JPH0322183B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a sealing material for artificial organs. As a sealing material for artificial organs, an aromatic diisocyanate and a mixture of castor oil and trimethylolpropane are reacted to form an initial addition product containing an NCO group, and this initial addition product is combined with castor oil or castor oil and trimethylolpropane. A polyurethane obtained by reticulation with a mixture (Japanese Patent Publication No. 58-26366) and a cycloalphatate diisocyanate, and the general formula
R′-(NH ₂ )m, m>2, R″-(OH)n, n>2
A non-foaming urethane obtained by mixing the aromatic polyamine or alkyl polyol represented by
58-75556) is known. However, recently there has been a demand to significantly reduce eluates from the sealing part of an artificial organ based on standards for dialysis artificial kidney devices, and these urethanes cannot be said to have a small amount of eluates. The present inventors have arrived at the present invention as a result of intensive studies aimed at obtaining a sealing material for artificial organs with less eluate and an artificial organ using the same. That is, the present invention
Hexamethylene diisocyanate (hereinafter referred to as HDI) based NCO as at least a part of the polyisocyanate in a sealing material for artificial organs made of polyurethane of polyisocyanate and polyol.
This is a sealing material characterized by using a terminal prepolymer, and using an amine polyol as a polyol and other polyols as necessary. As the amine polyol used as the polyol component in the present invention, an oxyalkylated derivative of an amino compound having at least two active hydrogen atoms can be used. The amino compounds include ammonia, alkanolamines, monoamines, and polyamines (aliphatic, aromatic, alicyclic, or heterocyclic polyamines). Examples of these amino compounds include those described in JP-A-54-122396 and JP-A-54-101899 as amino compounds used in the production of amine-based polyether polyols. Specific examples include ammonia, alkanolamines [mono-, di-, or trialnol ( _C2 - _C4 ) amines (triethanolamine, etc.]),
Monoamines (aliphatic monoamines such as monomethylamine, stearylamine; aromatic amines such as aniline ₎ , polyamines [aliphatic polyamines such as alkylene ( _C2-6 ) diamines (ethylenediamine, propylene diamine, etc.);
Polyalkylene polyamines (diethylenetriamine, triethylenetetramine, etc.), aromatic polyamines (phenylenediamine, tolylenediamine, diphenylmethanediamine, xylylenediamine, etc.), alicyclic polyamines (cyclohexylenediamine, isophoronediamine, etc.), complex Examples include cyclic polyamines [piperazine, aminoalkyl-substituted piperazine (aminoethylpiperazine, etc.)]. These amino compounds must have at least 2 active hydrogen atoms, usually 2 to 7
, preferably 2 to 5, more preferably 3 to 5
Those with 4 active hydrogen atoms are suitable.
Two or more of these amino compounds may be used in combination. Although oxyalkylated derivatives of amino compounds can be produced by various methods, they are generally produced by adding alkylene oxide to an amino compound. Examples of alkylene oxides include ethylene oxide (referred to as EO), propylene oxide (referred to as PO), 1,2-1,3- or 2,3-
Examples include butylene oxide, tetrahydrofuran, styrene oxide, and epichlorohydrin. The alkylene oxides may be used alone or in combination of two or more, and in the latter case, block addition, random addition, or a mixture of both may be used. Among the alkylene oxides, preferred are PO and/or EO, particularly preferred are
PO alone or a combined system of PO and EO (usually 30:70 to 99:1 in weight ratio, particularly 70:30 to 90:10). The reactivity can be further increased by chipping EO at the terminal to make it primary. Addition of alkylene oxide can be carried out by conventional methods, either without catalyst or in the presence of a catalyst (alkali catalyst, amine catalyst, acidic catalyst) (particularly in the latter stages of alkylene oxide addition) under normal or elevated pressure. It will be held in The amino compound can be used as it is or in a suitable medium [inert liquid (xylene, dimethylformamide, etc.), active hydrogen atom-containing liquid (water, polyhydric alcohol such as ethylene glycol, glycerin, etc.), or the polyoxyalkyl of the amino compound prepared in advance. alkylene oxide can be added in the presence of a compound]. The number of moles of alkylene oxide added is usually 1 mole or more, preferably 2 to 20 moles, per active hydrogen atom of the amino compound. The molecular weight per hydroxyl group of the amine polyol can be varied freely within a range that does not inhibit the curing rate, but is generally 25 or more, preferably 50 to 1200, more preferably 50 to 800. Specific examples of amine polyols include triethanolamine, tetrakishydroxypropylethylenediamine, and pentakishydroxypropyldiethylenetriamine. Other polyols include low molecular polyols and high molecular polyols (polyether polyols, castor oil polyols, polyester polyols, etc.). Low molecular weight polyols include divalent ones such as ethylene glycol, diethylene glycol, propylene glycol,
1,4-butanediol, 1,6-hexanediol, neopentyl glycol, hydrogenated bisphenol A, etc.), trivalent or higher valences (trivalent to octavalent ones)
Examples include glycerin, trimethylolpropane (TMP), hexanetriol, pentaerythritol, sorbitol, seuclose, and trialkanolamines (triethanolamine, etc.). The equivalent weight of the low molecular weight polyol is usually 30-200, preferably 30-100. As the polyether polyol, alkylene oxide (carbon number 2 to 4) of the above-mentioned low molecular weight polyol is used.
Examples include adducts of alkylene oxides such as ethylene oxide, propylene oxide, butylene oxide) and ring-opening polymers of alkylene oxides, specifically polyethylene glycol,
Contains polypropylene glycol and polytetramethylene glycol. The equivalent weight of the polyether polyol is usually 200-1500, preferably 200-500. Examples of castor oil-based polyols include castor oil and polyester polyols of castor oil fatty acids and low-molecular-weight polyols (diglycerides, monoglycerides of castor oil fatty acids, mono-, di-, or triester of castor oil fatty acids and trimethylolpropane, etc.). The equivalent weight of the castor oil polyol is usually 200-1000, preferably 200-600. Polyester polyols include polycarboxylic acids (aliphatic saturated or unsaturated polycarboxylic acids such as adipic acid, azelaic acid, dodecanoic acid,
Linear or branched polyester polyols of maleic acid, phthalic acid, itaconic acid, dimerized linoleic acid; aromatic polycarboxylic acids such as phthalic acid and isophthalic acid) and polyols (the above-mentioned low-molecular-weight polyols and/or polyether polyols); A polylactone polyol, for example, based on an initiator (glycol (ethylene glycol, etc.), triol, etc.), which is then reacted with (substituted) caprolactone (ε-caprolactone, α-methyl-ε-
polyol, such as polycaprolactone polyol, which is obtained by addition polymerizing caprolactone, ε-methyl-ε-caprolactone, etc.) in the presence of a catalyst (organometallic compound, metal chelate compound, fatty acid metal acylate, etc.); a carboxyl group and/or OH Examples include polyether ester polyols obtained by addition-reacting alkylene oxides (eg, ethylene oxide, propylene oxide, etc.) to polyesters having groups. The equivalent weight of the polyester polyol is usually 200-1500, preferably 200-1000. Among these polyols, preferred are low molecular weight polyols (especially 1,4-butanediol,
trimethylolpropane and glycerin), polyether polyols (especially polyethylene glycol), and castor oil-based polyols (especially castor oil). In the polyol component, the amount of amine polyol is usually 1 to 100% by weight, preferably 5 to 50% by weight. If the amount of amine-based polyol is less than 1% by weight, curing with polyisocyanel will be slow and catalysts [amine-based, metal (tin, sulfur-based) catalysts] must be used, which is undesirable because they will precipitate as eluates. . Other active hydrogen-containing compounds that may be used if necessary include amines (aliphatic polyamines such as ethylenediamine, aliphatic monoamines such as n-
butylamine, amino alcohols such as mono- or diethanolamine, mono- or dipropanolamine, aminoethylethanolamine, etc.). Among these, preferred are amino alcohols, and particularly preferred is mono- or diethanolamine. The active hydrogen-containing group ( _NH2 group, NH group, etc.) equivalent of amines is usually 30 to 500, preferably 30 to 500.
It is 300. Other active hydrogen-containing compounds include polycarboxylic acids (aliphatic saturated or unsaturated polycarboxylic acids such as adipic acid, azelaic acid, dodecanoic acid, maleic acid, fumaric acid, itaconic acid,
Dimerized linoleic acid; aromatic polycarboxylic acids such as phthalic acid, isophthalic acid) can also be used. The equivalent weight of the polycarboxylic acid is usually 50 to 500, preferably 50 to 200. The amount of polyol in the polyol and other active hydrogen-containing compounds used if necessary is usually 10 to
100% by weight, preferably 50-100% by weight. The HDI-based NCO-terminated prepolymer used as at least a part of the polyisocyanate in the present invention includes those obtained from HDI and/or modified HDI, a polyol, and, if necessary, another active hydrogen-containing compound. Examples of modified HDI include modified products of HDI (modified products containing carbodiimide groups, uretdione groups, uretoimine groups, urea groups, Biuret groups and/or isocyanurate groups), and specifically,
Examples include water-denatured products of HDI. Examples of the polyol include those similar to the other polyols described above, and examples of other active hydrogen-containing compounds include those similar to the other active hydrogen-containing compounds described above. In the HDI-based NCO-terminated prepolymer, the NCO/active hydrogen-containing group ratio between HDI and/or modified MDI and the active hydrogen-containing compound is usually 1.1-10, preferably 1.5-6, particularly preferably 2-4. During the prepolymerization reaction, the reaction temperature is usually 40~
The temperature is 140°C, preferably 60-120°C. The reaction is usually carried out without a solvent, but if necessary, a solvent inert to the isocyanate group [aromatic hydrocarbons (toluene,
xylene, etc.), ketones (methyl ethyl ketone,
methyl isobutyl ketone, etc.) or mixtures of two or more thereof], and these solvents can be removed later by topping. Other polyisocyanates can be used with the HDI-based NCO-terminated prepolymer if necessary. Such polyisocyanates include aliphatic polyisocyanates (excluding HDI and modified HDI) having 2 to 12 carbon atoms (excluding carbon in the NCO group);
Alicyclic polyisocyanate with 4 to 15 carbon atoms, aromatic polyisocyanate with 8 to 12 carbon atoms, 6 carbon atoms
~20 aromatic polyisocyanates, modified products of these polyisocyanates (such as modified products containing carbodiimide groups, uretdione groups, uretimine groups, urea groups, Biuret groups and/or isocyanurate groups), their NCO, terminal prepolymers and A mixture of two or more of these may be used. Such polyisocyanates include ethylene diisocyanate, tetramethylene diisocyanate, dodecamethylene diisocyanate, 1,
6,11-undecane triisocyanate, 2,
2,4-trimethylhexane diisocyanate,
Lysine diisocyanate, 2,6-diisocyanate methyl caproate, bis(2-isocyanate ethyl) fumarate, bis(2-isocyanate ethyl) carbonate, 2-isocyanate ethyl-2,6-diisocyanate hexanoate; isophorone diisocyanate (IPDI) , dicyclohexylmethane diisocyanate (hydrogenated
MDI), cyclohexylene diisocyanate, methylcyclohexylene diisocyanate (hydrogenated
TDI), bis(2-isocyanatoethyl)-4-
Cyclohexene-1,2-dicarboxylate;
Xylylene diisocyanate, diethylbenzene diisocyanate; trimerized products of IPDI, etc.; tolylene diisocyanate (TDI), crude TDI, diphenylmethane diisocyanate (MDI), polyphenylmethane polyisocyanate (PAPI; crude)
MDI), modified MDI (carbodiimide modified etc.), naphthylene diisocyanate; and mixtures of two or more of these. NCO prepolymers include NCO-terminated prepolymers of these polyisocyanates and polyols and other active hydrogen-containing compounds. As the polyol and other active hydrogen-containing compounds, the same ones as the other polyols and the same ones as the other active hydrogen-containing compounds can be used. In this case, the NCO/active hydrogen-containing group ratio in the NCO-terminated prepolymer is usually 1.1 to 10, preferably 1.5 to 6, particularly preferably 2 to 5.
It is. The prepolymerization reaction can be carried out in the same manner as in the case of HDI-based NCO-terminated prepolymers. Among these polyisocyanates, aromatic diisocyanates are preferred, and MDI and its modified products are particularly preferred. The amount of HDI-based NCO-terminated prepolymer in the polyisocyanate is usually 10 to 100% by weight, preferably 25% by weight.
~90% by weight. If the amount of HDI-based NCO-terminated prepolymer is less than 10% by weight, it is difficult to significantly reduce the amount of eluate. When polyurethane is obtained from a polyisocyanate and a polyol, the NCO/OH equivalent ratio of the polyisocyanate and polyol is generally 0.95 to 4.0, preferably 1° to 2°, particularly preferably 1.0 to 1.4. When polyisocyanate and polyol are mixed, they usually cure at room temperature, and the gelation time is 5 to 60 minutes.
It's a minute. Full curing typically takes 24 to 72 hours at room temperature. However, if necessary, the gelation time and the time until complete hardening can be shortened by heating to 40 to 50°C. After complete curing, polyurethane usually has Shore A hardness of 60 to 100 and resin strength of 200 to 500 Kg/cm ²
(Using JIS No. 3 dumbbells, resin thickness approximately 0.5 mm, crosshead speed 50 mm/min). This polyurethane can be used as a bonding or sealing material when embedding embedding materials such as hollow fibers (hollow systems) in artificial organs such as artificial kidneys (dialysers), oxygenators and the like, as well as for bonding dialysis membranes or organ substitutes. Used as a sealant for vessels. Hollow fibers such as cellulose, acrylic, polyvinyl alcohol, polyamide, and polysulfone are generally used as the embedding material. As a method for embedding these hollow fibers, for example, the centrifugal molding method described in Japanese Patent Publication No. 57-58963, Japanese Patent Publication No. 57-58964, West German Patent No. 1544107, etc. can be used. Other known embedding methods may also be used, such as those described in Japanese Patent Publication No. 58-26366, German Patent No. 1236476, British Patent No. 970400, and the like.
The sealing material can be processed at room temperature. Curing of polyurethane progresses in a short time, and after about 1 hour at room temperature, it gels to the extent that the seal will not deform even if the dialyzer is removed from the centrifuge after about 30 minutes at elevated temperatures, such as 50℃. do. The artificial organ (dialyzer for artificial dialysis) sealed with the sealing material of the present invention may be similar to that described in JP-A-58-75556 (drawings) except for the sealing material. The sealing material of the present invention has very little eluate, and in this respect is particularly advantageous for hemodialysis. Furthermore, since the sealing material of the present invention is colorless and transparent and does not contain bubbles, it is advantageous when used for embedding hollow fibers in a dialysis machine for hemodialysis. Furthermore, no shrinkage occurs during curing, and there is no fear that the hollow fibers will be crushed. The adhesion of the sealant to the hollow fibers is extremely good. Furthermore, this sealing material has no tendency to swell, which is particularly important when used in dialysis machines for blood cleaning. This sealing material is harmless and can be advantageously used, especially in hemodialysis and the like, where non-toxic materials are important. The sealing material of the present invention is also very suitable as a sealing material for hollow fibers or membranes in other artificial organs such as artificial lungs or plasma separators and the like. In the present invention, when an aminated product is used in place of the amine polyol, curing becomes too rapid. The present invention will be further explained below with reference to Examples, but the present invention is not limited thereto. Production Examples 1 to 3 and Comparative Production Example 1 (Production of polyisocyanate) 2 equipped with a stirrer, thermometer and nitrogen inlet tube
HDI and an active hydrogen-containing compound were charged into a four-necked colben, heated to 90 to 100°C under a nitrogen stream, and reacted for 8 hours with stirring to obtain HDI-based NCO-terminated prepolymers (Production Examples 1 to 3). . Separately, MDI and an active hydrogen-containing compound were charged into a 1-volume four-necked colben equipped with a stirrer, a thermometer, and a nitrogen inlet tube, and the mixture was heated to 60 to 70°C under a nitrogen stream and reacted with stirring for 8 hours to form an MDI system. N.C.O.
Terminal prepolymers were obtained (Production Examples 1 to 3, Comparative Production Example 1). This was added to the above two colbens and mixed to obtain a uniform polyisocyanate (Production Examples 1 to 3). Details are shown in Table-1.

[Table] Examples 1 to 3, Comparative Example 1 To 100 g of each of the polyisocyanates of Production Examples 1 to 3 and Comparative Production Example 1, calculated amounts of polyols (tetrakis hydroxypropyl ethylenediamine (THPEDA) and castor oil) were added as shown in Table 2. Tokkosho has developed a dialyzer filled with hollow fibers by mixing
It was injected according to the method of No. 57-58963 and molded at 40°C by centrifugation.

[Table] Test Examples 1 to 3 Comparative Test Example 1 Elution test of hollow adhesive part The dialyzer molded in Examples 1 to 3 and Comparative Example 1 was disassembled and the hollow adhesive part was cut out.
(approximately 50 g), shredded into approximately 1 cm square pieces. Add 200ml of water to this and shake gently at 40℃ for 2 hours.
Warmed. After cooling, the supernatant liquid was taken, and this liquid was used as a test liquid. Using water as a control, the absorbance at a wavelength of 220 mm with a layer length of 10 mm was measured by the absorption measurement method of the Japanese Bureau. At this time, the lower the absorbance, the less eluate, which is desirable as a sealing material. Elution tests were conducted for Examples 1 to 3 and Comparative Example 1. The results are listed in Table-3.

【table】

Claims (1)

[Claims] 1. In a sealing material for artificial organs made of polyurethane of polyisocyanate and polyol, a hexamethylene diisocyanate-based NCO-terminated prepolymer is used as at least a part of the polyisocyanate, and an amine-based polyol and other materials as necessary are used as the polyol. A sealing material characterized by the use of polyol. 2. The sealing material according to claim 1, wherein the prepolymer is a prepolymer of hexamethylene diisocyanate and an active hydrogen-containing compound with an NCO/active hydrogen-containing group ratio of 1.1 to 10. 3. Claim 1, wherein the content of the prepolymer in the polyisocyanate is 10 to 100% by weight.
The sealing material described in item 1 or 2. 4. Claims 1 to 4, wherein the content of the amine polyol in the polyol is 1 to 100% by weight.
The sealing material according to any of Item 3. 5. The sealing material according to any one of claims 1 to 4, wherein the other polyol is a polyol selected from the group consisting of 1,4-butanediol, glycerin, trimethylolpropane, castor oil, and polyethylene glycol.