JPH0257270A - Method for suppressing elution of organic compound from porous membrane - Google Patents

Abstract

PURPOSE:To suppress the elution of org. substances even in high pressure steam sterilization by applying activation treatment to the surface of a porous membrane and the inner surfaces of the pores thereof containing a crystal nucleus forming agent or a stabilizer to chemically bond a hydrophilic high-molecular compound to the surface of the membrane and the inner surfaces of pores. CONSTITUTION:A porous membrane used as a membrane material is prepared by activating the surface of a polypropylene porous membrane to form a polymerization start point on a propylene molecule and supplying a hydrophilic monomer to the treated surface to chemically bond a hydrophilic polymer to the surface of the membrane and the inner surfaces of pores. Even when this membrane is subjected to high pressure sterilization, the hydrolyzable compound such as the crystal nucleus forming agent or stabilizer used at the time of the preparation of the membrane to be contained therein is not eluted. As the crystal nucleus forming agent to be used, there is an org. heat-resistant substance having an m.p. of 150 deg.C or higher, pref., 200-250 deg.C and a gelling point equal to or higher than the crystallization start temp. of polypropylene to be used.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a method for suppressing the elution of organic compounds that easily elute from a polypropylene porous membrane used in a body fluid filter.

(Prior Art) Body fluid filters include blood filters, plasma separators, plasma component separators, etc., and these have recently come to be widely applied clinically. Accordingly, these body fluid filters must have high performance and high safety, and must have as little influence on living organisms as possible. Therefore, the materials used in body fluid filters, especially those used as filtration membranes, must be of high performance and do not affect living organisms.

Conventionally, cellulose acetate, polyvinyl alcohol, polyester, polycarbonate, etc. have been used as materials for filtration membranes. However, membranes manufactured from these materials have insufficient membrane properties such as mechanical strength, porosity, and plasma separation ability.

Recently, with regard to permeable membranes for plasma separation, polyolefin polymers have attracted attention as materials with low complement activity, and studies are underway on permeable membranes using polyolefin polymers.

When producing a permeable membrane using a polyolefin polymer, particularly polypropylene, a crystal nucleating agent and a stabilizer are usually blended into the polypropylene polymer. That is, a crystal nucleating agent is added to the polypropylene polymer to reduce the size of the polypropylene particles, thereby controlling the gap between the solid phases, that is, the diameter of the pores formed, and adding a stabilizer. It is used to stabilize polypropylene during the production of porous membranes.

On the other hand, in order to use a body fluid filtration device safely, it must be sterilized, but when sterilizing a body fluid filtration device, it is necessary to consider the effect that the residue will have on living organisms after sterilization. As a sterilization method, formalin sterilization and ethylene oxide gas sterilization have problems when considering the influence of residues on living organisms, and γ-ray sterilization and high-pressure steam sterilization are more preferable.

However, when a body fluid filtration device using a permeable membrane containing the above-mentioned crystal nucleating agent and stabilizer is sterilized with gamma rays, the decomposition and deterioration of the material due to gamma rays, especially when porous polypropylene is used as a filtration membrane. When using membranes, deterioration of the polypropylene membrane becomes a problem, and when high-pressure steam sterilization is performed, crystal nucleating agents and stabilizers added during porous membrane manufacturing tend to elute. The amount of additives must be kept to a very small amount, or the conditions for high-pressure steam sterilization must be considered, which may complicate the operation.Furthermore, when using a body fluid filter, sufficient cleaning must be performed. There were problems such as the need for

(Problems to be Solved by the Invention) The present inventors conducted various studies to solve the above problems, and found that the surface and pore inner surface of the porous membrane containing the crystal nucleating agent or stabilizer We have discovered that the elution of these organic substances can be suppressed even during high-pressure steam sterilization by activating the membrane and chemically bonding a hydrophilic polymer compound to the surface of the membrane and the inner surface of the pores, and have developed the present invention. The purpose of the present invention is to provide a method for suppressing the elution of organic compounds from a porous membrane.

(Means for Solving the Problems) That is, the present invention activates the surface and pore inner surfaces of a porous membrane that contains at least one type of hydrolyzable organic compound as a crystal nucleating agent and stabilizer. This is a method for suppressing the elution of organic compounds from a porous membrane, which is characterized by chemically bonding a hydrophilic polymer compound to the surface of the membrane and the inner surfaces of the pores after the chemical treatment.

Furthermore, the present invention will be explained in detail.

Polypropylene is preferred as the membrane material of the present invention, and polypropylene is not limited to propylene homopolymers, but may also include other monomers containing propylene as a main component (e.g.
There are block polymers with polyethylene), but preferably those with a melt index (M, 1.) of 5 to 70.
Preferably. Especially M, 1. is preferably from 5 to 40, and for the purpose of further increasing the strength of the membrane, it has a large molecular weight, that is, M, I.

It is preferable to use polypropylene blended with a low polypropylene, for example, M, 1.5 to 40 Novolipropylene L/Nni M, 1.0
．． 05 to 5 polypropylene mixed with 0 to 50 weight X is preferably used. Also, among the polypropylene.

Propylene homopolymers are particularly preferred, and those with high crystallinity are most preferred.

The crystal nucleating agent used in this method has a melting point of 15
It is an organic heat-resistant substance having a gelling temperature of 0° C. or higher, preferably 200 to 250° C., and a gel point higher than the crystallization initiation temperature of the polypropylene used. - For example, 1.3.
2.4-dibenzylidene sorbitol, 1.3.2.4
-bis(p-methylbenzylidene)sorbitol, ■,
3.2.4-bis(p-ethylbenzylidene) sorbitol, sodium bis(4-t-butylphenyl)phosphate, sodium benzoate, and the like. Among these, 1.
3.2.4-dibenzylidene sorbitol, 1.3.
2.4-bis(P-ethylbenzylidene) sorbitol and 1.3.2.4-bis(domethylbenzylidene) sorbitol are preferred because they are less likely to elute into the blood.

In addition, as stabilizers, calcium stearate, calcium oleate, pentaerythrityl-tetrakis [3
-(3,5-ditau-4hydroxyphenyl)copropionate, dilaurylthiodipropionate, distearylthiodipropionate, dimethyl succinate-1-
(2-hydroxyethyl)-4-hydroxy-2,2,
Examples include 6,6-titramethylpiperidine polycondensate.

A method for manufacturing a porous membrane from a composition containing these additives may be carried out by any conventional method. After being discharged in the form of a flat film, it is cooled and solidified with a liquid polyether, and then the organic filler is extracted and removed, followed by heat fixation.

The organic filler used in this method can be uniformly dispersed in the polypropylene while the polypropylene is melted;
In addition, it is necessary that it is easily soluble in the extract liquid. Examples of such fillers include liquid paraffin (number average molecular weight 100 to 2000), α-olefin oligomers [e.g. ethylene oligomer (number average molecular weight 100 to 2000),
~2000), propylene oligomer C number average molecular weight 1
00-2000), ethylene-propylene oligomer (
(number average molecular weight 100-2000), paraffin wax (number average molecular weight 100-2500), various hydrocarbons, etc., and preferably liquid paraffin.

Inside the obtained membrane, compounds used as organic fillers, stabilizers and crystal nucleating agents are present.

Therefore, in order to suppress the elution of these organic compounds,
This membrane must be activated to chemically bond hydrophilic polymers to the membrane surface and pore surfaces. As the activation means, for example, any means such as low-temperature plasma irradiation, ozone treatment, corona discharge treatment, ultraviolet ray irradiation, γ-ray irradiation, or electron beam irradiation may be employed, and preferably low-temperature plasma irradiation. After active sites are formed on the surface of the polypropylene molecular membrane and the pore surfaces in this manner, a hydrophilic polymer is chemically bonded by supplying a hydrophilic monomer and carrying out graft polymerization.

The wood-philic monomers that can be used are generally acrylic, methacrylic, unsaturated amide, diene, and triene-based monomers that can be radically polymerized1.For example, (meth)acrylamide, N-methyl (meth) ) acrylamide, N,N-dimethyl(meth)acrylamide,
N,N-methylethyl (meth)acrylamide, N,N
-diethyl (meth)acrylamide, (meth)acrylic acid, 2-hydroxyethyl (meth)acrylate, etc., with N,N-dimethylacrylamide being most preferred.

Next, the present invention will be explained in more detail with reference to Examples.

Example 1 and Comparative Examples 1 and 2 400 parts by weight of liquid paraffin and 0.3 parts by weight of 1 as a crystal nucleating agent per 100 parts by weight of polypropylene
．． 3.2.4-Bis(P-ethylbenzylidene)sorbitol and calcium stearate as stabilizer0.
1 part by weight, pentaerythrityl-tetrakis [3-(3
, 5-ditau-4-hydroxyphenyl)] propionate 0.05 parts by weight, dilaurylthiodipropionate 0.1 parts by weight, dimethyl-1-(2-hydroxyethyl)-4-hydroxy-2 succinate, Pellets obtained by melt-kneading 0.3 parts by weight of 2,6,6-titramethylbiperidine polycondensate are extruded through a T-die, cooled and solidified, and liquid paraffin is extracted with a solvent to obtain an average pore diameter of 0. 5μm
A porous polypropylene membrane was obtained.

The porous membrane obtained in this way is then subjected to low-temperature plasma (A
r, 0.1 torr) for 10 seconds, then N, N
- Supply dimethylacrylamide and react at 25°C for 5 minutes to coat the membrane surface and pore surface with water-soluble polymer polyN,N
- Dimethylacrylamide bonded hydrophilic porous polypropylene membrane was obtained 2 Using this hydrophilic polypropylene porous membrane, the membrane area was 0.
A 3rn' disc-shaped laminated filter was placed in a polycarbonate filter container, filled with RO water, and then autoclaved at 115° C. for 30 minutes.

In the filter thus obtained, the UV absorption of the filling liquid in the filter was measured as an indicator of the amount of hydrolysis products,
In addition, using bovine blood with a hematocrit of 40"1, the blood flow rate was Loom Q/min, and the diaphragm pressure (THP) was 25 mmt (
g. An in vitro plasma separation experiment was conducted at 37°C, and the separated plasma flow rate was measured 10 minutes after the start of one separation.

As Comparative Example 1, a similar filter was made using an untreated polypropylene porous membrane with the same composition as in the example without a water-soluble polymer bound thereto, and the same high-pressure steam sterilization was performed, followed by the same evaluation. did.

As Comparative Example 2, the amount of the crystal nucleating agent was 0.1 part by weight, and an untreated polypropylene porous membrane with the same composition as in the example was used, the same filter was made, and the same high-pressure steam sterilization was performed. After that, the evaluation was made in the same way.

The results are shown in Table 1. In Comparative Example 1, the separated crystal flow rate, that is, the filtration performance was good, but the UV absorption was 0.15, and 2Ω cleaning was required before use. In Comparative Example 2, an improvement in UV absorption was observed, but leakage of blood into the filtered plasma was observed in a plasma separation experiment, and it was determined that the membrane 1 strength was too weak to withstand practical use.

The filter of the present invention shown in the examples has a good separated plasma flow rate and a very small amount of UV absorption of 0.01, and has excellent performance and
The effectiveness of the present invention was confirmed by providing safety.

1st table ratio...Maximum absorption value at 220 nm or more and 350 nm or less $2...Cannot be measured due to blood leakage (Effect) As mentioned above, polypropylene is used as a membrane material by activating the surface of the polypropylene porous membrane. After forming a polymerization initiation point on the molecule, a hydrophilic monomer is supplied to chemically bond the hydrophilic polymer to the membrane surface and pore surface.The porous membrane is then sterilized using high-pressure steam. However, the hydrolyzable compounds contained in the membrane, such as crystal nucleating agents and stabilizers used during membrane manufacturing, do not elute, and the membrane itself is a hydrophilic porous membrane, making it difficult to separate body fluids. When used as a membrane, the porous membrane for body fluid filtration devices can be provided, which has good separation ability and has both excellent performance and safety.

Claims (3)

[Claims] (1) After activating the surface and pore inner surfaces of a porous membrane that contains at least one type of hydrolyzable organic compound as a crystal nucleating agent and stabilizer, the membrane surface and pores are activated. A method for suppressing the elution of organic compounds from a porous membrane, characterized by chemically bonding a hydrophilic polymer compound to the inner surface. (2) The organic compound from the porous membrane according to claim 1, wherein the hydrolyzable organic compound is an ester, an acid anhydride, an acid chloride, an acid amide, an alkyl halide, an acetal, an ether, or a saccharide. elution suppression method. (3) The activation treatment is low-temperature plasma treatment, ozone treatment, corona treatment, ultraviolet irradiation treatment, γ-ray irradiation, or electron beam irradiation. Elution suppression method.