JPS5841883B2 - Plasma separation membrane and its manufacturing method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a plasma separation membrane that efficiently separates plasma from blood.

More specifically, the present invention relates to a plasma separation membrane that is made of cellulose acetate hollow fibers and has a high plasma separation ability, and a method for producing the same.

Conventionally, various methods have been devised and put into practical use to separate blood into blood cells and plasma, but a membrane filtration method has been adopted as a method that causes less damage to blood cells and allows for reuse.

This membrane is used with an average pore size of 0.05 to 1.0μ, but recent research has shown that even with an average pore size of 0.7μ, blood cells may be filtered or hemolysis may occur depending on the membrane material and manufacturing method. There is.

Further, even if plasma separation is possible, the degree of plasma separation is extremely slow, and therefore it is necessary to increase the membrane area.

The hollow fiber membranes that have been developed for this purpose are called pre-filtered hollow fibers, and have a significantly different separation function from semipermeable membranes such as ultrafiltration membranes and reverse osmosis filtration membranes, and are used for the separation of substances with large molecular weights. It is something that can be done.

This pre-membrane hollow fiber has excellent plasma separation ability, but
The requirements for shortening plasma separation time and miniaturization are still insufficient.

The present inventors have developed a hollow fiber that has a high plasma separation rate, does not leak blood cells, does not cause hemolysis or coagulation of blood cells, and can be used for various purposes after plasma separation, as well as being able to collect blood directly from patients. After conducting plasma separation using the hollow fibers of the present invention, we conducted intensive research to develop a membrane material that is safe enough to mix blood cells and plasma and re-inject it into a patient. If it has a certain tissue structure in the direction, the flow of blood cells will be smooth, the blood cells will not be damaged, and at the same time as the plasma flows on the membrane surface, it will cross the membrane in a direction perpendicular to the blood flow direction and separate the blood cells. The present invention has been successfully developed.

That is, the separation membrane of the present invention is a hollow fiber membrane in which at least 500 or less fibrils are oriented in the axial direction of the hollow cavity on at least the inner surface of the membrane.

Similar fibrils may also be provided on the outer surface.

This membrane consists of cellulose acetate, solvent, metal compound,
A spinning dope consisting of an added solvent is discharged from an annular spinning hole, and an internal coagulating liquid having a slow coagulating effect on the spinning dope is discharged from the center of the annular spinning hole in a fixed amount to create a coagulation bath below the annular spinning hole. In the step of coagulating, coagulating, and winding, the value obtained by dividing the winding speed by the discharge speed of the spinning dope from the annular spinning hole (hereinafter referred to as draft) is 1.5 to 6.0.
Obtained by spinning.

In the present invention, fibrils are aggregates of cellulose that coagulate and precipitate when cellulose acetate in the spinning dope discharged from the annular spinning hole gels and coagulates on the outer surface of the hollow fiber and the inner surface in the hollow cavity. It is.

The axial direction of the hollow hollow portion is the axial direction in which the hollow existing in the center of the hollow fiber is continuous in the length direction of the hollow fiber.

Orientation in the range of 0 to 500 means that the angle between the axial direction of the hollow part and the long axis direction of the fibril is in the range of 0 to 500 on the outer and inner surfaces of the hollow fiber where fibrils are present. say.

As is clear from the above description, 0° indicates that the long axis direction of the fibril coincides with the axial direction of the hollow cavity.

The long axis direction of fibrils refers to the main linear direction when cellulose coagulates and precipitates, aggregates and joins together to form a linear pattern.

On the other hand, when drawing an annular or oval shape as a result of joining,
Refers to the long axis direction of the annular or oval shape formed.

The present fibrils can be observed under an electron microscope at a magnification of 800 times, preferably 2,400 to 8,000 times.

According to a preferred embodiment of the invention, the plasma separation rate is 4
0 to 75-A- is obtained.

Here, the plasma separation rate can be determined by bundling hollow fibers for plasma separation and incorporating them into a plasma processing device with an inner diameter equivalent filtration area of 0.5 mm. The pressure on the blood side at the inlet of the blood processing device is 150 (e) Hg, and the pressure on the outside of the hollow fiber is 100 to Hg.
(differential pressure 250 timHg), the rate of plasma discharged from the furnace can be expressed in ml, /*n.

Other blood, such as fresh blood, whose hematocrit value and total protein have been adjusted in the same manner as above may also be used.

The most important thing in blood treatment is to avoid hemolysis and coagulation.

In particular, hemolysis is due to damage and destruction of red blood cells.

The solution to this problem is the central point [(2), which shows the rheological properties of blood fluid, and when blood flows through capillaries, blood cells flow through the center of the blood vessel and concentrate at the central axis of the blood vessel. say.

] Utilizing the effect of
For example, the size of the hollow cavity (inner diameter) is made small so that blood cells pass through the hollow shaft part rather than the inner wall of the hollow cavity.

That is, fibrils of cellulose acetate, which is a membrane material, are formed on the inner wall surface, and these fibrils are oriented at 5o0 or less in the axial direction of the hollow cavity, which is the blood flow direction.

Due to the orientation of the fibrils mentioned above, a large amount of plasma collects on the inner wall surface,
It passes through the thickness of the hollow wall membrane and exits to the outer surface, and blood cells are present in the hollow cavity.

Surprisingly, the orientation of the fibrils allows the plasma separation rate to be extremely high, allowing blood cells to be separated without damaging them.

Conventionally, hollow fibers for artificial kidneys and plasma separation have mainly been made of cellulose, and some have fibrils in the hollow cavities that serve as blood flow passages.

However, there are very few that are oriented in the axial direction of the hollow cavity, and even if they are oriented, the plasma separation rate is low.

Fibrils exist in the membrane filtration type hollow fiber disclosed in JP-A-51-93786, and although they are partially oriented, the angle that the fibril direction makes with the hollow axial direction is approximately 90.
The plasma separation rate is close to 40 m17.

Furthermore, in order to increase the plasma separation rate, it is necessary to make the concentration effect more pronounced and to limit the outer diameter, inner diameter, and membrane thickness, which are the shape of the hollow fiber.
It is preferable that the diameter is σ~5μ and the outer diameter is 550~1ooμ.

On the other hand, if the plasma separation rate is too high, only the blood cells in the blood will exist in the hollow part of the hollow fiber, and fluidity will be lost and blood clots will occur, making it unusable and used only for research separation. However, only a film that can be obtained is obtained.

In this sense, the plasma separation rate is preferably 75 ml, A- or less.

Note that complete plasma separation can be achieved by reducing the size of the hollow fiber.

In the production method of the present invention, cellulose acetate is dissolved in a solvent (for example, acetone, a mixed solvent of acetone and methanol, acetone and ethanol, etc.), and a metal compound and an additive solvent are added to prepare a spinning stock solution.

The metal compound is at least one type of monovalent or divalent cationic metal hydrochloride, nitrate, bromide, or iodide;
Examples include sodium nitrate, calcium chloride, magnesium chloride, lithium bromide, lithium iodide, and those containing crystal water can also be used.

The added solvent is a saturated cyclic-hydric alcohol having 5 to 10 carbon atoms.
It consists of at least one kind of cyclic hydrocarbons.

For example, cyclohexanol, cyclopentanol,
These include decalin, tetralin, and cyclohexane.

The prepared spinning dope is discharged from the annular spinning hole, and at the same time an internal coagulating liquid (for example, methanol water, ethanol water, acetone water, etc.) having a slow coagulation effect on the spinning dope is discharged from the center of the annular spinning hole.

) is quantitatively flowed out, introduced into a coagulation bath located below the annular spinning hole, coagulated, and wound into a hollow fiber.

In this winding process, the winding speed (unit: m/*π conversion) is adjusted to the discharge speed of the spinning dope from the annular spinning hole (unit: m/'
van conversion), that is, the trough I· is 1.
It is important to perform spinning within the range of 5 to 6.0.

Conventionally, the draft when spinning using the above spinning dope was 1
．． It was less than 5, and spinning was particularly performed near trough 1-1.

This is because the draft imparts a stretching effect to the spinning dope discharged from the annular spinning hole before and after solidification, inhibiting microphase separation, and thus does not result in the formation of membrane-filled hollow fibers.

Furthermore, there is a general belief in this technical field that drafts should not be applied, and it is also true that a porous network structure is difficult to form when external forces are applied.

To this end, various ideas have been devised for semi-dry, semi-wet or dry-wet spinning methods.

However, the production of hollow fibers with a small molecular weight cut-off, such as in dialysis and gas separation, does not require the microphase separation of the present application.
A draft may be applied.

Those with a high molecular weight cutoff, such as pre-membrane hollow fibers,
In particular, the draft of microparticles, which are produced by a furnace in units of μ, is around 1, and the spinning method is such that the particles mostly fall under their own weight and pass through a hollow space over a short distance.

The present invention is based on overcoming this conventional wisdom and increasing the draft.

Increasing the draft during spinning means that the drawing force of the difference between the winding speed and the discharge speed is concentrated in the part where the spinning stock solution discharged from the annular spinning hole has fluidity before and after it gels and solidifies. and the fibrils undergo orientation.

As a result of this orientation and the progress of gelation and coagulation, a linear fibril conjugate appears on the outside and surface of the hollow fiber.

When increasing the draft during spinning, spun yarn breakage tends to occur, but this can be solved by known methods employed in conventional dry and wet spinning techniques.

In particular, if the spinning stock solution contains metal compounds or additive solvents, the spinnability will decrease and the occurrence of thread breakage will increase. This can be achieved by setting suitable spinning conditions.

The most effective technique in the present invention is to reduce the winding speed and the annular spinning hole diameter.

As described above, the present invention is most suitable for blood processing, particularly plasma separation, but is also suitable for separating fine particles in a solution in which the fine particles are deformable and form a suspension as a whole, and is suitable for use in emulsion oil preparations in textile factories. It can be directly used for oil and water separation, concentration of milk particles from milk dilution solution, concentration of latex dilution solution, clarification of beer, grape wine, sake, juice, etc.

It is also possible to use a clarification furnace for inorganic particle suspensions, sterilize filtration, and produce ultrapure water, making it extremely excellent.

Examples of the present invention are further shown below.

Example 1 The spinning stock solution was 162 gr of cellulose acetate with a degree of acetylation of 54.3% and a degree of polymerization of 190, and 408 gr of a mixed solvent of 326 gr of acetone and 82 gr of methanol as a 'Fl medium.
, 86 gr of calcium chloride dihydrate as a metal compound, and 344 gr of cyclohexanol as an added solvent were stirred to form a completely homogeneous solution and defoamed.

This spinning dope was discharged from an annular spinning hole.

50 mm from the internal coagulation liquid outflow hole in the center of the annular spinning hole.
The 1% Vo methanol aqueous solution was quantitatively discharged and passed through 8Qmrn air downward, and then led to a coagulation bath of 50 Vo1% methanol aqueous solution, and the coagulated hollow fibers were treated in the methanol bath.

The following conditions were adopted in this spinning, and the results shown in Table 1 were obtained.

Comparative examples outside the draft range of the method of the present invention have fibril orientation, but the plasma separation rate is low.

The amount of water permeation is the amount of sterile water permeated at 100 ml LHg for 1 hour before flowing blood into the blood processing device using each of the hollow fibers described above, converted into units of l/m hr mmHg.

Figure 1 shows the inner surface of the comparative example, Figure 2 shows the inner surface of the present invention (1), and Figure 3 shows the inner surface of the present invention (3).
This is a magnified electron micrograph.

Example 2 The components of the spinning stock solution were exactly the same as in Example 1, and the composition was 11.4 wt% of cellulose acetate and 28.9 wt% of acetone.
wt%, methanol 7.2wt Toshio Tohoka Calcium 9
．． A spinning dope containing 43.4 wt of cyclohexanol and 43.4 wt of cyclohexanol was spun in the same manner as in Example 1.

Conditions and results different from Example 1 are shown in Table 2.

FIG. 4 is an electron micrograph at 500 magnification of the inner surface of the hollow fiber of the comparative example and FIG. 5 of the present invention.

[Brief explanation of the drawing]

FIGS. 1 and 4 are electron micrographs showing the inner surface of the conventional product, and FIGS. 2.3.5 are electron micrographs showing the inner surface of the product of the present invention.

Claims (1)

[Claims] 1. A hollow fiber membrane made of cellulose acetate, with fibrils on the hollow inner surface extending 000 mm in the axial direction of the hollow cavity.
A membrane for plasma separation, characterized in that the membrane is oriented in a range of 50' to 50'. 2. A spinning dope consisting of cellulose acetate, a solvent, a metal compound, and an additive solvent is discharged from the annular spinning hole, and at the same time, the coagulated solution of the spinning dope is discharged from the center of the annular spinning hole, and flows into the coagulation bath below the annular spinning hole. A method for producing a membrane for plasma separation, characterized in that in the steps of guiding, coagulating, and winding up, the ratio of the winding speed to the discharge speed of the spinning dope discharged from the annular spinning hole is 1.5 to 6.0.