JPS621539B2 - - Google Patents

Description

[Detailed description of the invention]

[Industrial Application Field] The present invention relates to a biological fluid treatment device,
More specifically, the present invention relates to a coating method for preventing the outflow of coal dust from the surface of granular activated carbon for treating biological fluids and the adsorption of plasma proteins and other blood components to the surface of granular activated carbon. [Prior art] In addition to being frequently used as a detoxification method for resuscitation from coma caused by serious liver diseases such as fulminant hepatitis and cirrhosis, overdosing of sleeping pills and anesthetics, and ingestion of toxic substances such as pesticides, etc. Direct blood perfusion using various adsorbents including activated charcoal has become widely used for the purpose of removing bilirubin to improve symptoms of jaundice and supplementing dialysis therapy by removing medium molecular weight substances for renal failure. I came. It has been revealed that spherical activated carbon is the most effective and safest adsorbent used for the purpose of removing various poisonous substances and waste products. However, the granular activated carbon used for these purposes generally has a high surface fastness and is particularly smooth, but if the surface is not coated, it may be difficult to wash it thoroughly. Furthermore, even if handled carefully, there is a large possibility that coal dust will flow out, even if only in small amounts, due to collisions and friction between the column and the activated carbon during filling, sterilization, transportation, etc. It is extremely difficult to do so. Furthermore, the decrease in blood concentration of various blood components, including plasma proteins such as albumin, fibrin, and globulin, due to adsorption to the surface of activated carbon exceeds 50% of each component in one clinical use, and 70 to 70
It can even reach 80%. In order to improve these defects on the surface of uncoated granular activated carbon for direct blood perfusion therapy, attempts have been made to coat it with various cellulose derivatives, proteins, hydrophilic synthetic polymers, etc., and to immobilize the anticoagulant heparin. Regarding the effect of preventing the outflow of coal dust, granular activated carbon with immobilized anticoagulant cannot be said to be effective, and in addition to the boiling cleaning process, filling the column while immersed in water, heat sterilization, and transportation. At present, there are very few products that can fully guarantee safety, such as the coating layer being easily destroyed during such procedures, and even if the coating layer is completely formed, it cannot prevent blood components from adhering to it. [Purpose of the Invention] In order to improve these drawbacks, the present inventors have repeatedly conducted comparative studies on the use of various synthetic and animal/vegetable polymers, and have developed a solution of a specific highly hydrophilic synthetic polymer. Coating using
We have discovered that a hydrophilic resin coat made by insolubilizing this in combination with a crosslinking agent has extremely good ability to prevent outflow of coal dust and ability to prevent adhesion to plasma proteins and blood components, and we have continued our research. Thus, the present invention was completed. [Structure of the Invention] That is, the present invention provides a method for producing an adsorbent for biological fluid treatment by coating granular activated carbon with a synthetic resin composition, in which poly(glycerol monoacrylate), poly(glycerol monomethacrylate) is used as the coating agent. , and a copolymer consisting of monomers constituting these polymers and 20 mol% or less of a different monomer, and the resulting film is cross-linked using one or a mixture of two or more selected from the group consisting of - A coating method for granular activated carbon characterized by making it insolubilized, and furthermore, coating a crosslinking agent on a coating agent film and crosslinking and insolubilizing the film by heating, or
This method involves partially reacting and bonding crosslinking agent molecules to a coating agent polymer before coating, and then crosslinking and insolubilizing the resulting film by heating. The granular activated carbon that can be used in the present invention does not matter whether the raw material is a natural product or a synthetic product, except for powdered activated carbon granulated using a binder with a particularly low cohesive force. It can be applied to various things, but it is possible to simplify the cleaning process before and after coating.
We use spherical activated carbon made from thermosetting resin as a starting material, which has no possibility of elution of harmful components such as heavy metals and benzopyrene derivatives, and has excellent surface robustness and smoothness. Of course, this is ideal. Coating agents that can be used in the present invention include poly(glycerol monoacrylate)
In addition to poly(glycerol monomethacrylate), as long as the monomers constituting these polymers are the main components, different monomers may be copolymerized in an amount of about 20 mol% or less. However, if the amount of different monomers exceeds about 20 mol %, disadvantages such as not being able to form a good hydrogel layer or the strength of the hydrogel layer decreasing due to too low crosslinking density will occur. The content in the body needs to be about 20 mol% or less. These polymers can be used alone, or two or more of them can be mixed to modify the properties of a single coating agent. As a crosslinking agent that can be used to crosslink and insolubilize these coating agents in the present invention, generally any low to medium molecular weight substance that easily reacts with the active hydrogen of a plurality of -OH groups can be used. type can also be used, but from the viewpoint of ease of use and toxicity, it is better to use medium-molecular substances with a molecular weight of about 250 or more. Examples of such crosslinking agents include silanes, etc. In addition to trimethoxysilanes, bis(trimethoxysilanes), tris(trimethoxysilanes), and polyisocyanates such as toluene diisocyanate and diphenylmethane diisocyanate, 2 or 3 silanes are present in one molecule. Liquid or organic solvent soluble urethane resin prepolymers having -NCO groups or more, and polyglycidyl compounds such as pyrogallol triglycidyl ether, resorcinol dicrycidyl ether, glycidyl glycidyloxybenzoate,
In addition to diglycidyl phthalate, bisphenol A diglycidyl ether, and the like, divalent or trivalent or more polyvalent acid chlorides such as adipic dichloride and phthalic acid dichloride can also be used. Furthermore, one or more polyfunctional vinyl monomers selected from the group consisting of ethylene glycol diacrylate, diethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, glycidyl methacrylate, etc., are added during the synthesis of the coating agent polymer. amount of monomer used
It is added in a range of 0.01 to 5 mol%, and one or more vinyl or glycidyl groups in the polyfunctional vinyl monomer type crosslinking agent molecules are left until after coating, and this is used as a crosslinking agent. It's okay. Various general methods can be used to apply the coating agent to the granular activated carbon, and in the case of a liquid, solution, or emulsion coating agent, it may be dipped or sprayed and then dried; In the case of a powder, a method can be applied in which the coating agent is sprayed while heating one or both of the granular activated carbon and the coating agent, and if necessary, the coating agent is heated and hardened, and then cooled and solidified. Next, as a method for crosslinking and curing the coating agent applied in this way, there is a method for introducing a vinyl group or a glycidyl group of a polyfunctional monomer for crosslinking into the coating agent by copolymerization. , crosslinking can be carried out by heating in the presence or absence of a catalyst; on the other hand, when silanes, polyisocyanates, polyglycidyl compounds, acid chlorides, etc. are used as crosslinking agents, The crosslinking agent molecules may be partially reacted with the coating agent polymer and coated after being bonded in advance, and the resulting film may be crosslinked and cured by heating.Alternatively, after the coating agent is applied and dried, further It is also possible to apply a crosslinking agent corresponding to the composition of the coating agent by spraying or the like, and then heat it to crosslink and harden it. [Effects of the Invention] All coating layers obtained by carrying out the present invention are hydrophilic and swell with water in an aqueous solvent to form a so-called hydrogel. It exhibits high anticoagulant properties due to its strong electrostatic repulsive force against blood cell components, and maintains the high adsorption capacity inherent to granular activated carbon during blood purification treatment of approximately 3 to 5 hours. I can do it. Further describing the features of the present invention, in general, after this type of hydrogel layer is left in an aqueous solvent for a long time, it is easily damaged by heat, collision, friction, etc., resulting in partial or total peeling. However, since the coating layer obtained by carrying out the present invention is appropriately cross-linked and insolubilized, it can be used without any substantial damage even under such severe conditions. This invention has an excellent effect of preventing the outflow of coal dust, and can be said to be an extremely significant invention. Next, the present invention will be explained in more detail with reference to Examples. Example 1 A resol type phenolic resin was granulated and cured using a p-toluenesulfonic acid catalyst.
Using a carbide obtained by heating phenolic resin beads of 0.8 to 1.0 mmφ at 800 °C for 30 minutes in a nitrogen gas atmosphere, the carbide was heated at 990 to 1000 °C for 10 minutes using a rotary furnace.
Activation rate 82% after time steam activation, particle size 0.6~0.8mm
A spherical activated carbon of φ was prepared. After washing and drying this activated carbon 1, a 0.5% aqueous solution 2 of poly(glycerin monomethacrylate) having a number average molecular weight of 18,000 obtained by radical polymerization in an aqueous solvent was prepared.
After soaking in and stirring gently for 30 minutes at room temperature, 65
It was stretched onto a mesh stainless steel wire mesh and air-dried at room temperature. After further drying at 80°C for 12 hours, 3.1 times the mole of diphenylmethane diisocyanate (MDI) was added to a 20% methyl ethyl ketone solution of polyethylene glycol triol with a number average molecular weight of 1500, and the mixture was reacted at 80°C for 12 hours. Coating was performed by spraying 100 ml of a crosslinking agent solution containing a 0.2% solution of a urethane prepolymer synthesized in advance. After air-drying, it was heated at 80°C for 10 hours, then heated at 120°C for 20 hours to react, and was cured and dried. The mixture was placed in a beaker with an equal amount of distilled water, washed five times on a boiling water bath while exchanging water every hour, and then taken up onto the wire mesh and dried by heating at 120°C for 12 hours. Example 2 Activated carbon 1 prepared in Example 1 was washed with water and dried, and the molar ratio was determined using glycerin monoacrylate and methyl methacrylate as main components and diethylene glycol dimethacrylate as a crosslinking agent.
A 90:10:0.2 mixture was copolymerized with a 10-fold solution of azobisisobutyronitrile in ethanol at 60°C for 8 hours, and a polymer with a number average degree of polymerization of 570 was dissolved in ethanol. It was made into a 0.8% solution. After immersing in this coating agent 1 and leaving it at room temperature for 20 minutes with gentle stirring, it was lifted onto the wire mesh used in Example 1 and air-dried, heated at 60°C for 6 hours, then at 80°C for 6 hours, and then further heated at 80°C for 6 hours. 20 at 120℃
It was dried and crosslinked by heating for hours. Uncoated and coated activated carbon samples prepared by carrying out the above examples were subjected to the following tests along with commercially available granular coconut shell activated carbon. (1) Measurement of the number of released coal dust Fill a 20ml glass bottle with sample activated carbon along with distilled water for injection, shake at 37℃ and 2Hz for 48 hours, and separate the activated carbon with a stainless steel wire mesh.
The number of generated coal dust of 2 μφ or more was measured using a Coulter counter. (2) Measurement of uric acid adsorption rate 0.1 g of activated carbon sample was added to 10 ml of uric acid aqueous solution (C = 20 mg/dl), and after shaking at 37°C and 2 Hz for 5 minutes, the residual concentration of uric acid was determined by liquid chromatography. It was measured. (3) Measurement of thrombocytopenia rate Fill a polycarbonate column with 100 ml of sample activated carbon, sterilize it, and pass through this column to collect 12 kg of activated carbon.
The rate of thrombocytopenia after 3 hours of direct blood perfusion was measured using a Coulter counter using a mongrel adult dog.

[Table] The uncoated activated carbon trial-produced in Example 1 has significantly improved coal dust outflow rate and uric acid adsorption rate compared to commercially available coconut shell granular activated carbon, making it more suitable as a material for biological fluid treatment devices. One thing is clear. However, when it comes into direct contact with blood, platelets adhere to it significantly, making it dangerous to put it into practical use as it is. On the other hand, in the case of the activated carbons of Examples 1 and 2 that were coated according to the present invention, the outflow of coal dust was significantly suppressed compared to uncoated activated carbon, and the uric acid adsorption rate was 10%. Although the platelet reduction rate decreased by ~25%, a significant improvement was observed in the thrombocytopenia rate, indicating that the product had sufficient quality to withstand use as activated carbon for blood purification.

Claims (1)

[Claims] 1. A method for producing an adsorbent for biological fluid treatment by coating granular activated carbon with a synthetic resin composition, wherein the coating agent includes poly(glycerol monoacrylate), poly(glycerol monomethacrylate), and The resulting coating is crosslinked and insolubilized using one or a mixture of two or more selected from the group consisting of monomers constituting the polymer and copolymers consisting of 20 mol% or less of different monomers. A method for coating granular activated carbon, which is characterized by: 2. A method for coating granular activated carbon according to claim 1, characterized in that a crosslinking agent is coated on a coating agent film, and the film is crosslinked and insolubilized by heating. 3. The granular activated carbon according to claim 1, characterized in that the coating agent polymer is coated after partially reacting and bonding crosslinking agent molecules to the coating agent polymer, and the resulting film is crosslinked and insolubilized by heating. coating method.