Air leak sealing device

Abstract

To close air leak of a peripheral part of bronchi where a bronchoscope cannot enter hitherto.SOLUTION: An air leak closure device includes a catheter insertable into a forceps hole of a bronchoscope, which is a catheter having a chemical injection adapter, and an ultra-thin endoscope or an inner catheter. The air leak closure device can observe and specify reliably and stably an air leak site by allowing an endoscope to reach up to a peripheral part of bronchi where a bronchoscope cannot enter hitherto, and can perform air leak closure treatment even in the case of the peripheral part of bronchi.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a device for closing air leakage in the thoracic cavity using a biological tissue adhesive. More specifically, the present invention relates to a device for closing air leakage, including a catheter that can be inserted into the forceps hole of a bronchoscope and has a chemical solution injection adapter, and an ultra-thin endoscope.

Background Art

[0002] Pneumothorax is a condition in which air flows into the thoracic cavity, which is normally maintained at negative pressure, for some reason, and the negative pressure in the thoracic cavity cannot be maintained, causing the lung to collapse. Most cases are caused by air leakage from pulmonary cysts (bullae). The number of cases of pneumothorax treated in Japan is less than 40,000 per year, and it is a common disease in the field of thoracic surgery. More than half of the cases are treated conservatively by thoracic drainage by inserting a thoracic tube, but the average length of hospitalization is 11.0 days. Also, the recurrence rate from the first to the second recurrence is said to be 30 - 40%, and the recurrence rate from the second to the third recurrence is 70%. Therefore, many problems remain in conservative treatment. Also, the number of surgeries is about 14,000, and most of them are performed using a thoracoscope. Although the recurrence rate can be suppressed to less than 10%, surgical invasion is required, and the medical cost is also high. The purposes of treating pneumothorax include recovery from respiratory disorders, closure (stopping) of air leakage, and prevention of recurrence.

[0003] For closing (stopping) air leakage, a technique has been developed to embolize the responsible bronchus using a bronchoscope with silicon packing, a coil, fibrin glue, etc. However, problems such as recurrence due to detachment of the packing and impairment of lung ventilation function due to the relatively wide range of the embolized area remain. Also, the decisive problem with these existing bronchoscope-based treatments was the uncertainty of the treatment effect due to the inability to accurately identify the responsible bronchus of the air leakage and observe / treat near its end ((Non-Patent Documents 1-3).

[0004] Known bio-adhesives used in surgical procedures include Tisseel (registered trademark: Immuno AG), the world's first fibrin glue preparation developed in 1978; Beriplast (registered trademark) P (Hoechst Japan Co., Ltd.), developed in 1988 in Japan; and Volheal (registered trademark: KM Biologics Co., Ltd.), developed in 1991. Fibrin glue consists of four components: (i) freeze-dried fibrinogen powder, (ii) fibrinogen solution (containing aprotinin), (iii) freeze-dried thrombin powder, and (iv) thrombin solution (containing calcium chloride). Solution A is prepared by dissolving (i) in (ii), and solution B is prepared by dissolving (iii) in (iv). Solutions A and B are mixed at the tissue adhesion surface and used for tissue adhesion and closure.

[0005] One of the devices for fibrin glue preparations used to close air leaks in the pleural cavity is the Beriplast® P Endoscopic Catheter (Sumitomo Akita Bake Co., Ltd.), which is a dedicated accessory for the Beriplast® P (CSL Behring Co., Ltd.) Combi Set. This is a catheter with a maximum outer diameter of 2.5 mm, designed so that solution A (fibrinogen solution) and solution B (thrombin solution) are injected separately into a single tube with two blocked routes (holes), and the two solutions are mixed at the tip (Non-Patent Literature 4).

[0006] Typically, a bronchoscope (electronic endoscope or fiberscope), which is a lung camera consisting of a thin, flexible tube with a tip diameter of 3-6 mm used to diagnose the lungs and bronchi, is used to identify the air leak site. Then, the device is inserted into the forceps channel (approximately 1.7-3 mm in diameter) of the bronchoscope, and the leak is occluded with fibrin glue. Therefore, the tip diameter of a bronchoscope that can accommodate a 2.5 mm diameter Berip endoscopic catheter is approximately 3-6 mm. [Prior art documents] [Patent Documents]

[0007] [Patent Document 1] Kohei Jitsuhei 03-047609 [Patent Document 2] WO1994 / 07420 [Patent Document 3] Japanese Patent Publication No. 2001-157716 [Patent Document 4] Japanese Patent Publication No. 7-184952 [Patent Document 5] Actual registration 3172382 [Non-patent literature]

[0008] [Non-Patent Document 1] Chest. 2005 Dec;128(6):3955-65. [Non-Patent Document 2] Intern Med. 2011;50(11):1169-73. [Non-Patent Document 3] Intern Med. 2020 Aug 1; 59(15): 1835-1839. [Non-Patent Document 4] CSL Behring Product Information List: Beriplast (Registered Trademark) P CombiSet for Tissue Adhesion "Accessory Equipment Handbook" Website: https: / / csl-info.com / products / beriplast05 (Confirmed December 1, 2020) [Overview of the project] [Problems that the invention aims to solve]

[0009] In the treatment of intrapleural air leak closure using fibrin glue preparations, identifying the site of the air leak using a bronchoscope is essential. However, currently used bronchoscopes have a tip outer diameter of 3-6 mm, making it impossible to insert the camera into bronchi smaller than this diameter. Therefore, if the air leak site is in the peripheral part of the bronchus that cannot be accessed by a bronchoscope, air leak closure treatment becomes impossible. [Means for solving the problem]

[0010] The inventors of this invention have diligently conducted research to solve the above problem. First, in order to reach the peripheral parts of the bronchi that cannot be penetrated with a conventional bronchoscope, they considered using next-generation ultra-thin endoscopes (1 mm diameter) (Panasonic i-PRO Sensing Solutions Co., Ltd.) or ultra-thin vascular endoscopes (0.49 mm) (Olivas Co., Ltd.).

[0011] By using a bronchoscope in combination with a next-generation ultra-thin endoscope, it would be possible to approach the periphery of the bronchus responsible for pneumothorax from within the bronchi and inject fibrin glue precisely into the air leak site (e.g., bulla). This would allow for more reliable closure of pneumothorax without invasiveness to the body (avoiding surgical invasiveness), while minimizing the atelectasis area. However, this requires inserting an ultra-thin endoscope into the bronchoscope's forceps channel (approximately 1.7-3 mm in diameter), confirming the air leak site with the ultra-thin endoscope, and simultaneously placing the tip of a catheter for fibrin glue injection near that site and delivering two different fibrin glue solutions separately. No existing technology has been able to achieve this simultaneously. Furthermore, ultra-thin endoscopes lack a lens cleaning function, and during insertion, the lens adheres to the bronchial wall, resulting in poor visibility due to bronchial mucus and oil, making it difficult to obtain reliable and stable images.

[0012] In vitro experiments have revealed that, in order to effectively induce bronchial obstruction using fibrin glue, it is important to simultaneously inject both the fibrinogen solution and the thrombin solution of the fibrin glue.

[0013] To simultaneously inject both fibrinogen and thrombin solutions of fibrin glue under bronchoscopy, a double-lumen catheter is required. However, when using a standard double-lumen catheter consisting of a proximal lumen and a distal lumen, one lumen must pass through to allow the next-generation endoscope to pass through, which increases the diameter and prevents the catheter tip from reaching the distal part of the bronchi (bronchioles).

[0014] Therefore, in order to observe and identify the air leak site by reaching the peripheral part of the bronchi, which could not be reached by a bronchoscope, with a camera (endoscope), we have found that by combining a catheter that can be inserted into the forceps channel of a bronchoscope with an ultra-thin camera (endoscope), the camera (endoscope) can reach the peripheral part of the bronchi and reliably obtain stable images. Furthermore, after removing the ultra-thin camera (endoscope) from the catheter, another catheter (inner catheter) is inserted into the catheter (outer catheter), and the outer catheter of the two double-tube catheters is equipped with a drug injection adapter. By injecting either fibrinogen solution or thrombin solution into the drug injection adapter of the outer catheter and the inner catheter, respectively, the two solutions mix at the air leak site to form a fibrin glue preparation, thereby closing the air leak site, and thus completing the present invention.

[0015] Therefore, the present invention includes the following: [1] A device for closing air leaks, comprising a catheter that can be inserted into the forceps channel of a bronchoscope and is equipped with a drug injection adapter (hereinafter referred to as the "external catheter"), and an ultra-thin endoscope or internal catheter. [2] The air leak sealing device according to [1], wherein the drug injection adapter has a structure that includes two lumens and an opening therefor, by providing a separate lumen branched from the lumen of the outer catheter. [3] The air leak closure device according to [2], wherein a stopper is attached to the opening of the drug injection adapter and a valve is installed near the opening of the outer catheter on the side into which the ultra-thin endoscope or inner catheter is inserted. [4] An air leak closure device according to any one of [1] to [3], wherein the diameters of the bronchoscope, the forceps channel of the bronchoscope, the outer catheter, and the ultra-thin endoscope or inner catheter are in the order of bronchoscope, forceps channel of the bronchoscope, outer catheter, and ultra-thin endoscope or inner catheter, the outer catheter is positioned within the inner wall of the forceps channel of the bronchoscope, and the ultra-thin endoscope or inner catheter is positioned within the inner wall of the outer catheter. [5] The diameter of the bronchoscope is 3 to 6 mm, the diameter of the forceps channel of the bronchoscope is 1.7 to 3 mm, the diameter of the outer catheter is 1.67 mm or more and less than 3 mm, the diameter of the ultra-thin endoscope is 0.5 mm or more and less than 1 mm, and the diameter of the inner catheter is less than 1 mm. The air leakage closure device according to [4]. [6] A catheter that can be inserted into the forceps channel of a bronchoscope, the catheter having a chemical solution injection adapter (hereinafter referred to as an "outer catheter"), and an inner catheter that can be inserted inside the outer catheter. The air leakage closure device. [7] The chemical solution injection adapter has a structure including a lumen branched into two by providing a separate lumen branched from the lumen of the outer catheter, and a release port thereof. The air leakage closure device according to [6]. [8] A plug is attached to the release port of the chemical solution injection adapter, and a valve is installed near the release port of the outer catheter on the side where the inner catheter is inserted. The air leakage closure device according to [7]. [9] The diameters of the bronchoscope, the forceps channel of the bronchoscope, the outer catheter, and the inner catheter are in order of increasing size, the outer catheter is disposed within the inner wall of the forceps channel of the bronchoscope, and the inner catheter is disposed within the inner wall of the outer catheter. The air leakage closure device according to any one of [6] to [8].

[10] The diameter of the bronchoscope is 3 to 6 mm, the diameter of the forceps channel of the bronchoscope is 1.7 to 3 mm, the diameter of the outer catheter is 1.67 mm or more and less than 3 mm, and the diameter of the inner catheter is less than 1 mm. The air leakage closure device according to [9].

[11] The outer catheter and the inner catheter form a double-lumen catheter shape. The air leakage closure device according to any one of [6] to

[10] .

[12] The outer catheter and the inner catheter form a coaxial type double-lumen catheter. The air leakage closure device according to

[11] .

[13] A double-lumen catheter characterized in that the tips of the outer catheter and the inner catheter are aligned. The air leakage closure device according to

[11] or

[12] .

[14] A device for closing air leakage as described in any one of [6] to

[13] , which is used to close air leakage with a biological tissue adhesive, and the biological tissue adhesive is delivered to the air leakage site through an outer catheter and an inner catheter.

[15] A device for closing air leakage as described in

[14] , wherein the biological tissue adhesive is a fibrin glue preparation, and the fibrin glue preparation consists of a fibrinogen solution and a thrombin solution.

[16] A device for closing air leakage as described in

[15] , wherein each of the fibrinogen solution and the thrombin solution of the fibrin glue preparation is delivered to the air leakage site through either the outer catheter or the inner catheter from separate syringes, and fibrin glue is formed at the air leakage site to close the air leakage.

Advantages of the Invention

[0016] So far, in a bronchoscope with forceps holes large enough to insert a catheter capable of simultaneously injecting both solutions of fibrin glue, an ultra-thin diameter camera (endoscope) can reach the peripheral part of the bronchus of 3 mm or less that could not be penetrated before, and the air leakage site can be reliably and stably observed and identified. Even in the peripheral part of the bronchus of 3 mm or less, air leakage closure treatment can be performed. Furthermore, by using a coaxial type double-lumen catheter, the fibrinogen solution and the thrombin solution of the fibrin glue preparation can be simultaneously delivered to the air leakage site, and fibrin glue can be effectively formed at the air leakage site to reliably close the air leakage. Additionally, in a coaxial type double-lumen catheter, by structuring the end of the outer catheter on the side where the chemical solution is injected, which is opposite to the side inserted into the forceps hole of the bronchoscope, with a chemical solution injection adapter, the fibrinogen solution or the thrombin solution of the fibrin glue preparation can be easily injected into the outer catheter.

Brief Description of the Drawings

[0017] [Figure 1]The diagram shows a schematic view of the air leak closure device of the present invention as seen from the side of insertion into the forceps channel of a bronchoscope, in two embodiments: (A) for observing and identifying the air leak site in the peripheral part of the bronchus, and (B) for applying a fibrin glue preparation to the air leak site. The bronchoscope 1 (approximately 4 mm in diameter) is equipped with a forceps channel 2 (a continuous cavity from the entrance to the end), and an outer catheter 4 (approximately 2 mm in diameter) is inserted into the forceps channel 2. In embodiment A, an ultra-thin endoscope 5 (1 mm in diameter) is inserted into the outer catheter 4. In embodiment B, an inner catheter 6 (less than 1 mm in diameter) is inserted into the outer catheter 4. 1: Bronchoscope (approximately 4 mm in diameter); 2: Forceps channel (a continuous cavity from the entrance to the end); 3: Camera; 4: Catheter (approximately 2 mm in diameter); 5: Ultra-thin endoscope (1 mm in diameter); 6: Inner catheter (less than 1 mm in diameter). [Figure 2] This is a photograph showing an example of a multi-lumen catheter. Reference URL: https: / / www.kango-roo.com / mv / 272 / (Accessed December 1, 2020) [Figure 3] This is a schematic diagram showing the relationship between each component of the air leak closure device of the present invention and the trachea, bronchi, bronchioles, and terminal bronchioles. [Figure 4] This is a photograph showing a computed tomography image of a miniature pig's lung one week after treatment for air leaks. [Figure 5] This is a photograph showing a sample of lung tissue from a miniature pig. [Figure 6] This schematic diagram shows that the outer catheter on the side where the drug solution is injected, opposite to the side inserted into the forceps channel of the bronchoscope, has a structure equipped with a drug solution injection adapter. A: Rubber stopper on the drug solution injection adapter side. B: Anti-reflux valve. C: Release port of the catheter on the side where the ultra-thin endoscope or inner catheter is inserted. [Figure 7] This is a schematic diagram showing the lumen portion of the drug injection adapter of the external catheter on the side where the drug solution is injected, opposite to the side inserted into the forceps channel of the bronchoscope. A: Rubber stopper on the drug injection adapter side; B: Anti-reflux valve. The shaded area is the lumen portion. [Figure 8]This is a schematic diagram showing an ultra-thin endoscope inserted into the outer catheter on the side opposite to the side inserted into the forceps channel of a bronchoscope, where the drug solution is injected. A: Rubber stopper on the drug solution injection adapter side; B: Anti-reflux valve; D: Ultra-thin endoscope. [Figure 9] Figure 8 is a schematic diagram illustrating the state when performing lens cleaning / leak testing of the ultra-thin endoscope lens by water injection / air injection through the opening of the drug injection adapter of the external catheter with the ultra-thin endoscope inserted. A: Lens cleaning / air injection of the ultra-thin endoscope lens by water injection; B: Ultra-thin endoscope. The shaded areas are lines through which gas / liquid passes. [Figure 10] This is a schematic diagram illustrating the state when switching from a single-lumen catheter to a double-lumen catheter in the air leak closure device of the present invention. It shows the state after withdrawing the ultra-thin endoscope from the outer catheter and inserting the inner catheter into the outer catheter. The upper diagram shows the state in which the inner catheter is being inserted into the outer catheter, and the lower diagram shows the state after the inner catheter has been inserted into the outer catheter. A: Inner catheter. [Figure 11] Figure 10 is a schematic diagram showing the state of fibrin glue application in an air leak closure device with the inner catheter inserted into the outer catheter. It shows the case where thrombin solution is injected into the inner catheter and fibrinogen solution is injected into the drug injection adapter of the outer catheter. A: Fibrinogen solution; B: Thrombin solution. [Modes for carrying out the invention]

[0018] In a first embodiment, the present invention provides an air leak closure device comprising a catheter insertable into the forceps channel of a bronchoscope and equipped with a drug injection adapter (hereinafter also referred to as the "external catheter") and an ultra-thin endoscope. The device of the present invention in this embodiment is used to identify the bronchus responsible for the air leak and to observe the area near its terminal. In this embodiment, the ultra-thin endoscope is placed inside the catheter and used in a single lumen configuration. In the air leak closure device of the present invention, the diameters of the bronchoscope, the forceps channel of the bronchoscope, the catheter equipped with the drug injection adapter, and the ultra-thin endoscope increase in the order of bronchoscope, forceps channel of the bronchoscope, catheter equipped with drug injection adapter, and ultra-thin endoscope, with the catheter positioned within the inner wall of the forceps channel of the bronchoscope and the ultra-thin endoscope positioned within the inner wall of the catheter. The air leak closure device in this embodiment is used to access the air leak at the terminal of the bronchus. In this configuration, to avoid hindering lung expansion, a valve (anti-reflux valve) is installed at the opening on the side into which the ultra-thin endoscope is inserted, and a stopper (rubber stopper) is attached to the opening on the other end of the drug injection adapter to prevent air leakage. These also have the effect of preventing the inflow of mucus and other substances from the bronchi into the catheter. The position where the valve is installed is not particularly limited as long as it is near the opening on the side into which the ultra-thin endoscope is inserted, but it can be approximately 5mm to 30mm from the opening. Furthermore, with this type of air leak closure device, with the ultra-thin endoscope inserted into the outer catheter, lens cleaning of the ultra-thin endoscope by water injection and leak testing by air injection can be performed from the opening of the drug injection adapter. Water injection and air injection can be done from sources other than syringes. The main purpose of water injection is to clean the ultra-thin endoscope. When the field of view is impaired by mucus and oil in the bronchi, water injection can improve the fogging of the ultra-thin endoscope lens. Air insufflation is primarily used to identify air leak points and to perform leak tests after injection of biotissue adhesives such as fibrin glue. Air insufflation can also be used for aspiration if the injection site for biotissue adhesives such as fibrin glue is expected to be hindered by a large amount of mucus or blood. However, since this can lead to contamination of the catheter, thorough irrigation of the lumen is necessary after use for aspiration. The installed anti-reflux valve is also effective in these operations.In the air leak closure device of the present invention, when using fibrin glue, it is preferable that the diameter of the tip of the forceps channel of the bronchoscope is 1.7 to 3 mm (the outer diameter of the tip of the bronchoscope having the forceps channel is approximately 3 mm to 6 mm), the diameter of the catheter is 1.67 mm or more and less than 3 mm, and the diameter of the ultra-thin endoscope is 0.5 mm or more and less than 1 mm, from the viewpoint of resistance to drug flow.

[0019] In a second embodiment, the present invention provides an air leak closure device, which includes a double-tube catheter insertable into the forceps channel of a bronchoscope and equipped with a drug injection adapter. The air leak closure device in this embodiment is used to close the air leak site with a biotissue adhesive after identifying the bronchus responsible for the air leak. That is, the air leak closure device in the second embodiment is used in the air leak closure device of the first embodiment to deliver the biotissue adhesive to the air leak site through the catheter after the ultra-thin endoscope has been removed from the catheter. Here, the catheter is preferably a coaxial double-lumen catheter in which the inner catheter is positioned inside the outer catheter. In the air leak closure device of the first embodiment, the catheter is a single lumen and also serves as the outer tube of the ultra-thin endoscope, used for the purpose of placing the tip at the target site. However, if both solutions of fibrin glue are injected into a single lumen, coagulation will progress within the catheter lumen, causing the catheter to become occluded. To avoid this, the catheter needs to have two or more lumens, but at the same time, miniaturization must be achieved for the intended use. This combination is made possible by inserting an even smaller diameter catheter (inner catheter) into the catheter (outer catheter) after withdrawing the ultra-thin endoscope, thereby creating a double-lumen catheter. Preferably, the inner catheter has a diameter of less than 1 mm. In such a double-lumen catheter, drug solution can be injected into the inner catheter without any particular problem, but injecting drug solution into the outer catheter is difficult because it involves injecting into the narrow space between the inside of the outer catheter and the outside of the inner catheter, making effective drug injection difficult. Therefore, in this invention, to facilitate drug injection into the outer catheter, a structure called a "drug injection adapter" is provided on the side of the outer catheter where the drug solution is injected (the side opposite to the side inserted into the bronchoscope's forceps channel). This "drug injection adapter" has a structure with two branched lumens by providing a separate lumen branched from the original catheter lumen, and it has an opening and a lumen that leads from the opening into the inside of the outer catheter. The drug solution is injected from the opening through the lumen into the inside of the outer catheter.By providing a structure called a "drug injection adapter" on the outer catheter in this way, it becomes easy to inject two types of drugs separately into the outer catheter and the inner catheter without them mixing. Figure 11 shows an example where thrombin solution is injected into the inner catheter and fibrinogen solution is injected into the drug injection adapter of the outer catheter, but it is also possible to inject fibrinogen solution into the inner catheter and thrombin solution into the drug injection adapter of the outer catheter. A fibrin glue preparation consisting of fibrinogen solution and thrombin solution is preferred as the biotissue adhesive. The fibrinogen solution and thrombin solution of the fibrin glue preparation are each delivered separately to the air leak site from each lumen of the double lumen, where fibrin glue is formed and the air leak is closed.

[0020] Bronchoscopy: The air leak closure device of the present invention includes a catheter (external catheter) that can be inserted into the forceps channel of a bronchoscope and is equipped with a drug injection adapter, and an ultra-thin endoscope. Of these, the bronchoscope (electronic scope or fiberscope) is used to observe the inside of the bronchi, collect tissue and cells to make an accurate diagnosis (bronchoscopy), and treat diseases that narrow the bronchi (bronchoscopy). A bronchoscope is a thin, flexible tube with a diameter of 3 to 6 mm that is used to look inside the bronchi, which are connected to the lungs deep in the chest. Bronchoscopes usually have a consistent hole called a forceps channel, and various treatment instruments can be inserted through the entrance of the forceps channel (forceps opening) and brought out from the tip of the forceps channel of the endoscope. Various treatment instruments have been developed, and it is said that there are about 500 different types. A bronchoscope has the same structure as a gastroscopy camera, but it is much thinner than a gastroscopy camera. Bronchoscopy is a procedure performed to accurately diagnose respiratory diseases, such as those affecting the lungs or bronchi, using a bronchoscope (bronchofiberscope). It involves inserting the bronchoscope (bronchofiberscope) into the trachea and bronchi through the mouth or nose and throat to observe the lumen and collect specimens such as tissue, cells, and secretions.

[0021] Although bronchoscopes (bronchofiberscopes) are much thinner than gastrocameras, those equipped with channels for inserting instruments such as catheters have a tip outer diameter of 3-6 mm, making them inaccessible to relatively narrow bronchi, bronchioles, and terminal bronchioles. Therefore, in this invention, observation and treatment near the terminal bronchus are not performed using the camera of the bronchoscope (bronchofiberscope) itself, but rather using a catheter placed in the forceps channel of the bronchoscope, and further using an ultra-thin endoscope placed inside the catheter.

[0022] catheter: A catheter is a flexible tube used in medical procedures. It is inserted into body cavities such as the pleural cavity and abdominal cavity, tubular areas such as the digestive tract and ureters, or blood vessels, and is used for draining bodily fluids, infusion of medications or contrast agents, and intravenous administration. During catheterization, a guidewire may be used in conjunction with the catheter. In such cases, the guidewire leads the way, and the catheter is guided by the guidewire.

[0023] Catheters include angiography catheters (including microcatheters), balloon catheters, cardiac catheters (used for cardiac catheterization and endovascular treatment (catheter therapy)), pulmonary artery catheters (Swan-Ganz catheters), cerebrovascular catheters, indwelling vascular catheters, suction catheters (drains), and endoscopic dispensing tubes, all of which can be used in the present invention.

[0024] In this invention, any catheter can be used as long as it can be placed in the forceps channel of a bronchoscope (bronchofiberscope) and an ultra-thin endoscope can be placed within its inner wall; however, a double-lumen catheter is preferred. Catheters include single-lumen catheters with one administration route, double-lumen catheters with two routes, triple-lumen catheters with three routes, and quad-lumen catheters with four routes. Each administration route of catheters with two or more lumens is independent, and drug solutions do not mix within the catheter. In this invention, the first embodiment uses a single-lumen catheter with one administration route, and the second embodiment uses a double-lumen catheter with two administration routes. However, when using a double-lumen catheter, a double-lumen catheter consisting of a normal proximal lumen and a distal lumen requires the passage of a next-generation endoscope through one of the lumens, resulting in a larger diameter and preventing the catheter tip from reaching the peripheral part of the bronchus (bronchioles). Therefore, in the second embodiment of this invention, it is particularly preferable to use a coaxial type double-lumen catheter. In other words, a coaxial double-lumen catheter can be created by passing a smaller-diameter catheter (for example, a 1mm diameter catheter) inside a larger-diameter catheter (for example, a 2mm diameter catheter) of two catheters with different diameters. For example, a catheter with an outer diameter of less than 1.0mm can be placed inside a catheter with an inner diameter of more than 1.0mm. By configuring such a coaxial double-lumen catheter, fibrinogen solution or thrombin solution can be separately passed through the larger-diameter catheter (hereinafter referred to as the "outer catheter") and the smaller-diameter catheter (hereinafter referred to as the "inner catheter"), and both solutions can be simultaneously injected into the air leak site to pinpoint occlusion of the air leak site with fibrin glue. To place the catheter inside a bronchoscope (bronchofiberscope), for example, the catheter can be passed through the forceps channel, which is an access port for passing bronchoscope instruments.Furthermore, as described below, the external catheter on the side opposite to the side inserted into the bronchoscope's forceps channel, which is used to inject the drug solution, has a structure equipped with a "drug solution injection adapter."

[0025] Ultra-thin endoscope (camera): In this specification, an ultra-thin endoscope refers to an endoscope whose diameter is significantly smaller than that of a normal endoscope. Specifically, it generally includes endoscopes with a diameter of 0.5 mm or more and less than 1 mm, but it does not have to be within this diameter range as long as it can be placed inside the outer catheter.

[0026] In the air leak closure device of the present invention, an ultra-thin endoscope is placed inside a catheter, and the catheter is placed inside a bronchoscope. Because the ultra-thin endoscope has an extremely small diameter (0.5 mm or more, but less than 1 mm), it can reach the peripheral part of the bronchus that cannot be penetrated with a normal bronchoscope, making it possible to identify the air leak site in the peripheral part of the bronchus. As the ultra-thin endoscope, an improved version of the 1.8 mm diameter intravascular endoscope developed by Panasonic i-PRO Sensing Solutions Co., Ltd., such as the ultra-thin endoscope (1 mm diameter) or the ultra-thin intravascular endoscope (0.49 mm) (Olivas Co., Ltd.) can be used, but is not limited to these.

[0027] Drug injection adapter: In this specification, a drug injection adapter refers to a catheter having a structure with two branched lumens, provided at the end opposite to the end inserted into the bronchus, by branching off from the lumen of the original catheter (see Figures 6-11). A drug injection adapter having such a structure provides an opening from a newly provided separate lumen, separate from the opening from the lumen of the original catheter. In the first embodiment of the present invention, an ultra-thin endoscope is inserted into the opening from the lumen of the original catheter, and in the second embodiment of the present invention, an internal catheter is inserted. A backflow prevention valve is installed at the opening from the lumen of the original catheter to avoid hindering lung expansion, and a rubber stopper is attached to the newly provided separate lumen to prevent air leakage, also to avoid hindering lung expansion. These backflow prevention valves and rubber stoppers have the effect of preventing the inflow of mucus and other substances from the bronchi into the catheter. In the first embodiment of the air leak closure device, with an ultra-thin endoscope inserted into the catheter, lens cleaning of the ultra-thin endoscope by water injection and leak testing by air injection can be performed through the opening of the drug injection adapter. Water and air injection can be performed from sources other than syringes. The main purpose of water injection is to clean the ultra-thin endoscope. When the field of view is impaired by mucus or oil in the bronchi, water injection can improve lens fogging. Air injection is mainly for identifying air leak points and for leak testing after injection of biotissue adhesives such as fibrin glue. Air injection can also be used for aspiration if the target site for injection of biotissue adhesives such as fibrin glue is expected to have a large amount of mucus or blood, which may hinder embolization. However, since this can lead to contamination of the catheter, thorough rinsing of the lumen is necessary after use for aspiration. The installed anti-reflux valve is also effective in these operations.

[0028] Air leak sealing devices: The air leak closure device of the present invention includes a catheter equipped with a drug injection adapter that can be inserted into the forceps channel of a bronchoscope, an ultra-thin endoscope, and an internal catheter. The ultra-thin endoscope is included in the kit if a disposable product is used, but may not be included if a reusable product is used. In some embodiments, the contents of the kit are sterile and sealed.

[0029] Biomedical tissue adhesive: The air leak closure device of the present invention is used to close air leaks in the bronchi using a biotissue adhesive. Biotissue adhesives are agents used for tissue adhesion and closure, and include sheet-type tissue adhesives and liquid tissue adhesives, but in the present invention, liquid tissue adhesives, in particular fibrin glue formulations, are preferred. Specifically, Volheel® tissue adhesion formulations can be used. The fibrin glue consists of four components: (i) freeze-dried fibrinogen powder, (ii) fibrinogen solution (containing aprotinin), (iii) freeze-dried thrombin powder, and (iv) thrombin solution (containing calcium chloride). Solution A is prepared by dissolving (i) in (ii), and solution B is prepared by dissolving (iii) in (iv). By delivering and mixing solutions A and B at the air leak site in the bronchi, adhesion and closure of the air leak site can be achieved.

[0030] The present invention will be described in detail below with reference to examples, but the present invention is not limited in any way by these examples.

[0031] Materials, equipment, methods, etc.: As the fibrin glue preparation, Volheal® Tissue Adhesion Preparation 3 mL was used. An ultra-thin endoscope (1 mm diameter), an improved version of the 1.8 mm diameter intravascular endoscope developed by Panasonic i-PRO Sensing Solutions Co., Ltd., was inserted into the bronchus through the forceps channel, which is an access port for passing instruments of a thin bronchoscope. [Examples]

[0032] Configuration of an air leak closure device combining an ultra-thin endoscope, a thin bronchoscope, and a catheter: Figure 1 shows the configuration of the air leak closure device of the present invention. A 2 mm diameter catheter is passed through the forceps channel, which is the access port for the treatment instrument of a narrow bronchoscope with a diameter of 4 mm, and an ultra-thin endoscope with a diameter of 1 mm is passed inside this catheter. This configuration is inserted into the bronchus to reliably and stably observe and identify the site of the air leak.

[0033] The tip of a 2mm diameter catheter is fixed at the air leak site, and the ultra-thin endoscope is withdrawn from the catheter. A 1mm diameter catheter is passed inside the 2mm diameter catheter to reconstruct a double-lumen catheter. At this time, the tips of both the 2mm and 1mm diameter catheters are aligned. Fibrin glue solution A is injected into the 2mm diameter catheter, and fibrin glue solution B is injected into the 1mm diameter catheter. This allows solutions A and B to mix at the tips of both catheters, forming fibrin. [Examples]

[0034] Construction of a double-lumen catheter for injecting fibrin glue preparations: To inject the fibrin glue preparation, a 2mm diameter catheter was passed through the forceps channel, which is the access port for inserting the instrument of a 4mm diameter bronchoscope. Another 1mm diameter catheter was then passed inside this to create a double-lumen catheter. In constructing the double-lumen catheter, the optimal combination of a 2mm diameter catheter and a 1mm diameter catheter was compared and investigated.

[0035] Insertion test: We evaluated whether a 120cm length of catheter could be easily inserted along the curve of a 4mm diameter bronchoscope with a 180° upward curvature, without the use of instruments or other aids, and whether kinking (catheter bending) occurred after five insertions and withdrawals. The results are summarized in Table 1. For numbers 1-14 and 19, the entire 120cm could be inserted without kinking. However, for number 15, the material was too rigid, making insertion difficult and resulting in kinking. For numbers 16-18, the material was too soft, making insertion difficult and resulting in kinking. Additionally, for numbers 20-25, the material was prone to bending, making insertion difficult and resulting in kinking.

[0036] Table 1 TIFF0007831752000001.tif243166 [Examples]

[0037] Fluid flow test of the internal catheter: In designing the double-lumen catheter, catheters with an outer diameter of less than 1.0 mm were designated as inner catheters, and those with an inner diameter greater than 1.0 mm were designated as outer catheters. As a result, the candidate inner catheters were numbers 4, 5, 13, and 14, and the candidate outer catheters were numbers 6, 7, and 8. First, both fibrin glue solutions were passed through the candidate inner catheters, and their viscosity was measured. (Note that catheter number 6 had the largest lumen that met the requirements for an outer tube, and its inner diameter was 1.35 mm, so this test was only performed on tubes with an outer diameter smaller than that.) Specifically, the drug solution was filled to 50% of a 3 mL syringe, fixed to a push-pull gauge and electric stand, and then the test speed of the electric stand was set to 50 mm / min. The plunger of the syringe was pushed to pass the solution through the catheter, and the maximum pushing force was recorded (n=1). If the pushing force exceeded 20 Newtons (hereinafter, "N"), the test was immediately stopped and recorded as being outside the acceptable range.

[0038] The results of the fluid flow test are summarized in Table 2. For the fibrinogen solution, the pressing force exceeded 20N in all cases, but for the thrombin solution, fluid flow was possible in cases 4, 5, and 13. Table 2: Inner catheter TIFF0007831752000002.tif38160 [Examples]

[0039] Fluid flow test using a double-lumen catheter: Based on the results of Example 3, it was considered desirable to use the inner catheter for injecting thrombin solution. Therefore, thrombin solution was passed through the inner catheter and fibrinogen solution through the outer catheter, and the maximum pressing force due to the passage of each solution was recorded in the same manner as in Example 3 (n=1).

[0040] The results of the fluid flow test are summarized in Table 3. For the fibrinogen solution, the pressing force did not exceed 20 N in any case, and for the thrombin solution, fluid flow was possible in all cases from A to E. Table 3: Combinations of external and internal catheters TIFF0007831752000003.tif49170 [Examples]

[0041] Operability evaluation test: For the combinations that yielded favorable results in Example 4, an operability evaluation test was conducted by a specialist physician. Each evaluation item was assessed on a three-point scale (○: operation can be performed without stress, △: operation itself can be performed, ×: the intended operation cannot be performed). The results of the operability evaluation test are summarized in Table 4. Table 4 TIFF0007831752000004.tif66162 [Examples]

[0042] Feasibility test: Feasibility tests were performed on options A through E, which were evaluated in Example 5. An artificial air leak was created in a pig lung using scissors, and 3 mL each of fibrinogen solution and thrombin solution were simultaneously injected using a double-lumen catheter. Air leak closure was possible with all catheters. Among A through E, option A was considered the most preferable. [Examples]

[0043] Fabrication of a drug infusion adapter using a double-lumen catheter: In the double-lumen catheter of the present invention, drug solution can be injected into the inner catheter without any particular problem. However, injecting drug solution into the outer catheter is difficult because it is injected into the narrow space occupied by the inside of the outer catheter and the outside of the inner catheter. Therefore, in order to facilitate the injection of drug solution into the outer catheter, the present invention provides a structure called a "drug solution injection adapter" on the side of the outer catheter into which the drug solution is injected (the side opposite to the side inserted into the forceps channel of the bronchoscope). This "drug solution injection adapter" has a structure with two branched lumens by providing a separate lumen that branches off from the original catheter lumen, and has an opening and a lumen that leads from the opening to the inside of the outer catheter. The drug solution is injected from the opening through the lumen into the inside of the outer catheter. By providing this structure called a "drug solution injection adapter" on the outer catheter, it becomes easy to inject two types of drug solutions into the outer catheter and the inner catheter separately without them mixing.

[0044] Figures 6-11 show schematic diagrams of the drug injection adapter. Figure 6 shows an overall view of the drug injection adapter of the external catheter. The shaded area shown in Figure 7 is the lumen. Figure 8 shows the state with the ultra-thin endoscope inserted, and in this state, the air leak area at the terminal of the bronchus is approached. At this time, to avoid hindering lung expansion, a backflow prevention valve (B) is installed at the opening on the ultra-thin endoscope side, and a rubber stopper (A) is attached to the opening of the drug injection adapter to prevent degassing. These also have the effect of preventing the inflow of mucus and other substances from the bronchus into the catheter. Figure 9 is a schematic diagram of water and air being supplied from the opening of the drug injection adapter when the ultra-thin endoscope is inserted. The lines through which gas and liquid pass are shown as shaded areas. Note that water and air can be supplied from sources other than syringes. The main purpose of water supply is to clean the ultra-thin endoscope. When the view is obscured by mucus or oil in the bronchi, water insufflation improves the fogging of the lens of the ultra-thin endoscope. Air insufflation is primarily used to identify air leak points and to perform leak tests after injecting embolic agents such as fibrin glue. It can also be used for aspiration if the target site for injection of embolic agents such as fibrin glue is expected to be hindered by a large amount of mucus or blood. However, since this can lead to contamination of the catheter, thorough rinsing of the lumen is necessary after use for aspiration. The installed anti-reflux valve is effective in these operations as well. Figure 10 shows the process of switching from a single-lumen to a double-lumen catheter. In single-lumen mode, it also serves as the outer sheath of the ultra-thin endoscope and is used to place the tip at the target site. However, if both lumens of fibrin glue are injected into a single lumen, coagulation will progress within the catheter lumen, causing the catheter to become blocked. To avoid this, the catheter needs to have two or more lumens, but at the same time, miniaturization must be achieved for the intended use. To achieve both, as shown in Figure 10, after withdrawing the ultra-thin endoscope, it is replaced with another catheter (inner catheter), creating a double-lumen catheter with the original catheter (outer catheter) and the inner catheter, thus achieving the above objective. Figure 11 is a schematic diagram showing the state when applying fibrin glue to the drug injection adapter with the inner catheter inserted as shown in Figure 10.One syringe of fibrin glue (fibrinogen solution in Example 8 below) can be inserted into the drug injection adapter or connected via a Luer lock. On the other hand, the other syringe of fibrin glue (thrombin solution in Example 8 below) can be inserted into the inner catheter or connected via a Luer lock. Simultaneous injection of both solutions is necessary for embolization of the bronchial tube responsible for air leaks, so the syringes of both fibrin glue solutions are designed to be placed parallel to each other, with the heights of both syringes aligned after insertion of the inner catheter. [Examples]

[0045] Treatment of air leaks using the air leak sealing device of the present invention: Using the double-lumen catheter: I (outer catheter: Chuko Kasei Kogyo Co., Ltd. AWG16, inner catheter: Flon Kogyo Co., Ltd. F-8007-02) found in Examples 4-6 and the drug injection adapter described in Example 7, we conducted verification experiments to determine whether air leak treatment was actually possible. Miniature pigs were selected as the animal model for air leaks. First, after general anesthesia was administered to the miniature pigs, a U-shaped incision was made in their chests with a scalpel. A 4mm diameter bronchoscope was inserted through the mouth of the miniature pig and inserted as far as possible. A catheter with a diameter of approximately 2mm was passed through the forceps channel of the bronchoscope, and a 1mm diameter ultra-thin endoscope (Panasonic i-PRO Sensing Solutions Co., Ltd.) was passed inside this catheter. This configuration was inserted into the bronchus and further advanced toward the surface of the lung, until the tip of the ultra-thin endoscope reached near the surface of the pleura. Using a thin endoscope, the light from the lung surface was transmitted through the tissue, which was grasped with forceps. A pleural defect of approximately 5 mm was then created using a scalpel, and a large air bubble the size of a salmon roe emerged from the pleural defect site. After fixing a catheter with a diameter of approximately 2 mm, the thin endoscope was removed from the outer tube of the catheter, and an inner catheter with a diameter of approximately 1 mm was inserted in its place, creating a double-lumen catheter. A fibrin glue injection device consisting of two syringes was attached to the opposite end of the double-lumen catheter. Fibrinogen solution was passed through the outer catheter, and thrombin solution through the inner catheter, and 3 mL of each solution was injected simultaneously. The cessation of the lung fistula was visually confirmed. The miniature pig was closed and extubated. After the miniature pig woke up, spontaneous breathing was confirmed, and it was observed for one week, but no respiratory abnormalities were observed.

[0046] One week after the procedure, computed tomography was performed on the miniature pig under general anesthesia to check the lung expansion, and good lung expansion was observed (Figure 4). Furthermore, thoracotomy was performed to confirm that there was no leakage. After euthanasia under anesthesia, a partial lung resection was performed around the point where a pleural defect of approximately 5 mm had been created, and the lung was fixed with formalin to prepare a specimen. The presence of fibrin glue in the alveoli was confirmed (Figure 5). [Industrial applicability]

[0047] The air leak closure device according to the present invention can be used to close air leaks within the pleural cavity. In particular, the air leak closure device according to the present invention can be used in pneumothorax treatment methods by reaching an endoscope to the distal part of the bronchus to observe and identify the site of the air leak and effectively forming a fibrin glue preparation at the site of the air leak.

Claims

1. A device for closing air leaks, comprising a catheter that can be inserted into the forceps channel of a bronchoscope and is equipped with a drug injection adapter (hereinafter referred to as the "outer catheter"), and an ultra-thin endoscope or inner catheter that can be inserted into the outer catheter, It features a configuration that allows switching between a single-lumen configuration with an ultra-thin endoscope inserted into the outer catheter and a double-lumen configuration with an inner catheter inserted into the outer catheter. The bronchoscope diameter is 3-6 mm, the bronchoscope forceps channel diameter is 1.7-3 mm, the outer catheter diameter is 1.67 mm or more and less than 3 mm, the ultra-thin endoscope diameter is 0.5 mm or more and less than 1 mm, and the inner catheter diameter is less than 1 mm. Here, The aforementioned air leak sealing device is used to seal the air leak with a biotissue adhesive, and the biotissue adhesive is delivered to the air leak site through an outer catheter and an inner catheter. The biological tissue adhesive is a fibrin glue preparation, and the fibrin glue preparation consists of fibrinogen solution and thrombin solution. The fibrin glue preparations, fibrinogen solution and thrombin solution, are each delivered to the air leak site from separate syringes through either an outer catheter or an inner catheter. The inner catheter is used for injecting thrombin solution, and the outer catheter is used for injecting fibrinogen solution. A device for sealing air leaks.

2. The air leak sealing device according to claim 1, wherein the drug injection adapter has a structure that includes two lumens, each branched by providing a separate lumen branching off from the lumen of the outer catheter, and an outlet for that lumen.

3. The air leak closure device according to claim 2, wherein a stopper is attached to the opening of the drug injection adapter, and a valve is installed near the opening of the outer catheter on the side into which the ultra-thin endoscope or inner catheter is inserted.

4. An air leak closure device according to any one of claims 1 to 3, wherein the diameters of the bronchoscope, the forceps channel of the bronchoscope, the outer catheter, and the ultra-thin endoscope or inner catheter are progressively larger in the order of bronchoscope, forceps channel of the bronchoscope, outer catheter, and ultra-thin endoscope or inner catheter, the outer catheter is positioned within the inner wall of the forceps channel of the bronchoscope, and the ultra-thin endoscope or inner catheter is positioned within the inner wall of the outer catheter.

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