JPH0290928A - Blood purification material and apparatus - Google Patents

Abstract

PURPOSE:To provide a blood purification membrane and blood purifier excellent in the comparability with a living body by using a permeable membrane consisting chiefly of modified cellulose and/or cellulose ester wherein the hydrogen atoms of its hydroxyl group are substituted with a specified functional group. CONSTITUTION:The hydrogen atoms of at least part of hydroxyl groups of cellulose and/or cellulose ester are substituted with a functional group represented by the formula I (wherein R<1> and R<2> are the same or different and alkyl group having 1-5 hydrogen or carbon atoms and R<3> and R<4> are the same or different and hydrogen atom or methyl group). At this time, not less than 0.3% of all of the hydroxyl groups of the cellulose are substituted therewith. The use of a selective permeable membrane consisting chiefly of this modified cellulose as a blood purification membrane brings about improved compatibility with a living body such as controlling a temporary decrease in the number of leukocytes.

Description

Detailed Description of the Invention <Industrial Application Field> The present invention relates to modified cellulose and/or modified cellulose ester in which at least some of the hydrogen atoms of hydroxyl groups in cellulose or cellulose ester are replaced with specific functional groups. The present invention relates to blood purification materials and blood purifiers mainly based on blood purification materials and blood purification devices.

<Prior Art> In recent years, hemodialysis has become extremely popular as a treatment for patients with renal failure, and hemofiltration, plasma exchange using plasma separation, double filtration, and the like have been developed. In the blood purifiers used in these treatments, hollow fiber membranes are mainly used to increase the effective membrane area within a compact container. Blood purifiers filled with an adsorbent made of activated carbon particles or the like coated with a porous film are also in practical use.

The most commonly used membrane material for these blood purifiers is cellulose, which has safety and excellent separation characteristics backed up by years of use.

However, even though cellulose blood purification membranes have such excellent properties, they do not cause a temporary drop in white blood cell concentration during dialysis therapy, which is difficult to directly relate to the specific symptoms of dialysis patients. Improvements such as preventing the activation of complement components from occurring as much as possible and lowering the dosage of anticoagulants such as heparin used during treatment, in other words, improving so-called biocompatibility. desired.

<Problems to be Solved by the Invention> The purpose of the present invention is to improve the drawbacks of the conventional blood purification membranes made of cellulose, etc., and to provide a modified cellulose and/or modified cellulose ester that is highly compatible with living organisms. An object of the present invention is to provide a blood purification membrane and a blood purification device using the same.

In particular, we provide a blood purification membrane made of modified cellulose and/or modified cellulose ester with improved biocompatibility, which reduces transient white blood cell reduction phenomenon and complement component activation phenomenon, and a blood purification device using the same. is intended to provide.

Means for Solving the Problems> The present invention provides a blood purification material based on cellulose and/or cellulose ester, at least a portion of which has been modified by substitution, wherein the substitution The hydrogen atoms of at least some of the hydroxyl groups of Or represents a methyl group. 1. A blood purification material characterized by being substituted with a functional group represented by Alternatively, the selective adsorbent comprises cellulose and/or cellulose ester in which at least some of the hydrogen atoms of the hydroxyl groups are substituted with functional groups represented by the structural formula (I>).

The cellulose used in the present invention may be any material as long as it can be formed into a membrane used for blood purification, but regenerated cellulose is usually preferably used. Regenerated cellulose includes cellulose esters that are at least mostly saponified, cellulose regenerated by cuprammonium method,
Examples include viscose rayon. Specific examples of other celluloses include celluloses such as methylcellulose and ethylcellulose in which some of the hydrogen atoms of the hydroxyl groups are substituted with lower alkyl groups. Practically speaking, regenerated cellulose produced by saponification of cellulose ester or by the copper ammonia method is advantageously used.

Specific examples of cellulose esters include cellulose monoacetate and cellulose diacetate.

The shape of the blood purification membrane of the present invention is hollow fiber.

In addition to tubular and planar adsorbents, examples include thin film forms formed on the surface of granular or fibrous adsorbents.

In the case of blood purifiers such as hemodialysis, hemofiltration, double filtration, and artificial lungs, hollow fiber membranes are suitable because they can easily increase the effective membrane area within a compact container.

If the part that comes into contact with blood during blood interaction is substituted with a functional group represented by the general formula (1), biocompatibility will be improved, especially the temporary reduction of white blood cells observed at the beginning of the contact period with blood. It has the effect of suppressing the reduction and activation of complement.

The substitution ratio is in the range of 0.3% or more, that is, the average number of substituents per unit of glucose anhydride (C6H1[lOs > 0.01 or more) is likely to have the effect of increasing biocompatibility. suitable.

In the case of cellulose ester, the remaining hydroxyl groups are substituted with a functional group represented by the general formula (I>, and the substitution ratio is preferably 0.01 or more per glucose anhydride unit.

In addition, as for the upper limit value of the replacement ratio, even if the replacement ratio is too high, the effect of increasing the ratio may be difficult to obtain, and from the viewpoint of manufacturing cost, it should be 20% or less, more preferably 10% or less. It's practical.

The blood purification membrane of the present invention is characterized by mainly using such modified cellulose and/or cellulose ester, but other materials such as polymethyl methacrylate may be used as long as the properties are not impaired. A polymer may also be used in combination.

The method for producing the blood purification membrane of the present invention includes a method in which cellulose and/or cellulose ester is first modified and then formed into a hollow fiber membrane, and a method in which cellulose and/or cellulose ester is formed into a hollow fiber membrane, etc. There is a method of modifying the membrane after it is assembled into a blood purifier.

The blood purifier of the present invention is characterized in that a selectively permeable membrane mainly made of modified cellulose as described above is used as a blood purification membrane.

When the permselective membrane is a hollow fiber type blood purifier using a hollow fiber membrane, for example, the hollow fiber bundle is housed in a cylindrical container,
Both ends were adhesively fixed to the inner wall surface of the container with a resin such as polyurethane to form a partition, and both ends were cut to open the hollow part, and then the ladder was fixed to the blood inflow hemlock and the blood outflow ladder. Things can be given. In the case of a hemodialyzer, dialysate inlets and outlets 82 are usually provided on both sides of the container to communicate with the gap between the hollow fiber bundles.

In addition, when the permselective membrane is a thin film formed on the surface of a granular adsorbent, for example, a cylindrical container is filled with the adhesive, and porous plates are provided at both ends to fix the adsorbent. Practically preferred is one in which a header for blood inflow and a ladder for blood outflow are fixed to the outside.

The blood purification t4 of the present invention also includes modified cellulose itself in the form of pellets, flakes, etc., which adsorbs and separates components such as bilirubin to be removed from the blood.

The blood purifier of the present invention is characterized by using the selectively permeable membrane mainly composed of the improved cellulose and 7' or cellulose ester. It may have any shape, and is not limited to these specific structures.

In the case of a hollow fiber type blood purifier, cellulose hollow fiber membranes, cellulose ester hollow fiber membranes, etc. may be used in combination with the permselective membrane mainly made of improved cellulose, as long as the biocompatibility is not impaired. It's okay.

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

<Example> Using a bundle of regenerated cellulose hollow fibers (inner diameter 200 μ) (2000 hollow fibers, length 300 mm), a dialyzer was assembled in the usual manner with divinyl sulpon and dialkylamine (R2NH: R is an alkyl group) A treatment solution prepared by dissolving a treatment agent and sodium carbonate in distilled water was filled into the hollow fiber blood side of the dialyzer, heat-treated at 135°C for 10 minutes, and then thoroughly washed with hot water. Also, water permeability and dialysis performance were measured.

The results are shown in Table 1. Here, the degree of substitution of functional groups for cellulose hydroxyl groups was varied by varying the amount of treatment agent.

The complement consumption rate is measured as follows.

The membrane was immersed in serum to give a surface area of 50 cm2 per ml of serum and incubated at 37°C for 1 hour. After separating and removing the membrane from the serum, the complement value in the serum was determined by the method of Mayer et al. (Experimental Immun.

Chemistry p133 Thomas, 19
61) using 50% hemolytic complement value (CH2O), and the decrease from the complement value of blank, ie, serum that is not brought into contact with the membrane, is expressed as the complement consumption rate.

In addition, when the carbon number of the alkyl group of the substituent is 6 or more, it is difficult to handle it and it is difficult to use it in practice.

In addition, the degree of substitution was determined by elemental analysis.

<Effects of the Invention> According to the present invention, there is provided an improved blood purification material that has improved biocompatibility, particularly the activation phenomenon of complement components, without impairing the original performance of the membrane, etc., and blood using the same. It has an excellent effect of increasing the purifier's value by 1.

Claims (1)

[Scope of Claims] 1) A blood purification material mainly composed of cellulose and/or cellulose ester, at least a portion of which has been modified by substitution, wherein the substitution is at least a portion of the cellulose and/or cellulose ester. The hydrogen atom of the hydroxyl group is expressed by the following general formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼... (I) [However, R^1 and R^2 may be the same or different, hydrogen atoms or carbon atoms number of 1 to 5 represents an alkyl group, R^3,
R^4 are the same or different and represent a hydrogen atom or a methyl group. ] A blood purification material characterized by being substituted with a functional group represented by the following. 2) The substitution accounts for 0.3% of the total hydroxyl groups in cellulose.
The blood purification material according to claim 1, which has the above-mentioned properties. 3) In a blood purifier using a permselective membrane or a selective adsorbent as a blood purification material, the permselective membrane or selective adsorbent has hydrogen atoms of at least some of the hydroxyl groups represented by the following structural formula (I). A blood purifier comprising cellulose and/or cellulose ester substituted with the functional groups shown. ▲There are mathematical formulas, chemical formulas, tables, etc.▼...(I) [However, R^1 and R^2 are the same or different and represent a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, R^3,
R^4 are the same or different and represent a hydrogen atom or a methyl group. ]