CN105924497B - Inspissator - Google Patents
Inspissator Download PDFInfo
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- CN105924497B CN105924497B CN201610108598.5A CN201610108598A CN105924497B CN 105924497 B CN105924497 B CN 105924497B CN 201610108598 A CN201610108598 A CN 201610108598A CN 105924497 B CN105924497 B CN 105924497B
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- aqueous solution
- film
- inspissator
- protein
- concentrated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
- C07K1/14—Extraction; Separation; Purification
- C07K1/34—Extraction; Separation; Purification by filtration, ultrafiltration or reverse osmosis
Abstract
Inspissator.Coelomic fluid will be filtered and, it can be achieved that powerful concentration and ensuring the high-recovery of protein in the inspissator that is concentrated of the protein aqueous solution that generates.The seperation film (60) of inspissator (22) is constituted as follows: 60% or more and 80% porosity below when being scaled 200 μm of internal diameter of hollow-fibre membrane using the liquid level rising value of the seperation film of capillary rise method measurement is 60mm~150mm, when implementing makes the protein aqueous solution stoste of concentration 3g/dL obtain the enrichment process of the concentrate of protein aqueous solution with the logical liquid of 50mL/ minutes speed of flow velocity, meet condition (1), (2).(1) pressure difference is 500mmHg or less between maximum film when 5L protein aqueous solution stoste being concentrated, (2) when pressure difference is set as B between film when pressure difference is set as A, 5L protein aqueous solution stoste is concentrated between film when 2L protein aqueous solution stoste being concentrated, B/A≤1.6.
Description
Technical field
The present invention relates to the inspissators of the coelomic fluids such as ascites, hydrothorax, pericardial fluid.
Background technique
Such as the cure as difficultly curing ascites disease, there is following ascites filtering and concentrating intravenous method (Cell-free and again
Concentrated Ascites Reinfusion Therapy): ascites is acquired from patient, which is filtered, removal cancer is thin
The causative agents such as born of the same parents, bacterium generate the protein aqueous solution comprising albumin etc., the protein aqueous solution are concentrated later, will
The concentrate is re-injected to internal.
It is usually used in the concentration of above-mentioned protein aqueous solution to have the inspissator connecting with ascites treatment loop (referring to patent
Document 1,2).The inspissator has the seperation films such as hollow-fibre membrane in body interior, makes the moisture of protein aqueous solution by dividing
It separates for protein aqueous solution to be concentrated from film.
Existing technical literature
Patent document
Patent document 1: Japanese Unexamined Patent Publication 5-220219 bulletin
Patent document 2: Japanese Unexamined Patent Publication 5-168699 bulletin
Summary of the invention
Problems to be solved by the invention
However, the viscosity for the protein aqueous solution for being filtered by ascites etc. and being generated is high, protein adhesiveness is high, therefore,
Even if protein is also adhered to seperation film, and it is more that seperation film starts the case where generating blocking for a small amount of concentration of 1L or so.It opens
When beginning to generate blocking, moisture is difficult to the emptying aperture by seperation film, therefore, it is impossible to moisture removal is fully removed from protein aqueous solution,
It is difficult to realize 5 times or so of powerful concentration.Herein, concentration rate refers to, the protein aqueous solution amount before concentration is divided by dense
It is worth obtained from contracting liquid measure.On the other hand, it is desirable to when inhibiting blocking, if improving the porosity of seperation film, current protein
Also it can be leaked out together with moisture by the emptying aperture of seperation film.As a result, the egg in the protein solution (concentrate) being concentrated
The rate of recovery of white matter is lower.
The application is made in view of above-mentioned aspect, it is intended that the egg that will be filtered the coelomic fluids such as ascites and generate
In the inspissator that white matter aqueous solution is concentrated, realizes powerful concentration and ensure the high-recovery of protein.
The solution to the problem
The inventors of the present invention's discovery: by the way that the porosity of the seperation film of inspissator and hydrophilicity are adjusted to defined model
It encloses, so as to realize powerful concentration and realize high protein recovery, so far completes the present invention.
That is, the solution of the present invention includes following.
(a) a kind of inspissator, for the protein aqueous solution for filtering coelomic fluid and generating to be concentrated by seperation film
Inspissator,
Aforementioned separation membrane is constituted as follows: 60% or more and 80% porosity below and utilization capillary rise method are surveyed
The liquid level rising value of fixed aforementioned separation membrane is 60mm~150mm when being scaled 200 μm of internal diameter of hollow-fibre membrane, is implementing to make
The protein aqueous solution stoste of concentration 3g/dL leads to liquid with 50mL/ minutes speed of flow velocity and obtains the concentration of protein aqueous solution
In the case where the enrichment process of liquid, meet following conditions (1), (2).
(1) by 5L protein aqueous solution stoste be concentrated when maximum film between pressure difference be 500mmHg hereinafter,
(2) pressure difference is set as A, 5L protein aqueous solution stoste is dense between film when 2L protein aqueous solution stoste being concentrated
In the case that pressure difference is set as B between film when contracting, B/A≤1.6.
(b) inspissator according to (a), wherein aforementioned separation membrane is constituted as follows: in the feelings for implementing aforementioned enrichment process
Under condition, the following conditions of further satisfaction (3), (4).
(3) protein recovery of the concentrate obtained when 2L protein aqueous solution stoste being concentrated is 40% or more,
(4) protein recovery of the concentrate obtained when 5L protein aqueous solution stoste being concentrated is 70% or more.
(c) inspissator according to (b), wherein in aforementioned condition (4), 5L protein aqueous solution stoste is concentrated
When the obtained rate of recovery of the albumin of concentrate be 80% or more.
(d) inspissator according to any one of (a)~(c), wherein aforementioned separation membrane is constituted as follows: before implementation
In the case where stating enrichment process, further satisfaction is following (5).
(5) pressure difference is set as A, by 10L protein aqueous solution stoste between film when 2L protein aqueous solution stoste being concentrated
In the case that pressure difference is set as C between film when concentration, C/A≤1.5.
(e) inspissator according to any one of (a)~(d), wherein substrate used in aforementioned separation membrane is polysulfones
System, ethylene-vinyl alcohol system, acetate fiber prime system, polyethylene-based, polyester based polymer alloy (PEPA), polymethyl methacrylate
It is (PMMA) or polyacrylonitrile.
(f) inspissator according to any one of (a)~(e), wherein aforementioned separation membrane is hollow-fibre membrane.
(g) inspissator according to (f), wherein aforementioned separation membrane is the hollow-fibre membrane of polysulfones system.
The effect of invention
According to the present invention, coelomic fluid will be filtered and in the inspissator that is concentrated of the protein aqueous solution that generates, Ke Yishi
Existing powerful concentration and the high-recovery for ensuring protein.
Detailed description of the invention
Fig. 1 is the explanatory diagram for showing the summary of composition of ascites processing system.
Fig. 2 is the explanatory diagram of the longitudinal section of inspissator.
Fig. 3 is figure of the pressure difference relative to the variation of stoste concentration amount between showing film.
Fig. 4 is to be exaggerated schematic diagram obtained from seperation film.
Fig. 5 is the explanatory diagram for showing the summary of ascites processing system of embodiment.
Description of symbols
1 ascites processing system
22 inspissators
60 seperation films
Specific embodiment
Hereinafter, being illustrated referring to attached drawing to the preferred embodiment of the present invention.It should be noted that attached drawing is upper and lower
The positional relationships such as left and right are namely based on positional relationship shown in the drawings as long as no special provision.The dimensional ratios of attached drawing are unlimited
Due to the ratio of diagram.In turn, the following embodiments and the accompanying drawings is for illustrating example of the invention, is not only to be defined in the present invention
The embodiment.In addition, the present invention can be carried out various modifications without departing from its purport.
Fig. 1 is the ascites processing system 1 for being shown as having the body cavity liquid treating system of inspissator 22 of present embodiment
Composition summary explanatory diagram.
As shown in Figure 1, ascites processing system 1 has the ascites treatment loop 10 for example as fluid loop.Ascites
Treatment loop 10 includes the ascites bag 20 as coelomic fluid reservoir；Filter 21；Inspissator 22；As concentrate reservoir
Concentration ascites bag 23；Connect the first flow path 24 of ascites bag 20 and filter 21；Connect the of filter 21 and inspissator 22
Two flow paths 25；With connection inspissator 22 and the third flow path 26 that ascites bag 23 is concentrated.
Ascites bag 20 is, for example, the container formed by the resin of the soft property such as polyvinyl chloride, can store and adopt as from patient
The ascites of the coelomic fluid of collection.
Filter 21 has filter membrane 30, and the filter membrane 30 removes the specific cause of disease object such as cancer cell, bacterium from ascites
Matter, by the hollow-fibre membrane shape for passing through the protein aqueous solution (filtered fluid) comprising protein such as albumin in addition to this
At.In filter 21, such as ascites is supplied to from the entrance of the primary side (inside of hollow-fibre membrane) of filter membrane 30, the ascites
It is discharged by filter membrane 30 to the secondary side (outside of hollow-fibre membrane) of filter membrane 30, so as to filter ascites.Filter
The primary side of 21 filter membrane 30 exporting and not being connected to by the ingredient of filter membrane 30 by the not shown drain portion of drain.
In addition, such as ascites is supplied to from the entrance of the secondary side (outside of hollow-fibre membrane) of filter membrane 30, which passes through filtering
Film 30 is discharged to the primary side (inside of hollow-fibre membrane) of filter membrane 30, so that ascites can also be filtered.
First flow path 24 is, for example, the pipe of the soft property such as polyvinyl chloride, from the outlet of ascites bag 20 and the filtering of filter 21
The entrance of the primary side of film 30 connects.In first flow path 24 for example equipped with tube pump 40, the ascites of ascites bag 20 can be sent to mistake
Filter 21.It should be noted that tube pump 40 can also be not provided with and fall the ascites of ascites bag 20 by gravity and be supplied to
Filter 21.
Inspissator 22 has seperation film 60, and the seperation film 60 will be by that will pass through the moisture removal in the filtered fluid of filter 21
And the hollow-fibre membrane being concentrated is formed.Inspissator 22 has cylindrical container 50, in the inside of cylindrical container 50, along its length
It spends direction and is configured with seperation film 60.The inside (space) of seperation film 60 is provided in the upper and lower part of cylindrical container 50
Mouth 51,52, is provided with 2 mouths 53,54 in the outside (space) of seperation film 60 in the side surface part of cylindrical container 50.Inspissator
The mouth 51 on 22 top is connected to via second flow path 25 with filter 21.The mouth 52 of the lower part of inspissator 22 is via third flow path 26
It is connected to concentration ascites bag 23.The mouth 53 of the side surface part of inspissator 22 and the moisture removed are by the not shown drain of drain
Portion's connection.In addition, the mouth 54 of filter 22 is for example closed.In inspissator 22, such as protein aqueous solution is from seperation film 60
The entrance of primary side (inside of hollow-fibre membrane) is supplied to, moisture contained in the protein aqueous solution by seperation film 60 to
The secondary side (outside of hollow-fibre membrane) of seperation film 60 is detached from, so as to condensing protein aqueous solution.For inspissator 22
Composition details it is aftermentioned.
Second flow path 25 is, for example, the soft property pipes such as polyvinyl chloride, from the outlet of the secondary side of the filter membrane 30 of filter 21
It is connect with the mouth 51 of the primary side of the seperation film 60 of inspissator 22.It is for example provided with tube pump 70 in second flow path 25, it can will be by
The filtered fluid that filter 21 filters is sent to inspissator 22.
Third flow path 26 is, for example, the soft property pipes such as polyvinyl chloride, from the mouth 52 of the primary side of the seperation film 60 of inspissator 22
It is connect with concentration ascites bag 23.
Concentration ascites bag 23 is, for example, the container formed by the resin of the soft property such as polyvinyl chloride, can be stored comprising by dense
The concentrate for the protein that contracting device 22 is concentrated.
Then, the composition of inspissator 22 is illustrated.Fig. 2 is the longitudinal section for showing the summary of composition of inspissator 22
Explanatory diagram.
Inspissator 22 as described above there is cylindrical container 50 to match in the inside of cylindrical container 50 along its length direction
It is equipped with the seperation film 60 as hollow-fibre membrane.Cylindrical container 50 is by cylindric container body portion 50a and closed container main body
The top cover 50b of the both ends open of portion 50a is constituted.Mouth 51,52 is formed in top cover 50b, and mouth 53,54 is formed in container body portion 50a.
The both ends of seperation film 60 are at the both ends of cylindrical container 50 by the Embedding Material 80 of curable resin by encapsulating
Processing.Cylindrical container 50 is fixed at the both ends of seperation film 60 as a result, is formed with seperation film 60 at the both ends of cylindrical container 50
Each hollow-fibre membrane inside opening open end 81.The hollow-fibre membrane of the seperation film 60 of the inside of cylindrical container 50
Outer space is connected to the mouth 53,54 of the side surface part of cylindrical container 50.The inner space of the hollow-fibre membrane of seperation film 60 passes through
Open end 81 is connected to mouth 51,52.By above-mentioned composition, the protein aqueous solution as filtered fluid is from mouth 51 to seperation film 60
Inner space flow into, the moisture of the protein aqueous solution is flowed out by seperation film 60 to the outer space of seperation film 60, can be with
Moisture removal is removed from protein aqueous solution and is concentrated.The moisture flowed into the outer space of seperation film 60 can be from 53 row of mouth
Out.In addition, by the inner space of seperation film 60 eliminate the protein aqueous solution of moisture from mouth 52 to concentration ascites bag 23 with
The form of concentrate is discharged.
Seperation film 60 is constituted as follows: 60% or more and 80% porosity below and utilization capillary rise method measure
The liquid level rising value of aforementioned separation membrane be 60mm~150mm when being scaled 200 μm of internal diameter of hollow-fibre membrane, implement to make it is dense
The protein aqueous solution stoste of 3g/dL is spent to lead to liquid with 50mL/ minutes speed of flow velocity and obtain the concentrate of protein aqueous solution
Enrichment process P in the case where, meet following conditions (1), (2).
(1) pressure difference is 500mmHg or less between maximum film when 5L protein aqueous solution stoste being concentrated.
(2) pressure difference is set as A, 5L protein aqueous solution stoste is dense between film when 2L protein aqueous solution stoste being concentrated
In the case that pressure difference is set as B between film when contracting, B/A≤1.6.
That is, as shown in Figure 3, for seperation film 60, making the protein aqueous solution stoste of concentration 3g/dL with flow velocity
In the case that 50mL/ minutes speed is led to liquid and is concentrated in the seperation film 60, when 5L protein aqueous solution stoste is concentrated
Maximum film between pressure difference (maximum value of the difference of the pressure of the pressure and secondary side of the primary side of seperation film 60) be 500mmHg with
Under and B (by 5L protein aqueous solution stoste be concentrated when film between pressure difference)/A (and by 2L protein aqueous solution stoste be concentrated when
Pressure difference between film) it is that 1.6 modes below adjust porosity and hydrophilicity.Curve S1, S2, S3 in Fig. 3 show satisfaction
Above-mentioned condition (1), the seperation film of (2), curve S4, S5 show the condition of being unsatisfactory for (1), the seperation film of (2).
It should be noted that porosity is defined by following formula.
Porosity=(Y-X) × 100/Y
X: the weight of a certain amount of film
Y: it is assumed that weight when a certain amount of film of X is filled up by substrate (when not having gap).
In the present invention, porosity is necessary for 60% or more and 80% or less.More preferably 65% or more and 80% hereinafter, such as
Fruit is 65% or more and 75% or less then further preferred.When less than 60%, when concentration, is easy to produce blocking, and it is not preferable.Separately
Outside, when being greater than 80%, protein leakage when concentration becomes larger, for not preferably.Seperation film is flat membrane shape rather than doughnut
Porosity also is calculated using above-mentioned formula when membranaceous.
In the present invention, hydrophilicity is measured by capillary rise method.So-called capillary rise method refers in the present invention,
One end of the hollow opening oral area of the hollow-fibre membrane one side of flat membrane (the case where flat membrane for) is impregnated in aqueous solution, after a certain period of time
The method of the height of the water surface for the liquid level that measurement distance is risen using capillarity.Specifically refer to, at preceding place below
Reason (P), (Q), i.e. by seperation film with distilled water for injection cleaned (P), make seperation film sufficiently dry (Q) after, will dry
One end of seperation film afterwards is impregnated in aqueous solution, measures the water for the liquid level that distance is risen using capillarity after a certain time
The method of the height in face.
In the case where the seperation film of tubular structure, rise about capillary, it is commonly known to have relational expression below.
H=2 γ cos θ/r ρ g
H: the lifting height apart from liquid side
γ: the surface tension of liquid
θ: contact angle (from the contact surface of solid and liquid to the angle of liquid and the contact surface of gas)
R: pipe radius
ρ: the density of liquid
G: acceleration of gravity
That is, by measurement r (pipe radius), ρ (fluid density), h (lifting height apart from liquid side), so as to measure
The surface tension of liquid, according to the relational expression, tubular body structure inner surface is to the wet easiness of liquid, i.e. hydrophily, hydrophobic
Property degree can according to the liquid level in capillary rise degree and evaluate.
Therefore, doughnut inner surface can also be measured to water by above-mentioned capillary rise method in the case where seperation film
The degree of the wet easiness of solution, i.e. hydrophily (hydrophobicity).In addition, even if the seperation film different for internal diameter, passes through measurement
Liquid level rising value and internal diameter in each capillary carry out the internal diameter that the seperation film as benchmark is scaled according to the relationship of above formula
Correction, so as to by the degree of each hydrophily (hydrophobicity) using the shape of the liquid level rising value of the seperation film of the internal diameter as benchmark
Formula is absolutely compared.In the present invention, as liquid level rising value, the school that the internal diameter of hollow-fibre membrane is scaled to 200 μm is used
Positive value.When measuring the capillary rising value of seperation film, moisture rate, the internal diameter of seperation film impact measured value, it is therefore necessary to
Measured in advance moisture rate and internal diameter.Moisture rate as seperation film, it is necessary to for 5% hereinafter, when moisture rate is greater than 5%, seperation film
It is difficult to embody the hydrophobic property of substantially possessed inner surface, capillary rising value becomes to show big measurement
Value, can not accurately be measured.
When measuring the liquid level rising value of the aqueous solution based on capillarity, minute is also important.Seperation film
When being further hydrophily, the speed for the aqueous solution being gradually increasing becomes faster, and in the measurement in the short time, measured value can generate wave
It is dynamic.In addition, it is difficult to a large amount of samples of single-time measurement.Practical minute preferably by seperation film be impregnated in after aqueous solution by
At the time of 5 seconds or more, the appropriate time that is more practicably preferably set within 3 minutes.Value in the present invention, after showing 1 minute.
In the case that seperation film is flat membrane, hydrophilicity is investigated by contact angle (chemical brief guide etc.), or is set as using same
The liquid level rising value based on capillary rise method in 200 μm of internal diameter of hollow-fibre membrane of the same composition of one material.
In the present invention, the rising value of the aqueous solution measured by capillary rise method, the internal diameter of hollow-fibre membrane changed
It calculates and is necessary for 60mm or more and 150mm or less for 200 μm of corrected value.More preferably 65mm or more and 145mm hereinafter, if it is
70mm or more and 140mm or less are then further preferably.As described later, in the case where too low lower than 60mm, i.e. hydrophily, or
In the case where excessively high higher than 150mm, i.e. hydrophily, the constraint protein layer F1 of separation membrane surface also becomes blocked up, concentration rate
It reduces, it is not preferable.
When as shown in Figure 4, such as in seperation film 60 leading to liquid protein aqueous solution, total volume, that is, hole of the part 60a
When gap rate is high, when separation, is not likely to produce blocking, can carry out powerful concentration, be but then protein also with moisture one
It rises and passes through, the rate of recovery of protein reduces.Think by adjusting porosity to suitable range, it is permeable so as to ensure
It measures and passes through protein.
In turn, it will usually think, the egg that irreversibly accumulation has protein aqueous solution can be formed on the surface of seperation film 60
The constraint protein layer F1 of white matter and reversibly accumulation have the free protein layer F2 of protein.The constraint protein layer F1 and from
By protein layer F2 accumulate and thickness increase when, generate seperation film 60 blocking, through seperation film 60 permeable amount reduce, concentration
Rate reduces.Herein, present inventor etc. thinks, the thickness for fettering albumin layer F1 is adjusted to relatively thin and inhibits to block.
It was found that the thickness of constraint protein layer F1 depends on the hydrophilicity of seperation film 60.That is, discovery: film is whole to be dredged
Under the too strong situation both of these case of the hydrophily of aqueous too strong situation and opposite mulch entirety, protein be easily adhered in
Seperation film 60, constraint protein layer F1 thicken.The present invention is by adjusting the porosity of seperation film 60 and hydrophilicity as a result,
To be suitably worth, so that the thickness for fettering protein layer F1 is adjusted to suitable range, accordingly ensure that seperation film 60 is permeable
Amount realizes high enrichment factor, and inhibits leakage of the protein from seperation film 60, it is ensured that the high-recovery of protein.
Substrate used in seperation film 60 is the ethylene-vinyl alcohols systems, acetate fiber prime system, polyethylene such as polysulfones system, Eval
System, polyester based polymer alloy (PEPA), polymethyl methacrylate system (PMMA) or polyacrylonitrile, particularly preferably polysulfones
The substrate of system.In addition, hydrophilicity is adjusted by implementing to add the hydrophilicity-imparting treatment of hydrophilic agent into substrate, make
For hydrophilic agent, for example: the ethylene-such as polyvinylpyrrolidone, polyethylene glycol, polyvinyl alcohol, polypropylene glycol, Eval
Ethenol copolymer, hydroxyethyl acrylate etc..The adjustment of the hydrophilicity of seperation film 60 by adjusting such as substrate kind
Class, the amount of hydrophilic agent, the type of hydrophilic agent carry out.
In addition, the porosity of seperation film 60 is for example in the case where the seperation film being open using hot-stretch by adjusting drawing
It stretches temperature, tensile speed, stretch roller diameter to carry out.In addition, passing through in the case where carrying out wet spinning using double-spinneret etc.
The velocity of discharge of polymer dope, the composition of interior liquid, spinning temperature are adjusted to carry out.
According to the present embodiment, between maximum film the value of pressure difference will not become larger (even if in the enrichment process P of rated condition into
Row 5L concentration can also maintain 500mmHg or less) and film between pressure difference climbing it is small (in enrichment process P B/A≤1.6 with
Under), it is therefore contemplated that the range that the porosity of seperation film 60 and hydrophilicity are set as specifically being worth as a result,
The thickness for fettering protein layer F1 can be adjusted to the range of desired value.It is as a result, that the protein for filtering ascites and generating is water-soluble
In the inspissator that liquid is concentrated, it can be ensured that the permeable amount of seperation film 60 inhibits leakage of the protein from seperation film 60, because
This, may be implemented the high-recovery of powerful concentration and realization protein.
In above embodiment, seperation film 60 as follows constitute: 60% or more and 80% porosity below and utilize hair
When the liquid level rising value of the aforementioned separation membrane of tubule rise method measurement is scaled 200 μm of internal diameter of hollow-fibre membrane for 60mm~
150mm is implementing that the protein aqueous solution stoste of concentration 3g/dL is made to obtain albumen with the logical liquid of 50mL/ minutes speed of flow velocity
It, can be with the following conditions of further satisfaction (3), (4) in the case where the enrichment process P of the concentrate of matter aqueous solution.
(3) protein recovery of the concentrate obtained when 2L protein aqueous solution stoste being concentrated is 40% or more.
(4) protein recovery of the concentrate obtained when 5L protein aqueous solution stoste being concentrated is 70% or more.
Under above situation, for seperation film 60, by the way that porosity and hydrophilicity to be set as to the range of desired value, from
And the leakage of the protein in seperation film 60 can be reduced, realize the high-recovery of protein.
In addition, for seperation film 60, it can be to be obtained when 5L protein aqueous solution stoste being concentrated under above-mentioned condition (4)
The rate of recovery of albumin of concentrate be further that 80% or more mode sets porosity and hydrophilicity.
In addition, in above embodiment, seperation film 60 is constituted as follows: 60% or more and 80% porosity below and
It is when being scaled 200 μm of internal diameter of hollow-fibre membrane using the liquid level rising value of the aforementioned separation membrane of capillary rise method measurement
60mm~150mm is implementing to obtain the protein aqueous solution stoste of concentration 3g/dL with the logical liquid of 50mL/ minutes speed of flow velocity
To the concentrate of protein aqueous solution enrichment process P in the case where, can be with the following conditions of further satisfaction (5).
(5) pressure difference is set as A, by 10L protein aqueous solution stoste between film when 2L protein aqueous solution stoste being concentrated
In the case that pressure difference is set as C between film when concentration, C/A≤1.5.
That is, seperation film 60 (10L protein aqueous solution stoste is concentrated with implementing in the case where enrichment process P, C
When film between pressure difference)/A (and by 2L protein aqueous solution stoste be concentrated when film between pressure difference) be 1.5 modes below adjust
Porosity and hydrophilicity.
It is believed that under above situation, it can be by the rising of pressure difference between film when carrying out 10L concentration in enrichment process P
Rate be suppressed to it is smaller, therefore even if for a long time more protein aqueous solutions are concentrated, pressure difference will not rise between film, can will
The thickness of compacted zone F1 is maintained suitable value.Ascites will be filtered as a result, and the protein aqueous solution that generates be concentrated it is dense
In contracting device, it can be ensured that the permeable amount of seperation film 60 inhibits leakage of the protein from seperation film 60, therefore high magnification may be implemented
Concentration, and realize protein high-recovery.
More than, the preferred embodiment of the present invention is illustrated while referring to attached drawing, but the present invention is not limited to above-mentioned
Example.It will be apparent to those skilled in the art that it is contemplated that each in thought range described in claim
Kind modification or fixed case, it is thus understood that these also would naturally fall with technical scope of the invention.
Such as the composition of the inspissator 22 in above embodiment is not limited to this.In addition, the ascites with inspissator 22
The composition of processing system 1 is also not limited to this.The seperation film 60 of inspissator 22 can be hollow-fibre membrane, as long as egg can be separated
The moisture of white matter aqueous solution, or other kinds of film, such as flat membrane.
In addition, the present invention also can be applied to by other than ascites other coelomic fluids, for example hydrothorax, pericardial fluid concentration it is dense
Contracting device.
Embodiment
In embodiment below, show in the present invention ascites concentration rate and final protein recovery carry out
The experimental result of verifying.In the present embodiment, the liquid of the protein aqueous solution before simulation concentration is known as " stoste ".
As shown in Figure 5, configure stoste reservoir 100, inspissator 101, concentrate reservoir 102, pressure gauge 103,
104,105 and pump 106,107, be attached with circuit.As pressure gauge, Manometer (NIDEC COPAL is used
ELECTRONICS CORP. manufacture, PG-200-102GP-P).Pump uses the roller pump (RP-1000) of EYELA Co. Ltd. system,
Pump 106 is set in such a way that flow velocity is 50mL/ minutes, and pump 107 is set in such a way that flow velocity is 40mL/ minutes.
The production method > of < stoste
Production uses the simulation ascites comprising blood cell ingredient of the blood of ox.Firstly, by added with the liver as anti-coagulants
The bovine blood of plain sodium injection (10,000 units/bovine blood 1L) is centrifuged, and obtains plasma layer, layer of red blood cells and erythrocyte sedimentation rate palm fibre
Each solution of yellow layer (buffy coat), they are separately recovered, blood plasma is thus obtained.Then, with filter (Asahi Kasei medical treatment
The ascites filter AHF-MO-W of Co., Ltd.'s manufacture) filtered plasma, physiological saline is then mixed, to be prepared into albumen
The stoste 10L of matter concentration 3.0 (g/dL), albumin concentration 1.5 (g/dL).
The measuring method of < protein concentration and the calculation method > of protein recovery
Protein concentration is measured by Biuret Method.Use automatic analysing apparatus (Tokyo trade medical system Co., Ltd.
Manufacture, Biolis24i), use Iatro TPII with reagent as measurement (LSI Medience Corporation is manufactured).
Albumen quality in stoste is set as TP1, when the albumen quality of concentrate is set as TP2, protein recovery uses
Following formula calculates.
Protein recovery=TP2/TP1 × 100 (%)
The measuring method of < albumin concentration and the calculation method > of the albumin rate of recovery
Albumin concentration is measured by BCG method.Use automatic analysing apparatus (Tokyo trade medical system Co. Ltd. system
Make, Biolis24i), Iatrofine ALBII (LSI Medience Corporation system is used as measurement reagent
It makes).
Albumin amount in stoste is set as ALB1, when the albumin amount in concentrate is set as ALB2, the albumin rate of recovery
It is calculated using following formula.
The albumin rate of recovery=ALB2/ALB1 × 100 (%)
The measuring method > of pressure difference between < film
When pressure shown in pressure gauge 103, pressure gauge 104, pressure gauge 105 is set to P1, P2, P3, pressure between film
Official post is calculated with following formula.
Pressure difference=(P1+P2)/2-P3 (mmHg) between film
The calculation method > of the ratio between pressure difference (B/A, C/A) between < film
Pressure difference is set as B between film when pressure difference is set as A (mmHg), stoste 5L processing between film when by stoste 2L processing
(mmHg), pressure difference is set as C (mmHg) between film when stoste 10L is handled.Between film the ratio between pressure difference be set as above-mentioned B and C divided by A,
Value obtained from decimal point the 2nd is rounded up.
< concentration rate >
The amount of the stock solution is set as 10L, it is regard as concentration rate divided by the resulting value of concentration liquid measure X, carries out as described below
Determine.
Concentration rate is 5 times of 〇
Concentration rate less than 5 times ×
In the present embodiment, the flow for pumping 106 is 50mL/ minutes, and pumping 107 flow is 40mL/ minutes, so if
Total amount concentration can be carried out in the case where not blocking, then it is 2L that liquid measure, which is concentrated, and concentration rate is 5 times.
The final protein recovery > of <
Albumen quality in stoste is set as TP1, when the albumen quality in finally obtained concentrate is set as TP3, finally
Protein recovery is calculated using following formula.
Final protein recovery=TP3/TP1 × 100 (%)
In addition, determining final protein recovery as described below.
Final protein recovery is 50% or more 〇
Final protein recovery less than 50% ×
(embodiment 1)
As inspissator, using 200 μm of internal diameter, 45 μm of film thickness, length 330mm, porosity 78%, it is based on capillary rising
The liquid level rising value 110mm's of method is dense by polysulfones/hollow fiber membrane-type formed of polyvinylpyrrolidone doughnut 9000
Contracting device.Show the result in table 1.
(embodiment 2)
As inspissator, using 185 μm of internal diameter, 45 μm of film thickness, length 330mm, porosity 73%, it is based on capillary rising
Method liquid level rising value 120mm (with 200 μm of internal diameter convert value) by polysulfones/polyvinylpyrrolidone doughnut 10600
In addition to this hollow fiber membrane-type inspissator that root is formed carries out experiment similarly to Example 1.Show the result in table 1.
(embodiment 3)
As inspissator, using 185 μm of internal diameter, 45 μm of film thickness, length 330mm, porosity 60%, it is based on capillary rising
Method liquid level rising value 120mm (with 200 μm of internal diameter convert value) by polysulfones/polyvinylpyrrolidone doughnut 10600
In addition to this hollow fiber membrane-type inspissator that root is formed carries out experiment similarly to Example 1.Show the result in table 1.
(embodiment 4)
As inspissator, using 185 μm of internal diameter, 45 μm of film thickness, length 330mm, porosity 72%, it is based on capillary rising
Method liquid level rising value 150mm (with 200 μm of internal diameter convert value) by ethylene-vinyl alcohol copolymer (Eval) doughnut
In addition to this hollow fiber membrane-type inspissator of 10600 formation carries out experiment similarly to Example 1.Show the result in table
1。
(embodiment 5)
As inspissator, using 200 μm of internal diameter, 45 μm of film thickness, length 330mm, porosity 80%, it is based on capillary rising
The liquid level rising value 110mm's of method is dense by polysulfones/hollow fiber membrane-type formed of polyvinylpyrrolidone doughnut 9000
In addition to this contracting device carries out experiment similarly to Example 1.Show the result in table 1.
(embodiment 6)
As inspissator, using 200 μm of internal diameter, 45 μm of film thickness, length 330mm, porosity 63%, it is based on capillary rising
The liquid level rising value 70mm's of method is dense by polyether sulfone/hollow fiber membrane-type formed of polyvinylpyrrolidone doughnut 9000
In addition to this contracting device carries out experiment similarly to Example 1.Show the result in table 1.
(embodiment 7)
As inspissator, using 200 μm of internal diameter, 45 μm of film thickness, length 330mm, porosity 70%, it is based on capillary rising
The hollow fiber membrane-type inspissator of the liquid level rising value 60mm of method formed by Triafol T doughnut 9000 removes this
Except, carry out experiment similarly to Example 1.Show the result in table 1.
(comparative example 1)
As inspissator, using 200 μm of internal diameter, 45 μm of film thickness, length 330mm, porosity 52%, it is based on capillary rising
The liquid level rising value 180mm of method by 9000 hollow-fibre membranes formed of ethylene-vinyl alcohol copolymer (Eval) doughnut
In addition to this type inspissator carries out experiment similarly to Example 1.Show the result in table 1.
(comparative example 2)
As inspissator, using 185 μm of internal diameter, 45 μm of film thickness, length 330mm, porosity 55%, it is based on capillary rising
Method liquid level rising value 110mm (with 200 μm of internal diameter convert value) by polysulfones/polyvinylpyrrolidone doughnut 10600
In addition to this hollow fiber membrane-type inspissator that root is formed carries out experiment similarly to Example 1.Show the result in table 1.
[table 1]
Industrial availability
The present invention realizes high magnification in inspissator that the protein aqueous solution that generates is concentrated that will filter coelomic fluid
Concentration and ensure when the high-recovery of protein to be useful.
Claims (11)
1. a kind of inspissator, the concentration that the protein aqueous solution generated will to filter coelomic fluid is concentrated by seperation film
Device,
The seperation film is constituted as follows: 60% or more and 80% porosity below and using capillary rise method measurement
The liquid level rising value of the seperation film is 110mm~150mm when being scaled 200 μm of internal diameter of hollow-fibre membrane, is made in implementation dense
The protein aqueous solution stoste of 3g/dL is spent to lead to liquid with 50mL/ minutes speed of flow velocity and obtain the concentrate of protein aqueous solution
Enrichment process in the case where, meet following conditions (1) and (2),
(1) by 5L protein aqueous solution stoste be concentrated when maximum film between pressure difference be 500mmHg hereinafter,
(2) when pressure difference is set as A, 5L protein aqueous solution stoste is concentrated between film when 2L protein aqueous solution stoste being concentrated
Film between in the case that pressure difference is set as B, B/A≤1.6.
2. inspissator according to claim 1, wherein the seperation film is constituted as follows: implementing the enrichment process
In the case of, the following conditions of further satisfaction (3) and (4),
(3) protein recovery of the concentrate obtained when 2L protein aqueous solution stoste being concentrated is 40% or more,
(4) protein recovery of the concentrate obtained when 5L protein aqueous solution stoste being concentrated is 70% or more.
3. inspissator according to claim 2, wherein in the condition (4), 5L protein aqueous solution stoste is concentrated
When the obtained rate of recovery of the albumin of concentrate be 80% or more.
4. inspissator described in any one of claim 1 to 3, wherein the seperation film is constituted as follows: described in implementation
In the case where enrichment process, further satisfaction is following (5),
(5) pressure difference is set as A, 10L protein aqueous solution stoste is concentrated between film when 2L protein aqueous solution stoste being concentrated
When film between in the case that pressure difference is set as C, C/A≤1.5.
5. inspissator described in any one of claim 1 to 3, wherein substrate used in the seperation film is polysulfones
System, ethylene-vinyl alcohol system, acetate fiber prime system, polyethylene-based, polyester based polymer alloy (PEPA), polymethyl methacrylate
It is (PMMA) or polyacrylonitrile.
6. inspissator according to claim 4, wherein substrate used in the seperation film is polysulfones system, Ethylene vinyl
Alcohol system, acetate fiber prime system, polyethylene-based, polyester based polymer alloy (PEPA), polymethyl methacrylate system (PMMA) or
Polyacrylonitrile.
7. according to claim 1~3, inspissator described in any one of 6, wherein the seperation film is hollow-fibre membrane.
8. inspissator according to claim 4, wherein the seperation film is hollow-fibre membrane.
9. inspissator according to claim 5, wherein the seperation film is hollow-fibre membrane.
10. inspissator according to claim 7, wherein the seperation film is the hollow-fibre membrane of polysulfones system.
11. inspissator according to claim 8 or claim 9, wherein the seperation film is the hollow-fibre membrane of polysulfones system.
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| JP2015036742A JP6397781B2 (en) | 2015-02-26 | 2015-02-26 | Concentrator |
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| JP7131038B2 (en) * | 2018-04-04 | 2022-09-06 | 東洋紡株式会社 | Hollow fiber membrane for ascites filtration |
| TWI794706B (en) * | 2019-12-27 | 2023-03-01 | 日商旭化成醫療股份有限公司 | Test solution for evaluating protein recovery performance of body cavity fluid concentrator and manufacturing method thereof |
| JP7402680B2 (en) * | 2019-12-27 | 2023-12-21 | 旭化成メディカル株式会社 | Test liquid for evaluating protein recovery performance of body cavity fluid concentrator and its manufacturing method |
| JP7395348B2 (en) * | 2019-12-27 | 2023-12-11 | 旭化成メディカル株式会社 | Evaluation test method for body cavity fluid concentrator |
| TWI808366B (en) * | 2019-12-27 | 2023-07-11 | 日商旭化成醫療股份有限公司 | Evaluation test method for body cavity fluid concentrator |
| WO2022265104A1 (en) * | 2021-06-18 | 2022-12-22 | ニプロ株式会社 | Concentrator |
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| CN105924497A (en) | 2016-09-07 |
| JP6397781B2 (en) | 2018-09-26 |
| JP2016154809A (en) | 2016-09-01 |
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