JPH0622607B2 - Seal material for artificial organs - Google Patents

Description

TECHNICAL FIELD The present invention relates to a sealing material for artificial organs.

[Conventional technology]

Conventionally, as a sealing material for artificial organs, there is polyurethane made of hexamethylene diisocyanate-based NCO prepolymer, amine-based polyol, and castor oil (see, for example, Japanese Patent Laid-Open Publication No. Sho.
60-58156 publication).

[Problems to be solved by the invention]

However, in the autoclave sterilization process, the sealing material is peeled off from the container.

[Means for solving problems]

The present inventors have arrived at the present invention as a result of extensive studies on a sealing material that does not peel from the container in the autoclave sterilization step. That is, the present invention is a sealing material for artificial organs made of polyurethane of polyisocyanate and polyol, from polyisocyanate and amine polyol (A) and other polyol (B) as polyol.
A sealant for artificial organs, characterized by using an OH-terminated urethane prepolymer.

In the present invention, di- or trialkanolamine can be used as the amine-based polyol. Specific examples include diethanolamine, triethanolamine and N-methyldiethanolamine. Among these, preferred is N-methyldiethanolamine.

Other polyols include low molecular weight polyols and high molecular weight polyols (polyether polyols, castor oil-based polyols, polyester polyols, etc.). The low molecular weight polyol is divalent, such as ethylene glycol, diethylene glycol, propylene glycol, 1,4-butanediol, 1,6-hexanediol, neopentyl glycol, hydrogenated bisphenol A, etc. (Trivalent to octavalent), for example, glycerin, trimethylolpropane (TMP), hexanetriol, pentaerythritol, sorbitol, cucrose and the like. The equivalent weight of the low molecular weight polyol is usually 30 to 200, preferably 30 to 100.

Examples of the polyether polyol include an alkylene oxide (alkylene oxide having 2 to 4 carbon atoms such as ethylene oxide, propylene oxide, butylene oxide) adduct of the above low molecular weight polyol and a ring-opening polymer of the alkylene oxide, and specifically, polyethylene glycol. , Polypropylene glycol and polytetramethylene glycol. The equivalent weight of the polyether polyol is usually 200 to 1500, preferably 200 to 500.

Examples of castor oil-based polyols include castor oil and polyester polyols of castor oil fatty acid and low molecular weight polyol (such as diglyceride, monoglyceride of castor oil fatty acid, mono-, di- or triester of castor oil fatty acid and trimethylolpropane). The equivalent of castor oil-based polyol is usually 200 to 1000, preferably 200.
~ 600.

Examples of polyester polyols include polycarboxylic acids (aliphatic saturated or unsaturated polycarboxylic acids such as adipic acid, azelaic acid, dodecanoic acid, maleic acid, fumaric acid, itaconic acid and dimerized linoleic acid; aromatic polycarboxylic acids such as phthalic acid. And isophthalic acid) and a polyol (the above-mentioned low molecular weight polyol and / or polyether polyol) in a linear or branched polyester polyol; a polylactone polyol such as an initiator [glycol (ethylene glycol, triol, etc.)] (Substituted) caprolactone (ε
-Caprolactone, α-methyl-ε-caprolactone,
(eg, ε-methyl-ε-caprolactone) is subjected to addition polymerization in the presence of a catalyst (organometallic compound, metal chelate compound, fatty acid metal acylate, etc.) such as polycaprolactone polyol; Examples thereof include polyether ester polyols obtained by the addition reaction of alkylene oxides (for example, ethylene oxide, propylene oxide, etc.) with the polyesters. The equivalent weight of the polyester polyol is usually 200 to 1500, preferably 200 to 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 type polyols (especially castor oil).

In the polyol component, the amount of amine-based polyol is (A) and (B)
Usually 10-90%, preferably 20-80% based on the total weight of
%. When the amount of the amine-based polyol is less than 10%, the curing with the polyisocyanate becomes slow. If it exceeds 90%, the hardness of the resin becomes too high and the workability deteriorates.

Aliphatic polyisocyanates such as ethylene diisocyanate, tetramethylene diisocyanate, hexamethylene diisocyanate (HD
I), 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; cycloaliphatic polyisocyanates such as isophorone diisocyanate (IPDI), Dicyclohexylmethane diisocyanate (hydrogenated MDI), cyclohexylene diisocyanate, methylcyclohexylene diisocyanate (hydrogenated TDI),
Bis (2-isocyanatoethyl) -4-cyclohexene-1,2-dicarboxylate; aromatic polyisocyanates such as tolylene diisocyanate (TDI), diphenylmethane diisocyanate (MDI), naphthylene diisocyanate, xylylene diisocyanate, diethylbenzene diisocyanate And modified polyisocyanates (carbodiimide group, uretdione group, uretoimine group, urea group, biuret group and / or isocyanurate group modified product) and a mixture of two or more thereof.

Of these, preferred are aliphatic polyisocyanates and cycloaliphatic polyisocyanates, and particularly preferred are HDI and IPDI.

NCO / OH ratio is usually 0 in OH-terminated urethane prepolymers.
It is 1 to 0.9, preferably 0.12 to 0.5. If it is less than 0.1, the adhesiveness is lowered, and if it exceeds 0.9, gelation tends to occur.

As a method for producing an OH-terminated urethane prepolymer, a polyol component having an active hydrogen group is introduced into polyisocyanate to synthesize an NCO-terminated prepolymer. N in this case
The CO / OH ratio is usually 1.1 to 5.0, preferably 1.5 to 3.0. The reaction temperature is usually 50 to 110 ° C. Reaction time is usually 3-5
It's time. The end point of the reaction is when the NCO% value remains unchanged.

After the NCO% value has become constant, add an amine polyol and
Obtain an H-terminated urethane prepolymer. NCO / OH in this case
The ratio is usually 0.1 to 0.5, preferably 0.15 to 0.3. The reaction temperature is usually 40 to 90 ° C. The reaction time is 1 to 3 hours. The end point of the reaction is detected by an infrared spectrometer when the absorption due to the NCO group disappears.

In the polyurethane formed from the OH-terminated urethane prepolymer and the polyisocyanate, the polyisocyanate includes the same ones as described above, and the preferable ones are also the same.

The NCO / OH ratio in polyurethanes from OH-terminated urethane prepolymers and polyisocyanates is usually 0.9 to 1.5, preferably 1.0 to 1.2. If it is less than 0.9 or more than 1.5, the adhesiveness to the container is deteriorated.

As a method for producing a polyurethane from an OH-terminated urethane prepolymer and polyisocyanate, after weighing each component,
React at room temperature by mixing with a static mixer or mechanical mixer.

The gel time is 3 to 60 minutes, and complete curing requires 12 to 48 hours. The time when the curing does not change is defined as the complete curing (reaction end point).

By increasing the curing temperature (30 to 50 ° C), the time until complete curing can be shortened.

The artificial organs to which the sealing material of the present invention is applied include hollow fiber type, membrane type and coil type artificial kidneys, artificial lungs, and plasma separation modules. The amount of sealing material depends on the shape of the artificial organ, but in the case of hollow fiber type, it is about 20-50g for a module of about 500 hollow fibers and about 10,000 for a hollow fiber type module.
It is 100 to 200 g.

The usage of the sealing material is shown below.

Separately decompress the polyisocyanate and polyol (0.
1mmHg x 2 hours). The two liquids are weighed and mixed at room temperature, and the hollow fiber is embedded in a polycarbonate container by a centrifugal molding method. An example of the centrifugal molding method is described in JP-B-57-58963.

The resin gels 30 minutes after injection and the module can be removed from the molding machine. Cure at 40 ° C for 2 days to complete curing. Then use the autoclave to 121
It is commercialized by sterilization treatment by steam heating at ℃ for 1 hour. The sterilization treatment can be carried out by a method other than steam, for example, ethylene oxide gas or γ-ray irradiation. Sterilization treatment by steam heating is highly safe for the human body because it does not use a sterilizing agent. However, a material that can withstand high temperatures is required, and the sealing material of the present invention is particularly advantageous in this respect.

〔Example〕

The present invention will be further described below with reference to examples, but the present invention is not limited thereto.

Details of the OH-terminated urethane prepolymer and polyisocyanate are as follows. (Parts in the examples indicate parts by weight.) (1) OH-terminated urethane prepolymer (OH-1) After reacting 298 parts of castor oil and 177 parts of HDI, 527 parts of N-methyldiethanolamine was charged, and after the reaction, OHV 40
An OH-terminated urethane prepolymer with a viscosity of 3800 cps / 25 ° C was obtained.

(OH-2) Polypropylene glycol (molecular weight 950) 441 parts and HDI 156 parts were reacted, and then N-methyldiethanolamine 442 parts were charged, and after the reaction, OHV 360, viscosity 3000 cps / 25
An OH-terminated urethane prepolymer at ℃ was obtained.

(OH-3) After reacting 282 parts of castor oil and 221 parts of IPDI, N-
Charge 497 parts of methyldiethanolamine and after reaction, OHV
An OH-terminated urethane prepolymer having a viscosity of 395 and a viscosity of 4900 cps / 25 ° C was obtained.

(2) Polyisocyanate (N-1) From 528 parts castor oil and 472 parts HDI, NCO% 17.1%,
A polyisocyanate having a viscosity of 1800 cps / 25 ° C was obtained.

(N-2) From 50 parts of H ₂ O and 950 parts of HDI, NCO% 23.2%, viscosity 20
A polyisocyanate of 00 cps / 25 ° C was obtained.

(N-3) Polyisocyanate having an NCO% of 21.0% and a viscosity of 2500 cps / 25 ° C was obtained from 459 parts of castor oil and 541 parts of IPDI.

(3) Comparative product (OH-4) 612 parts of castor oil and 388 parts of N-methyldiethanolamine were mixed to obtain an OH blended product having OHV 463 and a viscosity of 200 cps / 25 ° C.

(OH-5) 500 parts of castor oil, 100 parts of N-methyldiethanolamine and 400 parts of tetrakishydroxypropylethylenediamine were mixed to obtain OHV 468 and a viscosity of 2000 cps / 25 ° C.
An OH compound was obtained.

Examples 1 to 7 and Comparative Examples 1 to 4 OH-terminated urethane prepolymers and polyisocyanates were combined as shown in Table 1 to obtain sealing materials. The following test was performed using this sealing material.

The cellulose hollow fiber was inserted into a polycarbonate container and fixed with a sealing material by a centrifugal molding method. After curing at 40 ° C for 2 days, blood circuit connecting parts were attached to make a module. After that, sterilization treatment was performed by steam heating at 121 ° C. for 1 hour in an autoclave.

In Examples 1 to 7, no peeling occurred on the adhesive surface between the sealing material and the container.

In Comparative Examples 1 to 4, the sealing material was peeled from the container, so that the purpose of the sealing material could not be achieved. (The results are shown in Table-2.) It is desired that the amount of resin elution (water or organic solvent) of the sealing material for artificial organs is small. It is shown that Examples 4 to 6 are superior to Comparative Examples 3 to 4 as the sealing material also in the elution performance.

[Effects of the Invention] The sealing material of the present invention has the following effects.

Does not peel in the autoclave sterilization process.

Since the sealing material has excellent adhesion to the polycarbonate container, it withstands sterilization treatment by high pressure steam using an autoclave and does not peel off.

Little elution amount with organic solvent.

Compared with the conventional type described in Japanese Patent Laid-Open No. 60-58156, CHCl ₃ extraction reduces the amount to 1/8 to 1/10. This means that when used in the human body, the components eluted from the sealing material into the blood are reduced and the safety is improved.

The transparency of the resin is excellent.

Even if foreign matter is mixed in, molding defects such as the hollow fiber being bent or bent, and adhesion defects due to stains on the container occur, the transparency is good and it is easy to find.

The sealing material of the present invention is useful for artificial organs because it exhibits the above effects.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Masahiro Imanishi 1-11, Hitotsubashi-honcho, Higashiyama-ku, Kyoto-shi, Kyoto Sanyo Chemical Industry Co., Ltd. Examiner Misao Takanashi

Claims (3)

[Claims] 1. A sealant for an artificial organ, comprising a polyurethane of polyisocyanate and polyol, wherein polyisocyanate and amine polyol are used as the polyol.
A sealant for artificial organs, characterized by using an OH-terminated urethane prepolymer from (A) and another polyol (B). 2. The sealing material according to claim 1, wherein the amount of the amine-based polyol is 10 to 90% based on the total weight of (A) and (B). 3. The sealing material according to claim 1 or 2, wherein the amine-based polyol is dialkanolamine and / or trialkanolamine.