JPS60150757A - Hollow yarn membrane type artificial lung - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention [Technical Field] The present invention relates to a hollow fiber membrane oxygenator, and in particular, a hollow fiber membrane that is a porous polyethylene hollow fiber membrane having characteristic strip-shaped micropores and a full gas exchange membrane. Regarding type artificial lungs.

[US technology]

Conventionally, non-porous membranes such as silicone membranes and porous membranes made of hydrophobic materials such as Teflon and polypropylene have been used as demolding oxygenators. Further, the membrane type is a flat membrane type and a hollow fiber membrane type, and the hollow fiber membrane type is superior because it allows for miniaturization of the device. (Examples of oxygenators using thread membranes in porous materials include, for example, Japanese Patent Application Laid-Open No. 160098/1982 and Japanese Patent Laid-open No. 136456/1989.) However,
The porous hollow fiber membrane in 1 also has (1) insufficient gas exchange performance (particularly in carbon dioxide removal ability);
(2) There is a drawback that blood or plasma leaks when used for a long time.

[Purpose of the invention]

In view of the current situation, the present inventors conducted intensive studies with the main purpose of improving the gas exchange performance of the hollow fiber membrane oxygenator and preventing leakage of blood, etc., and as a result, completed the present invention. Ta.

[Structure of the invention]

That is, the gist of the present invention is as follows: 1) The micropores have a laminated structure in which the inner wall surface of the hollow fiber membrane is interconnected with the outer wall surface, and the micropores are characterized by the following characteristic values, Porosity is 30-90 vot%, water permeability is 4
Use a porous polyethylene hollow fiber membrane with a weight of 7 cm2 or more as a gas exchange membrane'1cIP! Hollow fiber membrane oxygenator with f symptoms.

(Li) It is a strip-shaped microvoid arranged in the direction of the fibers, and the average length ('tv) and the average hit (dv) in the direction of the fibers.
), 2v=cL2~5 pm, Lv/clv=3
~50, (2) When the strip-shaped micropores are measured by the bubble point method, the bubble point is 1 kg/α2 ~ 12 kg/cr.
falls within the range of n2.

The hollow fiber membrane of the present invention is made of polyethylene, and has a unique membrane structure not seen in the past. In other words, they are strip-shaped micropores arranged in the direction of the fibers. If the direction of the fibers is smaller than this range, the gas exchange performance will not be sufficient, and if it is larger than this range, the evaporation of water vapor will be large and the outer wall surface of the hollow fiber membrane will be damaged. It adheres to the carbon dioxide and reduces the ability to remove carbon dioxide.

On the other hand, when the strip-shaped micropores are measured by the bubble point method described below, the bubble point is 1 kg/cm2 to 15
It must be within the range of kg/cm2.

If it is less than 1 kg7cm2, water vapor evaporation will increase as described above, and the carbon dioxide removal ability will decrease over time. Also, there is a high risk of leakage of blood, etc. If the weight exceeds 15kgZ, the gas exchange performance will not be sufficient.

Even if the membrane material is hydrophobic, blood or plasma may pass through the membrane if it is porous because the blood is placed under pressure. The inventors investigated various conditions under which blood, etc. would not leak within the normal operating pressure range of a model oxygenator, and found that the above-mentioned characteristic strip-shaped micropores have a water permeability pressure measured by the measurement method described below. It was found that there was no leakage of blood etc. when the weight was 4 kg/crn2 or more, and the present invention was completely completed.

Furthermore, such a hollow fiber membrane has a porosity of 30 to 90 vo
It is necessary to fall within the range of 1%. With non-porous membranes such as silicone membranes, gas dissolves in the membrane and passes through by diffusion, but with porous membranes, gas passes through the pores of the membrane in a volumetric flow.The gas exchange performance of porous membranes is It is generally said to be excellent in However, in the polyethylene of the present invention, the gas permeation rate in the non-porous part is very low compared to silicone, so the number of pores is an extremely important factor in improving blood gas exchange performance. Become. According to studies by the present inventors, when expressed as total porosity, oxygen addition ability and carbon dioxide removal ability are opaque when the number of open pores is less than 30 vo1%. If it exceeds 90 vol 1%, the strength of the hollow fiber membrane itself becomes opaque, and there is a very high risk of pinholes occurring when handling or using the hollow fiber membrane. A more favorable porosity range is 40 to 90.
vo1%.

Moreover, the inner diameter I'm of such a hollow fiber membrane is 100 to 500
Preferably it is μm. If it is less than 100 pm, the hydrodynamic resistance of blood becomes very large, and the degree of hemolysis becomes extremely large. Furthermore, blood also tends to coagulate inside the hollow fiber membrane. If it exceeds 500 pm, the gas exchange performance will be low and it will be impossible to assemble a device that can withstand practical use.

The film thickness is preferably 10 to 150 μm. 10μ
If it is less than m, the strength of the hollow fiber membrane decreases, and defects such as flattened holes are likely to occur. If it exceeds 150 μm, the gas permeation resistance becomes large and the optical performance cannot be achieved.

Such a polypatylene hollow fiber membrane has a melt index of 1 to 15, preferably 0.955 or more, preferably 0.960
High-density polyenalene with a density of 100 to 100% is used as a total starting material with a density of 100 to 100% by using a nozzle for producing hollow fiber membranes in the temperature range of 135 to 215°C.
0000, followed by cold stretching by 5 to 200% at a temperature of 40°C or lower, followed by hot stretching in one or multiple stages in a temperature range of 40 to 130°C, during which cold stretching and The total amount of stretching including hot stretching is in the range of 100 to 900%, and then, if necessary, heat celatra is performed in a temperature range of 100 to 120°C.

FIG. 1 schematically shows an example of the structure of the surface of a hollow fiber membrane obtained by such a method.

In FIG. 1, 1 is a strip-shaped microhole (j), Lv.

dv indicates the length of one rectangular micropore and the inner diameter.

The average JV and billable VC can be determined by randomly extracting them from the field of view observed using a scanning electron microscope and calculating the arithmetic average.

FIG. 2 shows an example of a hollow fiber membrane oxygenator incorporating such a porous polyethylene hollow fiber membrane. Cylinder (2)
Hollow fiber membranes (3) are arranged almost parallel inside the cylinder body (
2), and the hollow part is open at both ends. When blood flows inside the hollow fiber membrane, the blood flows through the inlet (
4), flows through the hollow part of the hollow fiber membrane (3), and then exits the hollow fiber membrane oxygenator through the outlet (5). - 1,000,000 oxygen or a gas containing oxygen is introduced into the hollow fiber membrane oxygenator through the inlet (6), flows through the gas chamber (8), exchanges gas with blood, and then enters the hollow fiber membrane oxygenator through the outlet (7). Exit the thread membrane oxygenator. - When blood is to flow into the space outside the hollow fiber membrane, the blood is introduced from the inlet (6) and the blood is discharged from the outlet (no). Also, gas is introduced from the inlet (4) and the hollow fiber membrane It passes through the hollow part and is discharged from the discharge port (5).Figure 2 ■The hollow fiber membrane oxygenator is just one example, and it is possible to use various types if handling ease is taken into account. Not even 1.

As mentioned above, the hollow fiber membrane oxygenator, which incorporates a porous polyethylene hollow fiber membrane with characteristic strip-shaped micropores, has superior gas exchange performance compared to conventional oxygenators. Open-heart surgery is possible because it can be made smaller and lighter, and therefore has the characteristics of less blood brimming, as well as extremely little change in carbon dioxide removal ability over time and no leakage of blood, etc. Needless to say, it is also very useful for long-term extracorporeal circulation (10M0), etc.

〔Example〕

Hereinafter, the invention will be explained in more detail with reference to Examples, and the measuring method used in the present invention was as shown below.

(1) '2 Porosity: Measured using a mercury intrusion porosimeter C Carlo Erba Model 221).

(2) Water permeability pressure; porous polyethylene hollow fiber membrane 96f
A module was created by bundling them in an 11-shape and solidifying all the hollow openings with V-tan resin, and the effective length of the fC6 medium fiber membrane was set to 20z. Pressurized water whose temperature was controlled at 25°C was raised inside the hollow interior of this module at intervals of α25 klil/m2 (the holding time at each pressure was 30 sec).
The amount of water permeating through the hollow fiber membrane was measured using a measuring cylinder. The relationship between the pressure and the amount of permeated water was plotted, the two points where the amount of permeated water was 50 ml and 20 mL were connected with an m line, and the intersection with the pressure axis was taken as the permeated pressure. The pressure unit was kg/6n2. (3) Bubble point: A module was created by bundling 48 porous polyethylene hollow fiber membranes into a U-shape and solidifying the inner opening with urethane resin.

The effective length of the hollow fiber membrane was 20c1n. After this module was immersed in F 99.5 VO 1% ethanol and the ethanol was allowed to penetrate into the inside of the hollow fiber membrane (the temperature of the ethanol was 25°C), nitrogen gas F 11 was added into the hollow interior at intervals of 97 cm2. The pressure was increased to a normal level (the holding time at each pressure was 10θθC, fc). Visually observe how the pressure balance is broken and bubbles are generated in the ethanol.
The nitrogen gas pressure at which bubbles were uniformly generated throughout the hollow fiber membrane was defined as the bubble point. Pressure unit is 9/6n2
And so.

(4) Blood gas analysis: Blood gas analyzer (Corning Co., Ltd. 1
58 type) to measure blood pH, oxygen concentration, and carbon dioxide concentration.

Examples 1 to 4 and Comparative Examples 1 to 3 Various conditions were changed according to the method described in the specification Table 1
A porous polyethylene hollow fiber membrane having the characteristic values shown in was fabricated. These hollow fiber membranes were bundled to produce a hollow fiber membrane oxygenator having an effective length of 9 cm and a membrane area of 1.2 m2 as shown in FIG. The light filling rate of the hollow fiber membrane inside the oxygenator cylinder was 50% in all cases.

Fresh heparinized bovine blood with a hematocrit value of 55% and a hemoglobin concentration of 11.7 l/dt is introduced into a venous blood preparation device,
Inlet conditions are 02 saturation Elv02=65±5%, C02
Venous blood with partial pressure PvO02=45±5 turns Hf was prepared. Bovine blood heated to 37°C by a heat exchanger was sent through the prototype oxygenator inlet (4) at a blood flow rate of 1200 mt/min to the oxygenator's gas chamber (8) at 1212-0 O/m1.
100% 02 gas was blown with flow i. Gas exchange in the blood is carried out in such a circuit, and 1 hour after the start, 5
02 additional capacity of 15 hours.

The CO2 removal ability and the presence or absence of leakage of blood, etc. were measured.

The O2 addition capacity and CO2 removal capacity are calculated by measuring the O2 concentration, Co2 concentration, and pH in blood collected before and after oxygenation using a blood gas analyzer. If there was a shortage of blood during the measurement, the measurement was continued after readjusting to the venous blood conditions described above.

02 addition capacity of each oxygenator measured in this way.

The results of the 002 removal ability and the presence or absence of leakage of blood etc. are shown in Table 2. Hollow fiber membrane oxygenator falling within the scope of non-invention (Example A
The 02 addition ability and CO2 removal ability of Nos. 1 to 4) were both good, and there was very little change over time. On the other hand, when the porosity was low as in Comparative Example A1, the 02 addition ability and CO□ removal ability were extremely low and impractical.

Also, like Comparative Example 2, the water permeability pressure is 2.0 Yu/an2
When using a hollow fiber membrane with a low temperature, plasma leakage was observed, and as a result, the gas exchange performance deteriorated over time, making it useless as a hollow fiber membrane oxygenator3. The inner diameter of the hollow fiber membrane is 550μ as in Comparative Example A5.
When the diameter is as large as m, the level of gas exchange performance is extremely low and is not practical.

As described above, the gas exchange performance of the hollow fiber membrane oxygenator according to the invention is extremely good, and there is little decrease in stiffness over time. Furthermore, there is no leakage of blood, etc., and it can be used for a long time from a safety point of view.

Table-1 Table-1 2

[Brief explanation of drawings]

FIG. 1 is a schematic diagram showing an example of the structure of the porous polyethylene inner wall fiber membrane surface used in the invention. Figure 2 shows
This is an example of an uninvented hollow fiber membrane oxygenator. 1... Rectangular micro urinary hole Lv... Length dv of the rectangular micro urinary hole in the fiber longitudinal direction...
- Width of the rectangular micro-urinary hole 2 ... Cylindrical body of the hollow fiber membrane type oxygenator 3 ... Porous polyethylene hollow fiber membrane 4 ... Blood or gas inlet 5 ... Blood or gas outlet 6 ...Gas or blood inlet port A...Gas or blood outlet port 8...Gas or blood chamber (space outside the medial membrane) 9...
The arrow in FIG. 1 indicates the fiber length direction. Applicant: Mitsubishi Rayon Co., Ltd.

Claims (1)

[Claims] 1) The micropores have a laminated structure in which the inner wall surface of the hollow fiber membrane is interconnected with the outer wall surface, and the micropores are characterized by the following characteristic values, and the porosity is 30. A hollow fiber membrane oxygenator characterized in that a porous polyethylene hollow fiber membrane having a VOI% of ~90 VOI% and a water permeability of 4' to 9/cm2 or more is used as a gas exchange membrane. (1) Filled with strip-shaped micropores arranged in long fibers,
Average length (tv) and average hit (av) to fiber length Gallo
) and n■=α2~571m, lv/dv=3~5
(2) When the strip-shaped micropores are measured by the bubble point method, the weight falls within the range of bubble point method to 15 kg/crn2. 2) The inner diameter of the porous polyethylene hollow fiber membrane is 100 to 50
The hollow fiber membrane oxygenator according to claim 1, wherein the membrane thickness is 10 to 150 μm. 3) The porosity of the porous polyethylene hollow fiber membrane is 30 to 9
The hollow fiber membrane oxygenator according to claim 1 or 2, which has a content of 0 vol%.