JPS5910226B2 - "Filtration" type body fluid purification device - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a P-type body fluid purification device that dilutes a high molecular weight substance in a body fluid with a patient's own overpurified body fluid and increases the r-permeation efficiency without using a dialysate.

Conventionally, in artificial kidney devices, a dialysis method has been widely used in which blood and external fluid (dialysate) are brought into contact through a cellulose-based permeable membrane, and waste products in the blood are permeated into the dialysate.

However, with this device, in addition to waste products, low-molecular weight substances such as vitamins, amino acids, and other useful components also permeate into the dialysate and are lost from the body each time dialysis is performed, and the components to be dialysed are not always proportionate. due to insufficient permeability to, for example, urea and medium molecular weight substances,
Trace amounts of harmful metabolites that should be removed accumulate, which is thought to be the cause of, for example, uremia.

In addition, the current purifying device requires a larger device and a large amount of dialysate, so the purchase cost of dialysate, adjustment and measurement equipment, equipment and machinery for management, and these costs are high. In addition to requiring installation and storage space, it also requires a large number of personnel for preparation and adjustment, and the cost is generally high.

As mentioned above, this device has many disadvantages both physiologically and economically.

On the other hand, as a method that does not use dialysate, various adsorption-type or f-transfer type artificial kidney devices using activated carbon or the like have been studied and researched.

However, in adsorption-type artificial kidney devices, blood cells such as red blood cells or enzymes in the blood come into direct contact with adsorbents such as activated carbon, which may cause an adverse effect on the blood cells or deactivate the enzymes, and water collection may be difficult. It has drawbacks such as being unable to do so.

Furthermore, four methods are currently being considered for the f-type artificial kidney device.

Next, each will be explained individually.

The first method involves removing excess plasma containing waste products and low molecular weight substances from blood through a permeable membrane, and returning concentrated blood containing blood cell components and high molecular weight substances to the body.

However, in this method, when a permeable membrane with a pore size suitable for permeating waste products is used, clogging occurs due to high molecular weight substances such as blood proteins and other influences, and the permeation efficiency decreases over time. , or it becomes impossible to pass through the water.

Furthermore, since excess plasma is removed, there is a risk of dehydration in the patient, and there are disadvantages in that the excess plasma, which is a useful low-molecular-weight substance, is removed with each treatment.

The second method involves separating blood through a permeable membrane into concentrated blood containing blood cell components and high-molecular-weight substances, and abundant plasma containing waste products and low-molecular-weight substances, removing toxins from the excess plasma using an adsorbent, etc. After adjusting electrolytes and removing excess water, the blood is mixed with concentrated blood and returned to the body.

However, this method has the disadvantage that when a permeable membrane having a pore size suitable for permeating waste products is used, the f-permeation efficiency decreases or r-permeation as shown in the first method becomes impossible.

The third method is to dilute blood with an artificial body fluid (plasma) such as physiological saline or Ringer's solution, and pass the diluted blood in an amount corresponding to the dilution through a permeable membrane to the liquid containing waste products and low molecular weight substances.
It is removed as excess plasma and returned to the body.

However, although this method has good P overefficiency in the permeable membrane,
It is impossible to recover useful low-molecular weight substances contained in hyperplasma, and since a diluent is used instead of dialysate, the cost of the diluent and incidental equipment are no different from the dialysis method.
In addition, if the supply of diluent is stopped or insufficient for some reason, only concentrated blood will be returned to the body through filtration, and the patient may be at risk of dehydration. It has its drawbacks.

The fourth method is to defiltrate blood in two stages using two types of permeable membranes with different pore sizes, pass the excess plasma in the first stage through an adsorbent such as activated carbon, and then pass the filtered plasma through an adsorbent such as activated carbon. The substance is completely passed through a second-stage permeable membrane, toxins are removed, electrolytes are adjusted, excess water is removed, and the excess plasma is mixed with concentrated body fluids and returned to the body.

However, in this method, the first
This method includes problems such as a decrease in f-permeation efficiency or the impossibility of f-permeation as shown in the method described above, and the difficulty in manufacturing the permeable membrane because the second-stage r-permeation requires precision in the pore diameter of the permeable membrane. It cannot be said to be realistic.

As described above, the prior art has many drawbacks and problems that must be solved medically, technically and economically.

The purpose of the present invention is to eliminate the medical and economic disadvantages that occur when external liquids such as dialysate in dialysis or diluted liquid in P-filtration method are used, and to improve the adsorption method and P-filtration method that do not use external liquid. By eliminating the medical, functional, and technical drawbacks and problems that occur in cases of P hyperpurification, by using the patient's own P hyperpurified body fluid as a diluent, we can obtain the same r hyperefficiency as when using external fluids, and further It is an object of the present invention to provide a medically safe and economical r-type body fluid purification device that selectively adsorbs and removes only wastes and harmful substances in f-liquid or converts them into harmless substances.

The present invention provides a filtration device that separates body fluid into purified body fluid and P liquid through a permeable membrane, a purifier equipped with purification means for obtaining purified P liquid from the sap, and a purifier that separates body fluid into purified body fluid and P liquid. A pump is provided in at least one of a flow path that leads the body fluid as a diluent to the inlet of the f-filter, a flow path on the purification liquid side, and an r-liquid side flow path that leads the r-liquid to the purification means. This is an r-type body fluid purification device characterized by the following.

The device of the present invention preferably has a mixer at the inlet as a means for diluting body fluid, and a permeable membrane with an average pore diameter of 0.003 to
It consists of a molecular permeation membrane having a diameter of 1μ and a thickness of 0.05 to 3μ, and a support having pores larger than the pores of the molecular permeation membrane, and f
The filter device is provided with a means for flowing diluted body fluid approximately parallel to the permeable membrane,
The purification means is an immobilized enzyme and a membrane filter, and the purification device is characterized in that the number of purifiers is plural.

Hereinafter, one embodiment of the present invention will be described based on the drawings.

Embodiment 1 Figure 1 shows an apparatus according to the present invention in use with a partially cut section. In the figure, the filter 1 is made of polyacrylic or a material that does not coagulate body fluids such as blood. For example, in a container 2 made of a transparent hard plastic whose inner wall is coated with heparin, a pore diameter of O. OO3~1μ preferably pore size 0.00
5. A molecular P membrane 4 having a thickness of 0.006 to 0.006 μ and a thickness of 0.05 to 3 μ is coated with a support 5 made of cellulose or a plastic membrane to be described later, or a non-woven fabric or fabric having larger pores than the molecular membrane. A permeable membrane 3 is provided,
The permeable membrane 3 of the container 2 has a body fluid inlet 7 as an inlet 6 on the molecular permeation membrane 4 side, an inlet 8 for purified fluid adjacent to this, and an outlet 9 for purified body fluid on the side corresponding to the inlet 6. The purifier 11 is provided in a container 12 made of hard, preferably transparent plastic such as polyethylene, polypropylene, or polycarbonate. Purification means 13 such as activated carbon, ion exchange resin, immobilized enzyme, Memplan filter, adsorbent such as zeolite, reaction aid, filter, etc.
The container 12 is provided with an inlet 14 for liquid f and an outlet 15 for purification liquid on the side corresponding to this population 14.
The conduit 16 is a channel means for introducing the F liquid in a tube made of polyvinyl chloride or other transparent semi-rigid plastic that does not coagulate body fluids such as blood, and the conduit 17 is for introducing the purified P liquid in a tube of the same quality as the conduit 16. The pump part is a conduit such as an elastic silicone tube as a channel means for guiding the flow, and the pump 18 is an air non-contact type pump such as a roller tube pump, and the conduits 19 and 20 are air-contact type pumps such as a roller tube pump. A clear plastic tube connected to a means of body fluid collection or return, such as a needle, made of polyvinyl chloride or other material that does not clot blood or other body fluids.
1 is a roller clamp, a plate clamp, etc.

In use, the invention is preferably filled with a filling fluid such as artificial body fluid, such as physiological saline or Ringer's solution, or artificial plasma, to remove air within the device.

When the drain 21 of the conduit 19 is opened, blood is treated with an anticoagulant such as heparin, for example, and is introduced into the device by blood pressure, passes through the filter 1, and is returned to the body through the conduit 20.

At this time, the purified f-liquid inlet 8 of the r-filter 1 passes through the conduit 16, the purifier 11, and the conduit 17 from the outlet 10 of the effluent of the f-filter 1.
Since the circuit leading to the pump 18 is a closed system, when the pump 18 is inactive, the blood does not flow through the permeable membrane 3 and is therefore returned to the body without being passed through.

Next, when the pump 18 is operated while blood is being introduced, the artificial body fluid filled in the f-liquid purification circuit is transferred to the defilter 1.
The purified P solution flows into the filtration device 1 from the inlet 8 of the 0 inlet section 6 and dilutes the blood.

The diluted blood has increased fluidity and is separated into purified blood containing blood cell components and high molecular weight substances and P liquid due to the pressure difference across the permeable membrane 3 generated by the operation of the pump 18. The permeable membrane 30 is sucked into the permeable membrane 30. Among the wastes and harmful substances that are large enough to permeate through the pores of the permeable membrane 4, only low molecular weight substances are permeated together with water as a solvent as the P liquid and purified through the conduit 16. At this time, the molecule P
Since the support 5 of the permeable membrane 4 has larger pores than the molecular deliquid membrane 4, clogging and reduction in P permeability will not occur.

The purifier 11 selectively adsorbs waste and harmful substances in the stream fluid with an adsorbent such as activated carbon, decomposes them with immobilized enzymes, synthesizes them and converts them into harmless substances, or adjusts electrolytes with an ion exchange resin or uses a membrane filter. Purify the P solution using purification methods such as sterilization and foreign matter removal.

This purified P liquid is then continuously transferred to the inlet 6 of the filter by means of a pump 18 through the conduit 17 as a blood diluent instead of the filling artificial body fluid.

In addition, the blood is diluted with a diluent with less waste and harmful substances, that is, an artificial body fluid and purified P liquid, and on the other hand, low molecular weight substances containing waste and harmful substances permeate through the molecular permeation membrane 4. Since it is filtered together with water as a solvent, f
The blood discharged from the outlet 9 of the filter device 1 is purified blood containing blood cell components and high molecular weight substances with little waste and harmful substances.

The permeator of this device is equipped with a molecular permeation membrane having pores with an average pore diameter of 0.003 to 1 μ and a thickness of 0.05 to 3 μ;
By using a permeable membrane made of a support having pores larger than the pores of the permeable membrane, the present invention eliminates the permeability of conventional cellulose-based permeable membranes, which have pore diameters of 0.002 μm or less and membrane thicknesses of 11 to 20 μm. It can permeate waste products of low molecular weight substances and medium molecular weight substances such as urea as R liquid,
Moreover, the permeation resistance is low.

Here, if the average pore diameter of the filter membrane is less than 0.003μ, the waste products of medium molecular weight substances cannot pass through, and if it is more than 1μ, blood cell components or high molecular weight substances are not allowed to pass through. This is not desirable.

If the thickness of the membrane is less than 0.05 μm, it will be difficult in terms of strength, and if it is more than 3 μm, the molecular permeability will decrease, making it difficult to communicate the pores during membrane production.

Embodiment 2 FIG. 2 shows an apparatus according to another embodiment of the present invention in which a partial cutting section is provided. , a mixer 22 at the inlet 6 of the filter, and a purifier 2 in addition to the purifier 11.
3, a pump 24 is provided in place of the drain.

The mixer 22 is preferably a cylindrical container made of transparent hard plastic such as polyacrylic or polypropylene, and has an inlet 25 for body fluid and an inlet 26 for purified swab made of the same material.
The purifiers 11 and 23 are arranged so that the liquids mix with each other, and the outlets for diluted body fluids are provided on the sides corresponding to these inlets 25 and 26 by the same material, and the purifiers 11 and 23 are made of containers of the same quality as in Example 1.
The purifier 11 is filled with immobilized enzyme asparaginase on the inlet 14 side and the immobilized enzyme aspartase on the outlet 15 side as purification means, and the purifier 23 is provided with a membrane filter 27 having 0.45 μm pores as purification means. pump 2
It is an air non-contact type pump such as a 4-halo roller tube pump.

When this device is used on a leukemia patient who has been administered asparagine and pumps 18 and 24 are activated, blood treated with an anticoagulant, such as heparin, is transferred by pump 24 to a mixer, and the blood transferred by pump 18 is transferred to a mixer. The artificial body fluid filled in the liquid purification circuit causes turbulence in the mixer 22 to dilute and mix the blood, and the sufficiently diluted blood is transferred to the filter 1.

The f liquid of the diluted blood transferred to the filter is transferred to the purifiers 11 and 23 in the same manner as in the first embodiment.

Since this filter 1 does not require dilution means, it can be made smaller accordingly.

The purifier 11 decomposes asparagine in the sap into aspartic acid and ammonia using the immobilized enzyme asparaginase, and synthesizes poisonous ammonia and fumaric acid in the liquid into non-toxic aspartic acid using the immobilized enzyme aspartase. Detoxifies and purifies the liquid.

Since the immobilized enzyme that is the purifying means of the purifier 11 cannot be sterilized in the purifier 23, bacteria and fine particles adhering to the immobilized enzyme are further sterilized and foreign substances are removed from the purified f liquid using a membrane filter for purification. .

This purified f liquid is transferred to the mixer by the pump 18, dilutes the blood, and purified blood is obtained by the same action as in Example 1.

As mentioned above, providing a mixer upstream of the P-filter as a means of diluting body fluids eliminates the means for diluting the P-filter, which reduces the size of the P-filter or The use of membranes can increase the flow volume.

In addition, by using an immobilized enzyme and a membrane filter as a purification means, the immobilized enzyme acts as a reaction aid and does not adsorb waste products and harmful substances in the F solution. By decomposing and synthesizing it and converting it into useful components or harmless substances, the Menpuran filter can remove bacteria and fine particles released from immobilized enzymes that cannot be sterilized.

Furthermore, although both Examples 1 and 2 are examples in which blood was purified, the present invention can also be used for body fluids such as ascites and pleural effusion.

By providing a means for allowing the diluted body fluid diluted in the mixer of the present invention to flow almost parallel to the permeable membrane, the surface of the permeable membrane is constantly washed, and gelation due to high molecular weight substances such as proteins is prevented. It can prevent concentration polarization.

There are many types of materials for the permeable membrane that can be used in the present invention, such as polyvinyl alcohol, folysulfone, nylon, nitrocellulose, cellulose acetate, polyester, polyurethane, polytetrafluoroethylene, and polyacrylonitrile, which can be selected as appropriate.

In addition to the flat shape mentioned in Examples 1 and 2, the shape of the permeable membrane using these materials of the present invention is a tube shape,
Hollow fibers, bag shapes, etc. can be used, and permeable membranes in these shapes can be further folded, bent, rolled, etc., such as coil type, keel type, hollow fiber type, etc. You can also use

Purification means that can be used in the present invention include activated carbon, zirconium, silconium phosphate, silconium oxide, zirconium hydroxide, iron hydroxide, titanium hydroxide, ethylene-maleic anhydride copolymer, microencapsulated ethylene-maleic anhydride copolymer. There are adsorbents such as coalescence, styrene-maleic anhydride copolymer, microencapsulated styrene-maleic anhydride polymer, oxidized starch, polyacrolein, polyamide fiber, cellulose, and modified forms of these, which can be used for decomposition or synthesis. There are immobilized enzymes such as immobilized enzyme urease, immobilized enzyme asparaginase, and immobilized enzyme aspartase as agents, ion exchange resins as electrolyte adjusting agents, and filters as means for sterilization and foreign matter removal. be.

Another aspect of the present invention is to create an integrated device by combining a mixer and an R-filter, a de-filter and a purifier, a purifier and a mixer, and a mixer, a P-filter, and a purifier to further reduce the size. It's okay.

Moreover, as another aspect of the present invention, a plurality of mixers, defilters, and purifiers may be provided.

Examples of the types of purifiers include those for artificial kidneys, artificial livers, artificial kidneys and livers, and those for removing poisonous drugs, depending on the type, quantity, and composition of the purifying means.

These purifiers can be of the same type or different types and connected in series, in parallel, or in series and parallel to increase the purification efficiency, increase the amount of purified fluid, or have the function of an artificial kidney and liver.

Further, even if a P liquid discharge means such as a three-way stopcock or a component replenishment means such as pretamine is added to the conduit 16 as a discharge port for the f liquid, the basic operation of the present invention will not be impaired.

In addition, a Pellicon cassette (manufactured by Nippon Millipore Limited) was used as the P filter of the present invention, a Pellicon molecular P filter membrane (manufactured by Nippon Millipore Ltd.) was used as the permeable membrane, and the purifier was filled with the adsorbent described later. An experiment was conducted by circulating 5 liters of an aqueous solution (described later) instead of body fluids to the device of the present invention and setting the overflow rate to 3.7 liters/hr. stable f
While maintaining the overefficiency, the purifier was able to purify the r-liquid and obtain a purified aqueous solution as expected.

Experimental examples and their results will be described below.

Example 1 Aqueous solution Albumin 2.3% Inulin 0.05% Creatinine 0.05% Permeable membrane Pericone molecular f membrane (nominal molecular weight limit 25000) Adsorbent As a result of an experiment with a mixture of ethyl cellulose 10f and activated carbon powder 20g, it was found that Inulin and creatinine concentrations decreased over time, whereas albumin concentrations did not change.

FIG. 3 is a graph showing changes in the concentration of inulin creatinine in the purified aqueous solution in this experiment.

Example 2 Aqueous solution Gelatin 1.5% Inulin 0.05% Creatinine 0.05% Permeable membrane Pericone 1,000 F permeable membrane (nominal molecular weight limit 10,000) Adsorbent Gelatin microcapsule (mixture of gelatin IOS', 10 g of activated carbon, and water ioofI) As a result of the experiment, the concentration of inulin and creatinine in the purified aqueous solution decreased over time, but the concentration of gelatin did not change.

FIG. 4 is a graph showing changes in the concentrations of inulin and creatinine in the purified aqueous solution in this experiment.

Since the present invention uses the patient's own purified body fluid as the diluent, even if the supply of diluent stops or is insufficient due to an accident during treatment, external fluid can be used as the diluent. Compared to the conventional method, body fluids are returned without being concentrated, making it extremely medically safe and easy to handle.

In addition, the present invention does not remove the P fluid from body fluids and uses it effectively as a diluent, so compared to the dialysis method and the f-filtration method that removes the P fluid, there is no removal or discharge of useful components, and a closed system circuit is required. The risk of infection is low.

Since the present invention only requires a device having dilution and purification functions and a pump for transferring the P liquid, it can be made smaller, requires less installation space, and can be lower in price.

Since the present invention does not use a large amount of external fluid such as a diluent after dialysis, it is extremely economical as it does not require drug costs or storage.

The present invention is a method in which blood cell components and enzymes in body fluids are returned without coming into contact with purification means, so it produces extremely natural purified blood that does not affect blood cell components or deactivate enzymes. That's what you get.

The present invention can easily have the function of an artificial kidney device, an artificial liver device, an artificial kidney liver device, or a poison drug removal device by changing the type, amount, and composition of the purifying means.

As described above, the present invention has many advantages.

[Brief explanation of the drawing]

FIG. 1 is a schematic diagram showing an embodiment of the r-type body fluid purification device according to the present invention, and FIG. 2 is a schematic diagram showing another embodiment of the present invention.
FIGS. 3 and 4 are graphs showing experimental results of the present invention. 1...F filter, 3...Permeable membrane, 11.
... Purifier, 13 ... Purification means, 18.
...Pump, 22...Mixer, 23...
...Purifier.

Claims (1)

[Scope of Claims] 1. A purifier provided with a P filter for separating body fluid into purified body fluid and effluent through a permeable membrane, and a purification means for obtaining purified f-liquid from said effusion; at least one of a flow path that leads the purification f liquid as a diluent to the inlet of the swab device together with the body fluid, a flow path on the purification f liquid side, and a flow path on the P liquid side that leads the purification liquid to the purification means. A P-type body fluid purification device characterized by being provided with a pump. 2. The depletion-type body fluid purification device according to claim 1, wherein the population section includes a mixer as a means for diluting the body fluid. 3 The permeable membrane has an average pore diameter of 0.003 to 1μ and a thickness of 0.0
2. The P-permeable body fluid purification device according to claim 1, comprising a molecular permeable membrane having a diameter of 5 to 3 μ and a support having pores larger than the pores of the molecular permeable membrane. 4. The R-pass type body fluid purification device according to claim 2, wherein the P-pass device is provided with means for flowing the diluted body fluid approximately parallel to the permeable membrane. 5. The f-type body fluid purification device according to claim 1, wherein the purification means is an immobilized enzyme and a membrane filter. 6. The f-type body fluid purification device according to claim 1, wherein the number of purifiers is plural.