NL8402870A - METHOD AND DEVICE FOR TREATING BLOOD PLASMA - Google Patents

Description

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Method and device for treating blood plasma.

This invention relates to a method of treating blood plasma.

It is sometimes desirable to remove substances from blood plasma to obtain desired substances from the blood of donors or to remove unwanted substances from the blood of a patient.

For example, in U.S. Patent 4,243,532, it has been proposed to continuously treat plasma separated from the blood cells by flowing it through a purifying agent to which the impurities are adsorbed (examples: activated carbon, aluminum oxide, silicic acid, aluminosilicate, zirconium phosphate, zeolite and ion exchangers ) after which the treated plasma is combined again with the separated blood cells and returned to the patient.

It has now been found that blood plasma from which other blood components have been separated can be advantageously treated by adding to the plasma an agent for precipitating components therefrom, removing the resulting precipitate from the plasma and removing the precipitant from the plasma. before mixing it with the separated components.

In a preferred embodiment, the precipitant is a salt, most preferably Na 2 SO 4. Preferably, further, the immunoglobulins are precipitated, and preferably the blood is continuously withdrawn from a patient and the treated plasma is continuously combined with the separated blood components and returned to the patient.

To form the precipitate, the excipient can be added directly to the plasma, but also by dialysis. Supplementary fluid 840 28 70 - 2 - * can be added to the treated plasma before returning it to the patient, and the plasma concentration can be monitored by measuring the optical density of the plasma after the excipient has been added but before precipitation is removed.

The preferred apparatus for carrying out the method comprises a microporous membrane part for separating the plasma from the other blood components, a microporous membrane filter for separating the precipitate, a dialyzer for removing the precipitant and excess water, and a by-pass valve for introducing separated plasma directly into a return pipe in case the conductivity of the treated plasma is not within the limits of acceptability.

A preferred embodiment of the invention will now be described with reference to the accompanying drawing which is a schematic of a blood plasma treatment apparatus according to the invention.

The device is a device 10 for continuously treating blood B1 which comes from a patient via line 12 and returns as treated blood Bq via line 14 to that patient. Line 12 connects to a peristaltic blood pump 16 and to a membrane separator 18 (the structure and operation of which is described in U.S. Patent Application 307,489 filed October 1, 1981); it delivers plasma P to outlet 20 and a concentrated mixture Bc of other blood components to outlet 22.

Peristaltic pump 28 passes both plasma line 24 connecting to outlet 20 and line 26 connecting to a supply of Na 2 SO 2 solution at a strength of 24 g / 100 ml. The inner cross-section of pipes 24 and 26 are chosen such that the ratio between the flow rates of Na 2 SO 2 solution and plasma is 3.9: 1. Beyond pump 28, plasma line 24 connects to by-pass valve 30 (with which the plasma goes directly to return line 14 in appropriate cases) and then connects to line 26 at line 32, whereupon immunoglobulins precipitate.

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Plasma / salt line 34 connects terminal 32 to filter 36, which in construction corresponds to the pleated membrane dialyser described in U.S. Patent 4,239,625, except that in this case an approximately 0.17 ram thick microporous membrane is used. whose pores are on average 0.6 jsa. that there are Vexar retainers on either side of the pleated membrane, and that the tips of the membrane folds need not be potted. The plasma enters the dialyser through the blood inlet and exits 10 (on the other side) through the dialysate outlet, and the other blood connection and dialysate connection are blocked.

Downstream of the filter 36, there is a salt-removing dialyzer system 38 consisting of three series-connected dialyzers, each similar in construction to that of U.S. Patent 4,239,625, except that in the first two dialyzers the membranes are "high". flux membranes Enka 280 HDF ”of 1.9 m2. Dialyzer system 38 is connected to a dialysate preparation and supplying device (eg corresponding to the Centry 2 system of the Cobe Laboratories in Lakewood,

Colorado, described in U.S. Patent 3,990,973).

The dialysate is generally of standard quality.

Downstream of the dialysis system 38, there is a peristaltic dual-line return pump 40 through which both plasma line 42 and supplement line 44 pass. Pipes 42 and 44 are the same size so that equal flow rates pass through if there are no clamps. In conduit 42 there is a conductivity meter 64. in conduit 44 there is an air detector 46 and a tap 48 which prevents flow through conduit 44 when no make-up liquid is added.

Pipes 42 and 44 converge at point 50 and that is connected by line 52 to connection point 54, but via bypass valve 30 (which in the unusual position not only plasma 35. line 24 on return line 14 but also line 52 at connection point 32). From point 54, the treated blood returns to the patient through return line 14.

Drain lines 56 and 58 with associated valves 60 and 62 for drawing samples are on lines 34 and 42.

5 When used, a patient is connected to lines 12 and 14. Blood pump 16, double plasma pump 28, return pump 40 and separator 18 are controlled as described in U.S. Patent Application 307,489, whereby part 18 separates plasma and blood cells without damage to the cells, in connection point 32, 3.9 parts Dilute 24% Na 2 SO 4 solution with 1 dl of plasma to give a plasma / salt combination with 19 g of Na 2 SO 4 per 100 ml in line 34. At that Na2SO4 concentration, immunoglobulin and other proteins precipitate rapidly, and the precipitate 15 is removed in filter 36, which filter has sufficient capacity upstream of the membrane to store the immunoglobulin precipitate that, in the treatment of a single patient, with normal immunoglobulin concentrations. Na2SC> 4 and excess water (the latter by mixing 1 part of plasma with 3.9 parts of saline in point 32) are removed in dialysis system 38 and the treated plasma is pumped by pump 40 to connection point 54, where it is Concentrate B rich in blood cells is mixed,

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and from there it goes back to the patient. The rate of pump 40 is related to that of pump 28; they often run just as fast when valve 48 is closed and pump 40 gives half the flow of pump 28 when valve 48 is open, so that the flow returned to the patient is the same as that which was drawn from it. The flow rate of pump 40 can also be varied to influence the ultrafiltration performed in dialysis system 38.

If an incorrect conductivity is found by detector 64 during operation, bypass valve 30 is operated so that blood plasma from line 24 goes directly to terminal 35 54 and line 52 is connected to terminal 32.

Other embodiments of the invention are also possible, all of which are within the scope of this invention.

In the most preferred embodiment, the device does not include an aid for separating other blood components from the plasma, but is instead designed to interface with the Cobe Laboratories therapeutic plasma exchange system described in the aforementioned U.S. Patent Application. In that embodiment, conduit 24 is connected such that the plasma gets from the plasma pump of that exchange system and conduit 52 is connected to the connection point of that system corresponding to point 54, where bypass tap 30 is replaced by a similar type of tap in conduit 24 but then upstream of pump 28 and line 52. That embodiment could also be used with other aids for separating other blood components from the plasma.

Other precipitants and in other concentrations can also be used, which influences the nature of the precipitate that is generated. Other salts that precipitate proteins * 20 are those with ions in the Hofmeister series, including so "2, PO ~ 3, F'1, Cl-1, Br-1, f \ No" 1, CIO * 1, US- 1 (in order of decreasing precipitant capacity, see F. Franks, "Solvent Mediated Influence on Conformation and Activity of Proteins", (Symposium Press, London), p. 45). Also, the precipitating salt may be added gradually, for example, by using a dialyser instead of a terminal 32. Other tools may also be used to remove precipitate and precipitating salt or to separate the plasma from the other blood components -30 | 8402870 ii

Claims (19)

A method of treating blood plasma, wherein said plasma is separated from other blood components, the plasma is subjected to a treatment and the treated plasma is combined again with those other blood components, characterized in that the blood plasma from which those other components are separated treated by adding to the plasma an auxiliary agent for precipitating components therefrom, removing the resulting precipitate from the plasma and removing the precipitant from the plasma before mixing it with the previously separated blood components. Method according to claim 1, characterized in that the precipitating aid is a salt. Method according to claim 2, characterized in that the removal of the precipitating auxiliary consists of dialysis and the removal of excess liquid by ultrafiltration. 4. A method according to claim 2, characterized in that the removal of the precipitate consists of filtration. Process according to claim 4, characterized in that it is filtered through a microporous membrane. 6. A method according to any one of the preceding claims, wherein blood is drawn from a patient, the said separating and separating treatments are then performed and the treated plasma is returned to that patient together with the other blood components. 7. A method according to any one of the preceding claims, characterized in that immunoglobulins are separated from the plasma. Process according to any one of claims 2 to 7, characterized in that the salt used is Na 2 SO 4. 9. A method according to any one of claims 6, 7 or 8, characterized in that an additional liquid is added to the treated plasma before it is returned to the patient. 84 0 28 7 0 10. A method according to any one of the preceding claims, wherein plasma and adjuvant for two-pipe precipitation are supplied by a single peristaltic pump, so that the volume ratio between those two liquids is constant. A method according to any one of claims 2 to 10, wherein the conductivity of the plasma is monitored after the precipitating auxiliary has been removed therefrom, and a by-pass valve is operated if necessary to prevent in case of incorrect conductivity the treated blood returns to the patient. 12. Apparatus for treating blood plasma, containing devices for the continuous reception of plasma from which other blood components have been separated, and for continuously returning said plasma and mixing it with the blood components previously separated therefrom after said plasma has been treated, characterized in that there are also auxiliaries for adding an auxiliary agent which precipitates certain components from the plasma , to remove the precipitate from the plasma, and to remove the precipitating excipient from the plasma. Device according to claim 12, characterized in that there are also aids for separating certain blood components from the plasma. 14. Device according to claim 12 or 13, characterized in that the auxiliary means for removing the precipitating auxiliary is a dialyzer. j 15. Device as claimed in any of the claims 12, 13 or 14, characterized in that the precipitate removal aid is a filter. 16. Device according to claim 15, characterized in that the filter has a microporous membrane. 84 0 28 7 0 * r * * · - 8 - Device according to any one of claims 12 to 16, characterized in that it additionally has auxiliary means for continuously drawing blood from a patient and continuously returning the treated blood to that patient. 18. Method mainly according to the description. 19. Device mainly according to description and / or drawing. 10 84028 70