CA1151044A - Blood treatment apparatus and method of treating blood - Google Patents
Blood treatment apparatus and method of treating bloodInfo
- Publication number
- CA1151044A CA1151044A CA000375402A CA375402A CA1151044A CA 1151044 A CA1151044 A CA 1151044A CA 000375402 A CA000375402 A CA 000375402A CA 375402 A CA375402 A CA 375402A CA 1151044 A CA1151044 A CA 1151044A
- Authority
- CA
- Canada
- Prior art keywords
- plasma
- membrane module
- blood
- fraction
- pump
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
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- 239000008280 blood Substances 0.000 title claims abstract description 103
- 238000011282 treatment Methods 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 23
- 238000005194 fractionation Methods 0.000 claims abstract description 14
- 239000012528 membrane Substances 0.000 claims description 184
- 239000011148 porous material Substances 0.000 claims description 21
- 102000007562 Serum Albumin Human genes 0.000 claims description 16
- 108010071390 Serum Albumin Proteins 0.000 claims description 16
- 210000002966 serum Anatomy 0.000 claims description 16
- 239000012466 permeate Substances 0.000 claims description 5
- 238000005086 pumping Methods 0.000 claims description 4
- 238000000926 separation method Methods 0.000 abstract description 14
- 239000000126 substance Substances 0.000 abstract description 6
- 102000009027 Albumins Human genes 0.000 abstract description 5
- 108010088751 Albumins Proteins 0.000 abstract description 5
- 108010074605 gamma-Globulins Proteins 0.000 abstract description 5
- 208000023275 Autoimmune disease Diseases 0.000 abstract description 4
- 206010003210 Arteriosclerosis Diseases 0.000 abstract description 3
- 208000011775 arteriosclerosis disease Diseases 0.000 abstract description 3
- 230000002093 peripheral effect Effects 0.000 abstract description 3
- 238000005374 membrane filtration Methods 0.000 abstract description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 2
- 206010065929 Cardiovascular insufficiency Diseases 0.000 abstract 1
- 210000004379 membrane Anatomy 0.000 description 112
- 230000001276 controlling effect Effects 0.000 description 13
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- 238000012544 monitoring process Methods 0.000 description 7
- 229920000219 Ethylene vinyl alcohol Polymers 0.000 description 6
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- RZXDTJIXPSCHCI-UHFFFAOYSA-N hexa-1,5-diene-2,5-diol Chemical compound OC(=C)CCC(O)=C RZXDTJIXPSCHCI-UHFFFAOYSA-N 0.000 description 5
- 229920002451 polyvinyl alcohol Polymers 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
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- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 description 3
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 description 3
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 3
- 210000000601 blood cell Anatomy 0.000 description 3
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- 238000002616 plasmapheresis Methods 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
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- DNZMDASEFMLYBU-RNBXVSKKSA-N hydroxyethyl starch Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O.OCCOC[C@H]1O[C@H](OCCO)[C@H](OCCO)[C@@H](OCCO)[C@@H]1OCCO DNZMDASEFMLYBU-RNBXVSKKSA-N 0.000 description 2
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- 108010044091 Globulins Proteins 0.000 description 1
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- 206010018367 Glomerulonephritis chronic Diseases 0.000 description 1
- 208000024869 Goodpasture syndrome Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
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- 208000031981 Thrombocytopenic Idiopathic Purpura Diseases 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
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- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
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- 238000000502 dialysis Methods 0.000 description 1
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- 239000003792 electrolyte Substances 0.000 description 1
- 239000000727 fraction Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 238000002615 hemofiltration Methods 0.000 description 1
- 230000001951 hemoperfusion Effects 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
- A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
- A61M1/3472—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate
- A61M1/3482—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration with treatment of the filtrate by filtrating the filtrate using another cross-flow filter, e.g. a membrane filter
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
- A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
- A61M1/3621—Extra-corporeal blood circuits
- A61M1/3639—Blood pressure control, pressure transducers specially adapted therefor
Abstract
TITLE OF THE INVENTION
BLOOD TREATMENT APPARATUS AND METHOD OF TREATING BLOOD
ABSTRACT OF THE DISCLOSURE
The invention provides a blood treatment apparatus realizing double-step-membrane filtration, namely separation of blood into plasma and a corpuscular fraction and separation of high-molecular-weight substances (e.g. gamma-globulin) in the plasma from low-molecular-weight substances (e.g. albumin), as well as a method of treating blood.
The apparatus and method are effective e.g. in the treat-ment of blood of patients with peripheral circulatory insuf-ficiency due to arteriosclerosis and of patients with rheumatoid arthritis, which is an autoimmune disease.
BLOOD TREATMENT APPARATUS AND METHOD OF TREATING BLOOD
ABSTRACT OF THE DISCLOSURE
The invention provides a blood treatment apparatus realizing double-step-membrane filtration, namely separation of blood into plasma and a corpuscular fraction and separation of high-molecular-weight substances (e.g. gamma-globulin) in the plasma from low-molecular-weight substances (e.g. albumin), as well as a method of treating blood.
The apparatus and method are effective e.g. in the treat-ment of blood of patients with peripheral circulatory insuf-ficiency due to arteriosclerosis and of patients with rheumatoid arthritis, which is an autoimmune disease.
Description
il~10~
B~C~GROUND OF`T~!E INVENTION
Field of the Invention This invention relates to a blood treatment apparatus with an extracorporeal circuit, and more particularly to a blood treatment apparatus with two membrane modules different in performance. It also relates to a method of treating blood.
Description of the Prior Art Various blood treatment techniques such as hemodialysis using a dialysis membrane, hemofiltration with a filtration membrane and hemoperfusion with an adsorbent, among others, have come into wide clinieal use. Recently, a teehnique eall-ed plasmapheresis, whieh is one of the extracorporeal blood treatment teehniques, has been developed. Said plasmapheresis comprises first separating blood into plasma and corpuscular components and then treating the plasma by a certain teehnique, thereby removing pathogenie faetors. More detailedly, plasma-pheresis ineludes the plasma exchange method in whieh the plasma is exchanged for a plasma preparation and the specifie plasma component permeation method which comprises further fractionating the plasma, removing the problematic fraetion and returning the remaining fraetions, together with the eor-puscular eomponents, to the circulation. When viewed as a therapeutic means, the plasma exchange method is not always preferable beeause the whole amount of the plasma should be exchanged and therefore a large amount of a plasma preparation and a great expense therefor are required and because some adverse effects may be produced due to incomplete supplemen-tation of various physiologie substanees eontained in the plasma. On the contrary, the speeifie plasma eomponent per-meation method ean be regarded as a more desirable therapeutic .
~k ~1~10~
means, since only a part of the plasma is discarded while therest is returned to the circulation, whereby the two problems mentioned above can greatly be improved.
Pioneer studies o such specific plasma component permeation method have already been made and described. For example, there is a report by T. Agishi et al, published in the Japanese Journal of Medical Instrumentation, vol. 49, Supplement, p. 259-261 (1979). Also, a Japanese patent application laid open under No. 2444/1980 discloses a blood treatment apparatus in which a specific plasma component permeation method is realized in combination with a water-removing means.
However, these techniques known in the art, though called techniques, are no more than proposals of possibilities or theoretical apparatus. No invention can be found therein for an apparatus useful in the medical practice.
SUMMARY OF THE INVENTION
The present inventors have conducted an intensive research on the specific plasma component permeation method using a membrane, and have succeeded in developing a system apparatus which can be put to practical use and thereby completed the present invention.
According to one aspect of the invention there is provided a blood treatment apparatus with a first and a second membrane module, said apparatus comprising: a blood inlet circuit including a first pump, a first membrane module means including a semipermeable membrane having pores of a size for retaining a blood corpuscular fractisn and for permeation of a plasma fraction connected to said blood inlet circuit plasma outlet circuit means for the plasma separated by the first membrane module means, said plasma outlet circuit means including a pressure adjustment unit comprising ll~iO~a~
at least a second pump means for adjusting the plasma pressure so that it is within the range of from about -40 mmHg to 40 mmHg; a second membrane module means including a semipermeable membrane having pores of a size to permeate human blood serum albumin for plasma fractionation which fractionates the plasma from said plasma outlet circuit means into two fractions; plasma fraction outlet circuit means for expelling a high-molecular-weight fraction separated in the second membrane module means, said fraction outlet circuit means including a third pump positioned downstream of said second membrane module means; blood return circuit means for receiving a low-molecular weight fraction containing human blood serum albumin separated in the second membrane module means and combining the same with blood corpuscular fraction separated in the first membrane module means; and means for controlling the ratio between the rate of flow of the plasma flowing into the second membrane module means and the rate of the plasma fraction to be expelled from same to a predetermined value by controlling the flow rate ratio between said second and third pumps.
According to another aspect of the invention there is provided a method of treating blood comprising: separating plasma from the blood in a first membrane module utilizing a semipermeable membrane having pores of a size retaining a blood corpuscular fraction and permeating a plasma fraction;
pumping said plasma through a plasma outlet circuit having a first pump; adjusting the plasma pressure in said plasma outlet circuit to maintain said pressure in a range from about -40 mmHg to 40 mmHg; fractionating said plasma in a second membrane module into two fractions utilizing a semi-permeable membrane having pores of a size permeating a human blood serum albumin fraction; expelling a high-molecular-. '1 ~. - 3 -10~4 weight fraction separated in the second membrane module through a plasma fraction outlet circuit having a second pump positioned downstream of said second membrane module;
combining the low-molecular-weight fraction containing human blood serum albumin separated in said second membrane module with the blood corpuscular fraction separated in said first membrane module; and adjusting the ratio between the rate of flow of the plasma flowing into said second membrane module and the rate of plasma fraction being expelled from said second membrane module to a predetermined value by controll-ing the flow rate between said first and second pumps.
BRIEF DESCRIPTION OF THE DRAWING
In the accompanying drawings, Fig. 1 to Fig. 3 each is aschematic representation of an embodiment of the blood treatment apparatus in accordance with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the present invention, separation of blood into plasma and corpuscular components and separation of the plasma into a high-molecular-weight and a low-molecular-weight fraction are carried out using two membrane modules of different kinds. These modules are called a plasma separation membrane module or a first membrane module and a plasma fraction fractionation membrane module or a second membrane module, respectively. The membrane to be used in the first membrane - 3a -~510~
module, i.e. to be used for separating corpuscular components from plasma, is a microporous membrane having an average effective pore size of 0.02-0.4 micron, preferably about 0.1 micron, and, generally, a homogeneous microporous membrane, a microfiltration membrane or a so-called asymmetrical mem-brane comprising a porous supporting layer and a relatively dense microporous layer is preferred. Pore sizes larger than 0.4 micron often lead to hemolysis, whereas pore sizes smaller than 0.02 micron cut off such proteins as gamma-globulin, hence cannot give a plasma containing these proteins. E~amples of such membrane are substantially uniform microporous membranes made of polyvinyl alcohol (PVA) type polymers, separately developed by one of the present inventors, as well as other substantially uniform microporous membranes and asymmetrical membranes made of ethylene-vinyl alcohol (EVA) copolymers, cellulose derivatives (e.g. cellulose acetates), polyolefins, polyacry~onitriles,polyamides, polyesters, polysulfones, and so on. Preferred among these are PVA, EVA, cellulose deriva-tive and polysulfone membranes, which have good biocompatibility.
The membrane used in the second membrane module separates plasma into a high-molecular-weight fraction and a low-molecular-weight fraction. The boundary molecular weight can optionally be set depending on the desired purpose. The apparatus of the present invention can be used in the treat-ment of autoimmune diseases and thus, in an embodiment, the - molecular-weight cut-off boundary can be set at 100,000.
Pathogenic substances in autoimmune diseases are often present in the form bound to gamma-globulin having a molecular of about 160,000. Therefore, it is desirable that substances`having 30 molecular weights of about 160,000 and higher be removed but .
iQ~4 substances having lower molecular weights such as albumin useful to the organism and having a molecular weight of 67,000 be returned. Thus, setting the boundary molecular weight at 100,000 can result in rigid separation of the above-mentioned gamma~globulin and albumin. The boundary of molecular-weight cut-off should be selected depending on the molecular weight of the pathogenic substance to be removed, and in another case where an immune complex is the causative factor, it is set at 100,000-200,000.
As the second membrane, therç can be used any membrane that can fractionate plasma under pressure. In this sense, membranes having ultrafiltration capacity can widely be used.
No special limitations are placed on the membrane structure, and the above-mentioned uniform mi~roporous membranes, asymmetrical membranes and uniform gel membranes can bé used.
The term "uniform gel membranes" as used herein means mem-branes substantially having no micropores or tiny gap struc-tures among joined particles when observed in the dry or wet state under an electron microscope even at a magnifisation of 24,000.
The membranes mentioned above are used in the form of flat membranes or hollow fiber membranes and constitute mem-brane modules. In view of easiness of module preparation and possibility of miniaturization, hollow fiber membranes are preferred.
Fig. 1 is a schematic representation of an example of the blood treatment apparatus in accordance with the present in-vention. Referring to Fig. 1, blood is pumped through blood inlet circuit 3 equipped with pump Ml (1) and preferably also pressure gauge Pl (2) into plasma separation mem~rane module L~O~
4, where membrane 5 separates the blood into plasma and cor-puscular components. The plasma separated is pumped through plasma outlet circuit 9 equipped with pressure gauge P2 (8) and pump M2 (7) into plasma fractionation membrane module 10.
In the second membrane module, the plasma is fractionated by membrane 11, and the high-molecular-weight fraction is ex-pelled from the system through plasma fraction outlet circuit 14 equipped with pump M3 (12) and preferably also pressure gauge P3 for monitoring (13). The low-molecular-weight frac-tion which has permeated membrane 11 flows out through bloodreturn circuit 15. The corpuscular components coming from first membrane module 4 run through corpuscles outlet circuit 18 equipped with valve Vl (16) and preferably also pressure gauge Pl' for monitoring (17) and are combined with the low-molecular-weight plasma fraction coming through blood return circuit I5, to be returned to the organism.
Fig~-I shows only those consituents that are essential in the practice of the present invention. A drip chamber, a blood filter, a heparin infusion circuit,another plasma treatment module such as activated carbon column and so forth may be added thereto.
In the apparatus as shown in Fig. 1, the pressure indi-cated by pressure gauge P2 (8) is adjusted to a predetermined constant value by correlating pressure gauge P2 (8) with pump M2 (7)~ so that it can never become substantially negative.
For example, the number of revolutions of pump M2 is adjusted by an electric signal corresponding to the pressure indication of pressure gauge P2 so that the pressure on P2 can be kept constant. A characteristic feature of the apparatus of the present invention is that the apparatus is constructed so as to 1~10~4 maintain the pressure in the plasma outlet circuit at a con-stant level. Since the pressure exerted on blood in the first membrane module is also kept constant thereupon, such construction is very desirable for the purpose of preventing blood corpuscles from being damaged. It is also desirable that the pressure (Pl) exerted on blood by first pump Ml (1) be maintained at levels not exceeding a certain value, general-ly at 150 mmHg or below, preferably at 100 mmHg or below.
When easiness of handling in the practice is taken into con-sideration, the lowest limit value for Pl is about 0 mmHg.In addition to such conditions, it is also necessary to pre-vent the pressure on P2 in the plasma outlet circuit from be-coming substantially negative. The pressure which is not sub-stantially negative is -40 mmHg to 40 mmHg, preferably -20 mmHg to 20 mmHg. It is desirable that the pressure is in the neighborhood of 0 mmHg, i.e. atmospheric pressure. That the pressure on P2 becomes more negative means that a negative pressure is exerted also on first membrane 5 and the trans-membrane pressure (TMP) increases. Such increased TMP makes greater the differential pressure exertedon~the corpuscular components on the membrane surface, whereby the risk of cor-puscles being damaged is increased. Therefore, such excessive-ly negative pressure on P2 should be avoided. The TMP should preferably be not greater than 100 mmHg. Furthermore, a se-condary effect possibly produced by a negative pressure part in a blood treatment apparatus is that, if a part of the cir-cuit should be connected loosely, a foreign substance such as air would be allowed to penetrate into the circuit from the outside, which may lead to serious consequences. Adjustment of pressure on P2 so as not to become substantially nesative iiSl~ ~
is desirable also for prevention of such an accident.
Both first membrane _ and second membrane 11 change in performance with time due to adhesion of proteins and so on during blood treatment. Therefore, when the blood pressure exerted on membrane 5 is ~ept constant, the amount of plasma separated (Q3) changes with time. Since the second membrane module fractionates plasma under pressure, a change in amount of plasma entering the second membrane module will cause a change in the pressure condition and consequently a change in fractionation performance of the second membrane module.
Such a change must be avoided at any cost. For this end, the flow rate ratio between pump M2 (7) and pump M3 (12) must be adjust-ed to a constant value so that the pressure in the second membrane module can be kept constant even if the plasma amount Q3 is changing. Furthermore, for safety reasons, it is desir-able to provide the plasma fraction oùtlet circuit with pres-sure gaug~-~P3 (13) for directly monitoring the pressure in the second membrane module.
With a blood treatment apparatus constructed in the above manner, very good results can be obtained under a least possible influence on blood, since it is now possible to treat blood in a stable manner under conditions which produce a constant pres-sure on blood, without any substantial change in fractionation behavior of plasma.
Fig. 2 is a schematic representation of another example of the blood treatment apparatus in accordance with the present invention. Referring to Fig. 2, blood is pumped through blood inlet circuit 3 equipped with pump Ml (1) and preferably also with pressure gauge Pl (2) into plasma separation membrane ~, where the blood is separated into plasma and a corpuscular fraction by membrane 5. The plasma separated is pumped through plasma outlet circuit 9 equipped with flowmeter Fl (6), pump M2 (7) and preferably also pressure gauge P2 (8) into plasma frac-tionation membrane module _ . In the second membrane module, the plasma is fractionated by membrane 11, and the high-molecular-weight fraction is expelled through plasma fraction outlet cir-cuit 14 equipped with pump M3 (12) and preferably also with pressure gauge P3 (13). The low-molecular-weight fraction which has permeated membrane 11 is led out of the second memb-brane module through blood return circuit 15. The corpuscularfraction coming from first membrane module 4 runs through cor-puscles outlet circuit 18 equipped with valve Vl ~16) and pre-ferably also with pressure gauge Pl' (17) and is combined with the low-molecular-weight plasma fraction coming through blood return circuit 15, and the mixture is returned to the circulatory system of the organism.
! Fig. 2 shows only those constituents that are essential in the practice of the present invention. A drip chamber, a blood filter, a heparin infusion circuit, another plasma treatment module such as activated carbon and so forth may optionally be added. In the apparatus shown in Fig. 2, the amount, or rate of`flow, Q3, of plasma coming from first membrane module 4 is adjusted to a predetermined value by controlling valve Vl (16) and flowmeter Fl (6) in association with each other. Thus, valve 16 is adjusted by an appropriate means so that flowmeter 6 may indicate a constant value.
For example, opening and closing of valve 16 is controlled by an electric signal corresponding to the data furnished by the flowmeter. What is import with the first membrane module is that, in the plasma separation, damaging of blood corpuscles and consequential hemolysis can be prevented.
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To this end, the pressure Pl(2) produced by first pump Ml (1) is adjusted to 150 mmHg or below, preferably 100 mmHg or below. The lowest limit value is, as mentioned previously, about 0 mmHg. For observing the change of said pressure, it is preferable to provide pressure gauge Pl(2). Both first membrane 5 and second membrane 11 change in performance with time due to adhesion of proteins and so on during blood treat-ment. Therefore, even when the blood pressure on membrane 5 is kept constant, the amount of plasma separated, Q3, changes with time. To solve such problem, it is necessary to provide flowmeter Fl for directly monitoring plasma amount Q3 in the plasma outlet circuit.
¦ A characteristic feature of the apparatus of the present invention is that the apparatus is constructed so as to main-tain plasma amount ~3 at a constant level. This feature is in common with other embodiments of the invention to be men-tioned latér. When blood is treated at a constant plasma flow rate (Q3), the subsequent plasma fractionation can also be effected at a constant flow rate, so that blood treatment can be conducted as scheduled, therefore very efficiently from the viewpoint of therapeutic practice.
Furthermore, in the apparatus shown in Fig. 2, the pres-sure in plasma outlet circuit 9 (P2) must be adjusted so as not to become substantially negative by controllin~ flowmeter Fl (6) and pump M2 (7) in association with each other. A
negative pressure in circuit 9 produces a negative pressure on first membrane 5, whereby the transmembrane pressure (TMP) increases and consequently the differential pressure acting on the blood corpuscles on the membrane surface increases. The result is an increase in the risk of corpuscles being damaged, l~SiO ~
which should be avoided. As mentioned previously, the TMP
should preferably be not greater than 100 mmHg. Furthermore, a secondary effect possibly produced by a negative pressure part present in a blood treatment apparatus like the one in accordance with the invention is that, if a loosely connected part should be present in the circuit, a foreign matter such as air would penetrate into the circuit from the outside, which may lead to serious consequences. Also for prevention of such an accident, it is required that adjustment be made so as not to allow a negative pressure by controlling flowmeter Fl (6) and pump M2 (7) in association with each other. The pressure which is not substantially negative is a pressure not lower than -40 mmHg, preferably not lower than -20 mmHg. The upper limit is 40 mmHg or below, preferably 20 mmHg or below. A
pressure in the neighborhood of 0 mmHg, i.e. atmospheric pressure, is desirable.
The plasma introduced into plasma fractionation membrane module 10 is fractionated by membrane 11. Thus, the low-molecular-weight components permeate the membrane, while the high-molecular-weight components are excluded and expelIed from the system through pump M3. If the amount of plasma introduced, Q3, is constant, the amount of permeating components is determined by the amount of high-molecular-weight components that are expelled.
Therefore, the amount of low-molecular-weight components to be sent to the blood return circuit can be adjusted through the feed rate ratio between pump M2 and pump M3. Accordingly, in accordance with the present invention, the ratio of the amount of plasma which is introduced into module 10 to the amount of plasma which is withdrawn from said module is adjusted by con-trolling the flow rate ratio between pump M2 (7) and pump ~13 (12).
It is preferable to provide pressure gauge P3 (13) in the plasma fraction coutlet circuit for monitoring the pressure in said circuit.
The low-molecular-weight components which have permeated second membrane _ run through blood return circuit 15 and are combined with the corpuscular fraction from corpuscles outlet circuit 18 and returned to the organism.
Fig. 3 is a schematic representation of another blood treatment apparatus in accordance with the present invention.
As is evident on comparlson between Fig. 2 and Fig. 3, both the apparatus shown therein have common parts, with respect to which repeated description is avoided.
The plasma fraction separated in first membrane module 4 is sent our into plasma outlet circuit 9 equipped with pres-sure gauge P2 (8) and pump M2 (7) As compared with the apparatus shown in Fig. 2, the apparatus shown in Fig. 3 differs in that flowmeter Fl is absent and pressure gauge P2 is essential. In this apparatus, too, pump M2 (7) is adjusted so that the plasma outlet amount, Q3, can be kept at a pre-determined value. Furthermore, pressure gauge P2 (8) andvalve Vl (17) are controlled in association with each other so that the pressure within plasma outlet circuit 9 cannot become substantially negative. In addition, the plasma fractionation rate in the second membrane module is controlled by controlling the flow rate ratio between pump M2 (7) and pump M3 (12). The apparatus shown in Fig. 3 is composed of a smaller number of constituent parts as compared with the apparatus shown in Fig. 2, and has a simplified control circuit, and therefore reduction in manufacturing cost and facility of operation are expected.
~1~10~4 As a pressure adjustment unit comprising at least a pump (~12) for adjusting the plasma pressure so as not to become substantially negative, the pressure adjustment units as mentioned in FIG. l,2 and 3 are best ones,but the following pressure adjustment units are also used in this invention;
(l) pressure adjustment unit without controlling flou-meterFl(6) and pump~l2(7) in association with each other in FIG. 2.
B~C~GROUND OF`T~!E INVENTION
Field of the Invention This invention relates to a blood treatment apparatus with an extracorporeal circuit, and more particularly to a blood treatment apparatus with two membrane modules different in performance. It also relates to a method of treating blood.
Description of the Prior Art Various blood treatment techniques such as hemodialysis using a dialysis membrane, hemofiltration with a filtration membrane and hemoperfusion with an adsorbent, among others, have come into wide clinieal use. Recently, a teehnique eall-ed plasmapheresis, whieh is one of the extracorporeal blood treatment teehniques, has been developed. Said plasmapheresis comprises first separating blood into plasma and corpuscular components and then treating the plasma by a certain teehnique, thereby removing pathogenie faetors. More detailedly, plasma-pheresis ineludes the plasma exchange method in whieh the plasma is exchanged for a plasma preparation and the specifie plasma component permeation method which comprises further fractionating the plasma, removing the problematic fraetion and returning the remaining fraetions, together with the eor-puscular eomponents, to the circulation. When viewed as a therapeutic means, the plasma exchange method is not always preferable beeause the whole amount of the plasma should be exchanged and therefore a large amount of a plasma preparation and a great expense therefor are required and because some adverse effects may be produced due to incomplete supplemen-tation of various physiologie substanees eontained in the plasma. On the contrary, the speeifie plasma eomponent per-meation method ean be regarded as a more desirable therapeutic .
~k ~1~10~
means, since only a part of the plasma is discarded while therest is returned to the circulation, whereby the two problems mentioned above can greatly be improved.
Pioneer studies o such specific plasma component permeation method have already been made and described. For example, there is a report by T. Agishi et al, published in the Japanese Journal of Medical Instrumentation, vol. 49, Supplement, p. 259-261 (1979). Also, a Japanese patent application laid open under No. 2444/1980 discloses a blood treatment apparatus in which a specific plasma component permeation method is realized in combination with a water-removing means.
However, these techniques known in the art, though called techniques, are no more than proposals of possibilities or theoretical apparatus. No invention can be found therein for an apparatus useful in the medical practice.
SUMMARY OF THE INVENTION
The present inventors have conducted an intensive research on the specific plasma component permeation method using a membrane, and have succeeded in developing a system apparatus which can be put to practical use and thereby completed the present invention.
According to one aspect of the invention there is provided a blood treatment apparatus with a first and a second membrane module, said apparatus comprising: a blood inlet circuit including a first pump, a first membrane module means including a semipermeable membrane having pores of a size for retaining a blood corpuscular fractisn and for permeation of a plasma fraction connected to said blood inlet circuit plasma outlet circuit means for the plasma separated by the first membrane module means, said plasma outlet circuit means including a pressure adjustment unit comprising ll~iO~a~
at least a second pump means for adjusting the plasma pressure so that it is within the range of from about -40 mmHg to 40 mmHg; a second membrane module means including a semipermeable membrane having pores of a size to permeate human blood serum albumin for plasma fractionation which fractionates the plasma from said plasma outlet circuit means into two fractions; plasma fraction outlet circuit means for expelling a high-molecular-weight fraction separated in the second membrane module means, said fraction outlet circuit means including a third pump positioned downstream of said second membrane module means; blood return circuit means for receiving a low-molecular weight fraction containing human blood serum albumin separated in the second membrane module means and combining the same with blood corpuscular fraction separated in the first membrane module means; and means for controlling the ratio between the rate of flow of the plasma flowing into the second membrane module means and the rate of the plasma fraction to be expelled from same to a predetermined value by controlling the flow rate ratio between said second and third pumps.
According to another aspect of the invention there is provided a method of treating blood comprising: separating plasma from the blood in a first membrane module utilizing a semipermeable membrane having pores of a size retaining a blood corpuscular fraction and permeating a plasma fraction;
pumping said plasma through a plasma outlet circuit having a first pump; adjusting the plasma pressure in said plasma outlet circuit to maintain said pressure in a range from about -40 mmHg to 40 mmHg; fractionating said plasma in a second membrane module into two fractions utilizing a semi-permeable membrane having pores of a size permeating a human blood serum albumin fraction; expelling a high-molecular-. '1 ~. - 3 -10~4 weight fraction separated in the second membrane module through a plasma fraction outlet circuit having a second pump positioned downstream of said second membrane module;
combining the low-molecular-weight fraction containing human blood serum albumin separated in said second membrane module with the blood corpuscular fraction separated in said first membrane module; and adjusting the ratio between the rate of flow of the plasma flowing into said second membrane module and the rate of plasma fraction being expelled from said second membrane module to a predetermined value by controll-ing the flow rate between said first and second pumps.
BRIEF DESCRIPTION OF THE DRAWING
In the accompanying drawings, Fig. 1 to Fig. 3 each is aschematic representation of an embodiment of the blood treatment apparatus in accordance with the present invention.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the present invention, separation of blood into plasma and corpuscular components and separation of the plasma into a high-molecular-weight and a low-molecular-weight fraction are carried out using two membrane modules of different kinds. These modules are called a plasma separation membrane module or a first membrane module and a plasma fraction fractionation membrane module or a second membrane module, respectively. The membrane to be used in the first membrane - 3a -~510~
module, i.e. to be used for separating corpuscular components from plasma, is a microporous membrane having an average effective pore size of 0.02-0.4 micron, preferably about 0.1 micron, and, generally, a homogeneous microporous membrane, a microfiltration membrane or a so-called asymmetrical mem-brane comprising a porous supporting layer and a relatively dense microporous layer is preferred. Pore sizes larger than 0.4 micron often lead to hemolysis, whereas pore sizes smaller than 0.02 micron cut off such proteins as gamma-globulin, hence cannot give a plasma containing these proteins. E~amples of such membrane are substantially uniform microporous membranes made of polyvinyl alcohol (PVA) type polymers, separately developed by one of the present inventors, as well as other substantially uniform microporous membranes and asymmetrical membranes made of ethylene-vinyl alcohol (EVA) copolymers, cellulose derivatives (e.g. cellulose acetates), polyolefins, polyacry~onitriles,polyamides, polyesters, polysulfones, and so on. Preferred among these are PVA, EVA, cellulose deriva-tive and polysulfone membranes, which have good biocompatibility.
The membrane used in the second membrane module separates plasma into a high-molecular-weight fraction and a low-molecular-weight fraction. The boundary molecular weight can optionally be set depending on the desired purpose. The apparatus of the present invention can be used in the treat-ment of autoimmune diseases and thus, in an embodiment, the - molecular-weight cut-off boundary can be set at 100,000.
Pathogenic substances in autoimmune diseases are often present in the form bound to gamma-globulin having a molecular of about 160,000. Therefore, it is desirable that substances`having 30 molecular weights of about 160,000 and higher be removed but .
iQ~4 substances having lower molecular weights such as albumin useful to the organism and having a molecular weight of 67,000 be returned. Thus, setting the boundary molecular weight at 100,000 can result in rigid separation of the above-mentioned gamma~globulin and albumin. The boundary of molecular-weight cut-off should be selected depending on the molecular weight of the pathogenic substance to be removed, and in another case where an immune complex is the causative factor, it is set at 100,000-200,000.
As the second membrane, therç can be used any membrane that can fractionate plasma under pressure. In this sense, membranes having ultrafiltration capacity can widely be used.
No special limitations are placed on the membrane structure, and the above-mentioned uniform mi~roporous membranes, asymmetrical membranes and uniform gel membranes can bé used.
The term "uniform gel membranes" as used herein means mem-branes substantially having no micropores or tiny gap struc-tures among joined particles when observed in the dry or wet state under an electron microscope even at a magnifisation of 24,000.
The membranes mentioned above are used in the form of flat membranes or hollow fiber membranes and constitute mem-brane modules. In view of easiness of module preparation and possibility of miniaturization, hollow fiber membranes are preferred.
Fig. 1 is a schematic representation of an example of the blood treatment apparatus in accordance with the present in-vention. Referring to Fig. 1, blood is pumped through blood inlet circuit 3 equipped with pump Ml (1) and preferably also pressure gauge Pl (2) into plasma separation mem~rane module L~O~
4, where membrane 5 separates the blood into plasma and cor-puscular components. The plasma separated is pumped through plasma outlet circuit 9 equipped with pressure gauge P2 (8) and pump M2 (7) into plasma fractionation membrane module 10.
In the second membrane module, the plasma is fractionated by membrane 11, and the high-molecular-weight fraction is ex-pelled from the system through plasma fraction outlet circuit 14 equipped with pump M3 (12) and preferably also pressure gauge P3 for monitoring (13). The low-molecular-weight frac-tion which has permeated membrane 11 flows out through bloodreturn circuit 15. The corpuscular components coming from first membrane module 4 run through corpuscles outlet circuit 18 equipped with valve Vl (16) and preferably also pressure gauge Pl' for monitoring (17) and are combined with the low-molecular-weight plasma fraction coming through blood return circuit I5, to be returned to the organism.
Fig~-I shows only those consituents that are essential in the practice of the present invention. A drip chamber, a blood filter, a heparin infusion circuit,another plasma treatment module such as activated carbon column and so forth may be added thereto.
In the apparatus as shown in Fig. 1, the pressure indi-cated by pressure gauge P2 (8) is adjusted to a predetermined constant value by correlating pressure gauge P2 (8) with pump M2 (7)~ so that it can never become substantially negative.
For example, the number of revolutions of pump M2 is adjusted by an electric signal corresponding to the pressure indication of pressure gauge P2 so that the pressure on P2 can be kept constant. A characteristic feature of the apparatus of the present invention is that the apparatus is constructed so as to 1~10~4 maintain the pressure in the plasma outlet circuit at a con-stant level. Since the pressure exerted on blood in the first membrane module is also kept constant thereupon, such construction is very desirable for the purpose of preventing blood corpuscles from being damaged. It is also desirable that the pressure (Pl) exerted on blood by first pump Ml (1) be maintained at levels not exceeding a certain value, general-ly at 150 mmHg or below, preferably at 100 mmHg or below.
When easiness of handling in the practice is taken into con-sideration, the lowest limit value for Pl is about 0 mmHg.In addition to such conditions, it is also necessary to pre-vent the pressure on P2 in the plasma outlet circuit from be-coming substantially negative. The pressure which is not sub-stantially negative is -40 mmHg to 40 mmHg, preferably -20 mmHg to 20 mmHg. It is desirable that the pressure is in the neighborhood of 0 mmHg, i.e. atmospheric pressure. That the pressure on P2 becomes more negative means that a negative pressure is exerted also on first membrane 5 and the trans-membrane pressure (TMP) increases. Such increased TMP makes greater the differential pressure exertedon~the corpuscular components on the membrane surface, whereby the risk of cor-puscles being damaged is increased. Therefore, such excessive-ly negative pressure on P2 should be avoided. The TMP should preferably be not greater than 100 mmHg. Furthermore, a se-condary effect possibly produced by a negative pressure part in a blood treatment apparatus is that, if a part of the cir-cuit should be connected loosely, a foreign substance such as air would be allowed to penetrate into the circuit from the outside, which may lead to serious consequences. Adjustment of pressure on P2 so as not to become substantially nesative iiSl~ ~
is desirable also for prevention of such an accident.
Both first membrane _ and second membrane 11 change in performance with time due to adhesion of proteins and so on during blood treatment. Therefore, when the blood pressure exerted on membrane 5 is ~ept constant, the amount of plasma separated (Q3) changes with time. Since the second membrane module fractionates plasma under pressure, a change in amount of plasma entering the second membrane module will cause a change in the pressure condition and consequently a change in fractionation performance of the second membrane module.
Such a change must be avoided at any cost. For this end, the flow rate ratio between pump M2 (7) and pump M3 (12) must be adjust-ed to a constant value so that the pressure in the second membrane module can be kept constant even if the plasma amount Q3 is changing. Furthermore, for safety reasons, it is desir-able to provide the plasma fraction oùtlet circuit with pres-sure gaug~-~P3 (13) for directly monitoring the pressure in the second membrane module.
With a blood treatment apparatus constructed in the above manner, very good results can be obtained under a least possible influence on blood, since it is now possible to treat blood in a stable manner under conditions which produce a constant pres-sure on blood, without any substantial change in fractionation behavior of plasma.
Fig. 2 is a schematic representation of another example of the blood treatment apparatus in accordance with the present invention. Referring to Fig. 2, blood is pumped through blood inlet circuit 3 equipped with pump Ml (1) and preferably also with pressure gauge Pl (2) into plasma separation membrane ~, where the blood is separated into plasma and a corpuscular fraction by membrane 5. The plasma separated is pumped through plasma outlet circuit 9 equipped with flowmeter Fl (6), pump M2 (7) and preferably also pressure gauge P2 (8) into plasma frac-tionation membrane module _ . In the second membrane module, the plasma is fractionated by membrane 11, and the high-molecular-weight fraction is expelled through plasma fraction outlet cir-cuit 14 equipped with pump M3 (12) and preferably also with pressure gauge P3 (13). The low-molecular-weight fraction which has permeated membrane 11 is led out of the second memb-brane module through blood return circuit 15. The corpuscularfraction coming from first membrane module 4 runs through cor-puscles outlet circuit 18 equipped with valve Vl ~16) and pre-ferably also with pressure gauge Pl' (17) and is combined with the low-molecular-weight plasma fraction coming through blood return circuit 15, and the mixture is returned to the circulatory system of the organism.
! Fig. 2 shows only those constituents that are essential in the practice of the present invention. A drip chamber, a blood filter, a heparin infusion circuit, another plasma treatment module such as activated carbon and so forth may optionally be added. In the apparatus shown in Fig. 2, the amount, or rate of`flow, Q3, of plasma coming from first membrane module 4 is adjusted to a predetermined value by controlling valve Vl (16) and flowmeter Fl (6) in association with each other. Thus, valve 16 is adjusted by an appropriate means so that flowmeter 6 may indicate a constant value.
For example, opening and closing of valve 16 is controlled by an electric signal corresponding to the data furnished by the flowmeter. What is import with the first membrane module is that, in the plasma separation, damaging of blood corpuscles and consequential hemolysis can be prevented.
g il~10'~
To this end, the pressure Pl(2) produced by first pump Ml (1) is adjusted to 150 mmHg or below, preferably 100 mmHg or below. The lowest limit value is, as mentioned previously, about 0 mmHg. For observing the change of said pressure, it is preferable to provide pressure gauge Pl(2). Both first membrane 5 and second membrane 11 change in performance with time due to adhesion of proteins and so on during blood treat-ment. Therefore, even when the blood pressure on membrane 5 is kept constant, the amount of plasma separated, Q3, changes with time. To solve such problem, it is necessary to provide flowmeter Fl for directly monitoring plasma amount Q3 in the plasma outlet circuit.
¦ A characteristic feature of the apparatus of the present invention is that the apparatus is constructed so as to main-tain plasma amount ~3 at a constant level. This feature is in common with other embodiments of the invention to be men-tioned latér. When blood is treated at a constant plasma flow rate (Q3), the subsequent plasma fractionation can also be effected at a constant flow rate, so that blood treatment can be conducted as scheduled, therefore very efficiently from the viewpoint of therapeutic practice.
Furthermore, in the apparatus shown in Fig. 2, the pres-sure in plasma outlet circuit 9 (P2) must be adjusted so as not to become substantially negative by controllin~ flowmeter Fl (6) and pump M2 (7) in association with each other. A
negative pressure in circuit 9 produces a negative pressure on first membrane 5, whereby the transmembrane pressure (TMP) increases and consequently the differential pressure acting on the blood corpuscles on the membrane surface increases. The result is an increase in the risk of corpuscles being damaged, l~SiO ~
which should be avoided. As mentioned previously, the TMP
should preferably be not greater than 100 mmHg. Furthermore, a secondary effect possibly produced by a negative pressure part present in a blood treatment apparatus like the one in accordance with the invention is that, if a loosely connected part should be present in the circuit, a foreign matter such as air would penetrate into the circuit from the outside, which may lead to serious consequences. Also for prevention of such an accident, it is required that adjustment be made so as not to allow a negative pressure by controlling flowmeter Fl (6) and pump M2 (7) in association with each other. The pressure which is not substantially negative is a pressure not lower than -40 mmHg, preferably not lower than -20 mmHg. The upper limit is 40 mmHg or below, preferably 20 mmHg or below. A
pressure in the neighborhood of 0 mmHg, i.e. atmospheric pressure, is desirable.
The plasma introduced into plasma fractionation membrane module 10 is fractionated by membrane 11. Thus, the low-molecular-weight components permeate the membrane, while the high-molecular-weight components are excluded and expelIed from the system through pump M3. If the amount of plasma introduced, Q3, is constant, the amount of permeating components is determined by the amount of high-molecular-weight components that are expelled.
Therefore, the amount of low-molecular-weight components to be sent to the blood return circuit can be adjusted through the feed rate ratio between pump M2 and pump M3. Accordingly, in accordance with the present invention, the ratio of the amount of plasma which is introduced into module 10 to the amount of plasma which is withdrawn from said module is adjusted by con-trolling the flow rate ratio between pump M2 (7) and pump ~13 (12).
It is preferable to provide pressure gauge P3 (13) in the plasma fraction coutlet circuit for monitoring the pressure in said circuit.
The low-molecular-weight components which have permeated second membrane _ run through blood return circuit 15 and are combined with the corpuscular fraction from corpuscles outlet circuit 18 and returned to the organism.
Fig. 3 is a schematic representation of another blood treatment apparatus in accordance with the present invention.
As is evident on comparlson between Fig. 2 and Fig. 3, both the apparatus shown therein have common parts, with respect to which repeated description is avoided.
The plasma fraction separated in first membrane module 4 is sent our into plasma outlet circuit 9 equipped with pres-sure gauge P2 (8) and pump M2 (7) As compared with the apparatus shown in Fig. 2, the apparatus shown in Fig. 3 differs in that flowmeter Fl is absent and pressure gauge P2 is essential. In this apparatus, too, pump M2 (7) is adjusted so that the plasma outlet amount, Q3, can be kept at a pre-determined value. Furthermore, pressure gauge P2 (8) andvalve Vl (17) are controlled in association with each other so that the pressure within plasma outlet circuit 9 cannot become substantially negative. In addition, the plasma fractionation rate in the second membrane module is controlled by controlling the flow rate ratio between pump M2 (7) and pump M3 (12). The apparatus shown in Fig. 3 is composed of a smaller number of constituent parts as compared with the apparatus shown in Fig. 2, and has a simplified control circuit, and therefore reduction in manufacturing cost and facility of operation are expected.
~1~10~4 As a pressure adjustment unit comprising at least a pump (~12) for adjusting the plasma pressure so as not to become substantially negative, the pressure adjustment units as mentioned in FIG. l,2 and 3 are best ones,but the following pressure adjustment units are also used in this invention;
(l) pressure adjustment unit without controlling flou-meterFl(6) and pump~l2(7) in association with each other in FIG. 2.
(2) pressure adjustment unit controlling pressure gauge P2(8) and pump ~i2(7) in association with each other in stead of controlling flowmeter Fl(6) and pumpM2(7) in association with each other in FIG. 2.
(3) pressure adjustment unit controlling pressure gauge P2(8) and pump M2(7) in association with each other in FIG. 3.
~l~iiV`~
Furthermore, in accordance with the present invention, for supplementing that portion of plasma that has been removed in second filter 10, an albumin solution or hydroxy ethyl starch (HES) or other substitute fluids can be added to the treated plasma for introduction into the body of a patient.
In the practice of the present invention, in introducing such a substitute fluid, it is preferable that the rates of flow throught the pump for substitute fluid introduction and pump M3 (12) provided in high-molecular-weight fraction outlet circuit 14 are controlled in association with each other so that the amount of the high-molecular-weight fraction with-drawn be equal to the amount of the substitute fluid introduced. The substitute fluid can be introduced into the body neither too much nor too less.
In practicing the present invention, the associated control of pump M2 (7) and pump M3 (12) or of pump M3 (12) and the pump for substitute fluid introduction is preferably done by an electric means. Another possibility is that different inside diameters are given to the tubes connected to the respective pumps and the tubes are squeezed by one and the same driving roller, whereby the flow rates can be ad-justed according to the respective tube diameters.
The treatment system of the present invention can effectively be used in the treatment of the blood of patients with the following disorders: autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, chronic glomerulonephritis, Goodpasture syndrome, systemic lupus erythematosus, progressive systemic sclerosis, etc.
The following examples further illustrate the present invention.
:~Si~)~4 A first membrane module was constructed by incorp-orating into a cylindrical cartridge a polyvinyl alcohol hollow fiber membrane having a substantially uniform micro-porous structure with an average pore size of 0.04 micron, an inside diameter of 400 microns and membrane thickness of 200 microns, the membrane area being 0.15 m2. A second membrane module was prepared by incorporating into a cylindrical cartridge an ethylene-vinyl alcohol copolymer (EVA) hollow fiber membrane having an asymmetrical structure comprising a porous support layer and a microporous layer with an average micropore diameter of 110 angstroms, an inside diameter of 330 microns and a membrane thickness of 45 microns as disclosed in Japanese Patent Application Kokai (laid open) No.
35,969/1980, the membrane area being 0.9 m2. These membrane modules were built into the circuit shown in ~ig. 1, and the blood of a patient with peripheral circulatory disturbance due to corticotropin releasing factor (CRF) and arterio-sclerosis was treated.
For plasma separation in the first membrane module, the blood flow rate throught pump Ml was adjusted to 120 ml/
minute,and furthermore the pressure on Pl was maintained at 90 mmHg by adjusting valve Vl. The rate of flow of the plasma separated was about 30 ml/minute at the early stage but dropped to 20 ml/minute with the lapse of time. However, pump M2 and pressure gauge P2 were controlled in association with each other while monitoring by means of pressure gauge P2, so that gauge P2 always indicated a pressure within the range of 0 to -20 mmHg. In addition, pump M3 and pump M2 were controlled in association with each other, so that the flow ~1~10~
rate ratio therebetween was always 1/4. In this manner, the blood could be treated continuously for 2 hours. As a result, the percent immunoglobulin removal from the blood of the patient was 23%.
A first membrane module was constructed by incorp-orating a polyvinyl alcohol hollow fiber membrane having a substantially uniform microporous structure with an average pore size of 0.04 micron, an inside diameter of 400 microns and a membrane ~ickness of 200 microns into a cylindrical cartridge, the membrane area being 0.15 m2. Separately, a second membrane module was constructed by incorporating into a cylindrical cartridge an EVA hollow fiber membrane having an asymmetric structure comprising a porous support layer and a microporous layer with an average micropore diameter of 110 angstroms, an inside diameter of 330 microns and a membrane thickness of 45 microns Icf. Japanese Patent Application Kokai No. 35,969/1980), the membrane area being 0.9 m2. These membrane modules were built into the circuit shown in Fig. 2, and the blood of a patient with peripheral circulatory disturbance due to CRF and arteriosclerosis was treated.
For plasma separation in the first membrane module, plasma outlet rate Q3 was adjusted to 24 ml/minute on the average by controlling pump M2 while monitoring flowmeter Fl, and in addition, pump Ml and valve Vl were respectively adjusted so that pressure gauge Pl always indicated 100 mmHg.
The blood flow rate, Ql' was in the neighbourhood of 100 ml/
minute. The pressure gauge P2 always indicated a pressure within the range of 0 to -20 mmHg.
For fractionation of the plasma components coming ~l~iO~
from the first membrane module at a rate of 24 ml/minute into the second ;nembrane module, the flow rate ratio between pump M2 and pump M3 was adjusted to 4:1. Thus, the rate of dis-charge flow through pump M3 was about 6 ml/minute. The low-molecular-weight plasma fraction permeated the second membrane at a rate of 18 mllminute, and was combined with the concen-trated corpuscular fraction and returned to the patient. After continuoUs blood treatment in this manner for 3 hours, the percent immunoglobulin removal from the blood of the patient was 34%, and almost no changes were observed in electrolytes~
After the outbreak of the disease, the patient complained of a pain in the tiptoe, but after one blood treatment with this apparatus, the patient was free from such pain.
The same membrane modules (first and second) as used in Example 2 were built into the circuit shown in Fig. 3 for treatlng the blood of a patient with rheumatoid arthritis, an autoimmune disease. For plasma separation in the first membrane module, the blood flow rate (Ql) was adjusted to 120 ml/minute by controlling pump Ml, and the feed rate through~
pump M2 was adjusted to 22 ml/minute. Furthermore, a circuit was provided for control of valve Vl in association with pressure gauge P2 such that valve Vl was operated so as to maintaining the indication of gauge P2 within the range of 0 to -20 mmHg. The indication of pressure gauge Pl at that time was 80 mmHg. Hemolysis observed in this plasma separation procedure was 1 mg/dl as free hemoglobin. Thus was acheived ; good plasma separation with almost no substantial hemolysis.
The plasma sent out by pump M2 was deprived of high-molecular-weight fraction components in the second membrane module, then combined with the concentrated blood corpuscular fraction and returned to the patient. In this second membranefiltration, analysis revealed that the ratio between albumin and gamma-globulin (A/G) in the fluid expelled out of the system by pump M3 was 0.4. When compared with the ratio A/G
(0.6) for the plasma before filtration, this analytic result clearly indicates that a considerable amount of gamma-globulin was removed from the blood.
The flow rate ratio between pump M2 and pump M3 was adjusted to 4:1. Thus, the rate of discharge flow through pump M3 was about 5.5 ml/minute. The low-molecular-weight plasma fraction permeated the second membrane at a rate of 16.5 ml/minute, and was combined with the concentrated corpuscular fraction and returned to the patient.
_. ,
~l~iiV`~
Furthermore, in accordance with the present invention, for supplementing that portion of plasma that has been removed in second filter 10, an albumin solution or hydroxy ethyl starch (HES) or other substitute fluids can be added to the treated plasma for introduction into the body of a patient.
In the practice of the present invention, in introducing such a substitute fluid, it is preferable that the rates of flow throught the pump for substitute fluid introduction and pump M3 (12) provided in high-molecular-weight fraction outlet circuit 14 are controlled in association with each other so that the amount of the high-molecular-weight fraction with-drawn be equal to the amount of the substitute fluid introduced. The substitute fluid can be introduced into the body neither too much nor too less.
In practicing the present invention, the associated control of pump M2 (7) and pump M3 (12) or of pump M3 (12) and the pump for substitute fluid introduction is preferably done by an electric means. Another possibility is that different inside diameters are given to the tubes connected to the respective pumps and the tubes are squeezed by one and the same driving roller, whereby the flow rates can be ad-justed according to the respective tube diameters.
The treatment system of the present invention can effectively be used in the treatment of the blood of patients with the following disorders: autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, chronic glomerulonephritis, Goodpasture syndrome, systemic lupus erythematosus, progressive systemic sclerosis, etc.
The following examples further illustrate the present invention.
:~Si~)~4 A first membrane module was constructed by incorp-orating into a cylindrical cartridge a polyvinyl alcohol hollow fiber membrane having a substantially uniform micro-porous structure with an average pore size of 0.04 micron, an inside diameter of 400 microns and membrane thickness of 200 microns, the membrane area being 0.15 m2. A second membrane module was prepared by incorporating into a cylindrical cartridge an ethylene-vinyl alcohol copolymer (EVA) hollow fiber membrane having an asymmetrical structure comprising a porous support layer and a microporous layer with an average micropore diameter of 110 angstroms, an inside diameter of 330 microns and a membrane thickness of 45 microns as disclosed in Japanese Patent Application Kokai (laid open) No.
35,969/1980, the membrane area being 0.9 m2. These membrane modules were built into the circuit shown in ~ig. 1, and the blood of a patient with peripheral circulatory disturbance due to corticotropin releasing factor (CRF) and arterio-sclerosis was treated.
For plasma separation in the first membrane module, the blood flow rate throught pump Ml was adjusted to 120 ml/
minute,and furthermore the pressure on Pl was maintained at 90 mmHg by adjusting valve Vl. The rate of flow of the plasma separated was about 30 ml/minute at the early stage but dropped to 20 ml/minute with the lapse of time. However, pump M2 and pressure gauge P2 were controlled in association with each other while monitoring by means of pressure gauge P2, so that gauge P2 always indicated a pressure within the range of 0 to -20 mmHg. In addition, pump M3 and pump M2 were controlled in association with each other, so that the flow ~1~10~
rate ratio therebetween was always 1/4. In this manner, the blood could be treated continuously for 2 hours. As a result, the percent immunoglobulin removal from the blood of the patient was 23%.
A first membrane module was constructed by incorp-orating a polyvinyl alcohol hollow fiber membrane having a substantially uniform microporous structure with an average pore size of 0.04 micron, an inside diameter of 400 microns and a membrane ~ickness of 200 microns into a cylindrical cartridge, the membrane area being 0.15 m2. Separately, a second membrane module was constructed by incorporating into a cylindrical cartridge an EVA hollow fiber membrane having an asymmetric structure comprising a porous support layer and a microporous layer with an average micropore diameter of 110 angstroms, an inside diameter of 330 microns and a membrane thickness of 45 microns Icf. Japanese Patent Application Kokai No. 35,969/1980), the membrane area being 0.9 m2. These membrane modules were built into the circuit shown in Fig. 2, and the blood of a patient with peripheral circulatory disturbance due to CRF and arteriosclerosis was treated.
For plasma separation in the first membrane module, plasma outlet rate Q3 was adjusted to 24 ml/minute on the average by controlling pump M2 while monitoring flowmeter Fl, and in addition, pump Ml and valve Vl were respectively adjusted so that pressure gauge Pl always indicated 100 mmHg.
The blood flow rate, Ql' was in the neighbourhood of 100 ml/
minute. The pressure gauge P2 always indicated a pressure within the range of 0 to -20 mmHg.
For fractionation of the plasma components coming ~l~iO~
from the first membrane module at a rate of 24 ml/minute into the second ;nembrane module, the flow rate ratio between pump M2 and pump M3 was adjusted to 4:1. Thus, the rate of dis-charge flow through pump M3 was about 6 ml/minute. The low-molecular-weight plasma fraction permeated the second membrane at a rate of 18 mllminute, and was combined with the concen-trated corpuscular fraction and returned to the patient. After continuoUs blood treatment in this manner for 3 hours, the percent immunoglobulin removal from the blood of the patient was 34%, and almost no changes were observed in electrolytes~
After the outbreak of the disease, the patient complained of a pain in the tiptoe, but after one blood treatment with this apparatus, the patient was free from such pain.
The same membrane modules (first and second) as used in Example 2 were built into the circuit shown in Fig. 3 for treatlng the blood of a patient with rheumatoid arthritis, an autoimmune disease. For plasma separation in the first membrane module, the blood flow rate (Ql) was adjusted to 120 ml/minute by controlling pump Ml, and the feed rate through~
pump M2 was adjusted to 22 ml/minute. Furthermore, a circuit was provided for control of valve Vl in association with pressure gauge P2 such that valve Vl was operated so as to maintaining the indication of gauge P2 within the range of 0 to -20 mmHg. The indication of pressure gauge Pl at that time was 80 mmHg. Hemolysis observed in this plasma separation procedure was 1 mg/dl as free hemoglobin. Thus was acheived ; good plasma separation with almost no substantial hemolysis.
The plasma sent out by pump M2 was deprived of high-molecular-weight fraction components in the second membrane module, then combined with the concentrated blood corpuscular fraction and returned to the patient. In this second membranefiltration, analysis revealed that the ratio between albumin and gamma-globulin (A/G) in the fluid expelled out of the system by pump M3 was 0.4. When compared with the ratio A/G
(0.6) for the plasma before filtration, this analytic result clearly indicates that a considerable amount of gamma-globulin was removed from the blood.
The flow rate ratio between pump M2 and pump M3 was adjusted to 4:1. Thus, the rate of discharge flow through pump M3 was about 5.5 ml/minute. The low-molecular-weight plasma fraction permeated the second membrane at a rate of 16.5 ml/minute, and was combined with the concentrated corpuscular fraction and returned to the patient.
_. ,
Claims (12)
1. A blood treatment apparatus with a first and a second membrane module, said apparatus comprising:
a blood inlet circuit including a first pump, a first membrane module means including a semipermeable membrane having pores of a size for retaining a blood corpuscular fraction and for permeation of a plasma fraction connected to said blood inlet circuit plasma outlet circuit means for the plasma separated by the first membrane module means, said plasma outlet circuit means including a pressure adjustment unit comprising at least a second pump means for adjusting the plasma pressure so that it is within the range of from about -40 mmHg to 40 mmHg;
a second membrane module means including a semi-permeable membrane having pores of a size to permeate human blood serum albumin for plasma fractionation which fractionates the plasma from said plasma outlet circuit means into two fractions;
plasma fraction outlet circuit means for expelling a high-molecular-weight fraction separated in the second membrane module means, said fraction outlet circuit means including a third pump positioned downstream of said second membrane module means;
blood return circuit means for receiving a low-molecular weight fraction containing human blood serum albumin separated in the second membrane module means and combining the same with blood corpuscular fraction separated in the first membrane module means, and means for controlling the ratio between the rate of flow of the plasma flowing into the second membrane module means and the rate of the plasma fraction to be expelled from same to a predetermined value by controlling the flow rate ratio between said second and third pumps.
a blood inlet circuit including a first pump, a first membrane module means including a semipermeable membrane having pores of a size for retaining a blood corpuscular fraction and for permeation of a plasma fraction connected to said blood inlet circuit plasma outlet circuit means for the plasma separated by the first membrane module means, said plasma outlet circuit means including a pressure adjustment unit comprising at least a second pump means for adjusting the plasma pressure so that it is within the range of from about -40 mmHg to 40 mmHg;
a second membrane module means including a semi-permeable membrane having pores of a size to permeate human blood serum albumin for plasma fractionation which fractionates the plasma from said plasma outlet circuit means into two fractions;
plasma fraction outlet circuit means for expelling a high-molecular-weight fraction separated in the second membrane module means, said fraction outlet circuit means including a third pump positioned downstream of said second membrane module means;
blood return circuit means for receiving a low-molecular weight fraction containing human blood serum albumin separated in the second membrane module means and combining the same with blood corpuscular fraction separated in the first membrane module means, and means for controlling the ratio between the rate of flow of the plasma flowing into the second membrane module means and the rate of the plasma fraction to be expelled from same to a predetermined value by controlling the flow rate ratio between said second and third pumps.
2. The blood treatment apparatus of claim 1, wherein the pressure adjustment unit includes a pressure gauge; and means for controlling said second pump so as to prevent the pressure in the plasma outlet circuit means as indicated by said gauge from deviating from said range.
3. The blood treatment apparatus of claim 1 or 2 wherein the pressure in the plasma outlet circuit means is adjusted to -20 mmHg to 20 mmHg.
4. A blood treatment apparatus with a first and a second membrane module, comprising:
a blood inlet circuit including a first pump;
a first membrane module means including a semi-permeable membrane having pores for a size for retaining a blood corpuscular fraction and for permeation of a plasma fraction connected to said blood inlet circuit;
plasma outlet circuit means for the plasma separated by the first membrane module means, including a flowmeter and a second pump;
a second membrane module means including a semi-permeable membrane having pores of a size to permeate human blood serum albumin for plasma fractionation which fractionates the plasma from the plasma outlet circuit means into two fractions;
plasma fraction outlet circuit means for expelling a high-molecular-weight fraction separated in the second membrane module means, said fraction outlet circuit means including a third pump positioned downstream of said second membrane module means; and blood return circuit means for receiving a low molecular-weight fraction containing human blood serum albumin separated in the second membrane module means and combining same with the blood corpuscular fraction separated in the first membrane module means, said blood return circuit means including a valve, means for controlling said valve in association with said flowmeter for maintaining the pressure in the plasma outlet circuit means within a range of about -40 mmHg to 40 mmHg;
means for controlling the flow rate ratio between said second pump and said third pump so as to adjust the flow rate ratio between the plasma introduced into the second membrane module means and the plasma fraction to be expelled from same to a predetermined value.
a blood inlet circuit including a first pump;
a first membrane module means including a semi-permeable membrane having pores for a size for retaining a blood corpuscular fraction and for permeation of a plasma fraction connected to said blood inlet circuit;
plasma outlet circuit means for the plasma separated by the first membrane module means, including a flowmeter and a second pump;
a second membrane module means including a semi-permeable membrane having pores of a size to permeate human blood serum albumin for plasma fractionation which fractionates the plasma from the plasma outlet circuit means into two fractions;
plasma fraction outlet circuit means for expelling a high-molecular-weight fraction separated in the second membrane module means, said fraction outlet circuit means including a third pump positioned downstream of said second membrane module means; and blood return circuit means for receiving a low molecular-weight fraction containing human blood serum albumin separated in the second membrane module means and combining same with the blood corpuscular fraction separated in the first membrane module means, said blood return circuit means including a valve, means for controlling said valve in association with said flowmeter for maintaining the pressure in the plasma outlet circuit means within a range of about -40 mmHg to 40 mmHg;
means for controlling the flow rate ratio between said second pump and said third pump so as to adjust the flow rate ratio between the plasma introduced into the second membrane module means and the plasma fraction to be expelled from same to a predetermined value.
5. A blood treatment apparatus with a first and a second membrane module, comprising:
a blood inlet circuit including a first pump;
a first membrane module means including a semi-permeable membrane having pores of a size of retaining a blood corpuscular fraction and for permeation of a plasma fraction connected to said blood inlet circuit;
plasma outlet circuit means for the plasma separated in the first membrane module means, said plasma outlet circuit means including a pressure gauge and a second pump means;
a second membrane module means including a semi-permeable membrane having pores of a size to permeate human blood serum albumin for plasma fractionation which fractionates the plasma from the plasma outlet circuit means into two fractions;
plasma fraction outlet circuit means for expelling a high-molecular-weight fraction separated in the second membrane module means, said plasma fraction outlet circuit means including a third pump positioned downstream of said second membrane module means;
blood return circuit means for receiving a low molecular-weight fraction containing human blood serum albumin separated in the second membrane module means and combining it with the blood corpuscular fraction separated in the first membrane module means, said blood return circuit including a valve;
means for controlling said second pump so as to adjust the rate of flow of plasma from the first membrane module means to a predetermined rate;
means for controlling said valve in association with said pressure gauge so as to maintain the pressure in the plasma outlet circuit means within a range of about -40 mmHg to 40 mmHg; and means for controlling the flow rate ratio between the plasma flowing into the second membrane module means and the plasma fraction to be expelled from same to a predetermined value by controlling the flow rate ratio between said second pump and said third pump.
a blood inlet circuit including a first pump;
a first membrane module means including a semi-permeable membrane having pores of a size of retaining a blood corpuscular fraction and for permeation of a plasma fraction connected to said blood inlet circuit;
plasma outlet circuit means for the plasma separated in the first membrane module means, said plasma outlet circuit means including a pressure gauge and a second pump means;
a second membrane module means including a semi-permeable membrane having pores of a size to permeate human blood serum albumin for plasma fractionation which fractionates the plasma from the plasma outlet circuit means into two fractions;
plasma fraction outlet circuit means for expelling a high-molecular-weight fraction separated in the second membrane module means, said plasma fraction outlet circuit means including a third pump positioned downstream of said second membrane module means;
blood return circuit means for receiving a low molecular-weight fraction containing human blood serum albumin separated in the second membrane module means and combining it with the blood corpuscular fraction separated in the first membrane module means, said blood return circuit including a valve;
means for controlling said second pump so as to adjust the rate of flow of plasma from the first membrane module means to a predetermined rate;
means for controlling said valve in association with said pressure gauge so as to maintain the pressure in the plasma outlet circuit means within a range of about -40 mmHg to 40 mmHg; and means for controlling the flow rate ratio between the plasma flowing into the second membrane module means and the plasma fraction to be expelled from same to a predetermined value by controlling the flow rate ratio between said second pump and said third pump.
6. The blood treatment apparatus of claim 4 or 5 wherein the pressure in the plasma outlet circuit means is adjusted to -20 mmHg to 20 mmHg.
7. A method of treating blood comprising:
separating plasma from the blood in a first membrane module utilizing a semipermeable membrane having pores of a size retaining a blood corpuscular fraction and permeating a plasma fraction;
pumping said plasma through a plasma outlet circuit having a first pump;
adjusting the plasma pressure in said plasma outlet circuit to maintain said pressure in a range from about -40 mmHg to 40 mmHg;
fractionating said plasma in a second membrane module into two fractions utilizing a semipermeable membrane having pores of a size permeating a human blood serum albumin fraction;
expelling a high-molecular-weight fraction separated in the second membrane module through a plasma fraction outlet circuit having a second pump positioned downstream of said second membrane module;
combining the low-molecular-weight fraction containing human blood serum albumin separated in said second membrane module with the blood corpuscular fraction separated in said first membrane module; and adjusting the ratio between the rate of flow of the plasma flowing into said second membrane module and the rate of plasma fraction being expelled from said second membrane module to a predetermined value by controlling the flow rate between said first and second pumps.
separating plasma from the blood in a first membrane module utilizing a semipermeable membrane having pores of a size retaining a blood corpuscular fraction and permeating a plasma fraction;
pumping said plasma through a plasma outlet circuit having a first pump;
adjusting the plasma pressure in said plasma outlet circuit to maintain said pressure in a range from about -40 mmHg to 40 mmHg;
fractionating said plasma in a second membrane module into two fractions utilizing a semipermeable membrane having pores of a size permeating a human blood serum albumin fraction;
expelling a high-molecular-weight fraction separated in the second membrane module through a plasma fraction outlet circuit having a second pump positioned downstream of said second membrane module;
combining the low-molecular-weight fraction containing human blood serum albumin separated in said second membrane module with the blood corpuscular fraction separated in said first membrane module; and adjusting the ratio between the rate of flow of the plasma flowing into said second membrane module and the rate of plasma fraction being expelled from said second membrane module to a predetermined value by controlling the flow rate between said first and second pumps.
8. The method of claim 7 wherein the pressure in said plasma outlet circuit is adjusted to between -20 mmHg and 20 mmHg.
9. A method of treating blood comprising:
separating plasma from the blood in a first membrane module utilizing a semipermeable membrane having pores of a size retaining a blood corpuscular fraction and permeating a plasma fraction;
pumping said plasma through a plasma outlet circuit including a flowmeter and a first pump;
fractionating said plasma in a second membrane module into two fractions utilizing a semipermeable membrane having pores of a size permeating human blood serum albumin;
expelling a high-molecular-weight fraction separated in the second membrane module through a plasma fraction outlet circuit having a second pump positioned downstream of said second membrane module;
combining, in a blood return circuit having a valve, the low-molecular-weight fraction containing human blood serum albumin separated in said second membrane module with the blood corpuscular fraction separated in said first membrane module;
controlling said valve in association with said flowmeter so as to maintain the pressure in said plasma outlet circuit within a range of from about -40 mmHg to 40 mmHg; and adjusting the ratio between the rate of flow of the plasma flowing into said second membrane module and the rate of plasma fraction being expelled from said second membrane module to a predetermined value by controlling the flow rate between said first and second pumps.
separating plasma from the blood in a first membrane module utilizing a semipermeable membrane having pores of a size retaining a blood corpuscular fraction and permeating a plasma fraction;
pumping said plasma through a plasma outlet circuit including a flowmeter and a first pump;
fractionating said plasma in a second membrane module into two fractions utilizing a semipermeable membrane having pores of a size permeating human blood serum albumin;
expelling a high-molecular-weight fraction separated in the second membrane module through a plasma fraction outlet circuit having a second pump positioned downstream of said second membrane module;
combining, in a blood return circuit having a valve, the low-molecular-weight fraction containing human blood serum albumin separated in said second membrane module with the blood corpuscular fraction separated in said first membrane module;
controlling said valve in association with said flowmeter so as to maintain the pressure in said plasma outlet circuit within a range of from about -40 mmHg to 40 mmHg; and adjusting the ratio between the rate of flow of the plasma flowing into said second membrane module and the rate of plasma fraction being expelled from said second membrane module to a predetermined value by controlling the flow rate between said first and second pumps.
10. The method of claim 9 wherein the pressure in said plasma outlet circuit is adjusted to between -20 mmHg and 20 mmHg.
11. A method of treating blood comprising:
separating plasma from the blood in a first membrane module utilizing a semipermeable membrane having pores of a size retaining a blood corpuscular fraction and permeating a plasma fraction;
pumping said plasma through a plasma outlet circuit having a first pump and a pressure gauge;
fractionating said plasma in a second membrane module into two fractions utilizing a semipermeable membrane having pores of a size permeating human blood serum albumin;
expelling a high-molecular-weight fraction separated in the second membrane module through a plasma fraction outlet circuit having a second pump positioned downstream of said second membrane module;
combining, in a blood return circuit having a valve, the low-molecular-weight fraction containing human blood serum albumin separated in said second membrane module with the blood corpuscular fraction separated in said first membrane module;
controlling said first pump so as to adjust the rate of flow of plasma from the first membrane module to a predetermined rate;
controlling said valve in association with said pressure gauge so as to maintain the pressure in said plasma outlet circuit in a range from about -40 mmHg to 40 mmHg; and adjusting the ratio between the rate of flow of the plasma flowing into said second membrane module and the rate of plasma fraction being expelled from said second membrane module to a predetermined value by controlling the flow rate between said first and second pumps.
separating plasma from the blood in a first membrane module utilizing a semipermeable membrane having pores of a size retaining a blood corpuscular fraction and permeating a plasma fraction;
pumping said plasma through a plasma outlet circuit having a first pump and a pressure gauge;
fractionating said plasma in a second membrane module into two fractions utilizing a semipermeable membrane having pores of a size permeating human blood serum albumin;
expelling a high-molecular-weight fraction separated in the second membrane module through a plasma fraction outlet circuit having a second pump positioned downstream of said second membrane module;
combining, in a blood return circuit having a valve, the low-molecular-weight fraction containing human blood serum albumin separated in said second membrane module with the blood corpuscular fraction separated in said first membrane module;
controlling said first pump so as to adjust the rate of flow of plasma from the first membrane module to a predetermined rate;
controlling said valve in association with said pressure gauge so as to maintain the pressure in said plasma outlet circuit in a range from about -40 mmHg to 40 mmHg; and adjusting the ratio between the rate of flow of the plasma flowing into said second membrane module and the rate of plasma fraction being expelled from said second membrane module to a predetermined value by controlling the flow rate between said first and second pumps.
12. The method of claim 11 wherein the pressure in said plasma outlet circuit is adjusted to between -20 mmHg and 20 mmHg.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP50735/1980 | 1980-04-16 | ||
| JP5073680A JPS56145860A (en) | 1980-04-16 | 1980-04-16 | Devide for treating blood |
| JP5073580A JPS56145859A (en) | 1980-04-16 | 1980-04-16 | Treating device for blood |
| JP50736/1980 | 1980-04-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1151044A true CA1151044A (en) | 1983-08-02 |
Family
ID=26391190
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000375402A Expired CA1151044A (en) | 1980-04-16 | 1981-04-14 | Blood treatment apparatus and method of treating blood |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US4350594A (en) |
| EP (1) | EP0038203B1 (en) |
| CA (1) | CA1151044A (en) |
| DE (1) | DE3171458D1 (en) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4350156A (en) * | 1980-05-29 | 1982-09-21 | Japan Foundation For Artificial Organs | Method and apparatus for on-line filtration removal of macromolecules from a physiological fluid |
| SE427619B (en) * | 1981-10-05 | 1983-04-25 | Gambro Lundia Ab | A filtering |
| US4431545A (en) * | 1982-05-07 | 1984-02-14 | Pall Corporation | Microporous filter system and process |
| JPS58206758A (en) | 1982-05-28 | 1983-12-02 | 株式会社クラレ | Blood serum separation apparatus |
| EP0112510A1 (en) * | 1982-11-30 | 1984-07-04 | "Continental Belro" | Process and apparatus to control the concentration of specific substances in a liquid |
| DE3310727A1 (en) * | 1983-03-24 | 1984-10-04 | B. Braun Melsungen Ag, 3508 Melsungen | METHOD AND DEVICE FOR SELECTIVE, EXTRACORPORAL SEPARATION OF PATHOLOGICAL AND / OR TOXIC BLOOD COMPONENTS |
| DE3570188D1 (en) * | 1984-02-24 | 1989-06-22 | Kuraray Co | Apparatus for the treatment of plasma |
| DE3422435A1 (en) * | 1984-06-16 | 1986-01-16 | B. Braun Melsungen Ag, 3508 Melsungen | METHOD AND DEVICE FOR SELECTIVELY SEPARATING PATHOLOGICAL AND / OR TOXIC SPECIES FROM BLOOD OR BLOOD PLASMA USING FILTER CANDLES |
| US4708713A (en) * | 1984-11-16 | 1987-11-24 | Anisa Medical, Inc. | Method and system for removing immunosuppressive components from the blood of mammals |
| US4721564A (en) * | 1985-10-22 | 1988-01-26 | Kuraray Co., Ltd. | Apparatus for the filtration of plasma from blood |
| US4728430A (en) | 1986-02-10 | 1988-03-01 | Millipore Corporation | Diafiltration method |
| US4789482A (en) * | 1986-02-10 | 1988-12-06 | Millipore Corporation | Method for separating liquid compositions on the basis of molecular weight |
| US4828543A (en) * | 1986-04-03 | 1989-05-09 | Weiss Paul I | Extracorporeal circulation apparatus |
| US4689152A (en) * | 1986-05-02 | 1987-08-25 | The Dow Chemical Company | Apparatus and method for multistage membrane phase separation |
| JPS6362504A (en) * | 1986-09-02 | 1988-03-18 | Mitsubishi Rayon Eng Co Ltd | Method for concentrating organic component in aqueous solution containing same |
| DE3634763A1 (en) * | 1986-10-11 | 1988-04-28 | Josef Magasi | DEVICE AND METHOD FOR CLEANING BLOOD |
| JPH0696098B2 (en) * | 1988-05-27 | 1994-11-30 | 株式会社クラレ | Hollow fiber type fluid treatment equipment |
| US5234608A (en) * | 1990-12-11 | 1993-08-10 | Baxter International Inc. | Systems and methods for processing cellular rich suspensions |
| GB9218239D0 (en) * | 1992-08-27 | 1992-10-14 | Pall Corp | Processing of protein-containing body fluids |
| US5368555A (en) * | 1992-12-29 | 1994-11-29 | Hepatix, Inc. | Organ support system |
| AU2201295A (en) * | 1994-04-08 | 1995-10-30 | Amicon, Inc. | Method and apparatus for isolation and purification of biologically active complexes |
| AU2069695A (en) * | 1995-03-13 | 1996-10-02 | Ao Forschungsinstitut Davos | An extracorporeal blood treatment apparatus and method for removal of free circulating infectious agents |
| US5833860A (en) * | 1995-08-28 | 1998-11-10 | Millipore Investment Holdings Limited | Centrifugal adsorptive sample preparation device and method |
| US6054051A (en) | 1996-01-17 | 2000-04-25 | Genentech, Inc. | Tangential-flow filtration system |
| IL131266A0 (en) | 1999-08-05 | 2001-01-28 | N S T Neurosurvival Technologi | Peptides and pharmaceutical compositions comprising same |
| WO2000010673A1 (en) * | 1998-08-24 | 2000-03-02 | Nst Neurosurvival Technologies Ltd. | Apparatus and method for capturing particles with surface exposure of anionic phospholipids from biological fluids |
| IL125908A (en) | 1998-08-24 | 2005-05-17 | Nst Neurosurvival Technologies | Peptides and pharmaceutical compositions comprising same |
| DE19854338B4 (en) * | 1998-11-25 | 2005-11-17 | Ulrich Dr.med. Saueressig | Method and device for renal replacement therapy |
| US8535258B2 (en) * | 2000-03-24 | 2013-09-17 | Immunocept, L.L.C. | Hemofiltration methods for treatment of diseases in a mammal |
| US7291122B2 (en) * | 2000-03-24 | 2007-11-06 | Immunocept, L.L.C. | Hemofiltration methods for treatment of diseases in a mammal |
| US6787040B2 (en) * | 2000-05-16 | 2004-09-07 | Immunocept, L.L.C. | Method and system for colloid exchange therapy |
| US8597516B2 (en) * | 2000-05-16 | 2013-12-03 | Immunocept, L.L.C. | Methods and systems for colloid exchange therapy |
| DE60220220T2 (en) * | 2001-08-10 | 2008-01-17 | KURARAY CO., LTD, Kurashiki | Blood treatment system |
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| DE102007039939B4 (en) * | 2007-08-23 | 2013-03-14 | Albutec Gmbh | Device for saving diafiltrate |
| US8123713B2 (en) * | 2008-08-12 | 2012-02-28 | Caridian Bct, Inc. | System and method for collecting plasma protein fractions from separated blood components |
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| US9814822B2 (en) * | 2015-08-27 | 2017-11-14 | Fresenius Medical Care Holdings, Inc. | Plasma generation with dialysis systems |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3539200A (en) * | 1967-10-12 | 1970-11-10 | Eaton Yale & Towne | Vehicle safety device |
| US3579441A (en) * | 1968-04-19 | 1971-05-18 | Hydronautics | Blood purification by dual filtration |
| DE7013380U (en) * | 1970-04-11 | 1971-06-16 | Sartorius Membranfilter Gmbh | DEVICE FOR DIALYSIS OF HUMAN BLOOD. |
| US3946731A (en) * | 1971-01-20 | 1976-03-30 | Lichtenstein Eric Stefan | Apparatus for extracorporeal treatment of blood |
| FR2129164A5 (en) * | 1971-03-17 | 1972-10-27 | Rhone Poulenc Sa | |
| DE2342072B2 (en) * | 1973-08-21 | 1975-08-14 | Forschungsinstitut Berghof Gmbh, 7400 Tuebingen | Portable artificial kidney |
| GB1558370A (en) * | 1975-09-26 | 1979-12-28 | Asahi Chemical Ind | Blood treating apparatus |
| CH615821A5 (en) * | 1976-05-31 | 1980-02-29 | Giulio Gentile | |
| US4185629A (en) * | 1977-10-18 | 1980-01-29 | Baxter Travenol Laboratories, Inc. | Method and apparatus for processing blood |
| DE2828512A1 (en) * | 1978-06-29 | 1980-01-17 | Fresenius Chem Pharm Ind | METHOD AND DEVICE FOR REALIZING SUBSTANCES IN A BODY LIQUID, IN PARTICULAR BLOOD, WITH ENZYMES |
-
1981
- 1981-04-08 US US06/252,245 patent/US4350594A/en not_active Expired - Lifetime
- 1981-04-13 EP EP81301613A patent/EP0038203B1/en not_active Expired
- 1981-04-13 DE DE8181301613T patent/DE3171458D1/en not_active Expired
- 1981-04-14 CA CA000375402A patent/CA1151044A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| US4350594A (en) | 1982-09-21 |
| EP0038203B1 (en) | 1985-07-24 |
| EP0038203A3 (en) | 1982-02-03 |
| DE3171458D1 (en) | 1985-08-29 |
| EP0038203A2 (en) | 1981-10-21 |
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