetrated into the tumor tissue 15.

  FIG. 7 is a diagram corresponding to the continuous flow injection step of step S3. In step S3, the surgeon operates the changeover switch 12 to deactivate the pulsation imparting unit 6. Then, as shown in FIG. 7, the liquid ejecting apparatus 1 ejects a continuous flow of the drug solution 4 from the nozzle 9 onto the tumor tissue 15. As a result, the drug solution 4 spreads throughout the tumor tissue 15 with the liquid reservoir 18 as a nucleus.

  In addition, when administering many chemical | medical solutions 4 in an injection direction, you may inject only by a pulse flow. When the chemical solution 4 is allowed to penetrate radially, the chemical solution may be ejected by a continuous flow after the pulse flow. Thus, it is preferable to switch between the pulse flow and the continuous flow in accordance with the shape of the mass of the tumor tissue 15.

  In the nozzle removal step of step S4, the operator operates the injection switch 11 to stop the pump 2. Then, the needle 13 is removed from the patient 14. The process of administering the drug solution 4 to the tumor tissue 15 is completed by the above process.

As described above, this embodiment has the following effects.
(1) According to this embodiment, the nozzle 9 is inserted into the tumor tissue 15. Then, a pulse flow of the drug solution 4 is ejected from the nozzle 9 to the tumor tissue 15. The pulse flow is a fluid in which the pressure fluctuation of the chemical solution 4 is repeated. High pressure is repeatedly applied to the tumor tissue 15 by jetting the pulse flow. Thereby, the tumor tissue 15 is softened. Since the tumor tissue 15 is softened, the drug solution 4 can be quickly penetrated into the tumor tissue 15.

  Furthermore, a liquid reservoir 18 is formed in the tumor tissue 15. The area where the liquid reservoir 18 of the drug solution 4 contacts the tumor tissue 15 is wider than the area where the tip of the nozzle 9 contacts the tumor tissue 15. And when the chemical | medical solution 4 osmose | permeates the tumor tissue 15, the one where the contact area of the chemical | medical solution 4 and the tumor tissue 15 is wide infiltrates early. Therefore, the medicinal solution 4 can be quickly penetrated into the tumor tissue 15.

  (2) According to this embodiment, after the tumor tissue 15 is softened and the liquid reservoir 18 of the drug solution 4 is formed, a continuous flow of the drug solution 4 is sprayed onto the tumor tissue 15. After the tumor tissue 15 is softened and the liquid reservoir 18 of the drug solution 4 is formed, the drug solution 4 easily penetrates into the tumor tissue 15, so that the continuous flow of the drug solution 4 quickly penetrates into the tumor tissue 15. Moreover, the chemical | medical solution 4 osmose | permeates radially by changing a pulse flow into a continuous flow. Therefore, when the mass of the tumor tissue 15 has a shape close to a sphere, it can be quickly infiltrated into the entire tumor tissue 15 by spraying with a continuous flow.

  (3) According to the present embodiment, the drug solution 4 can be easily penetrated into the tumor tissue 15. Therefore, it is possible to suppress the medicinal solution 4 from flowing out through the needle 13.

(Second Embodiment)
Next, an embodiment of the liquid ejecting apparatus will be described with reference to FIGS. FIG. 8 is a block diagram illustrating a configuration of the liquid ejecting apparatus. FIG. 9 is a schematic diagram for explaining a dosing method. This embodiment is different from the first embodiment in that the shape of the pulsation imparting section 6 shown in FIG. 1 is different. Note that description of the same points as in the first embodiment is omitted.

  That is, in this embodiment, the liquid ejecting apparatus 20 includes a pulsation imparting unit 21 as illustrated in FIG. The pulsation imparting unit 21 has the same function as the pulsation imparting unit 6 in the first embodiment. The pulsation imparting portion 21 has a shape that is long in one direction and is easy to be grasped by an operator. The pulsation imparting unit 21 is also referred to as a handpiece.

  An injection tube 22 is installed in the pulsation imparting unit 21. The injection tube 22 has the same function as the injection tube 8 in the first embodiment. A needle 13 is installed at one end of the injection tube 22. The ejection tube 22 has a shape longer than that of the ejection tube 8, so that the operator can easily hold the ejection tube 22 and insert the needle 13 into the patient 14.

  As shown in FIG. 9, in the nozzle installation process of step S <b> 1, the operator holds the pulsation imparting unit 21 and inserts the needle 13 into the patient 14. Then, the pulsation imparting unit 21 is held by the holding device 23. Since the liquid ejecting apparatus 20 has the pulsation imparting part 21 located near the needle 13, the pulse flow generated by the pulsation imparting part 21 can reach the nozzle 9 with little attenuation.

Note that the present embodiment is not limited to the above-described embodiment, and various changes and improvements can be added by those having ordinary knowledge in the art within the technical idea of the present invention. A modification will be described below.
(Modification 1)
In the first embodiment, the injection pipe 8 and the needle 13 are fixed using the adhesive tape 16. In addition, the injection tube 8 and the nozzle 9 may have a button-type indwelling needle structure. Thereby, the injection tube 8 and the needle 13 can be easily fixed to the patient 14.

(Modification 2)
In the first embodiment, one needle 13 is installed for the tumor tissue 15. When the tumor tissue 15 is large, a plurality of nozzles 9 may be installed for one tumor tissue 15. A plurality of needles 13 may be installed according to the shape of the tumor tissue 15. The chemical solution 4 can be permeated more quickly. This content can also be applied to the second embodiment.
In the present invention, the drug solution is infiltrated into the tumor tissue with the adaptation place being the brain, but it may be a place other than the brain. And it is not limited to the tumor tissue, but may be a medication to the inflamed tissue, but is not limited thereto.

  4 ... Chemical solution, 9 ... Nozzle, 15 ... Tumor tissue as tissue.

Claims (2)

Inserting a nozzle into the tissue;
Injecting a pulse flow of a drug solution from the nozzle onto the tissue. The dosing method according to claim 1, wherein
A dosing method comprising injecting a continuous flow of the drug solution into the tissue after injecting the pulsed flow.

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