JP2012229353A - Virus-removing material using acrylic acid-immobilized nonwoven fabric, and method for removing virus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a base material and a tool allowing flowing of a liquid containing a hepatitis virus such as blood without causing clogging, a reduction in removal of useful components contained in the liquid, and efficient removal of the virus in the liquid, and to provide a method for removing the virus using the same.SOLUTION: There is provided a polymer base material for adsorbing the hepatitis virus obtained by immobilizing (meth)acrylic acid on a nonwoven fabric containing a polyester or a polyolefin as a base material according to a graft polymerization reaction. Furthermore, there are provided the tool for removing the hepatitis virus using the polymer base material, and the method for removing the same.

Description

The present invention relates to a polymer substrate for adsorbing hepatitis virus obtained by immobilizing (meth) acrylic acid on a nonwoven fabric based on polyester or polyolefin by a graft polymerization reaction, and a hepatitis virus removing instrument using the polymer substrate And its removal method.

Hepatitis C is caused by chronic infection with hepatitis C virus (HCV), and a combination therapy of peginterferon and ribavirin is common as a therapeutic method using drugs. In patients with genotype 1b and a large amount of virus in the blood, the therapeutic result is about 50%, and since the rate of transition to cirrhosis and liver cancer is high, development of more effective treatment methods and drugs is desired. (Non-Patent Document 1). In general, treatment with drugs is known to have high therapeutic results when the amount of virus in the blood is low. When HCV in the blood is removed with a porous filter and combined with the drug, treatment is performed. There is a report that results are improved (Non-Patent Document 2).

In other words, it is presumed that the treatment results have been improved by reducing the amount of virus in the body. However, the method of removing with the above filter removes virus from plasma components by using two plasma separation membranes and plasma purification membranes, so the circuit configuration is complicated and virus can be removed from blood more easily. There is a further desire for a method of removal. In addition, since the plasma component purification membrane is an ultrafiltration membrane, there remains a problem that active components in plasma are also removed at the same time. Therefore, if a polymer base material capable of removing HCV more easily can be developed, it is possible to provide an HCV removal module with less burden on the patient.

As a technique for removing HCV so far, for example, Patent Document 1 and Patent Document 2 describe a method of removing a virus with a porous membrane.
Patent Document 3 describes that viruses and leukocytes are removed with a nonwoven fabric.
Patent Document 4 describes a method of performing multi-stage filtration with a filter having pores in which 99% or more of viruses are removed and the transmittance of a substance to be collected is 90% or more.
Non-Patent Document 3 describes that HCV is adsorbed and removed by dialysis, and in particular, the PS membrane efficiently removes HCV.
On the other hand, regarding a technique for performing surface modification of a nonwoven fabric, for example, Patent Document 5 describes a polyolefin nonwoven fabric in which a vinyl monomer is graft-polymerized.
Non-Patent Document 4 describes a technique of graft polymerization of acrylic acid on a PET non-woven fabric.

Japanese Patent Publication No. 61-168367 Japanese Patent Publication No. 01-148305 JP 2009-18177 A Japanese Patent Laid-Open No. 2000-569 Japanese Patent Laid-Open No. 08-273650

Viral Hepatitis-Advances in Basic and Clinical Research-Japanese Clinical Volume 62 Special Issue 7 (2004) A. K. Fujiwara et al. Hepatol. Res. , 37, 701 (2007) Dialysis Journal 43 (1): 55-60, 2010: “Examination of HCV adsorption due to different dialysis membrane materials in hemodialysis” Journal of Applied Polymer Science, Vol. 89, 1952-1958 (2003)

  In view of the prior art, the problem to be solved by the present invention is that a liquid containing hepatitis virus such as blood can be flowed without causing clogging, and the removal of useful components contained in the liquid is reduced and efficient. It is another object of the present invention to provide a substrate, an instrument, and a virus removal method using them, which can remove viruses in the liquid.

That is, the present invention relates to a material for removing hepatitis virus and a method for removing the same, and more specifically, hepatitis obtained by immobilizing (meth) acrylic acid on a nonwoven fabric using polyester or polyolefin as a substrate by a graft polymerization reaction. The present invention relates to a polymer substrate for adsorbing viruses, a hepatitis virus removing instrument using the polymer substrate, and a method for removing the same.

ADVANTAGE OF THE INVENTION According to this invention, the liquid which contains hepatitis viruses, such as blood, can flow without causing clogging, and the base material and instrument which can remove the virus in a liquid efficiently can be provided. .

It is drawing which shows the outline of the cartridge for virus removal provided with a nonwoven fabric.

That is, the present invention
1. A polymer substrate for adsorbing hepatitis virus, in which (meth) acrylic acid is immobilized on a nonwoven fabric by a graft polymerization reaction,
2. 1. The nonwoven fabric has polyester or polyolefin as a constituent component. A polymer substrate for adsorbing viruses according to claim 1,
3. 1. The hepatitis virus is hepatitis B virus or hepatitis C virus Or 2. A polymer substrate for hepatitis virus adsorption according to claim 1,
4.1. ~ 3. A hepatitis virus removing instrument comprising the polymer substrate for adsorbing hepatitis virus according to any one of
5.4. A method for removing hepatitis virus using the hepatitis virus removing instrument according to claim 1,
About.

Non-woven fabric The non-woven fabric for immobilizing (meth) acrylic acid used in the present invention can be used without particular limitation as long as it is based on a polymer compound that can immobilize (meth) acrylic acid by chemical reaction or physical adsorption. . As such a polymer compound, various compounds having high blood compatibility can be used. For example, olefin resin, styrene resin, sulfone resin, acrylic resin, urethane resin, ester Resin, ether resin or cellulose acetate, more specifically, polyethylene terephthalate, polyvinyl alcohol, ethylene vinyl alcohol copolymer, polymethyl methacrylate, polysulfone, polyether sulfone, polyacrylonitrile, polyethylene, polypropylene or poly- Examples thereof include 4-methylpentene.
The nonwoven fabric can be controlled in terms of basis weight, fiber diameter, thickness, average pore diameter, and the like by its production method and post-treatment, and an optimal one may be appropriately selected according to the purpose, and used without particular limitation. I can do it.
The basis weight is not particularly limited as long as it is in the range of 1 to 200 g / m ² , but it is considered that the surface area for adsorbing the virus increases as the basis weight increases. Therefore, it is necessary to appropriately perform an optimum design according to the target removal rate and processing capability.
The thickness is not particularly limited as long as it is in the range of 10 to 2000 μm, but it is necessary to appropriately design optimally according to the processing capacity and the space for incorporation into the module.
The fiber diameter is not particularly limited as long as it is in the range of 10 nm to 50000 nm. However, when the basis weight is the same, it is conceivable that the thinner the fiber diameter, the larger the surface area for adsorbing the virus.
In addition to this, an optimum one may be selected as appropriate within a range that is widely and generally assumed as the physical properties of the nonwoven fabric.

-Graft polymerization In this invention, the radical generate | occur | produced in the said nonwoven fabric and the ethylenically unsaturated group which (meth) acrylic acid has are made to react, and it is graft-polymerized to a polymer support body. In the graft polymerization, a known and commonly used method may be used. When an ionizing radiation source is used, α rays, β rays, γ rays, accelerated electron rays, X rays, etc. are mentioned. An electron beam is desirable. In the case of using a polymerization initiator, known and usual initiators such as benzoyl peroxide, diammonium cerium nitrate, azo compounds such as persulfate and AIBN can be used.

The ionizing radiation graft polymerization method is a simultaneous irradiation graft polymerization method in which the non-woven fabric is contacted with (meth) acrylic acid and irradiated with ionizing radiation, and a pre-irradiation graft polymerization method in which the non-woven fabric is pre-irradiated and then contacted with (meth) acrylic acid. Either of these is possible and can be selected according to the purpose.

Regarding the graft polymerization method using the polymerization initiator used in the present invention, a method in which an initiator and (meth) acrylic acid are added simultaneously, and after the initiator is once attached to the nonwoven fabric, (meth) acrylic acid is contacted. The method may be any of the polymerization method, (meth) acrylic acid once adhered to the nonwoven fabric, and then the initiator is added and polymerized. The method may be appropriately selected according to the physical properties of the nonwoven fabric substrate, the initiator and the solvent to be used. Just select it.

-Liquid containing hepatitis virus In this invention, in order to remove hepatitis virus, it has the characteristic of making the liquid containing the target hepatitis virus contact or pass through a nonwoven fabric. The liquid containing the hepatitis virus of the present invention is not particularly limited as long as it contains the hepatitis virus. More specifically, for example, a body fluid that is a human body fluid component, a culture solution containing hepatitis virus, and the like can be mentioned. More specific examples of body fluids include blood, saliva, sweat, urine, runny nose, semen, plasma, lymph, tissue fluid and the like.

The form of the virus removal instrument comprising the polymer substrate for adsorbing hepatitis virus obtained in the present invention is not particularly limited as long as it is a shape applicable to the above-mentioned use. For example, one or more nonwoven fabrics Can be fixed to the cartridge shown in FIG. 1, and a virus can be removed by injecting a liquid containing hepatitis virus into the cartridge and filtering through a nonwoven fabric. Moreover, in order to improve the removal efficiency of the hepatitis virus in a single process, two or more nonwoven fabrics can be used in the cartridge as needed.

As a method of using the hepatitis virus removing instrument of the present invention, it is brought into contact with a liquid containing hepatitis virus (for example, an aqueous solution containing hepatitis virus or a body fluid such as blood, plasma, serum, etc.) or passed through a non-woven fabric. Any method may be used as long as it can remove and separate the virus.

Further, the polymer substrate for adsorbing hepatitis virus of the present invention can remove the virus from the liquid by capturing the virus from the liquid containing the hepatitis virus, but captures the virus present in the air, It can also be used to remove viruses in the air.

Evaluation of hepatitis virus adsorption ability The hepatitis virus targeted in the present invention is characterized by being a hepatitis B or C virus. In this invention, in order to evaluate hepatitis virus adsorption ability, adsorption ability with respect to HCV E2 protein (His-tag) was evaluated. The E2 protein, together with the lipid membrane, constitutes the outer envelope (envelope) of the virus particle and plays an important role in virus entry. It is a protein that can be evaluated.
As shown in the following examples, the adsorption ability of HCV E2 protein was confirmed with the acrylic acid-immobilized polymer substrate of the present invention.

The following examples illustrate the invention in more detail.

Each measuring method in this example was performed by the following method.

Example 1
A polyester nonwoven fabric 50 cm ² (fiber diameter of 1 to ² μm, basis weight 50 g / m ² ) was placed in a 200 mL three-necked flask, 40 mL of acrylic acid was dropped and immersed for 1 hour. Thereto, 40 mL of a 5% nitric acid aqueous solution was dropped, and the inside of the flask was put in a nitrogen atmosphere on an ice bath. Under a nitrogen atmosphere, 200 mg of diammonium cerium nitrate was added and reacted at 80 ° C. for 1 hour. After completion of the reaction, a polyester nonwoven fabric washed with methanol and water and grafted with acrylic acid was obtained. The graft ratio at this time was 3%.
The graft ratio was evaluated according to the following formula.

Graft ratio (%) = {(weight of nonwoven fabric after graft reaction) − (weight of nonwoven fabric before graft reaction)} / weight of nonwoven fabric before graft reaction × 100

The non-woven fabric grafted with acrylic acid was cut into 5 cm ² , put in a microtube, added with 1% BSA / PBS solution as a blocking solution, and left at 4 ° C. overnight. The blocking solution was removed, 500 μL of a 2 μg / mL E2 solution (Abcam) was added, and the mixture was rotated at room temperature for 2 hours, and the amount of E2 before and after adsorption was measured by ELISA. The adsorption removal rate of HCV E2 was 91%.

(Comparative Example 1)
Biological evaluation similar to Example 1 was performed using a polyester nonwoven fabric (fiber diameter of 1 to 2 μm, basis weight of 50 g / m ² ) without using acrylic acid for graft polymerization. The adsorption removal rate of HCV E2 was 67%.
From the above examples and comparative examples, it is clear that the nonwoven fabric obtained by graft polymerization of acrylic acid performs virus removal more favorably.

The polymer substrate of the present invention and the instrument using the polymer substrate can be used for removing hepatitis virus.

1: Channel for introducing liquid containing hepatitis virus into holder 2: Holder for holding nonwoven fabric 3: Nonwoven fabric 4: Channel for discharging liquid from which hepatitis virus has been removed from the holder

Claims (5)

A polymer substrate for adsorbing hepatitis virus, in which (meth) acrylic acid is immobilized on a nonwoven fabric by a graft polymerization reaction. The virus-adsorbing polymer substrate according to claim 1, wherein the nonwoven fabric comprises polyester or polyolefin as a constituent component. The polymer substrate for adsorbing hepatitis virus according to claim 1 or 2, wherein the hepatitis virus is hepatitis B virus or hepatitis C virus. The hepatitis virus removal instrument provided with the polymeric base material for hepatitis virus adsorption in any one of Claims 1-3. The removal method of the hepatitis virus using the hepatitis virus removal instrument of Claim 4.

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