JPH0236878A - Immunodeficiency syndrome virus and/or agent for removing substance related thereto - Google Patents

Abstract

PURPOSE:To prevent the deterioration of symptom by using an agent for removing HIV in body fluids comprising a solid substance showing mild acid or mild basic property at its surface. CONSTITUTION:A solid substance showing mild acid or mild basic property is that shows mild acid or mild basic property when it is subjected to a dripped pH test at its surface, wherein the mild acid property means pH2.5-pH6.9 while the mild basic property means pH7.4-pH10.5. There are used various kind of solid substances showing the mild acid or mild basic property at their surfaces, but such solid substance as to show the mild acid property at its surface is preferable. As a representative case, there are plus ion exchange resin (SO3H type, COOH type), silica-alumina and hidroxiapertite-silica-alumina ternary sintered body. The shape of removing agent is in the form of powder, granule, plate or fiber type although, normally a granule body type having a dia. ranging from 0.1mm to 5mm is used.

Description

DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to the adsorption and removal of human immunodeficiency syndrome virus (hereinafter abbreviated as HIV) and/or its related substances from body fluids of patients.

[Conventional technology]

HIV has an affinity for human lymphocytes, especially Hel<T lymphocytes, and invades and destroys such lymphocytes. This results in a decline in the function of cellular immunity, and as a result, patients often die from opportunistic infections or benign tumors.

Currently, intensive research is being conducted to treat infectious diseases caused by HIV. For example, attempts have been made to produce a vaccine, but the HIV gene mutates easily, making it difficult to select antigens to target the vaccine. Mayu, suramin, HPA23, etc. have been used as specific inhibitors of reverse transcriptase, and attempts have been made to administer AZT and other drugs as DNA inhibitors, but it has been reported that good clinical results have not been obtained and there are significant side effects. has been done. Mayu, interferon is
No significant improvement effect has been obtained in clinical trials.

Furthermore, it is known that there is an increase in immune complexes and the presence of factors that suppress interleukin-2 production in the serum of HIV patients, and plasmapheresis has been attempted to remove these, but no results have been found to be satisfactory. Not obtained [PlasmaTherapy] January 23 (19
87)) o As mentioned above, many methods have been tried to treat infectious diseases based on HIV, but each treatment method has its limitations.

[Problem to be solved by the invention]

Based on the information that HIV is released in large quantities from T cells into the body fluids of patients infected with HIV in the early stages of infection or in the exacerbation stage, we used extracorporeal circulation therapy to release HIV into the body fluids. We thought that if we could reduce the amount of HIV and/or its related substances in plasma, it would be possible to prevent symptoms from worsening and, in turn, to prolong life.

Therefore, the object of the present invention is how to reduce HI in body fluids.
M and/or the idea is to remove the related substances, and to obtain a removal agent for that purpose.

=3 [Means for solving the problem] The purpose is to remove HIV and/or its related substances from body fluids made of solid substances whose surfaces are weakly acidic or weakly basic. Leopard, which is achieved by providing agents.

A feature of the present invention is the use of a solid material whose surface is weakly acidic or basic in order to remove HIV and/or its related substances from the body fluids of HIV-infected patients.

In the present invention, a solid substance whose surface is weakly acidic or weakly basic refers to a solid substance whose surface becomes weakly acidic or weakly basic by dropping a reagent on the surface of the solid substance.
6.9 or less, weak basicity means...7.4 or more and 10.5 or less. Field on the surface of solid material is 7.0 or more to 7.3
The following (non-polar polypropylene, quartz, 5O
aNa-type cation exchange resins, etc.) do not have the ability to adsorb and remove I-I IV and /''!, or related substances, and those with a surface density of less than 2.5 (strong acid-type cation exchange resins, etc.) (resins, etc.) or those with a value exceeding 10.5 (strongly basic anion exchange resins, etc.) tend to coagulate proteins in body fluids, making it difficult to efficiently remove HIV and related substances from body fluids. It is.

In the present invention, solid substances with a weakly acidic or slightly basic surface used for producing the remover include inorganic substances such as calcium phosphate (hydroxyapatite, etc.), alumina, silica, silica-alumina, and zirconia. Anion exchange resins (NH2@J), cation exchange resins (C old type, 5OBH type), sulfonation, carboxylation''!, ri are aminated polyolefins, sulfonated polystyrene, dialdehyde crosslinking, etc. Examples include those made of polymeric substances having polar groups such as insolubilized fL sulfonated, carboxylated or aminated polyvinyl alcohol.These substances can be molded into a desired shape (granules, etc.) by themselves and used as a remover. However, it can also be used supported on a relatively low-activity carrier or an inert carrier (porous glass, etc.).

Furthermore, polyhydroxyethyl methacrylate, polyacrylic acid, heparin, 5-dextran sulfate, etc. are used immobilized on a carrier.

In the present invention, various solid substances having a weakly acidic or basic surface as described above are used. Among them, a solid substance having a weakly acidic surface is preferable, and a typical example is a cation exchange resin (5OaH type, C0OH type), silica-alumina, and hydroxyapatite-silica-alumina ternary sintered bodies.

The solid substance used as a removing agent in the present invention may be any solid substance as long as only its surface is weakly acidic or weakly basic, excluding those that dissolve in body fluids. The solid material may be porous or non-porous. Since HIV and/or its related substances only need to be adsorbed to the surface of the solid material, it does not matter what kind of structure the inside of the solid material has. The material may be different from that of the surface. In the present invention, the shape of the remover may be powder, granule, plate, or fiber, but it usually has a diameter of 0.1 mg or more.
Granules within the range of 5 deafness are used. Furthermore, since the removing agent may be used in direct contact with blood cells 61, 1. Preferably, it is spherical so as not to damage the lfu sphere.

When a patient's body fluids (blood, plasma, etc.) (IL-treated) are treated with a removal agent manufactured using the above-mentioned solid substances, HIV and/or its related substances are adsorbed to the removal agent and removed from the body fluid. It is surprising and unexpected that HIV and/or its related substances can be effectively removed from body fluids by such treatment. It refers to metabolites produced by cells that are invaded by IV, as well as substances that suppress the activity of immune-complementary cells that are produced when viruses invade the body (immunosuppressive substances).

In the present invention, the removal agent made of the above-mentioned solid/substance is used by being packed into a column, and the column is provided with an inlet part and an outlet part of a shape that can be easily connected to a blood circuit.
Preferably, the Q column is equipped with a filter made of polyester or the like, which allows body fluids to pass through but not the remover, between the remover layer and the inlet/outlet part. Examples of Q columns include glass, polyethylene, polypropylene, polycarbonate, polystyrene, Columns made of polymethyl methacrylate, etc. can be used, but columns filled with such removal agents are usually sterilized (autoclave sterilization, γ-ray sterilization, etc.) before use.
Autoclavable polypropylene, polycarbonate, etc. are preferred.Using the aforementioned column, HIV and/or its related substances can be removed from the patient's body fluid by extracorporeal circulation. There are two types of extracorporeal circulation methods: (1) Blood collected from the patient's blood vessels is directly introduced into a column filled with a removal agent, and HIV and/or related substances in the heel blood are adsorbed and removed. , a method of returning purified blood to the patient's blood vessels.

(2) First, blood collected from the patient's blood vessels is separated into blood cells and plasma using a separation membrane, etc., and the separated plasma is introduced into a psychokinetic ram filled with a removal agent, and the HIV and plasma in the plasma are removed. /
Or, after adsorbing and removing related substances, the purified plasma is mixed with the above blood cells and returned to the patient's blood vessel.

Among the above two methods, loss of blood cell components (platelet adhesion,
The latter method (2) is practical because it can be operated with less hemolysis of red blood cells, etc.).

Such treatment can remove HIV and/or its related substances from the patient's body fluids, thereby preventing the patient's symptoms from becoming aggravated and prolonging the patient's life. In other words, during the exacerbation phase, HIV itself is released in large quantities from T cells as mentioned above, so if this can be removed, the tendency for exacerbation and deterioration can be prevented, and even when HIV-related substances are removed, HIV-related Since the antigen-antibody reaction caused by the substance is suppressed and the destruction of lymphocytes is suppressed, it is thought to have the effect of preventing the worsening of symptoms. Note that useful components in the body fluid may also be removed by such body fluid treatment, so in that case, it is desirable to replenish the patient with useful components.

〔Example〕

Examples 1 to 8 and Comparative Examples 1 to 3 (1) Specifications of the removal agent Experiments were conducted using a removal agent with the following specifications. Cells susceptible to HIV CEM (CCRF).

CEM, Flow Laboratories AT
CCNo. 19 AcuteLymphoblast
ic Leuckemia), propagated, and subcultured] The supernatant of the infected cell culture medium was treated with the above-mentioned removing agent. The details of the processing operation are as follows.

(]) Each remover was immersed in 0.5 f f 2 ml of mixed solution medium RPMI-1640, heated and degassed, and sealed and steam sterilized.

Cr+) HIV infected cell culture medium at 2000 rpm for 15 min.
The two serum liquid obtained by centrifugation for 1 minute was filtered through a 0.45 μm filter, and 4 ml of the obtained tear fluid and RPM11
640 mixed with 16 liters of milk.

(iii) 1i in a medium immersed in the remover of (1).
2 d of supernatant solution was added and left at room temperature for 30 minutes.

(1) (iii' + supernatant 'e) Pass through a 0.45 μm filter, and transfer 0.54 of the lacrimal fluid obtained in step 1 to a culture solution [5 x 106 cord blood lymphocytes] Interleukin 2 and phytohemeagritinin (Phytobema
-g)<1utinin) (PHA) was added to the culture, cultured for 48 hours, and then cultured in a 96-well multititer plate at a total volume of 100 μt] at 37°C for a predetermined period of time (3 minutes). 5 days) After incubation, the 0 (Vi) () sample was centrifuged at 100OG for 10 minutes, and the supernatant was filtered through a 0.45 μm filter.

(vii) The supernatant was used for antigen measurement, and the precipitate was applied to a slide glass to serve as a sample for fluorescence antibody method.

(vii) (1) to (vii) 7) As a control sample (sensitivity check) for the specimen used in the experiment, HI
The supernatant of V cultured cells was added to RPM I-1640 at 10-1
．． 10-2.10-810', prepared by diluting to 10-5 and used as a measurement sample for fluorescent antibody method (8) Confirmation of the removal effect of HIV and/or its related substances (6) Antigen Measurement of Concentration The antigen concentration in the culture solution was measured by the ELISA method using the Du Pont HIV Antigen Measurement Chiratra as described below.

(]) Specimen 180. 5 to c+t
% Triton x io o aqueous solution 20 μt was mixed.

0I)--Left overnight at room temperature.

(rr+> Automatic water washing was repeated 3 times.

(IV) 100 μIQ of biotinylated antibody solution was added and incubated at 37° C. for 2 hours.

(V) Automatic cleaning.

(Vl) t-s redish peroxidase (H
orse-radish peroxidase)
-Streptavidin
) 100 μtk was added and incubated for 15 minutes.

(v: r+ After automatic washing, 100 μt of dye “ortho-phenyle y-diamine J (0-phenyle
ne-diamine, 0PD) substrate aqueous solution was added.

(v+io) The reaction was stopped by adding 50 μt' of 4N-sulfuric acid aqueous solution.

(IX) Absorbance at 492 nm (blank: 620
Measure the HIM concentration (nt/ml) from the voltage detection line.
Fully calculated moxibustion.

The results are shown in Table 2.

Table 2 As shown in Table 2, the HIV antigen (P-24) was removed using neutral polypropylene, quartz, and SO3Na.
Almost no adsorption was observed using type cation exchange resin. However, it was observed that all of the removal agents whose surfaces were weakly acidic or weakly basic were able to adsorb and remove the antigen. especially,
A removing agent whose surface is weakly acidic, such as a SO3Hm or COOH type cation exchange resin or silica-alumina, showed an excellent antigen removal ability, that is, an excellent H2-V removal ability.

(B) Judgment by fluorescent antibody method
The presence of IV and/or its related substances was determined by the fluorescent antibody method as described below, and the performance of the remover was evaluated based on the determination results.

(1) HIV adsorption operation (r2Xl) - (Vl+
) Each of the precipitates obtained in ) was diluted with 1 volume of PBS.
Washed while rotating at low speed for a minute.

(ij) The washed and precipitated residue was suspended in 50 µt of PBS and applied in two spots per specimen onto a slide for measuring fluorescent antibodies.

After coating, the slide was immersed in methanol for fixation.

(]■) Add acetone to the fixed spot and air dry.

(V) (P-24) Antibody-PBS solution (volume ratio; 1:
40) Add 20 μt to each spot.

(Vl) This was incubated at 37° C. for 20 minutes, and then washed with a PBS solution for 20 minutes.

(Vfi) 20 μt of mouse anti-IgG antibody-PBS solution (volume ratio; 1:20) was added to each spot.

(viiD After incubating this at 37°C for 20 minutes, it was washed with a PBS solution for 20 minutes.

(+X) Streptavidin (5treptavidin
idin) 7 Luo v -1! y (fluor
escein)-PBS solution (volume ratio i1:5
0) Add 20 µt"ig to each spot and incubate it at 37°C for 10 minutes, then wash with PBS solution in the dark.

(XI) 1 part of 90% glycerin and 10 parts of PBS mixture
One drop was added per spot.

(Xii) Under ultraviolet irradiation, the presence or absence of fluorescent parts in each spot was observed using a microscope.
Shown in the table.

Table 3 Main code (+) (CeE)) eRPM
I-1640K Te10 '10-2.10-3.10-
4. Sample diluted to 10-5 (after 3 hours of incubation) Antigen was confirmed by this method in the control (+) (CG) diluted sample at 10", indicating the superiority of this method. As shown in Table 3, after 3 days of culture, the sensitivity of Examples 2.3.5.
The antigen production in 6.7 and 8 was ←). Although the antigen production in Examples 1 and 4 was not (→
The production of these antigens is slightly different from that of the comparative example. After 5 days of culture, antigen production for Examples 3.5 and 6 was not (g). On the other hand, Example 1.2.4.
Regarding 7 and 8, antigen production was observed. This is considered to be lower than these, since it is judged that the next 5 days of culturing after a very small amount of HIV remained resulted in the production of antigens that exceeded the detection limit.

Regarding the above-mentioned culture solution (sensitized with CEMa cells) treated with the removing agent, the amount of thymidine derivative taken up by immature lymphocytes was measured as described below to determine the overall effect of the removing agent.

(1) Lymphocytes collected from neonatal cord blood were adjusted to a number of 5 x 10' lymphocytes/ml.

(11) The lymphocytes were treated with RPMI 1640-10% F'BS (fresh calf serum) - 100 IU of penicillin.
/rrtl and 100 μg/ml Strefutomycin-1% PHA-Interleukin-2 (IL-2)
1 unit/p was added and cultured at 37°C for 48 hours.

(iii) Each specimen treated with the above removing agent (0
Mix 20 μt of the sample sensitized with 8M cells and 80 μt of the culture solution (11) and culture for 3 or 5 days.

(1) For each (lil) sample, add activated thymidine derivative ((methyl-1, 2°3H-) thyrnidine-5'-trip to a tank for 6 hours after incubation.
hosphate, ammonium salt,
3H-dTTP) was added at 1 μct1ri/well.

() After completion of the culture, lymphocytes were collected by filtration onto a Wattman glass filter, washed with 10 ml of aqueous solution of 5-trichloroacetic acid, further washed with 10 ml of methanol, and then air-dried.

(V+) Place this glass filter in a polyethylene container and add the extract (main component: toluene) to the
1. The total amount of 3H-dTTP incorporated into lymphocytes was measured using a scintillation counter. Here, 3H-dTTP incorporated into control (-) (Ce)
Based on the amount of H-dTTP, the effect of the remover was compared and studied based on the amount of 3H-dTTP taken up when a sample was treated with the remover. -The full results are shown in Table 4.

Table 4 As shown in Table 4, in the blank (+) (C■), culture 3
Blank ←) (Cθ)
This shows that the lintocytes are destroyed by HIv and cannot be taken up by thymidine derivatives. It is expected that this trend will become even more pronounced after five days.

On the other hand, when the HIV culture solution is treated with the removal agent, the uptake rate of thymidine derivatives does not significantly decrease even after 3 and 5 days when compared with the control ←) and the neutral removal agent. This suggests that not only f-11V itself (but also substances involved in the destruction of HIV lymphocytes) are removed by the weakly acidic or weakly basic removing agent.

The results shown in Table 4 roughly correspond to the results shown in Tables 2 and 3, but even though the HI antigen adsorption capacity in Table 2 is not that high, the survival of lymphocytes in Table 4 is high. There are also removal agents (for example, Example 1) that exhibit the following. This means that
This suggests the possibility that the remover adsorbs and removes not only HIV itself but also its related substances at the same time.

Determination of ability to remove HIV and/or its related substances by batch method HIV antigen concentration and antigen production were measured after 7 and 14 days using CEM cells and in the same manner as in (B). The procedure was as follows: To 0.2 ml of 0(,1) remover 0.5?/RPMI-164 was added two drops of supernatant of an HIV culture solution, and the mixture was shaken for 30 minutes.

()1) The entire supernatant liquid of (i) was collected and filtered with a 0.45 μm membrane filter.

c]:r:+ 0.5 ml of the P solution was used as a sample for antigen measurement.

(iv) (iii) 0.2 rrtl @ CE
M cells (5 x 105 cells/ml) were inoculated into RPMI-1640 culture solution 1.8 cm and cultured in a carbon dioxide incubator.

(V) Culture supernatant liquid was collected 4 days after inoculation, and one volume of fresh RPMI-1640 culture liquid was added.

(Vl) For 7 days after incubation, 1 ml of culture was collected and 1 ml of fresh RPMI-1640 aqueous solution was added. Anti-W, concentration and OE for the collected culture supernatant
Antigen production of I (IV) in M cells was measured by fluorescent antibody method.

(vii) On the 11th day after inoculation, perform all the same operations as in () 7'j.

(viii) Hanging 14 days after inoculation The same procedure as in (vi) was performed to measure antigen concentration and antigen production.

The measurement results are shown in Table 5. 0-fi q :E (by fluorescent antibody method and kit using IV-RPMI-1640 culture solution) The sensitivity of IIV antigen concentration should also be investigated. All of the measurement results are shown in Table 6.0 Thus, the measurement limit for antigen concentration is 0.03 ng, A
ce, and it becomes almost impossible to determine at a dilution rate of 10-2 to 10-3, but the detection limit of the fluorescent antibody method is 10-5.

Therefore, it is extremely important to determine the same sample using two detection methods. In addition, the antigen concentration measurement using the kit detects HIV (P-24), and 1
('HIV(P-24) with or without IV activity
As long as it is present in the supernatant of the culture solution, it can be detected by color development. In order to be careful, the I (IV antigen production ability id mo,!: OH
IV-RPMI-1640 solution 1 (7) 10-2~10
It is clear that these have an excellent ability to remove 7jHIV.

Table in the margin below: Antigen concentration: ng/m ) in the following manner, and measure the concentration of HIV antigen in the culture solution.

(1) Polypropylene column (capacity 1o4; inner diameter 1
5m) was filled with 41 remover and physiological saline.

(11) The entire column was sterilized by autoclaving.

(iii) The saline in the sterilized column was thoroughly replaced with mixed solution medium RPM Nee 1640.

(1) 50 plates of HIV culture solution (mixed solution medium RPMI-1640 containing 10% FI13S) (PH Near, 4
) was circulated through the column at a rate of 7 minutes for 1 hour.

(V) After circulation, measure the concentration of HIViJJJ in the culture solution. The results are shown in Table 7.

Table 7 below shows that HIV antigens are effectively removed from the HIV culture solution by the circulatory system.

(Vl) Furthermore, this was inoculated to OEM, and on the 7th and 14th
After 21 days, antigen concentration and antigen production by fluorescent antibody method were observed. All results are shown in Table 8. In Table 8, the antigen concentration is expressed as (+) for 0.04 ng/yrt1 or more, and 0.04 ng/d for more than 0.03 ng/d.
As shown in Table 8, OEM by fluorescent antibody method of sample solution processed by circulation method using mini module.
It can be seen that all the intracellular antigen production is (-), and that HIV can be efficiently adsorbed and removed.

(4) Determination of safety of removal agents Silica-alumina (Example 3), cation exchange resin (C
0OH type) (Example 5) and cation exchange resin (5O3
Type H) (Example 6) was treated in a mixed solution medium RPM11640 at 121°C for 20 minutes to obtain extracts. Add each extract to CEM cells and measure cytotoxicity. As a result, in all extracts, 90-95% of OEM cells survived 21 days after addition to OEM cells.

Comparative Example 4 Cation exchange resin Dowex 50'WX 8 (Dow Chemical, yh) (
surface ll+: 2.0) and anion exchange resin IRA
-75 [: Made by Nippon Organo Co., Ltd.] (1:12.0 of surface)
&'', the same operation as in Example 1 was performed, but the increase in viscosity of the culture solution was observed.

This suggests that when a patient's plasma is actually treated with the ion-exchange resin layer, an undesirable situation such as blood coagulation may occur, and the surface layer may be strongly acidic. Note that solid substances exhibiting strong basicity are not used in the present invention.

Examples 9 to 14 Silica sol [manufactured by Nichiwa Kagaku Kogyo @Yi, silica concentration 21.5 wt %l] and alumina sol [manufactured by Nissan Chemical Co., Ltd., alumina concentration 16.5 wt %] were mixed with each other as shown in Table 9. The mixture was mixed to achieve the desired composition ratio, and water was evaporated off on a hot plate in advance. This was fired in an electric furnace at 550°C for 3 hours. The obtained silica-alumina 012 was placed in a liquid medium RP.
MI-1640 (concentration 1.02 f/dt) 2 m
121° C., 20...091 ml was added thereto and shaken for 30 minutes to prepare a sample for measuring HIV adsorption ability.

Collect the supernatant liquid of the sample, filter it with a 0.457m filter, and measure the HIV concentration (P-24 antigen) in the tear fluid using the ELISA method as before. It was measured. The measurement results are shown in Table 9.

No. 9 We investigated adsorbents that maintain surface properties and have high adsorption activity against HIV, and as a result, we obtained a remover with high activity among the hydroxyapatite-silica-alumina ternary adsorbents. I discovered that.

Hydroxyapatite is simultaneously impregnated with silica sol and alumina sol to a predetermined concentration, water is evaporated and removed in advance, and then fired in an electric furnace at 550° C. for 3 hours.

Each of the obtained removers was 0.5? Weigh and liquid medium RPM
I-16402m, 1 at 121° C. 20 As shown above, it can be seen that the HIV removal ability of the silica-alumina-based removal agent is excellent in the region where the Si/l'-1 atomic ratio is high.

Examples 15-21 Hydroxyapatite is used as a material for implants and has excellent biocompatibility.

The present inventors added hydroxyapatite biosuitability = 32-...2rlLl, shook for 30 minutes, and found that HIV
This was used as a sample for measuring removal ability.

The supernatant of the sample was collected, passed through a 0.45IXn filter, and the HIV concentration in the tear fluid (P-24 anti-II
)'! - Measured by ELISA method in the same manner as above. The measurement results are shown in Table 10.

Table 10 Note that the hydroxyapatite used here (is Ca
/P: 1.50 was baked at 550°C for 3 hours and then used to make sure. As shown in Table B0, the particle size of the sample impregnated with silica and alumina and fired has a relatively low impregnation concentration of 5 to 10% compared to the HIM removal ability of hydroxyapatite alone. It can be seen that it exhibits high activity at certain concentrations. In this way, the fact that the silica-alumina concentration shows high activity in the low concentration region will ultimately lead to a decrease in the amount of silica-alumina.
desirable.

Examples 22-23 Silica alumina manufactured by Davison ■ (St/A7 atomic ratio 4.
40) was impregnated with a 0.79 weight ratio polymethacrylic acid hydroxyethyl ester (PHEMA)-ethyl solution so that the final ratio of PHEMA to silica-alumina was 1 weight ratio. After evaporating and removing ethanol while heating on a hot water bath, curing treatment was performed at 110°C for 2 hours. The HIV removal ability was evaluated using the same method as in the experiment using the hydroxyapatite-silica-alumina remover described above. went.

The measurement results are shown in Table 11.

Table 11 It was confirmed that the HIV removal ability was improved by coating with PHEMA as described above.

Although it is theoretically possible to increase the coating concentration of PI (BMA), in reality, when it is increased to 1.5 to 2.0%, an undesirable phenomenon of particles blocking occurs.Therefore, silica-alumina It is thought that the appropriate coating concentration of PHEMA on the substrate is about 1.

As described above, according to the present invention, it has been confirmed that 1 (IV and/or IV) can remove related substances and does not inhibit the growth of normal lymphocytes. By removing HIV and/''!, or related substances from the body fluids of patients in exacerbation stages (it is unknown that HIV increases rapidly in body fluids during exacerbation stages) using an extracorporeal circulation system. It is expected that this method will be able to prevent the worsening of patients' symptoms and prolong their lives, and such a method is also considered to be an auxiliary means for drug therapy using antiviral agents. It is also possible to use agents to purify blood products and concentrate HIV from blood for clinical testing.

〔Effect of the invention〕

According to the present invention, it is possible to provide a removing agent made of a solid substance whose surface is weakly acidic or weakly basic. When body fluids are treated using the removal agent, for example, by extracorporeal circulation, the human immunodeficiency syndrome virus itself and/or substances related to the virus can be effectively removed from the body fluids, thereby prolonging the patient's life. This can be expected, and the present invention is of great significance.

Patent applicant: Floor type company

Claims (1)

[Scope of Claims] 1. A removal agent for removing the human immunodeficiency syndrome virus itself and/or related substances of the virus in body fluids, which is made of a solid material whose surface is weakly acidic or weakly basic. 2. The removing agent according to claim 1, wherein the solid substance is a COOH type or SO_3H type cation exchange resin. 3. The removing agent according to claim 1, wherein the solid substance is silica-alumina. 4. The removing agent according to claim 1, wherein the solid substance is a ternary sintered body of hydroxyapatite-silica-alumina.