JPS6040864B2 - body fluid purification device - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a body fluid purification device for removing harmful substances present in body fluids such as blood and blood counts, and particularly to a device capable of removing substances with a high molecular weight with a high degree of selectivity. .

Many of the diseases that are considered incurable diseases are thought to be caused by unnecessary or harmful substances remaining in body fluids that should originally be removed from the body.

In general, if the molecular weight of unnecessary or harmful substances present in body fluids is small, it is now possible to remove them through dialysis, etc., in order to recover or alleviate the condition. There are quite a few groups that cannot be considered the same. For example, various Katsugen diseases such as rheumatoid arthritis would fall into this category. It has been discovered that abnormal proteins or their complexes with large molecular weights exist in the body fluids of patients with such incurable diseases. It is increasingly recognized that large proteins, specifically y-globulin, may be the main pathogenic factors.

Therefore, for its treatment, an important key is how to remove abnormal proteins, etc. from body fluids from the body. However, due to the large size of the abnormal molecules, the removal of small molecules through dialysis poses different difficulties, and the reality is that body fluid exchange is the only way to remove them. Conventionally, it has been clinically adopted to separate the patient's blood cells and blood waste using a centrifugal separator, discard the blood containing large harmful substances, and return the remaining blood cells and healthy bran to the body. ing.

However, this approach has reached an impasse due to high equipment costs and other reasons. A recent trend is to purify a patient's body fluids by filtering the blood bran using a filter device that blocks the penetration of blood cells, replacing it with normal frozen blood elutriation, and injecting it into the body. As far as purification effects are concerned,
It has achieved some success.

However, since frozen blood is used, serum hepatitis is easily induced, and a huge amount of frozen blood is required. Incidentally, it has been reported that one purification operation requires the blood of approximately 80 people. This poses a major obstacle to the dissemination of sufficient and continuous body fluid purification treatment, and has become a serious problem in medical treatment for intractable diseases. In view of the above circumstances, the present invention has been made for the purpose of providing a purification device that can eliminate the need for frozen plate competition in body fluid purification, and replaces patient blood with normal blood. Changing the conventional idea, we will remove only disease-specific molecules such as large proteins such as Y-globulin from the patient's blood acid by filtration, and leave the relatively small molecules necessary for the living body in the body fluid. That is. It is common to think that if large harmful molecules are treated in the reactor, small useful proteins will also be included in the reactor. , is the premise of the present invention.

Body fluids such as blood are a type of electrolyte solution, and proteins in body fluids have the property of being negatively charged and ionized at normal biological pH (or pH adjustment).

Therefore, by forming an electric field in the body fluid to be purified, it is possible to induce so-called open air migration in large and small proteins therein. Therefore, a protein fraction measurement method based on this haze phoresis has been known for a long time (for example, Izumi Kanai and Masamitsu Kanai, eds. "Summary of the Death Test Method").
27th edition, 20th to 21st edition, March 31, 1976, published by Kanehara Publishing Co., Ltd.), taking advantage of the fact that there is a difference in migration speed depending on the size of the molecular weight, and
The present invention was completed based on the discovery that by using two types of filter membranes, coarse and fine, with different permeation functions, it is possible to effectively remove only the unnecessary while leaving the necessary. That is, the feature of the present invention is to provide a first semipermeable membrane with a large pore size and a second semipermeable membrane with a pore size smaller than that of the first semipermeable membrane, and to A body fluid channel is formed between the permeable membrane through which body fluids such as blood and blood to be purified can flow, and on both sides of the body fluid channel, there is provided a furnace with the semi-transparent waist. A filtrate flow path is formed for discharging the filtered filtrate, and a cathode is provided in the filtrate flow path on the side of the first semi-permeable waist, and a cathode is provided in the filtrate flow path on the second semi-permeable waist side. Anodes are disposed in each of the side furnace fluid flow channels, and a voltage application mechanism capable of applying a predetermined voltage between the cathode and the anode is provided, and by applying the voltage, "the inside of the body fluid flow channel is The object of the present invention is to purify body fluids while causing haze migration in solutes in body fluids that are passed through the body.

The rough first semipermeable membrane should be removed from body fluids.

It has a pore size that allows unnecessary and harmful molecules such as large proteins such as purines to pass through, and when purifying blood, it is necessary to be able to prevent blood cells from passing through. On the other hand, the second semipermeable membrane has the ability to at least block the permeation of necessary (useful) proteins such as albumin, which are relatively smaller than the target object to be removed, and also has the ability to prevent the permeation of necessary (useful) proteins such as albumin, which are relatively smaller than the target object to be removed. Permeation of electrolyte ions necessary for the continuation of the phenomenon is allowed. When electrophoresis is induced in the solutes in the body fluid being circulated, negatively charged molecules or particles such as proteins are moved to the anode side, that is, the second semipermeable membrane side.

However, unnecessary molecules with large molecular weights have a molecular weight of 4.
Their movement speed (mobility) is lower than that of the necessary molecules, resulting in a biased concentration distribution in body fluids. Necessary molecules are prevented from permeating through the reactor filtrate channel where negative pressure is applied by pressurization or absorption by the second semipermeable membrane, but on the other hand, unnecessary molecules are large and therefore relatively The molecules necessary for this purpose are distributed on the first semipermeable membrane side, and the amount of liquid passing through the rough first semipermeable membrane side is overwhelmingly larger than that on the other side. At the same time, it is effectively filtered through the furnace filtrate flow path through the first semipermeable membrane. In this way, unnecessary and harmful molecules are removed from the body fluid without removing necessary molecules, so it is only necessary to replenish water etc. into the body fluid after or in parallel with the furnace operation. This makes it possible to effectively purify body fluids containing large unnecessary substances without the need for frozen blood bran, which is valuable and limited in quantity.

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

The figure is a schematic diagram schematically showing an example of a device according to the present invention.

Therefore, 2 is a furnace as a body fluid purifier, and inside its housing 4, a plurality of semipermeable membranes 6 with large pore sizes and semipermeable membranes 8 with small pore sizes are arranged alternately in parallel. 4 includes body fluid passages 10 and 12 through which body fluids such as blood or dish acid flow, and a filtrate passage 14 for discharging the filtrate that is heated through the semipermeable membranes 6 and 8. , 16, and 18 are formed alternately. The outermost channels are filtrate channels 14 and 18, respectively.
It becomes. Note that the case where the body fluid is blood will be described below. The two types of semi-permeable membranes 6 and 8 are both flat type, made of cellulose acetate or polyacrylonitrile, and function as ultrafilter membranes.
Molecular weight cutoff (cutoffPoi) of the coarse semipermeable membrane 6
nt) is selected to have a larger molecular weight than the target substance to be removed, such as large proteins such as y-globulin, so as to be able to pass therethrough.

Although the specific value varies depending on the target substance and cannot be generalized, it is currently 100,000 to 100,000.
It is reasonable to have a molecular weight cut-off of about 1,000,000, and in terms of pore size, a diameter in the range of about 1,000 to 2,000 A is suitable. This level is sufficient to prevent permeation of blood cells. On the other hand, the semipermeable membrane 8 with fine openings is not limited to a furnace filtration membrane such as a heterotropic membrane, but may be a normal dialysis membrane such as a cuprophane, and is made of a membrane so as to allow at least electrolyte ions, such as q-, to permeate through the membrane. On the other hand, the molecular weight cutoff is selected so as to prevent the permeation of useful hemophobic proteins such as albumin.

By the way, albumin is the main blood protein.
Conventionally, the main component of the frozen blood count, which is used for body fluid purification, is albumin, which is used to adjust the osmotic pressure of pig matter,
It plays an important role in maintaining H constant. Its molecular weight is 69,000. Therefore, the molecular weight cut-off of the fine semipermeable membrane 8 can be selected up to nearly 7 as long as it is large, and its lower limit can be appropriately set, for example, to a value of 50. In this embodiment, a commercially available dialysis membrane is used as the semipermeable membrane 8, and has a molecular weight cut-off of around 1300 and a pore size of about 60A. On the inlet side of the body fluid channels 10 and 12,
A blood supply confluence channel 20 that leads blood from the patient's body is branched and connected, and the patient's blood is transferred to the furnace by circulation means such as a blood pump 22 provided on the way of the supply channel 20.
be introduced within.

In addition, if the protein molecules in the blood cannot be sufficiently negatively charged with the pH of the blood to be purified, the blood pH is adjusted by an appropriate pH adjusting means, and the electricity of the proteins is adjusted. Efforts will be made to make the test negative. A dish fluid delivery channel 24 is connected to the outlet side of the body fluid channels 10 and 12, so that the blood in which a portion of the moisture containing harmful substances etc. has been treated in the filter device 2 is sent out of the device. It has become.

On the way of the dish liquid delivery channel 24, an electrolyte liquid supply mechanism 2 is provided.
6 is connected, and an electrolyte solution such as physiological saline is replenished and supplied to the concentrated blood after passing through the furnace through the liquid sending pump 28 and liquid sending channel 30, etc., and the component composition is adjusted. The blood is returned to the patient's body through the blood delivery channel 24. Note that it is also possible to provide the electrolyte supply mechanism 26 on the side of the blood supply flow path 20 and purify the blood that has been diluted in advance using the filter device 2 . The above-mentioned filtrate flow paths 14, 16, and 18 include a filtrate discharge flow path 32 that guides the filtrate passed through the semipermeable membranes 6 and 8 out of the system.
is connected, and a suction pump 34 is connected on the discharge flow path 32.
A negative pressure generating device such as the following is provided. Suction pump 34
By this operation, a negative pressure is applied to the furnace filtrate channels 14, 16, and 18, and the furnace filtrate containing unnecessary and harmful substances is successively discharged from the system. Note that the filtrate may be discharged from either side of the filtrate 2. A cathode 36 and an anode 38 are arranged in the outermost furnace filtrate channels 14 and 18 of the filtrate 2.

That is, the cathode 36 is placed on the coarse semipermeable membrane 6 side, and the other side is
Anodes 38 are attached to each side of the semipermeable membrane 8 having a fine membrane. These two poles 36, 38' are connected in series to the voltage applying mechanism 401. Although details of the mist pressure applying mechanism 40 are not shown, it includes a power source for applying a predetermined voltage between the two poles, and a voltage regulator (voltmeter, monitor, etc.) as necessary. In the body fluid purification device, if a voltage is applied between the cathode 36 and the anode 38, the charged molecules (or powder) in the blood flowing through the body fluid flow path Q, 12 in the furnace 2, Electromobility is induced depending on the molecular weight and the degree of electrification.

Protein molecules in the blood are negatively charged, and by applying a voltage that can cause useful protein molecules such as albumin to migrate toward the anode 38, the useful molecules are drawn toward the semipermeable membrane 8. However, since it cannot pass through the semi-permeable membrane 8, it passes through the body fluid channels 10 and 12 without being passed through the filtration fluid channel plaster 6 and the turtle 8. However, "albumin etc." The molecular weight is much larger due to y
- Large protein molecules such as globulins Large proteins move very slowly towards the anode 38 side.

In other words, the degree to which they are drawn toward the semipermeable membrane 8 side is small, and for this reason, many of the large protein molecules that are dispersed are left behind, so to speak, on the semipermeable membrane 6 side relative to albumin, etc. From the rough semi-permeable membrane 6, which has an overwhelmingly large amount of furnace filtrate, moisture, etc. is sucked into the filtrate channels 14 and 16.
It is used in a furnace. The removal efficiency of such large proteins depends on the voltage value applied between the two poles 36 and 38, the furnace speed at the rough semipermeable membrane 6 (suction amount of the suction pump 34), and the like.

In other words, in order to increase the self-removal efficiency, it is effective to lower the applied voltage to a certain extent and increase the furnace overspeed, but on the other hand, "useful molecules such as albumin are removed from the rough semipermeable membrane 6" Since there is a risk that albumin will be missed in the furnace, it is necessary to adjust the applied voltage and furnace overspeed so that the removal efficiency of large protein molecules such as y-globuliso is maximized within the range where albumin etc. are not passed through the furnace. desirable.
On the other hand, so-called electrolyte ions in the blood, such as H+, N
Regarding a+, CI-, etc., "anions pass through the semipermeable membrane 8 during open air migration, but those that exit the body fluid channel 10 migrate through the furnace filtrate channel 16 and pass through the body fluid channel blades 2. Even if CI- is reabsorbed at a high rate and finally reaches the anode 38, only CI- among the anions is removed as CI2-.On the other hand, the cations exiting from the body fluid flow path 12 are A similar phenomenon occurs to Q.Finally, only ~10 of the intestinal ions that reach the cathode are removed as 2 days.Therefore, during the furnace passage of large proteins, etc., electrolyte ions are removed. Although it is unavoidable that the above-mentioned applied voltage is applied, the only ions removed by the application of the voltage described above are ions such as Ni-10 and CI- (electrolysis), which lowers the pH of the subsequent replacement solution. Therefore, the replenishing fluid to be supplied to the blood that has passed through the furnace 2 should be a so-called electrolyte solution, such as physiological saline, or a normal HF replacement solution with a slightly lower pH. It is sufficient that the electrolyte solution is replenished by the electrolyte solution supply mechanism 26, and there is no need to use a conventional freezing tray for layer exchange. In the device, by flowing an electrolyte solution having a desired component composition through the filtrate passages 14, 16, and 181 of the filtration device 2, the filtration device can be operated while controlling blood conditions such as pH. You can also do it.

In that case, electrolyte supply and discharge channels for controlling blood conditions such as pH are connected to the furnace filtrate channels 14, 16, and 18, and delivery and discharge pumps provided in each channel are connected. It is desirable that the electrolyte solution is allowed to flow while a negative pressure is applied to the furnace filtrate channels 14, 16, and 18 due to the flow rate difference. In this way, by adjusting the pH of the electrolyte solution to alkaline, the blood pH
By making H more alkaline, thereby increasing the key aerophoretic mobility of proteins in the blood, large protein molecules can be removed more selectively.

In addition, by arranging more semipermeable membranes 6 and 8 in parallel than shown in the figure, the number of body fluid flow channels and furnace filtrate flow channels can be increased within a reasonable range, eliminating the need for large proteins. The overall ability to remove molecules is improved. On the other hand, if you are looking for a more compact and inexpensive purification device,
It is possible to have a simple structure in which filtrate flow channels are formed on both sides of a single body fluid flow channel, and the purpose can still be sufficiently achieved.

In the above explanation, blood has been taken as an example of the body fluid to be purified, but it is of course possible to distribute blood bran from which blood cells have been separated by an appropriate method such as centrifugation to the L body fluid drainage. Effective purification occurs in much the same way as with blood.

In this case, there is little reduction in removal efficiency due to adsorption of platelets and the like to the semipermeable membrane. In addition, it goes without saying that the present invention may be implemented in various modified forms without departing from the spirit of the present invention as set forth in the claims.

As described in detail above, the present invention purifies the body fluid while causing dew aerophoresis in the substance in the body fluid that is passed between two types of semipermeable membranes with different pore sizes. While removing large unnecessary substances from body fluids, it is possible to effectively leave useful substances with a molecular weight of 4, such as albumin, in body fluids, reducing the number of frozen blood that was previously required. without any dependence on
``It has extremely important significance because it will enable us to pursue sufficient and effective treatment for intractable diseases.''

[Brief explanation of the drawing]

The figure is a schematic diagram schematically showing an example of a device according to the present invention. 2: Furnace filter, 4: Housing, 6: Semipermeable membrane (first),
8: Semipermeable membrane (second), 10, 14: Body fluid flow path 14,
Tortoise 6, 18: Furnace filtrate flow path, 20; Blood supply flow path, 24:
Blood delivery channel, 26: Next to electrolyte supply machine, 32 Three furnace filtrate discharge channels, 36: Cathode, 38: Anode 40: Voltage application mechanism.

Claims (1)

[Claims] 1. A first semipermeable membrane having a large pore size, a second semipermeable membrane having a pore size smaller than the pore size of the first semipermeable membrane, and between the two types of semipermeable membranes. A body fluid flow path formed in the body fluid flow path through which body fluids such as blood and plasma to be purified flow, and a filtrate filtered through the semipermeable membranes formed on both sides of the body fluid flow path. a filtrate flow path for discharging the water, a cathode disposed in the filtrate flow path on the first semipermeable membrane side, and a cathode disposed in the filtrate flow path on the second semipermeable membrane side. Body fluid purification comprising: an anode; and a voltage application mechanism that applies a predetermined voltage between the cathode and the anode to induce electrophoresis in the body fluid flowing through the body fluid channel. Device. 2. The first semipermeable membrane and the second semipermeable membrane are alternately arranged in parallel, and the plurality of channels formed by the parallel arrangement alternately serve as the body fluid channel and the filtrate channel. 2. The device according to claim 1, wherein the cathode and the anode are respectively arranged in the outermost filtrate channels on both sides. 3. The device according to claim 1 or 2, wherein a predetermined electrolyte solution is allowed to flow through the filtrate channel.