JP2000005316A - Nitrogen monoxide supplying device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a device selectively lowering hemal resistance (blood pressure) at a specific part with minimum influence to the hemal resistance at the other parts. SOLUTION: This supplying device 1 is a conductor with a gas path 2 allowing gas to flow through in its lumen as a communicating means for supplying nitrogen monoxide or gas containing nitrogen monoxide into a living body from the outside of the living body, and a gas supplying part 3 is disposed at a part of the conductor. Then, the part 3 an air-permeable uniform film preventing the transmission of bubbles is disposed at a gas transmitting cross section communicating with the external surface of the conductor via the path 2.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a supply of nitric oxide for locally introducing nitric oxide or a gas containing nitric oxide into a body to relax vascular smooth muscle cells and to improve vascular resistance in a specific portion. About the system.

[0002]

2. Description of the Related Art If for some reason the lumen of the pulmonary artery is narrowed and the flow of blood flowing into the lungs is impaired, sufficient oxygenation of the blood cannot be performed, resulting in hypoxemia or heart failure. Blood retention causes blood pressure to rise, which can cause pulmonary hypertension. In addition, pulmonary hypertension leads to cardiac hypertrophy and circulatory failure. Therefore, nitric oxide inhalation therapy has recently attracted attention for the treatment of pulmonary hypertension, which frequently occurs before and after open heart surgery. Since nitric oxide has the action of relaxing vascular smooth muscle, inhaling nitric oxide from the patient's airway to relax the pulmonary arteries without lowering body blood pressure, lowering pulmonary vascular resistance and reducing pulmonary hypertension. It will improve.

[0003] However, since nitric oxide is rapidly bound to hemoglobin in the body and inactivated, in order to reduce the resistance of a target blood vessel, a considerable amount of nitric oxide must be inhaled. However, this nitric oxide has high reactivity and is supplied to the human body together with oxygen, so that harmful nitrogen oxides may be generated.
Furthermore, the inhalation of nitric oxide also has a problem that the flow rate of blood vessels other than the target blood vessel is increased by reducing the blood flow resistance of the blood vessel other than the target blood vessel, and the flow rate to the target blood vessel is relatively decreased. For example, if the flow of one of the bifurcated blood vessels is poor, we want to increase the flow rate of the defective blood vessel. And increase blood flow in the blood vessel. As a result, if the amount of blood flowing into the branch portion is constant, the ratio of the amount of blood flowing to the side of the blood vessel having a poor flow may be reduced, which may have an adverse effect.

[0004]

SUMMARY OF THE INVENTION An object of the present invention is to improve the above-mentioned problems of the prior art. That is, first, the vascular resistance at a specific site is selectively reduced without affecting the vascular resistance (blood pressure) of another site as much as possible. Second, administration of nitric oxide or a gas containing nitric oxide (hereinafter, also referred to as nitric oxide or NO, including these) to the living body within a range where the effect is effective, that is, the blood vessel resistance at a specific site can be reduced. The aim is to reduce the amount as much as possible to suppress the harmful effects of nitrogen oxides on living organisms. Third, the effect of NO administration, such as a decrease in vascular resistance to a target site, is to be achieved quickly and reliably.

[0005]

According to the present invention, as a result of intensive studies for solving the above-mentioned problems, the present inventors have come up with a nitric oxide supply device having the following structure. That is, as a communication means for supplying nitric oxide or a nitric oxide-containing gas into the living body from outside the living body, a conduit having a gas passage through which gas can flow in the lumen, at least a part of the conduit. A gas supply section provided in the gas supply section, wherein a gas permeable uniform membrane for preventing gas bubbles from being transmitted is provided on a gas permeable cross section communicating from the gas passage to the outer surface of the conduit; Device. FIG. 1 conceptually illustrates a state in which a conduit serving as a gas communication means is inserted into a target blood vessel and NO and nitrogen are selectively supplied to a specific site.

[0006]

Next, various embodiments of the nitric oxide supply device of the present invention will be described. As mentioned above,
The nitric oxide supply device is a conduit having a gas passage through which a gas can flow. For the sake of convenience, in this conduit, the end on the side that is held at the target site in the living body is called the distal end, and the opposite end is called the proximal end. One end of the gas passage in a closed state is a conduit formed at a blind end. Also,
The conduit need not be entirely gas permeable, but must be NO gas permeable, at least at the tip located at the target site. Rather, if only the tip is formed to be gas permeable, selective N
It may be preferable in terms of O supply. As described above, in order to supply nitric oxide from the lumen of the conduit to a specific site in the living body, a gas supply unit through which gas can pass is provided in a part of the conduit.

If the gas supply section simply has good gas permeability, the gas permeability can be improved by adopting a porous structure. However, if NO permeating through the conduit flows out into the living body as air bubbles. Causes various undesirable effects on the living body. For this reason, a structure that does not allow NO bubbles to flow out of the gas supply unit is required. for that reason,
A part of the gas permeable cross section that communicates from the gas passage to the outer surface of the conduit may be provided with a gas permeable homogeneous membrane that prevents the transmission of air bubbles, or a gas permeable cross section if the gas permeable material is good. The whole may be formed of a homogeneous film. From the viewpoint of making it difficult for thrombus to adhere, the outer surface of the conduit that comes into contact with the living body is preferably formed of a homogeneous film. The gas permeable homogeneous membrane preferably has a gas permeability coefficient in the range of 0.01 to 10.0 m ² /s.Pa×10 ^-14 , and is preferably in the range of 0.20 to 0.
Those having a gas permeability coefficient in the range of 80 m ² /s.Pa×10 ^-14 are more preferable. Suitable examples of the material include a silicone resin, a polyurethane, and an ultra-thin polyolefin film. Alternatively, a uniform film may be formed by variously combining the above materials. The gas permeable cross section preferably has a structure having good gas permeability as long as bubbles can be prevented from flowing out of the lumen to the outside. For example, portions other than the homogeneous membrane may be porous. It goes without saying that a certain pressure resistance is required so that the conduit can withstand the gas pressure during NO supply.

Further, as shown in FIG. 1, a structure may be adopted in which the conduit can supply different gases. In FIG. 1, nitrogen and NO
Although oxygen is supplied, oxygen and NO can be supplied by providing a hollow fiber for supplying oxygen and a hollow fiber for supplying carbon monoxide at the tip. Then, a plurality of gas passages may be formed to supply two or more types of gas into the blood vessel, and a different gas may flow through each gas passage. In this case, antithrombotic treatment such as immobilization of heparin, an anticoagulant on the surface, may be performed on the lumen of the conduit so that the thrombus does not adhere to the outer surface in this case. Also, in order to increase the NO gas permeation area of the gas supply unit, a large number of ultrafine hollow fibers composed of a homogeneous membrane with one end closed at the tip of the conduit may be potted with an adhesive to provide a gas supply unit composed of hollow fibers. desirable. Also in this case, it is desirable that the outer surface of the hollow fiber be subjected to antithrombotic treatment. Further, as described above, an air bubble detection means such as an ultrasonic catheter for air bubble detection may be provided for ensuring safety such as prevention of air bubble outflow.

[0009]

EXAMPLE When a gas supply unit composed of hollow fibers (hereinafter also referred to as hollow fibers) is provided at the distal end of a conduit using hollow fibers of a commercially available membrane oxygenator, the required gas permeability is determined. It was confirmed whether or not the hollow fiber membrane had. Measurement of gas permeability of nitric oxide and nitrogen and oxygen using a silicone hollow fiber membrane oxygenator with a membrane area of 0.3 m2 and 3000 fibers clinically used for extracorporeal circulation of neonates Was done. FIG.
As shown in (1), one end of the oxygenator was closed to form a blind end, and gas was injected from the other gas inlet. The injection gas is pure oxygen, pure nitrogen, or a mixed gas of nitrogen and nitrogen monoxide, and has a NO concentration of 46.
A total of 5 types of 6 ppm, 203.0 ppm, and 2005 ppm were used. For the measurement of the NO concentration, a NO concentration measuring device (ECL-88US, manufactured by Yanaco) using a chemiluminescence method using ozone was used. The pressure resistance of the oxygenator used in this example is about 0.087 MPa.

The relationship between the pressure applied to the silicone fiber and the flow rate of gas permeating the fiber was examined for each gas. Oxygen is about twice the gas permeability of pure nitrogen, and NO has almost the same or slightly higher gas permeability than oxygen. From this result, it can be confirmed that the gas pressure and the flow rate flowing into the lumen of the conduit in order to supply NO to the living body may be approximately the same as those in the case of transmitting oxygen.

Next, how the gas permeability differs depending on the membrane material was examined. Using an oxygenator having a module specification as shown in Table 1, the gas permeability of each membrane of the oxygenator was measured. As shown in Table 1, the measurement was performed on three types of artificial lungs: a silicone hollow fiber having a homogeneous film as a whole, a silicone-coated polypropylene hollow fiber, and a hollow fiber consisting of a three-layer film of polyurethane-polyethylene-polyurethane. .

[0012]

[Table 1]

As described above, the gas permeability was measured by closing one of the fiber membranes of the artificial lung to form a blind end and injecting gas from the other, and measuring the gas flow rate and gas concentration passing through the fiber. The measurement of the NO concentration is also as described in the previous embodiment. Each of the three types of modules studied in this example (gas films assembled and inserted into the housing) had a pressure resistance of about 1 atm. Table 2 shows the permeation flow rate of each gas of oxygen, nitrogen and nitric oxide under a predetermined pressure in order to show the membrane permeability of the above three kinds of materials. As shown in Table 2, N in the silicone hollow fiber
The permeation flow rate of O was 48 ml / min, which was almost equal to the permeation flow rate of oxygen of 44.7 ml / min, and about twice the permeation flow rate of nitrogen of 20.3 ml / min. Also in other films, NO showed a higher permeation flow rate than nitrogen and oxygen.

[0014]

[Table 2]

Table 3 shows the calculated three types of gas permeability coefficients of the respective membrane materials. As a result, it was confirmed that each membrane had sufficient permeation performance required to supply NO gas to a specific part of the living body.

[0016]

[Table 3]

[0017]

As described in the problem to be solved by the invention, NO can be directly supplied to a specific site by using the nitric oxide supply device of the present invention. Can be lowered. Next, by selectively supplying NO to a specific portion, the NO supply amount can be reduced, and as a result, generation of nitrogen oxides can be suppressed. In addition, the effect of lowering the blood pressure and the like can be more promptly and more reliably provided by directly supplying the specific portion. Furthermore, since the effect at a limited site can be confirmed, an effective site of action in a living body can be specified.

[Brief description of the drawings]

FIG. 1 is a schematic view showing an example of a nitric oxide supply device of the present invention.

[Explanation of symbols]

 1. 1. Nitric oxide supply device (conduit) Gas passage 3. Gas supply section

Claims (11)

[Claims] As a communication means for supplying nitric oxide or a gas containing nitric oxide from outside the living body to the living body,
A conduit having a gas passage through which a gas can flow in an inner lumen, wherein a part of the conduit is provided with a gas supply portion, and in the gas supply portion, gas bubbles are formed in a gas permeation cross-section communicating from the gas passage to an outer surface of the conduit. A nitric oxide supply device comprising a gas permeable homogeneous membrane for preventing permeation of water. 2. The nitrogen monoxide supply device according to claim 1, wherein the entire gas permeation cross section of the gas supply section is formed of the homogeneous membrane. 3. The nitric oxide supply device according to claim 1, wherein the homogeneous film is made of a silicone resin. 4. The nitric oxide supply device according to claim 1, wherein the homogeneous film is made of polyurethane and / or polyolefin. 5. The nitric oxide supply device according to claim 1, wherein most of the gas permeation cross section is formed porous. 6. The nitrogen monoxide supply device according to claim 1, wherein at least two of said gas passages are formed, and a different gas flows through each gas passage. 7. The nitric oxide supply device according to claim 1, wherein one of the gas passages is formed at a blind end. 8. The nitric oxide supply device according to claim 1, wherein the gas supply unit is formed of a hollow fiber membrane. 9. The method according to claim 1, wherein the homogeneous film has a thickness of 0.01 to 10.0 m ² / sP.
^9. The nitric oxide supply device according to claim 1, having a gas permeability coefficient in the range of a × 10 ⁻¹⁴ . 10. The nitric oxide supply device according to claim 1, wherein an outer surface of the conduit is subjected to antithrombotic treatment. 11. A nitric oxide supply device, characterized in that the conduit according to any one of claims 1 to 10 is provided with means for detecting bubbles.