JPS621300B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a method for manufacturing an adsorbent for cleaning biological fluids, and more specifically, the present invention relates to a method for manufacturing an adsorbent for cleaning biological fluids, and more specifically, a method for controlling the flow of coal dust from the surface of granular activated carbon for cleaning biological fluids, and adsorption of plasma proteins including blood cell components to the surface of granular activated carbon. The present invention relates to a coating method for preventing. It is often used as a means of resuscitation from coma caused by serious liver diseases such as fulminant hepatitis and cirrhosis, overdose of drugs such as sleeping pills, and ingestion of poisonous substances, as well as removal of bilirubin to improve symptoms of jaundice. As an auxiliary liver used for such purposes, direct blood perfusion using various adsorbents including activated carbon is common. In addition, attempts have been made to use this type of adsorbent column in combination with the aim of shortening the treatment time for hemodialysis and hemodialysis commonly performed for renal failure, and preventing medium- and high-molecular-weight toxins. It has become clear that activated carbon is the most effective adsorbent used for the purpose of removing these various poisons and wastes. However, although the granular activated carbon used for these purposes generally has a particularly smooth surface and is highly durable,
If the surface is not coated, even if the column is thoroughly cleaned and handled carefully, collisions and friction between the column and activated carbon during filling, sterilization, transportation, etc. will still generate coal dust, even if only in small amounts. There is a large possibility of leakage, and it is extremely difficult to eliminate it completely.
Furthermore, the loss of plasma proteins such as fibrin, γ-globulin, and albumin as well as blood cell components such as platelets due to adsorption to the surface of activated carbon exceeds 50% of the total content of each component per treatment, and the loss is 70 to 80% of the total content of each component per treatment. It is not uncommon for it to reach %. In order to improve these two deficiencies regarding the surface of granular uncoated activated carbon for direct blood perfusion therapy, attempts have been made to coat it with various hydrophilic polymers or cellulose polymers, or to adsorb the anticoagulant heparin. It goes without saying that granular activated carbon with immobilized heparin is effective in preventing the release of heparin, but it also prevents the coating layer from being destroyed during the boiling cleaning process, filling the column while immersed in water, heating sterilization, transportation, etc. This is likely to occur, and the current situation is that no one with sufficient reliability has been obtained. In addition, regarding the effect of preventing the adsorption of plasma proteins and blood cell components on the surface of activated carbon, even coatings coated with hydrophilic methacrylic acid ester, which is considered to be one of the most effective materials, can be prevented by direct blood perfusion for several hours. At present, it is unavoidable that about 50% of platelets are lost. In order to improve these drawbacks, the present inventors conducted comparative studies on the use of various synthetic and biologically derived polymers, and developed a polyurethane resin, a silicone resin, a polyurethane resin, a fluorine resin, or a microdomain block copolymer. The present invention was completed based on the discovery that a specific resin among the composite resins can provide particularly good antithrombotic properties and coal dust prevention ability. Granular activated carbon that can be used to carry out this invention can be used regardless of whether the raw material is a natural product or a synthetic product, except for powdered activated carbon granulated using a binder with particularly low cohesive force. Various materials can be used, but it is preferable to use thermosetting resin-based spherical activated carbon, which has a robust and smooth surface, because it simplifies the cleaning process prior to coating. . The silicone resin mainly having a dimethylsiloxane structure that can be used in the present invention refers to a silicone resin having a dimethylsiloxane structure as a main component and having 50
% or more of polysiloxane chains is necessary to maintain anticoagulant properties, but if the total amount is 50% or less, alkyl groups other than methyl groups, phenyl groups, substituted phenyl groups, vinyl groups After coating granular activated carbon with these polysiloxanes, the method of curing is to heat bake at 100 to 300°C for those with OH groups at the ends, or to cure vinyl groups. In addition to crosslinking using non-toxic catalysts such as peroxides and platinum-based catalysts, room temperature curing methods applying various condensation reactions such as dealcoholization, dealboxylation, dealdehyde, etc. can be similarly used. One or two of polyether polyols, polyester polyols, polyamide polyols, polyamide polyamino polyols, or polyamide polyamines that can be used in the present invention.
Polyurethane or polyurethane urethane resin synthesized from at least one species and polyisocyanate uses polyether, polyester, polyol having a polyamide structure, polyaminopolyol, or polyamine as the active hydrogen compound component, and preferably methylene diphthyl as the polyisocyanate component. An aromatic diisocyanate such as enyl diisocyanate (MDI) or naphthalene diisocyanate, or an aliphatic diisocyanate such as xylylene diisocyanate or hexane diisocyanate is used, and preferably polymethylene diamines or It is a liquid or soluble polyurethane or polyurethane urea resin synthesized through urethanization, urethanization, or chain extension reaction using one or more types of polymethylene glycols. The fluororesin or partially chlorinated fluororesin that can be used in this invention includes, for example, tetrafluoroethylene, hexafluoropropylene, polymers of various perfluoroolefins and partially chlorinated perfluoroolefins, and polymers of two or more of these monomers. These fluorine-containing monomers and/or partially chlorinated fluorine-containing monomers 50
mol% or more, and one or more mixtures of olefins such as ethylene, propylene, butylene, etc.
It is an emulsion or powder of copolymer resins consisting of 50 mol% or less. The hydrophobic block copolymer resin having a microdomain structure that can be used in this invention is as follows:
AB type, ABA type, ABC type, using two or more types of various monomers having unsaturated ethylenic double bonds,
It is a resin with a microdomain structure consisting of a block copolymer such as ABCD type, and monomers that can be used for these include conjugated diene monomers such as butadiene, isoprene, and 1,3-pentadiene, styrene, α-methyl Styrene, various styrene derivatives such as ρ-methoxystyrene, methyl methacrylate, ethyl methacrylate,
In addition to various aliphatic ester monomers such as methyl acrylate, vinyl formate, vinyl acetate, and vinyl propionate, acrylonitrile, alkyl vinyl ketones, acrylamide and its N-alkyl substituted products, all of which are free alcohols, amines, and carboxyls. Two or more monomers selected from acid-free polar or non-polar vinyls or dienes can be used in combination, but in order to provide excellent coagulability, the resulting block must be The copolymer such as a polymer needs to have a microphase separation structure of a sea-island structure or a lamella structure on the order of several microns to several tens of microns. These resins may be used alone or in combination of two or more. Various general methods can be used to coat granular activated carbon with a coating agent. In the case of a liquid, solution, or emulsion coating agent, it may be dried or hardened after dipping or spraying; For such products, a method can be applied in which one or both of the granular activated carbon and the coating agent are sprayed while being heated, and then heated and hardened or cooled and solidified. Also, silicone resin and polyurethane resin.
Undercoating is performed using a dilute solution of the coating agent of the present invention selected from the group consisting of fluorocarbon resins or block copolymer resins, or different types of coating agents such as collodion and hydroxyethyl methacrylate resins. After that, coating by the method of the present invention is particularly effective in preventing outflow of coal dust. All of the coating layers obtained by implementing the present invention are hydrophobic, and compared to conventional hydrogel type coatings, they are less susceptible to damage due to collisions or friction between activated carbon particles or against column walls, etc.
Furthermore, since it is highly inactive against blood cell components such as plasma proteins and platelets, it has high anticoagulant properties and can maintain the high adsorption capacity inherent to granular activated carbon during the treatment period of about 3 to 5 hours. The present invention will be explained below by way of examples. Example 1 Sulfuric anhydride in an amount of 2% of the resin amount was added to a resol type phenol varnish aqueous solution with a resin content of 60%, stirred uniformly, and immediately dropped into liquid paraffin at 100°C while stirring at 600 rpm. Phenol resin beads with a diameter of 0.8 to 1.2 mm are
Heat to 800℃ for 30 minutes to carbonize, then heat to 1000℃ in steam
After washing and drying the spherical activated carbon with an activation rate of 50%, it was immersed in a 1% toluene solution of dimethylpolysiloxane having 1.2% OH groups at the terminals, air-dried, and coated by heating at 220°C for 8 hours. Example 2 After washing and drying the spherical activated carbon used in Example 1,
Japanese Pharmacopoeia collodion diluted with ether
After dipping in a 0.2% solution and drying, an NCO-terminated polyurethane prepolymer was synthesized from polybutylene glycol with a molecular weight of 2000 and MDI, and 0.5% of polyurethane urea was chain-extended with ethylenediamine.
After immersion in MEK (methyl ethyl ketone) solution,
It was dried and coated at 120°C for 20 hours. Example 3 Petroleum pitch-based spherical activated carbon with a particle size of 0.4 to 0.8 mmφ was washed with water, dried, and submerged in a 0.3% acetone solution of cellulose 21/2 acetate.
Furthermore, an 8/2 (molar ratio) random copolymer triol of propylene glycol/ethylene glycol with a molecular weight of 1500 was made into an NCO-terminated polyurethane prepolymer using MDI, and a 0.3% tetrahydrofuran solution of a polyurethane resin chain-extended with ethylene glycol was sprayed with stirring. I coated it. Example 4 After washing and drying the spherical activated carbon used in Example 1,
3/4/3 of styrene/butadiene/styrene
(molar ratio) of ABA type block copolymer in a 0.6% toluene solution, and was coated by vacuum drying at 60°C. Comparative Example 1 The activated carbon used in Example 3 was applied by dipping after washing and drying with water to a 0.2% ethanol solution of a 6/4 (molar ratio) random copolymer obtained by radical copolymerization of hydroxyethyl methacrylate and vinyl acetate in ethanol. , dried at 120°C for 12 hours, further immersed in a 0.8% ethanol solution of the copolymer, dried at 120°C for 12 hours, and coated. Comparative Example 2 The spherical activated carbon used in Example 1 was washed with water, dried, immersed in a 1.0% solution of collodion used in Example 2, and then air-dried to coat it. Comparative Example 3 The spherical activated carbon used in Example 1 was washed with water and dried in an uncoated state, and then subjected to the following test. Comparative Example 4 After washing and drying the spherical activated carbon used in Example 3, it was subjected to the following test in an uncoated state. Table 1 shows the results of a coal dust flow test and a 3-hour direct blood perfusion experiment using artificially jaundiced adult mongrel dogs weighing 15 to 21 kg for the above eight types of activated carbon samples. (All measurements were repeated three times and the average value is shown.)

[Table] The number of released coal dust is calculated by filling a 20ml bottle with activated carbon together with physiological saline, shaking it at 50mm amplitude and 2Hz for 48 hours, removing the granular activated carbon with a coarse wire mesh, and pouring the liquid into paper with a pore size of 0.22μ. The samples were collected by filtration and counted under a microscope. A large amount of coal dust was released from the uncoated coals of Comparative Examples 3 and 4, and a considerable amount of coal dust was still released from the sample coated with a hydrophilic coating agent (Comparative Example 1), but the coating method of the present invention Substantially no coal dust was observed to flow out from the coated material. The adsorption capacity of bilirubin showed a high value in each example, but this was because there was almost no adhesion of blood components.
While this shows the inherent adsorption ability of the coated activated carbon, adsorption of blood components was unavoidable in each comparative example, and the layer in which these components were deposited was able to prevent bilirubin from being adsorbed. In addition, the values of platelet and total protein reduction rates determined by direct blood perfusion experiments using artificially jaundiced dogs were also
Comparative Examples 1 and 2 using conventional coating agents
In contrast, in Examples using the coating agent of the present invention, a significant improvement was observed. Since the present invention uses a hydrophobic film as described above, there is no decrease in strength even in physiological saline or body fluids, and the outflow of coal dust can be substantially prevented, and it is capable of preventing toxic substances such as bilirubin. This invention can be said to be extremely significant, as it maintains a high adsorption and removal ability for solutes such as alcohol and waste products, and also makes it possible to suppress the loss of active ingredients such as proteins and blood cells.

Claims (1)

[Scope of Claims] 1. In a method for producing an adsorbent for purifying biological fluids by coating granular activated carbon with a synthetic resin, the coating agent comprises: (A) a silicone resin in which 50% or more of the constituent units have a dimethylsiloxane structure; , (B) polyurethane or polyurethane urea resin synthesized from one or more of polyether polyols, polyester polyols, polyamide polyols, polyamide polyamino polyols, or polyamide polyamines and polyisocyanate, (C) foot A method for coating granular activated carbon, the method comprising using either a base resin or a partially chlorinated fluororesin, or (D) a hydrophobic block copolymer resin having a microdomain structure.