JPS60108052A - Hollow yarn type serum separation membrane - 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 The present invention relates to a hollow fiber plasma separation membrane, and more specifically to a hollow fiber plasma separation membrane that has sufficient mechanical strength required as a blood processing membrane and also has excellent plasma permeability. 2,
The present invention also relates to a hollow fiber plasma separation membrane having anti-hemolytic properties.

Plasma separation using membranes is used when the plasma of patients with drug poisoning, fulminant hepatitis, etc. is exchanged with normal plasma in a short period of time, and for pretreatment procedures for separating specific solutes in plasma. ing. In either case, whole blood is supplied to the hollow interior of a hollow fiber plasma separation membrane and filtered out through the outer wall to separate plasma components.

Important performances required of the membrane used for such plasma separation include the ability to efficiently separate blood cell components and plasma components and safety performance as a medical device. This safety performance includes guaranteeing mechanical strength to withstand physical impact and anti-hemolytic properties. The reason why this guarantee of mechanical strength is required is as follows. That is, 1. the plasma separation module requires priming, which also includes washing with physiological saline, immediately before use, and 1. complete defoaming.

During defoaming, it is difficult to completely defoam unless a physical impact is applied to the module. In reality, a method of hitting the module with forceps is used. Furthermore, physical shocks are applied to modules during module transport. If such an impact is applied to the separation membrane, the membrane will be damaged if it does not have sufficient mechanical strength, and the blood introduced inside the hollow fiber will leak through the hollow fiber wall, causing serious trouble. This is because it becomes The anti-hemolytic property is based on the fact that hemoglobin released from the inside of red blood cells after hemolysis is harmful to living organisms.

Hollow fiber separation If has traditionally been used for plasma separation
In order to avoid the above-mentioned troubles related to blood leakage, a film with a large thickness has been used. For example, a separation membrane with a thickness exceeding 100 μm was used, so the breaking strength was 90 f or more, and leakage did not occur much. However, as the membrane thickness increases, the filtration resistance increases, resulting in a lower plasma permeability. If this plasma permeability (the ability to efficiently separate blood cell components and plasma components) is low, plasma exchange and plasma collection will take a long time, which will place a physical and mental burden on the patient. Obtaining an enhanced membrane becomes as important as creating a blood leak-free membrane as mentioned above.

Of course, various separation membranes that can increase plasma permeability are also being studied. For example, a membrane with a large pore area that is effective for filtration by increasing the porosity of the inner and outer walls of a hollow fiber membrane has been prototyped.1 However, in this case, the mechanical strength decreases as the plasma separation performance increases. However, this method has the disadvantage of causing the serious problem of blood leak mentioned above.

These technical problems are contradictory, and a hollow fiber plasma separation membrane that satisfies both of them at the same time has not yet been obtained.

As a result of intensive research into hollow fiber plasma separation membranes that simultaneously provide these performances, the present inventors found that even if the wall thickness of the hollow fibers is thinned, the membrane's unique porosity, that is, the hollow fibers of the present invention. type plasma separation membrane, and the outer wall surface of the membrane has a pore area of 1.3
X 10""s+- or less pores are formed evenly distributed with a porosity of 40% or less, and the inner wall surface has a pore area of 1.8 X
This is a hollow fiber plasma separation membrane in which pores of 1cI" or less are formed in a network with a porosity of 60% or more, and the wall thickness of the upper membrane is 100μ or less.

An example of a Kameko micrograph (magnification: 5000x) of the inner and outer walls of the plasma separation membrane according to the present invention (examples described below) is shown in Figure 1 (
(inner surface) and Figure 2 (outer surface).

The pore area and pore area ratio referred to in the present invention are values actually measured from this electron micrograph using the following method.

(1) Hole area (md) of the outer wall of Hakuba Observed using an electron micrograph at 5000x magnification) Defined by the largest pore area of the inner and outer wall.

(2) Porosity ratio (%) of inner and outer wall surfaces Observed by electron micrographs magnified 5×5−) Defined as the ratio of the total area occupied by membrane pores per unit area of 5×5−.

Actually, it can be done as follows.

I OO In the present invention, the outer wall surface of the plasma separation membrane has a pore area of 1.3 x 10" or less and a porosity of 40% or less, and the inner wall surface has a pore area of 1.・8X
It is necessary that pores of IO"" or less be formed in a network shape with a porosity of 60% or more. Even if the inner wall surface is within the scope of the present invention, the membrane has a pore area of 1.3 x 10-2 m or less, with 40% or less of the pores exceeding 1.3 x 10-2 m.
A membrane in which pores of 4 or less are opened at a rate exceeding 40tII is desirable because its mechanical strength decreases, but it is also undesirable because its mechanical strength decreases.
A membrane in which less than 60% of pores of 10"J- or less are open is undesirable because the separation performance decreases. Mechanical properties are imparted.

Surprisingly, the hollow fiber plasma separation membrane having the above-mentioned surface asymmetrical structure has good mechanical properties, so even if the wall thickness is made thin, no problem arises regarding blood leakage. That is, a membrane with a wall thickness of 100 μm or less was obtained, and thus the plasma separation performance could be significantly improved.

Such a hollow fiber plasma separation membrane is produced by, for example, dissolving a polymer compound in a solvent and a swelling agent, spinning it into a hollow fiber, and immersing it in an aqueous coagulation bath containing the solvent and swelling agent. In a method for manufacturing a hollow fiber plasma separation membrane in which an aqueous coagulating solution containing a swelling agent is introduced to coagulate the outside of one hollow fiber, the concentration of the solvent and swelling agent in the coagulating solution introduced into one hollow fiber (OX heavy mouse %) and the concentration of the solvent and swelling agent in the coagulation bath outside the hollow fiber (a9% by weight). -0
This can be obtained by controlling 1(-Δ0) within the range of 2 to 20%.

In the above production method, polymer compounds such as cellulose esters (cellulose diacetate, cellulose triacetate, cellulose nitrate, etc.), bath agents such as N-methyl-2-pyrrolidone-1-dimethylformamide, and swelling agents such as polyethylene glyfur (average molecular Type 20
0~1ooo) etc. are used. A plasma separation membrane having the structure described above can only be produced by creating a difference between the amount of solvent and swelling agent in the coagulation solution introduced into the hollow fiber and the amount of solvent and swelling agent in the coagulation bath present outside the hollow fiber. It was done.

Furthermore, since the separation membrane according to the present invention has mesh-like pores formed on the inner wall surface, it also has excellent anti-hemolytic properties. That is, the red sphere can be supported on the fibril lines of the mesh, and the flow of blood plasma can be caused below the part where the sphere is held, facilitating movement in the axial direction.

As described above, the hollow fiber plasma separation membrane according to the present invention has sufficient mechanical strength required as a blood processing membrane, has excellent plasma permeability, and also has good anti-hemolytic properties. 1 It is something that can greatly contribute to the medical field in the future.

Examples of the present invention will be described below, but the present invention is not limited to these Examples.

Example 1, A plasma separation membrane having a thickness of 82 μm was manufactured in the following manner.

Spinning stock solution: 30% by weight of cellulose triacetate, N
-Methyl-2-pyrrolidone and polyethylene glycol (400) in a heavy ratio of 6:
Dissolved in the mixed solvent obtained by mixing 4.

Spinning: After heating the above-mentioned spinning dope to 121°C, spinning air is passed through a nozzle at 83°C to lead to a coagulation bath. A coagulating liquid is introduced into the hollow fiber during spinning.

Coagulation: N-methyl-2- as coagulation liquid (hollow fiber internal liquid)
An aqueous solution containing 70% by weight of pyrrolidone and polyethylene glycol (4oo), and an aqueous solution containing 74.3% by weight of N-methyl-2-pyrrolidone and polyethylene glycol (400) as a coagulation bath (outside the hollow fiber) were coagulated.

Post-treatment: After solidification, washing with water, then 50℃-90% by volume
Treat in a glycerin bath for 1 hour and dry.

The obtained hollow fiber separation membrane has a structure as shown in FIGS. 1 and 2. The properties of this film were as shown in Table 1.

Table 1 Shown as the load at break.

Calculate the following formula: Critical filtration rate - (separated plasma flow rate) / (supply blood flow rate) 1
00 (However, Ht-38%, supply blood flow rate 1009-) Note 1
Table 2 shows the results of measuring the same characteristics as above for two known types of plasma separation membranes.

Table 2

[Brief explanation of drawings]

Figures 1 and 2 show microscopic photographs of the plasma separation membrane which is self-explanatory in Book 9. 1゜inner wall 1+j i, J] figure, and the outer wall surface is shown in figure 2 1゜'+ff ifi' 1 applicant Toyobo Co., Ltd. Procedural amendment (voluntary) May 10, 1980 L Display of the case 1982 Patent Application No. 217543 2 Name of the invention Hollow fiber plasma separation membrane & amendment person case Relationship with Patent Applicant 2-2-8-4 Dojimahama, Kita-ku, Osaka City Claims column and Detailed Description of the Invention column (2) of the specification subject to amendment (2) Lines 17 and 11 of page 11 of the specification Line 19 [1,3X
I O-”-J and “1.axlo-’sJJ”
．． 3Xz o -' x -vrtl J and '1.8
x l O-" x 6000 5000 to 7J Defined by the maximum hole area.In other words, the maximum hole area of the inner and outer walls is actually measured (S
-). Since the actual measurement was taken from an electron micrograph with a magnification of 5,000 times, the true hole area can be calculated from this actual measurement surface i as follows. Correct to true pore area (+a+J)-8x x J. 5000 5000 (4) Change "x, 3x1o-'-" to "1" on the bottom line of page 6.
．． Correct to 3X I O-' X -vul J. 000 (5) Page 6, line 2, line 9, and line 11 “1
,8 xlo-'mj J [1,8X I O-''
X-”-+ad J000. (6) Page 6, lines 4 and 6 “1.5xxo
-"-" is corrected to "x, 3x z o-2x Tn7-J. ()) Maximum hole area of outer wall surface (-) in Table 1, page 10 of the same
"o, 6x z o-1" [o, 6 X I
O-"x-'--*** J000 Maximum hole area on inner wall (-) "1.5xx o-"
” is corrected to “1.5xlO””x ”J. 000 (8) Insert the following formula between the second and third lines from the bottom of page 10. "Actual measured hole area x 5oooX 1111-= o
, s x x o −” x5000 ' (9) Maximum pore area (-) on the outer wall surface in Table 2, page 11 of the same
"0.3X I O-" J and "1.oxlo-"
” to “0.3×10′″2×□” and “l +OX
10-" X-J, 5000 5000 Also, the maximum hole area on the inner wall surface (-) [o, a X 10-"
J and "5.0X10-'Jl'-0,8xlO'"
``×-Sat-'' and 15.0000 x l O-''' x-1-J. 000 pores of 1 or less are formed evenly distributed with a porosity of 40% or less, and the inner wall surface of the membrane has a pore area of 1.8
000 The lower pores are formed in a mesh shape with a porosity of 60% or more,
and a hollow fiber plasma separation membrane having a wall thickness of 100 μm or less.

Claims (1)

[Claims] The outer wall surface of the membrane is formed of pores with a pore area of 1.3 x 10" m or less and an average distribution of pores with a porosity of 40% or less, and the inner wall surface of the membrane has a pore area of 1.8 x 10" md or less. A hollow fiber plasma separation membrane, wherein the pores are formed in a mesh shape with a porosity of 60% or more, and the wall thickness of the membrane is 100 μm or less.