JPS5946965A - Serum fractionating apparatus - Google Patents

Abstract

(57) [Abstract] 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 device for improving filtration efficiency in membrane fractionation of plasma.

Recently, membrane-based blood filtration or blood filtration has attracted attention. For example, plasma is separated from blood, this plasma is further separated into a low-molecular fraction and a high-molecular fraction, and the useful parts are recovered and used for medical purposes and research purposes. .

However, plasma contains albumin, globulin, and other proteins, so it is viscous and therefore
A word that blocks high molecular weight substances and allows low molecular weight substances to pass through.
Conventional membrane filtration operations result in decreased performance due to transcutaneous application.
Satisfactory results were not obtained.

However, as a result of a detailed examination of the phenomenon of membrane filtration using bovine blood 11k and plasma in animal experiments, the present inventors found that the decline in filtration ability over time is due to the formation of a protein gel layer on the membrane surface. They discovered that this is greatly affected by the increase in filtration resistance passing through micropores, and conducted extensive research into ways to prevent the formation of protein gel layers, leading to the present invention.

The apparatus for separating plasma by membrane separation according to the present invention includes a means for mixing a membrane surface scraping substance having a particle size that does not pass through the micropores of a blood GK separation gland into plasma, and a means for separating a mixture of plasma and the substance into plasma fractionation. and a means for circulating circulation over the membrane surface of the membrane.

The present invention will be explained in further detail with reference to FIG. 1 attached hereto.

FIG. 1 shows a schematic diagram of plasma filtration. As shown in FIG. and the substance. This mixed solution is led to the plasma separator 4 through the circulation circuit 11, and the low molecular weight substances are passed through and sterilized. or send it to the next location depending on the purpose.
lk. Discarded using plasma separator 4.

The non-filtrate that has not been filtered, that is, the polymer substance fraction and the membrane surface scraping material, is discharged from the non-filtrate outlet L16 of the plasma separator 4 and is circulated to the mixing means again.

For example, a circulation pump 14 can be used for this circulation. In the poem, polymer substances are accumulated in the unfiltered 11ζ, and when its degree of filtration increases by -L, the pressure on the filtration/11 side increases, so the pressure is detected by the filtrate side pressure 11■2. Sometimes non-ih & over-fluid pumping 11 or 19 or 10 each time the liquid is drained prevents the accumulation of molecular substances.
00mβ.) You can set it as appropriate.

Plasma separators 4 and 119 used in the device of the present invention
The surface filtration material 2 and the conditions for its use will be explained in more detail. The filtration membrane of the plasma separator 4 is used by selecting the pore size of the membrane depending on the molecular weight or particle size of the substance to be dispersed and collected from the plasma.
Flat membranes or hollow fiber membranes with a pore size of m are used. For example, if a substance with a molecular weight less than albumin is filtered and collected as a filtrate, and immunoglobulins, complexes thereof, or normal proteins with a molecular weight larger than albumin are removed as a filtrate, 0.01 to 0. A membrane with a pore size of 0.3μrn is suitable. On the other hand, immunoglobulin M (Ig
When removing proteinaceous substances such as M), riboproteins, and immune complexes (1, C,) and collecting protein substances with lower molecular weights and body 11k as a filtrate, 0.04 to 0.1 μrn of borealis pus is collected. is suitable. Membrane materials include cellulose-based materials such as cellulose acetate-1, polyacrylic nitrile,
Polymethyl ivy acrylate, polyvinyl alcohol,
Polycarbonate, etc. Such hollow fibers include, for example, Japanese Patent Application Laid-open Nos. 51-93786 and 52-8418.
Some of these are described in Publication No. 3, etc. The pore size of the membrane is selected and used depending on the purpose, but the gist of the present invention is to reduce the pore size of the crotch in the original blood as a means to reduce the hyperactivity rate. Also, the grains i\ are large, so j) the micro 11+1 pores of the membrane are i! II Toshi no, ``
A means is provided for adding a thin film surface abrasion substance. In addition, a mixture of K and the substance is sent from the blood non-separator 5, flows out from the plasma separator 6, and is circulated again to the inlet of the filtration filter. -1 target filtrate
, &: Liquid extraction + 7, or a circuit is provided to send it to the next location.

In this way, when the mixed solution of plasma and the substance passes through the surface of the 111mm separation membrane, the curved zigzag separation membrane surface 4. 2I
The formation of a protein gel layer on the membrane surface can be prevented by imparting JiJ shearing force. Further, there is an effect of peeling off scale such as proteins deposited on the membrane surface by the membrane surface rubbing substance.

The film surface abrasion substances to be added include bubbles such as nitrogen and air, polyethylene, vinyl chloride J, hnylidene chloride, polyester, other synthetic 444 fats, and refined fine particulate substances of metals such as gold, silver, and iron. However, any one is fine. However, it is of course best to use one that does not contain harmful substances that react with the body 71ν or elute into body fluids.

Hereinafter, the present invention will be explained in more detail according to Examples.
It goes without saying that the scope of the present invention is not limited to these Examples.

Examples and Comparisons (Exhausted blood stagnation obtained when blood exchange therapy was performed on patients with systemic lupus erythematosus disease was obtained, and the average pore size was 0.04μ.
Using an experimental blood JIi fractionator made of cellulose diacetate hollow fibers with an effective area of 0.02 m and an effective area of 0.02 m, an experiment was conducted to recover albumin using the apparatus shown in Figure 1, and the changes in filtration performance over time and the filtration capacity were investigated. It was measured.

The excreted plasma used was albumin, globulin, and IgG.

IgΔ+IgM+β-riboprotein, immune complex (LC,)
, anti-DNA antibodies, etc. (albumin, globulin,
rgG, IgA) or harmful (less than 1 gM) proteins, electrolytes, water, etc.

The flow rate of the liquid pump (filtration rate) was 10.7 mn/min, and the flow rate of the circulation pump was 10 rrz2/min.

The experiment was carried out -1.

Experiment I: Membrane surface I. Using nitrogen as the permeate, mixing 1,
Use Trinobubuchi Chuunha (Ki〆U-nuki) as a step,
The space in the second part of the drip chamber was filled with nitrogen. Plasma was supplied to the 1-lithop chamber and circulated by a circulation pump, so that nitrogen was mixed into the plasma in the form of fine particles (particle i: 0.11 yen). The amount of nitrogen used is 5% by volume of plasma.

Experiment 2: Cellulose acetate was immersed in a drip chamber, and cellulose acetate microparticles (10,
January n) was mixed with blood IIn at a ratio of 5% to M.

Experiment 3: Plasma only and membrane surface scraping 1iiIt4)
I experimented without using it.

In each experiment, 11. useful substances such as albumin were collected by filtration.
The penetration rate was 70-80%, and the penetration rate for harmful substances such as anti-DNA was 15-25%. ii7 The results were as shown in the table below.

Measurement Item Experiment] Experiment 2 Experiment 3 Time (hr) until the pressure gauge responds to 300 Dragon u5 3 4 1 filtration:
Filtrate albumin concentration after 1 hour: 4g/old 48/old 1g/
The second part of the old pressure gauge shows the degree of membrane clogging. In the examples of the present invention (Experiments 1 and 2), it took a long time of 3 to 4 hours to reach 3001al18, but in the comparative example (
Experiment 3) was as short as 1 hour. In addition, in Experiment 3, which consisted of a plasma-only system without the addition of membrane abrasion substances, after 1 hour, i.
The albumin concentration of xV and lrν is I g/d1, but in Experiment 1 and the experiment employing the present invention, the albumin concentration of the filtrate was 4 g/dl, respectively. As described above, the albumin filtration ability was improved by four times by adding the membrane surface abrasion substance.

It is thought that the two-tr improvement in the θ & 171 ability prevents the i+4 transition (the protein 5i'7 of protein 5i'7 from passing through the membrane surface 1i). Therefore, according to the present invention, Experiment 1, Experiment 2, and Experiment 3 (experiments 1 and 2 had 11 pus compared with experiment 3, and protein 9" I 1. “Scale” and “
'Clogged' 4.1 Could not clear.

4 Fi of the drawing? i) l>l,; Explanation Figure 1 shows an example of a different device for this Komyo, an example of a 4th grade (1 Saekawa)
+x+-There it is.

■...Plasma, 2...1 metabolite, r)
...Mixing T stage, 4...Blood 11 separator, 5...
+In II input l, 6...Non-filtrate output lit,
7...lJ~liquid output ('', 8...liquid collection container, 9
and 10... Exhaust liquid discharge rj, II... Circulation port 1, I2... Liquid side pressure old, 1
;3...blood pressure gauge, 14...fl+'7 ring pump.

Claims (1)

[Claims] (2) A means for mixing a membrane surface scraping substance having a particle size that does not pass through the micropores of the plasma separation membrane into the plasma, and a means for circulating a mixed solution of the plasma and the substance over the membrane surface of the plasma separation membrane. A plasma separation device using membrane filtration, which is characterized by: