JP2011000132A - Gas-barrier medical tube having excellent heat resistance and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a medical tube which is excellent in safety by suppressing dissolution of a crosslinking agent into a liquid flowing inside the tube since the tube contains almost no harmful crosslinking agent, has gas-barrier properties sufficient for use in the medical field, has heat resistance and hot water resistance, and causes extremely low deterioration of the gas-barrier properties after heat sterilization.SOLUTION: The medical tube includes a modified ethylene-vinyl alcohol copolymer (C). The modified ethylene-vinyl alcohol copolymer (C) is obtained by modifying an unmodified ethylene-vinyl alcohol copolymer (A) with an epoxy compound (B) having a double bond. The amount modified by the epoxy compound (B) is 0.1-10% by mole relative to the amount of monomer units of the ethylene-vinyl alcohol copolymer (A). At least a part of the modified ethylene-vinyl alcohol copolymer (C) is crosslinked and has a gel fraction of 3 mass% or more.

Description

  Since the present invention is excellent in flexibility and transparency and contains almost no harmful cross-linking agent, the elution of the cross-linking agent to the liquid passing through the tube is suppressed, so that it is excellent in safety and used in the medical field. The present invention relates to a medical tube that has suitable gas barrier properties, has heat resistance that can withstand heat sterilization treatment such as retort sterilization treatment and autoclave sterilization treatment, and has extremely little deterioration in gas barrier properties after heat sterilization treatment.

  The medical tube of the present invention is a tube suitably used as a component of a medical device such as a blood circuit, a blood bag, a drug solution bag, a blood transfusion / infusion set, and a catheter. A medical tube that is heat-sterilized is preferable.

  Conventionally, polyvinyl chloride has been widely used not only for industrial use and general household use, but also for medical and welfare purposes. In particular, most disposable medical devices are manufactured using polyvinyl chloride. However, a relatively large amount of a plasticizer such as dioctyl phthalate is added to soft polyvinyl chloride, and the problem of elution of the plasticizer into blood or an infusion is pointed out from the viewpoint of safety of medical devices.

  On the other hand, from the viewpoint of preventing infection, medical devices are being made disposable, and it is required by law that these medical devices must be incinerated after use. Polyvinyl chloride, when supplied with sufficient oxygen and burned at a temperature of about 850 to 900 ° C., eventually becomes carbon dioxide, water, and hydrogen chloride, and hardly generates toxic chlorine-based substances such as dioxins. However, in reality, due to the lack of incinerators that can withstand high temperatures, the existence of small incinerators with insufficient incineration capacity, and the lack of dioxin treatment equipment, environmental pollution caused by dioxins and other toxic chlorine-based substances. Problems often arise.

  For this reason, recently, replacement of soft vinyl chloride with other materials as a material for medical devices, industrial use, and general household use has been studied.

  Polyethylene (PE), polypropylene (PP), ethylene-vinyl acetate copolymer (EVA), polyethyl methacrylate (PEMA), styrene-isobutylene copolymer hydrogen as medical tube materials that do not contain polyvinyl chloride Styrenic thermoplastic elastomers such as additives have been studied.

  For example, as a resin composition having excellent flexibility and suitable for medical use, Patent Documents 1 to 3 describe hydrogenated products of olefin resins and styrene-butadiene block copolymers (styrene-based thermoplastic elastomers). ) Has been proposed.

  Patent Documents 4 and 5 propose a multilayer tube comprising a base material layer and an adhesive layer. However, the adhesive layer is not dimensionally stable at an autoclave sterilization temperature (120 ° C.) or higher, and oxygen There is no mention of barrier properties.

  However, the tube made of PE, EVA, and PEMA is flexible, but has a problem that it is easy to kink with a single composition. Here, kinking means that the tubes are bent or twisted so that the inner surfaces of the tubes are in close contact with each other.

The resin compositions described in the above Patent Documents 1 to 3 have a feature that gives a molded article having excellent flexibility, and that no toxic gas such as dioxin is generated even when the molded article is incinerated. ing. However, the single-layer tube obtained from such a resin composition has the following problems, and there is room for improvement in these respects.
(1) When the emphasis is placed on flexibility, the ratio of styrene-based thermoplastic elastomer increases, resulting in insufficient heat resistance, such as deformation of the tube cross-section shape and adhesion between tubes after autoclave sterilization. In addition, the problem of insufficient tube restoration when the forceps are opened after closing with forceps cannot be ignored.
(2) When emphasis is placed on heat resistance and forceps resistance, the proportion of the styrene-based thermoplastic elastomer is reduced, and the flexibility is insufficient so that it is not sufficiently satisfactory as a medical tube. Furthermore, the oxygen barrier property is not sufficient.

  In addition, the multilayer tubes described in Patent Documents 4 and 5 are not dimensionally stable when the adhesive layer is above the oclave sterilization temperature (121 ° C.) and are connected by press fitting between the tubes. Therefore, since it is only adhered due to adhesiveness, the fitting portion is easily detached with a small force. In addition, since the adhesive force is generated by the heat of the autoclave, there is a possibility that the fitting part may come off at the time of sterilization or before the processing stage, which is considered unsuitable for the production of medical devices.

  In addition, ethylene-vinyl alcohol copolymers have oxygen barrier properties and are excellent in moldability, and are therefore used for plastic multilayer tubes in food applications and the like. However, medical tubes have a problem that delamination and whitening occur when exposed to high temperature and high pressure conditions such as autoclave sterilization.

  In order to solve the above problems, attention was paid to a crosslinking technique for the purpose of modifying an ethylene-vinyl alcohol copolymer. Various techniques for crosslinking an ethylene-vinyl alcohol copolymer have been studied. For example, Patent Document 6 describes that a compound having an epoxy group and an allyl group is blended with EVOH and then crosslinked by light or heat. Small and hardly cross-linked. This is probably because the epoxy group hardly reacts with EVOH. In addition, when the compound is produced, it is necessary to add a large amount of a compound having an epoxy group and an allyl group. Therefore, when this compound remains and is eluted, it is particularly sanitary when used for medical containers and pharmaceutical packaging applications. There is a concern that this could be a problem.

  In addition, in Patent Document 7 and Patent Document 8, EVOH is added with at least one crosslinking agent and crosslinking aid selected from polyfunctional allyl compounds, polyfunctional (meth) acrylic compounds, polyhydric alcohols and metal oxides, Although there is a description of irradiating with an electron beam to crosslink, there is a concern about a problem due to the remaining additive. Further, the cross-linking agent gelled by reacting with EVOH at the stage of melt-kneading, and there was a problem in long-term operation.

  Further, Patent Document 9 describes that EVOH is added with a compound having two or more allyl ether groups, irradiated with an electron beam, and cross-linked, but this also has a problem due to residual additives. It is done.

  Patent Document 10 describes a method in which triallyl cyanurate and triallyl isocyanurate are used as crosslinking agents, and these are melt-kneaded with EVOH and then irradiated with an electron beam to crosslink EVOH. Nurate and triallyl isocyanurate remain, and there is a concern about problems such as elution. Also. Triallyl cyanurate and triallyl isocyanurate gelled by reacting with EVOH at the stage of melt kneading, and there was a problem in long-term operation.

  Patent Document 11 describes a method in which an EVOH film is brought into contact with water to be in a water-containing state and is crosslinked by irradiation with an electron beam. However, in this method, there is a problem that it is necessary to immerse the film in water for a long time, and high-speed production is difficult.

  Patent Document 12 describes that the flexibility is improved while keeping gas barrier properties as much as possible by modifying EVOH with a specific epoxy compound. However, there is a drawback that the melting point is greatly lowered by modification, and as such, it is difficult to use in applications requiring heat resistance. Patent Document 13 describes a resin composition composed of a modified EVOH described in Patent Document 12 and an unmodified EVOH.

Japanese Patent Laid-Open No. 4-158868 JP-A-4-159344 JP-A-8-131537 Japanese Patent Laid-Open No. 9-159344 JP-A-9-123314 JP 63-8448 A JP-A-5-271498 JP-A-9-157421 JP-A-9-234833 Japanese Patent Laid-Open No. 62-252409 JP 56-49734 A WO02 / 092643 WO03 / 072653

  The present invention has been made to solve the above-mentioned problems, and since it contains almost no harmful cross-linking agent, elution of the cross-linking agent into the liquid passing through the tube is suppressed, and is excellent in safety. It has gas barrier properties suitable for use in foods, has heat resistance and hot water resistance that can withstand heat sterilization treatment such as retort sterilization treatment and autoclave sterilization treatment, and has extremely little deterioration in gas barrier properties even after heat sterilization treatment The object is to provide a medical tube. Moreover, it aims at providing the suitable manufacturing method for manufacturing such a tube.

  The subject is a medical tube comprising a modified ethylene-vinyl alcohol copolymer (C), wherein the modified ethylene-vinyl alcohol copolymer (C) is an unmodified ethylene-vinyl alcohol copolymer. (A) is obtained by modifying with an epoxy compound (B) having a double bond, and the amount of modification by the epoxy compound (B) having a double bond is an ethylene-vinyl alcohol copolymer (A ) Monomer unit of 0.1 to 10 mol%, at least a part of the modified ethylene-vinyl alcohol copolymer (C) is crosslinked, and the gel fraction thereof is 3% by mass or more. It is solved by providing a medical tube characterized in that.

  The above-described problem is a medical tube comprising a resin composition containing a modified ethylene-vinyl alcohol copolymer (C) and an unmodified ethylene-vinyl alcohol copolymer (D), wherein the modified ethylene-vinyl alcohol copolymer (C) The vinyl alcohol copolymer (C) is obtained by modifying an unmodified ethylene-vinyl alcohol copolymer (A) with an epoxy compound (B) having a double bond. The amount of modification by the epoxy compound (B) having a heavy bond is 0.1 to 10 mol% with respect to the monomer unit of the ethylene-vinyl alcohol copolymer (A), and at least a part of the resin composition is crosslinked. It is also solved by providing a medical tube characterized in that the gel fraction is 3% by mass or more.

  In the medical tube, it is preferable that the unmodified ethylene-vinyl alcohol copolymer (A) has an ethylene content of 5 to 55 mol% and a saponification degree of 90 mol% or more. It is also preferred that the epoxy compound (B) having a double bond is a monovalent epoxy compound having a molecular weight of 500 or less, particularly allyl glycidyl ether.

  Preferred embodiments of the medical tube of the present invention are extrusion-molded products, profile-formed products, injection-molded products, extrusion blow-molded products, co-extrusion blow-molded products, and co-injection-molded products.

  The medical tube of the present invention is preferably a layer made of a modified ethylene-vinyl alcohol copolymer (C) and a layer made of a resin (F) other than the modified ethylene-vinyl alcohol copolymer (C). It consists of the multilayer structure which has. Preferably, a layer comprising a resin composition containing a modified ethylene-vinyl alcohol copolymer (C) and an unmodified ethylene-vinyl alcohol copolymer (D) and a modified ethylene-vinyl alcohol copolymer are used. It consists of a multilayer structure which has a layer which consists of resin (F) other than a polymer (C). In these multilayer structures, the resin (F) is at least one selected from the group consisting of polyolefin, polyamide, polyester, polystyrene, polyurethane, polyvinylidene chloride, polyvinyl chloride, polyacrylonitrile, polycarbonate, acrylic resin, and polyvinyl ester. It is preferable that Moreover, it is also preferable that resin (F) is an elastomer.

  Preferred embodiments of the medical tube composed of the multilayer structure are an extrusion molded product, a deformed molded product, an injection molded product, an extrusion blow molded product, a co-extrusion blow molded product, and a co-injection molded product.

  The above-mentioned problem is a method for producing a medical tube comprising a modified ethylene-vinyl alcohol copolymer (C), and an unmodified ethylene-vinyl alcohol copolymer (A) is converted to an epoxy having a double bond. A modified ethylene-vinyl alcohol copolymer (C) is produced by modification with compound (B), a modified ethylene-vinyl alcohol copolymer (C) is formed, and a modified ethylene-vinyl alcohol copolymer is produced. It can also be solved by providing a method for producing a medical tube characterized in that at least a part of (C) is crosslinked and the gel fraction is 3% by mass or more.

  Moreover, the said subject is a manufacturing method of the medical tube which consists of a resin composition containing a modified ethylene-vinyl alcohol-type copolymer (C) and an unmodified ethylene-vinyl alcohol-type copolymer (D), The modified ethylene-vinyl alcohol copolymer (C) is produced by modifying the unmodified ethylene-vinyl alcohol copolymer (A) with an epoxy compound (B) having a double bond. A vinyl alcohol copolymer (C) and an unmodified ethylene-vinyl alcohol copolymer (D) are mixed to produce a resin composition, the resin composition is molded, and at least of the resin composition The problem can also be solved by providing a method for producing a medical tube characterized in that a part thereof is crosslinked and the gel fraction thereof is 3% by mass or more.

  In the said manufacturing method, it is preferable that the ethylene content of an unmodified ethylene-vinyl alcohol-type copolymer (A) is 5-55 mol%, and a saponification degree is 90 mol% or more. It is also preferable that the epoxy compound (B) having a double bond is a monovalent epoxy compound having a molecule of 500 or less, particularly allyl glycidyl ether.

  In the said manufacturing method, after making it bridge | crosslink, it is preferable to heat-sterilize by the pressure of 0.10-0.45MPa. At this time, the heat sterilization treatment is preferably retort sterilization treatment or autoclave sterilization treatment. Moreover, it is also preferable that the elution amount of the epoxy compound (B) eluted from the modified ethylene-vinyl alcohol copolymer (C) before crosslinking is 0.50 μg / g or less.

  In the production method described above, the modified ethylene-vinyl alcohol copolymer (C) is irradiated with at least one selected from the group consisting of electron beam, X-ray, γ-ray, ultraviolet ray and visible ray, or heated. It is also preferable to at least partially cross-link.

  That is, the object of the present invention is preferably achieved by the following method. First, an unmodified EVOH (A) is reacted with an epoxy compound (B) having a double bond. At this time, it is preferable to react with heating in the presence of a catalyst, and then deactivate the catalyst with an additive to remove excess epoxy compound (B). Thus, modified EVOH (C) having a double bond is produced. Preferably, after this is melt-molded or solution-coated, it is irradiated with at least one selected from the group consisting of electron beam, X-ray, γ-ray, ultraviolet irradiation and visible light, or modified EVOH (C) by heating. Is crosslinked. Alternatively, a modified EVOH (by applying at least one selected from the group consisting of electron beam, X-ray, γ-ray, ultraviolet irradiation, and visible light after filling a molded product obtained by melt molding or solution coating with the contents. C) is crosslinked. As described above, a medical tube made of modified EVOH (C) that maintains gas barrier properties and is excellent in heat resistance is provided. In addition, the resin composition in which the unmodified EVOH (D) is blended with the modified EVOH (C) having a double bond is similarly molded and crosslinked to maintain gas barrier properties and excellent heat resistance. A medical tube is provided.

  Since the medical tube of the present invention contains almost no harmful cross-linking agent, the elution of the cross-linking agent to the liquid passing through the tube is suppressed, which is excellent in safety and suitable for use in the medical field. It is a high-gas barrier medical tube that has heat resistance and hot water resistance that can withstand heat sterilization treatment such as retort sterilization treatment and autoclave sterilization treatment. Moreover, the manufacturing method of this invention is a suitable manufacturing method for manufacturing such a medical tube.

  The modified EVOH (C) used in the present invention is obtained by reacting an epoxy compound (B) having a double bond with the hydroxyl group of unmodified EVOH (A).

  The ethylene content of the unmodified EVOH (A) used in the present invention is preferably 5 to 55 mol%, more preferably 20 to 55 mol%, still more preferably 25 to 50 mol%. When the ethylene content is less than 5 mol%, the water resistance is poor, and when it is greater than 60 mol%, the gas barrier property is inferior. The ethylene content of the resulting modified EVOH (C) is the same as the ethylene content of the raw EVOH (A) that is the raw material.

  The saponification degree of the unmodified EVOH (A) is preferably 90 mol% or more, preferably 98 mol% or more, and more preferably 99 mol% or more. When the saponification degree is less than 90 mol%, the gas barrier property and the thermal stability are inferior.

  Further, as will be described later, the modified EVOH (C) used in the present invention is preferably obtained by allowing the unmodified EVOH (A) and the epoxy compound (B) to react in an extruder. In this case, the unmodified EVOH (A) is exposed to heating conditions. At this time, if the unmodified EVOH (A) contains an excessive amount of an alkali metal salt and / or an alkaline earth metal salt, the resulting modified EVOH (C) may be colored. Moreover, problems, such as a viscosity fall of modified EVOH (C), arise and there exists a possibility that a moldability may fall. Moreover, when using a catalyst like the after-mentioned, in order to deactivate a catalyst, it is preferable that those addition amounts are as small as possible.

  In order to avoid the above problem, the alkali metal salt contained in the unmodified EVOH (A) is preferably 50 ppm or less in terms of metal element. In a more preferred embodiment, the alkali metal salt contained in the unmodified EVOH (A) is 30 ppm or less, more preferably 20 ppm or less in terms of metal element. Further, from the same viewpoint, the alkaline earth metal salt contained in the unmodified EVOH (A) is preferably 20 ppm or less, more preferably 10 ppm or less in terms of metal element, and 5 ppm or less. Is more preferable, and it is most preferable that the alkaline earth metal salt is not substantially contained in the unmodified EVOH (A).

  The suitable melt flow rate (MFR) (under 190 ° C. and 2160 g load) of the unmodified EVOH (A) used in the present invention is 0.1 to 100 g / 10 minutes, preferably 0.3 to 30 g / 10. Min, more preferably 0.5 to 20 g / 10 min. However, those having a melting point near 190 ° C. or exceeding 190 ° C. were measured under a load of 2160 g and at a plurality of temperatures above the melting point, and in a semilogarithmic graph, the reciprocal absolute temperature was plotted on the horizontal axis, and the logarithm of MFR was plotted on the vertical axis. The value is extrapolated to 190 ° C. Two or more kinds of unmodified EVOH (A) having different MFRs can also be mixed and used.

  The epoxy compound (B) used in the present invention preferably has one epoxy group and one or more double bonds in the molecule. That is, it is preferably a monovalent epoxy compound. The molecular weight is preferably 500 or less. Those having a plurality of epoxy groups have a problem of crosslinking during modification. The type of double bond is particularly preferably a vinyl group which is a monosubstituted olefin, and next preferably a vinylene group or a vinylidene group which is a disubstituted olefin. Next preferred are trisubstituted olefins. Tetrasubstituted olefins are not suitable for the purposes of the present invention due to poor reactivity.

  Moreover, what can remove easily the thing added excessively from modified | denatured EVOH (C) as an epoxy compound (B) is preferable. As the removal method, it is practical to volatilize and remove from the vent of the extruder. Therefore, the boiling point is preferably 250 ° C. or less, and more preferably 200 ° C. or less. Moreover, it is preferable that carbon number of an epoxy compound (B) is 4-10. Specific examples of such an epoxy compound (B) include 1,2-epoxy-3-butene, 1,2-epoxy-4-pentene, 1,2-epoxy-5-hexene, 1,2-epoxy- Examples include 4-vinylcyclohexane, allyl glycidyl ether, methallyl glycidyl ether, and ethylene glycol allyl glycidyl ether, and particularly preferably allyl glycidyl ether. Moreover, it is also possible to wash and remove from the vent of an extruder, and it is also preferable in this case that an epoxy compound (B) is soluble in water.

  The reaction conditions of the epoxy compound (B) and the unmodified EVOH (A) are not particularly limited, but in the same manner as described in WO02 / 092643 (Patent Document 12), the unmodified EVOH (A ) Is preferably reacted with the epoxy compound (B). At this time, it is preferable to add a catalyst. In that case, it is preferable to add a carboxylate as a deactivator after the reaction. It is preferable to add the epoxy compound (B) to the unmodified EVOH (A) in a molten state in the extruder because it can prevent volatilization of the epoxy compound (B) and easily control the reaction amount. Excess epoxy compound (B) can be removed from the vent of the extruder. Furthermore, by washing the obtained pellets with warm water, the remaining epoxy compound (B) can be removed and at the same time, the remaining catalyst can be removed.

  The catalyst used in the present invention preferably contains a metal ion belonging to Groups 3-12 of the periodic table. What is most important as the metal ion used in the catalyst is that it has a moderate Lewis acidity. From this point, ions of metals belonging to Groups 3 to 12 of the periodic table are used. Among these, ions of metals belonging to Group 3 or Group 12 of the periodic table are preferable because they have appropriate Lewis acidity, and ions of zinc, yttrium, and gadolinium are more preferable. Among them, a catalyst containing zinc ions is optimal because it has an extremely high catalytic activity and the thermal stability of the resulting modified EVOH (C) is excellent.

  The addition amount of metal ions belonging to Groups 3 to 12 of the periodic table is preferably 0.1 to 20 μmol / g in terms of moles of metal ions with respect to the weight of unmodified EVOH (A). If the amount is too large, EVOH may be gelled during melt kneading, and more preferably 10 μmol / g or less. On the other hand, if the amount is too small, the effect of adding the catalyst may not be sufficiently achieved, and the amount is more preferably 0.5 μmol / g or more. In addition, since the suitable addition amount of the ion of the metal which belongs to periodic table group 3-12 changes also with the kind of metal to be used and the kind of below-mentioned anion, it adjusts suitably also considering those points. Is to be done.

  The anion species of the catalyst containing a metal ion belonging to Groups 3 to 12 of the periodic table is not particularly limited, but it is preferable that the conjugate acid contains a monovalent anion which is a strong acid equal to or higher than sulfuric acid. . This is because an anion in which the conjugate acid is a strong acid usually has a low nucleophilicity, so that it is difficult to react with the epoxy compound (B), and it is possible to prevent the loss of catalytic activity due to consumption of anionic species by the nucleophilic reaction. Further, by having such an anion as a counter ion, the Lewis acidity of the catalyst is improved and the catalytic activity is improved.

Monovalent anions in which the conjugate acid is a strong acid equivalent to or higher than sulfuric acid include sulfonate ions such as methanesulfonate ion, ethanesulfonate ion, trifluoromethanesulfonate ion, benzenesulfonate ion, toluenesulfonate ion; chlorine Halogen ions such as ions, bromine ions and iodine ions; perchlorate ions; tetrafluoroborate ions (BF ₄ ⁻ ), hexafluorophosphate ions (PF ₆ ⁻ ), hexafluoroarsinate ions (AsF ₆ ⁻ ), hexafluoro Anions having four or more fluorine atoms such as antimonate ions; tetraphenylborate derivative ions such as tetrakis (pentafluorophenyl) borate ions; tetrakis (3,5-bis (trifluoromethyl) phenyl) borate, bis (c Deca-7,8-dicarbaundecaborate deca borate) cobalt (III) ion, bis (undecamethylene 7,8-dicarbaundecaborate deca borate) iron (III) carborane derivative ions of the ion and the like.

  As described above, the catalyst used in the present invention preferably contains a monovalent anion whose conjugate acid is a strong acid equal to or higher than sulfuric acid, but all anionic species in the catalyst are the same anion. It need not be a seed. Rather, it is preferable that the conjugate acid simultaneously contains an anion which is a weak acid.

  Examples of anions in which the conjugate acid is a weak acid include alkyl anions, aryl anions, alkoxides, aryloxy anions, carboxylates, and acetylacetonates and derivatives thereof. Of these, alkoxide, carboxylate, acetylacetonate and derivatives thereof are preferably used.

  It is preferable that the number of moles of an anion in which the conjugate acid is a strong acid equal to or higher than that of sulfuric acid is 0.2 to 1.5 times the number of moles of metal ions in the catalyst. When the molar ratio is less than 0.2 times, the catalytic activity may be insufficient, more preferably 0.3 times or more, and even more preferably 0.4 times or more. On the other hand, when the molar ratio exceeds 1.5 times, the modified EVOH (C) may be gelled, and is more preferably 1.2 times or less. The molar ratio is optimally 1 time. In addition, when the raw material unmodified EVOH (A) contains an alkali metal salt such as sodium acetate, the amount of the anion whose conjugate acid is a strong acid equal to or higher than that of sulfuric acid is consumed as much as it is neutralized. You can increase the number.

  The method for preparing the catalyst is not particularly limited, but as a suitable method, a metal compound belonging to Groups 3 to 12 of the periodic table is dissolved or dispersed in a solvent, and the resulting solution or suspension is used. A method of adding a strong acid such as a sulfonic acid having a conjugate acid equal to or higher than that of sulfuric acid is mentioned. Examples of the metal compound belonging to Group 3-12 of the periodic table used as a raw material include alkyl metals, aryl metals, metal alkoxides, metal aryloxides, metal carboxylates, metal acetylacetonates and the like. Here, when a strong acid is added to a solution or suspension of a metal compound belonging to Groups 3 to 12 of the periodic table, it is preferably added little by little. The solution containing the catalyst thus obtained can be introduced directly into the extruder.

  As a solvent for dissolving or dispersing a metal compound belonging to Groups 3 to 12 of the periodic table, an organic solvent, particularly an ether solvent is preferable. This is because it hardly reacts even at the temperature in the extruder and the solubility of the metal compound is good. Examples of ether solvents include dimethyl ether, diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane, diethoxyethane, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, and the like. As the solvent to be used, a solvent that is excellent in solubility of the metal compound, has a relatively low boiling point, and can be almost completely removed by the vent of the extruder is preferable. In that respect, diethylene glycol dimethyl ether, 1,2-dimethoxyethane and tetrahydrofuran are particularly preferred.

  Further, in the above-described catalyst preparation method, instead of the strong acid to be added, a strong acid ester such as a sulfonic acid ester may be used. Since esters of strong acids are usually less reactive than strong acids themselves, they may not react with metal compounds at room temperature, but they are active in an extruder when placed in a high-temperature extruder maintained at around 200 ° C. A catalyst can be produced.

  As a method for preparing the catalyst, another method described below can be adopted. First, an aqueous catalyst solution is prepared by mixing, in an aqueous solution, a metal compound belonging to Groups 3 to 12 of the water-soluble periodic table and a strong acid such as sulfonic acid having a conjugate acid equivalent to or higher than sulfuric acid. At this time, the aqueous solution may contain an appropriate amount of alcohol. The obtained catalyst aqueous solution is brought into contact with unmodified EVOH (A), and then dried to obtain unmodified EVOH (A) containing the catalyst. Specifically, a method of immersing unmodified EVOH (A) pellets, particularly porous hydrous pellets, in the catalyst aqueous solution is preferable. In this case, the dry pellets thus obtained can be introduced into an extruder.

  The catalyst deactivator used is not particularly limited as long as it reduces the function of the catalyst as a Lewis acid. Alkali metal salts are preferably used. In order to deactivate a catalyst containing a monovalent anion whose conjugate acid is a strong acid equal to or higher than sulfuric acid, it is necessary to use an alkali metal salt of an anion of an acid weaker than the conjugate acid of the anion. By doing so, the counter ion of the metal ion belonging to Groups 3 to 12 of the periodic table constituting the catalyst is exchanged with a weak acid anion, and as a result, the Lewis acidity of the catalyst is lowered. The cation species of the alkali metal salt used for the catalyst deactivator is not particularly limited, and sodium salt, potassium salt and lithium salt are preferred as examples. Also, the anionic species is not particularly limited, and carboxylates, phosphates and phosphonates are exemplified as suitable ones.

  The use of a salt such as sodium acetate or dipotassium monohydrogen phosphate as the catalyst deactivator can significantly improve the thermal stability, but it may still be insufficient depending on the application. This is because metal ions belonging to Groups 3 to 12 of the Periodic Table still have some activity as a Lewis acid and thus act as a catalyst for the decomposition and gelation of the modified EVOH (C). it is conceivable that. As a method for further improving this point, it is preferable to add a chelating agent that strongly coordinates to ions of metals belonging to Groups 3 to 12 of the periodic table. As a result of such a chelating agent being able to strongly coordinate to the ions of the metal, the Lewis acidity can be almost completely lost, and a modified EVOH (C) excellent in thermal stability can be provided. Moreover, the strong acid which is the conjugate acid of the anion contained in a catalyst can also be neutralized as mentioned above by the said chelating agent being an alkali metal salt.

  Suitable chelating agents used as catalyst deactivators include oxycarboxylates, aminocarboxylates, aminophosphonates and the like. Specifically, examples of the oxycarboxylate include disodium citrate, disodium tartrate, and disodium malate. Aminocarboxylates include nitrilotriacetic acid trisodium, ethylenediaminetetraacetic acid disodium, ethylenediaminetetraacetic acid trisodium, ethylenediaminetetraacetic acid tripotassium, diethylenetriaminepentaacetic acid trisodium, 1,2-cyclohexanediamine tetraacetic acid trisodium, ethylenediamine diacetate. Illustrative examples include monosodium acetate and monosodium N- (hydroxyethyl) iminodiacetic acid. Examples of aminophosphonates include nitrilotrismethylenephosphonic acid hexasodium, ethylenediaminetetra (methylenephosphonic acid) octasodium, and the like. Of these, polyaminopolycarboxylic acid is preferred, and an alkali metal salt of ethylenediaminetetraacetic acid is most preferred in terms of performance and cost.

  The addition amount of the catalyst deactivator is not particularly limited and is appropriately adjusted according to the type of metal ion contained in the catalyst, the number of coordination sites of the chelating agent, etc., but the catalyst with respect to the number of moles of metal ions contained in the catalyst It is preferable that the molar ratio of the deactivator is 0.2 to 10. When the ratio is less than 0.2, the catalyst may not be sufficiently deactivated, more preferably 0.5 or more, and even more preferably 1 or more. On the other hand, if the ratio exceeds 10, the resulting modified EVOH (C) may be colored and the production cost may increase, more preferably 5 or less, and even more preferably 3 or less. It is.

  The method for introducing the catalyst deactivator into the extruder is not particularly limited. However, in order to uniformly disperse the catalyst deactivator, it is preferably introduced as a solution of the catalyst deactivator with respect to the molten modified EVOH (C). In consideration of the solubility of the catalyst deactivator and the influence on the surrounding environment, it is preferably added as an aqueous solution.

  The catalyst deactivator may be added to the extruder after melt-kneading unmodified EVOH (A) and epoxy compound (B) in the presence of the catalyst. However, it is preferable to add the catalyst deactivator after melt-kneading unmodified EVOH (A) and the epoxy compound (B) in the presence of a catalyst to remove the unreacted epoxy compound (B). As described above, when the catalyst deactivator is added as an aqueous solution, the catalyst deactivator is added before removing the unreacted epoxy compound (B). This is because water mixes in the epoxy compound (B), and the separation operation takes time. In addition, it is also preferable to remove moisture by a vent or the like after adding the aqueous solution of the catalyst deactivator.

  In the production method of the present invention, when a catalyst deactivator is used, a suitable production process includes (1) a melting step of unmodified EVOH (A); (2) a mixture of an epoxy compound (B) and a catalyst. Examples thereof include: an addition step; (3) a step of removing unreacted epoxy compound (B); (4) a step of adding a catalyst deactivator aqueous solution; and (5) a step of removing moisture under reduced pressure.

  From the viewpoint of carrying out the reaction smoothly, it is preferable to remove moisture and oxygen from the system. For this reason, you may remove a water | moisture content and oxygen using a vent etc. before adding an epoxy compound (B) in an extruder.

  The modification amount of the modified EVOH (C) by the epoxy compound (B) is in the range of 0.1 to 10 mol% with respect to the monomer unit of the unmodified EVOH (A), more preferably from 0.3 to It is in the range of 5 mol%, more preferably in the range of 0.5 to 3 mol%. When the amount of modification is 0.1 mol% or less, the effect of modification is small, and when it exceeds 10 mol%, there is a drawback that gas barrier properties and thermal stability are lowered.

  The preferred melt flow rate (MFR) of the modified EVOH (C) (190 ° C. under 2160 g load) is 0.1 to 100 g / 10 min, preferably 0.3 to 30 g / 10 min, more preferably 0.5 to 20 g / 10 min. However, those having a melting point near 190 ° C. or exceeding 190 ° C. were measured under a load of 2160 g and at a plurality of temperatures above the melting point, and in a semilogarithmic graph, the reciprocal absolute temperature was plotted on the horizontal axis, and the logarithm of MFR was plotted on the vertical axis. The value is extrapolated to 190 ° C.

  The modified EVOH (C) thus obtained is molded to produce a molded product used in the present invention. At this time, you may mix | blend resin and various additives other than modified | denatured EVOH (C). Among them, it is a particularly preferable embodiment to mold a resin composition in which unmodified EVOH (D) is blended with modified EVOH (C). In general, the production cost of the modified EVOH (C) is higher than that of the unmodified EVOH (D). Therefore, the modified EVOH (C) having a high double bond concentration and the unmodified EVOH (D) are mixed to obtain a desired two-component solution. It is economical to produce a resin composition having a heavy bond concentration. Since the modified EVOH (C) having a large modification amount can be easily produced by reacting in the extruder by the method as described above, such a resin composition can be easily obtained. It is also easy to adjust the double bond concentration of the resin composition according to the application. As the unmodified EVOH (D), the same as the unmodified EVOH (A) described above can be used.

  The blending mass ratio (C / D) in the resin composition containing the modified EVOH (C) and the unmodified EVOH (D) is not particularly limited. In order to obtain a molded product excellent in hot water resistance by setting the double bond concentration of the resin composition in a desired range, the lower limit of the ratio (C / D) is preferably 2/98, and 5/95. More preferably, it is more preferably 15/85 or more, and particularly preferably 20/80 or more. On the other hand, from the viewpoint of production cost and barrier properties, the upper limit of the ratio (C / D) is preferably 60/40, and more preferably 40/60.

  The method of blending the modified EVOH (C) and the unmodified EVOH (D) is not particularly limited. You may mix | blend by melt-kneading, and you may mix | blend in a solution. From the viewpoint of productivity, melt kneading is preferred, and for example, melt kneading using pellets of modified EVOH (C) and unmodified EVOH (D) is a preferred embodiment.

  In the resin composition containing the modified EVOH (C) and the unmodified EVOH (D), the amount of modification by the epoxy compound (B) is the monomer unit of the unmodified EVOH (A) and the unmodified EVOH (D). Preferably it is the range of 0.1-10 mol% with respect to the total amount of a monomer unit, More preferably, it is the range of 0.3-5 mol%, More preferably, it is 0.5-3 mol% % Range.

  Various additives may be added to the resin composition containing the modified EVOH (C) or the modified EVOH (C) and the unmodified EVOH (D) as necessary. Examples of such additives include sensitizers, curing agents, curing accelerators, antioxidants, plasticizers, ultraviolet absorbers, antistatic agents, colorants, fillers, or other polymer compounds. These can be blended as long as the effects of the present invention are not inhibited. Specific examples of the additive include the following.

  Sensitizer: benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin propyl ether, benzyl diphenyl disulfide, tetramethyl thiuram monosulfide, azobisbutyronitrile, dibenzyl, diacetyl, acetophenone, 2,2-diethoxyacetophenone, benzophenone, 2-chlorothioxanthone, 2-methylthioxanthone and the like.

  Curing agents: methyl ethyl ketone peroxide, cyclohexane peroxide, cumene peroxide, benzoyl peroxide, dicumyl peroxide, t-butyl perbenzoate, and the like.

  Curing accelerator: metal soap such as cobalt 2-ethylhexanoate, cobalt naphthenate, manganese 2-ethylhexanoate, manganese naphthenate, methylaniline, dimethylaniline, diethylaniline, methyl-p-toluidine, dimethyl-p- Amines such as toluidine, methyl-2-hydroxyethylaniline, di-2-hydroxyethyl-p-toluidine or salts thereof such as hydrochloric acid, acetic acid, sulfuric acid and phosphoric acid;

  Antioxidant: 2,5-dibutyl-t-butylhydroquinone, 2,6-di-t-butyl-p-cresol, 4,4′-thiobis- (6-t-butylphenol), 2,2′-methylene -Bis- (4-methyl-6-butylphenol), octadecyl-3- (3 ', 5'-di-t-butyl-4'-hydroxyphenyl) propionate, 4,4'-thiobis- (6-t- Butylphenol) and the like.

  Plasticizer: dimethyl phthalate, diethyl phthalate, dibutyl phthalate, wax, liquid paraffin, phosphate ester, etc.

  UV absorber: ethylene-2-cyano-3,3′-diphenyl acrylate, 2- (2′-hydroxy-5′-methylphenyl) benzotriazole, 2- (2′-hydroxy-3′-t-butyl-) 5'-methylphenyl) 5-chlorotriazole, 2-hydroxy-4-methoxybenzophenone, (2,2'-dihydroxy-4-methoxybenzophenone) and the like.

  Antistatic agents: pentaerythritol monostearate, sorbitan monopalmitate, sulfated oleic acid, polyethylene oxide, carbowax and the like.

  Colorant: carbon black, phthalocyanine, quinacridone, azo pigment, titanium oxide, bengara, etc.

  Filler: Glass fiber, mica, celite, calcium silicate, aluminum silicate, calcium carbonate, silicon oxide, montmorillonite, etc.

  Other polymer compounds: polyolefins such as ethylene-butene copolymers and ethylene-propylene copolymers; modified polyolefins modified with functional groups such as carboxyl groups; polyamides, polyesters, polystyrenes, polyvinylidene chloride, polyvinyl chloride, etc. .

  Depending on the above-mentioned purpose, if the resin composition of modified EVOH (C) containing additives as necessary is formed into a molded product by hot melt molding, the surface of the molded product based on another plastic or metal There is a method of using it as a coating agent after solution coating. The conditions in such a case will be described next.

  The medical tube of the present invention can be obtained by molding a modified EVOH (C) or a resin composition containing a modified EVOH (C) and an unmodified EVOH (D). The molding method is not particularly limited, and melt molding may be performed, or a molded product may be obtained by drying the solution. In the case of melt molding, the modified EVOH (C) may be used as it is without adding additives, or the modified EVOH (C), unmodified EVOH (D) and various additives may be supplied to the extruder. Alternatively, it may be molded as it is by melt-kneading. Further, it may be molded after being melt-kneaded and once pelletized, and a suitable means is adopted as appropriate.

  Although the molding temperature in melt molding varies depending on the melting point of the modified EVOH (C), the molten resin temperature is preferably about 120 ° C to 250 ° C.

  As the melt molding method, any molding method such as an injection molding method, a compression molding method, and an extrusion molding method can be employed. Among these, examples of the extrusion molding method include a T-die method, a hollow molding method, a pipe extrusion method, a linear extrusion method, a modified die molding method, and an inflation method. The shape of the molded product is arbitrary, and may be a pellet, a bottle, a pipe, a filament, a modified cross-section extrudate, or the like. Moreover, it is also possible to use the extrusion molded product obtained by the said extrusion molding method for secondary processes, such as uniaxial or biaxial stretching, or thermoforming.

  A preferred embodiment of the present invention is a medical tube composed of a multilayer structure. Specifically, it is a medical tube made of a multilayer structure having a layer made of modified EVOH (C) and a layer made of resin (F) other than the modified EVOH (C). Moreover, the medical tube which consists of a multilayer structure which has a layer which consists of a resin composition containing modified EVOH (C) and unmodified EVOH (D), and a layer which consists of resin (F) other than this resin composition. is there.

  The manufacturing method of the medical tube which consists of such a multilayer structure is not specifically limited, You may melt-mold. In the case of melt molding, coextrusion molding, co-injection molding, extrusion coating, etc. are employed.

  Although it does not specifically limit as resin (F), It is suitable that it is a thermoplastic resin. The resin (F) is not particularly limited, but at least one selected from the group consisting of polyolefin, polyamide, polyester, polystyrene, polyurethane, polyvinylidene chloride, polyvinyl chloride, polyacrylonitrile, polycarbonate, acrylic resin and polyvinyl ester is used. Illustrated. Examples of the polyolefin include low density polyethylene, medium density polyethylene, high density polyethylene, ethylene-vinyl acetate copolymer, ethylene-α-olefin (α-olefin having 3 to 20 carbon atoms) copolymer, ionomer, polypropylene, propylene ( Α-olefins having 4 to 20 carbon atoms) copolymers, polybutenes, polymethylpentenes or other olefins alone or copolymers, or these olefins alone or copolymers with unsaturated carboxylic acids or their anhydrides or esters. Examples include graft-modified ones. It is also preferable that the resin (F) is an elastomer.

  The multilayer structure is composed of a modified EVOH resin (C) layer used in the present invention or a layer composed of a resin composition containing modified EVOH (C) and unmodified EVOH (D) as C (C1, C2,. ..), when the resin (F) layer is F (F1, F2,...) And the adhesive layer provided as necessary is Ad, the film / sheet / bottle is C / F 2 Not only the layer structure but also C / F / C, F / C / F, F1 / F2 / C, F / C / F / C / F, C2 / C1 / F / C1 / C2, C / Ad / F, Arbitrary configurations such as C / Ad / F / C, F / Ad / C / Ad / F, and F / Ad / C / Ad / C / Ad / F are possible. Moreover, the resin which improves the adhesiveness of both resin may be mix | blended.

  When a resin composition containing modified EVOH (C) or modified EVOH (C) and unmodified EVOH (D) is solution-coated on the surface of a molded article, the above-mentioned modified EVOH (C) resin composition is publicly known. Used by dissolving or dispersing in a solvent for EVOH. Examples of the solvent include lower alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, 2-butanol, 2-methyl-2-propanol, and benzyl alcohol, and mixtures of these with water. Examples of the solvent include dimethyl sulfoxide, dimethylformamide, dimethylacetamide, N-methylpyrrolidone and the like. In particular, the mixed solvent of the lower alcohol and water is preferable.

  In the present invention, the substrate to which the modified EVOH (C) or a resin composition containing the same is applied is not particularly limited, and various plastic films, sheets, hollow containers or papers such as polyethylene, polypropylene, polyester, and polyvinyl chloride. , Natural rubber, synthetic rubber, metal and the like.

  As a coating method, a roller coating method, a spray coating method, a dip coating method, or any other known method can be applied.

  Further, depending on the type of the substrate, surface oxidation treatment, flame treatment, anchor coat treatment, primer treatment, etc. can be appropriately carried out in order to improve the adhesive force with the modified EVOH (C) or a resin composition containing the same. As the anchor treatment agent, a polyurethane compound or a polyester / isocyanate compound can be suitably used. The thickness of the anchor coat layer is practically about 0.05 to 3 μm.

  After apply | coating the solution of modified | denatured EVOH (C) or the resin composition containing the same to a base material, drying is performed. The drying temperature may be 30 to 150 ° C., preferably about 50 to 120 ° C. and heated for about 3 seconds to 5 minutes. When the crosslinking reaction described below is performed by irradiating at least one selected from the group consisting of electron beams, X-rays, γ-rays, ultraviolet rays, and visible rays, the drying conditions are desirably performed at a low temperature or in a short time.

  In the medical tube of the present invention, at least a part of the modified ethylene-vinyl alcohol copolymer (C) is crosslinked, and the gel fraction of the molded product is 3% by mass or more. It can be produced by crosslinking at least part of the modified EVOH (C) in the molded product obtained as described above. The above-mentioned molded product before crosslinking can be crosslinked by leaving it in the air for a long time, but usually at least one selected from the group consisting of electron beam, X-ray, γ-ray, ultraviolet ray and visible ray. It is desirable to perform crosslinking by irradiating or heating.

  When an electron beam, X-ray or γ-ray is used, the absorbed dose is preferably 1 kGy or more. More preferably, it is 1 kGy-1MGy, More preferably, it is 5 kGy-500 kGy, Especially preferably, it is 10 kGy-200 kGy. When the absorbed dose is larger than 1 MGy, the degradation of the modified EVOH (C) occurs, which causes problems such as a significant decrease in film strength and coloring, which is not preferable. On the other hand, when the absorbed dose is smaller than 1 kGy, the gel fraction is not improved and the desired performance such as hot water resistance cannot be obtained.

  In addition, when the multilayer structure used in the present invention is characterized by performing heat sterilization after filling the contents, as described above, it is difficult for whitening, deformation, and deterioration of barrier properties to occur due to improvement in hot water resistance. Become. This multilayer structure is suitable for medical tubes that need to be heat sterilized.

  A medical container having excellent storage stability can be obtained by filling the multi-layered structure with the contents and then heat sterilizing, particularly boiling sterilization or retort sterilization. Here, the retort sterilization process refers to a process in which a sealed object is sterilized with hot water under heating and pressurization using a high-pressure kettle. Here, the treatment conditions are usually 80 to 145 ° C. and 0.1 to 0.45 MPa for 30 to 90 minutes. For the retort sterilization treatment, various methods such as a recovery method, a replacement method, a steam method, a shower method, and a spray method are adopted. Immediately after performing the retort sterilization treatment, the medical container of the present invention may become white and opaque, but after removing the surface water of the packaging material, it becomes transparent by leaving it for a while. In the case where desiccation and gas barrier properties are more reliably restored, drying with hot air at 40 to 150 ° C. for 1 to 120 minutes is preferable. Other heat sterilization methods include a hot filling method and an autoclave heat sterilization method. Here, hot filling means filling the contents at 85 ° C. or higher and sterilizing, and autoclave sterilization processing is to put a gas such as saturated water vapor or hydrogen gas inside the pressure device and heat under pressure. This refers to the process of sterilizing microorganisms.

  It is important that the medical tube thus obtained has a water-phenol mixed solvent insolubility, that is, a gel fraction of 3% by mass or more. When this insolubility is less than 3% by mass, effects such as hot water resistance and heat resistance, which are objects of the present invention, are reduced. The insoluble rate is preferably 5% by mass, more preferably 10% by mass or more, and particularly preferably 20% by mass or more. Here, the insolubility rate of the water-phenol mixed solvent is 1 part by weight of a molded product in 100 parts by weight of a mixed solvent of water (15% by weight) -phenol (85% by weight) and dissolved by heating at 60 ° C. for 12 hours. Thereafter, filtration is performed, and the filtrate is evaporated to dryness. In this case, filtration is carried out using a filter device (filter paper, filter cloth, membrane) through which 100% of the dissolved uncrosslinked modified EVOH (C) permeates. In addition, when a filler is contained in the resin composition containing the modified EVOH (C) used in the present invention, the gel fraction is obtained by reducing the weight of the residue remaining after heating the insoluble matter of the solvent at 500 ° C. for 1 hour. calculate. When the molded product is a multilayer structure body, the gel fraction of the modified EVOH (C) layer or the resin composition layer containing the modified EVOH (C) and the unmodified EVOH (D) satisfies the above range.

  Since the medical tube obtained in the present invention contains almost no harmful cross-linking agent, elution of the cross-linking agent into the liquid passing through the tube is suppressed, and is excellent in safety and suitable for use in the medical field. It has gas barrier properties, has heat resistance and hot water resistance that can withstand heat sterilization treatment such as retort sterilization treatment and autoclave sterilization treatment, and also has a very low decrease in gas barrier properties after heat sterilization treatment. For example, it is preferably used as a component of a medical device such as a blood circuit, a blood bag, a drug solution bag, a blood transfusion / infusion set, and a catheter, and more preferably used as a medical tube subjected to heat sterilization.

  EXAMPLES Hereinafter, although an Example demonstrates this invention in more detail, this invention is not limited at all by these Examples. The evaluation was performed by the following method.

(1) Ethylene content of EVOH and degree of modification of modified EVOH A sample used for measurement was pulverized, and low molecular weight components were extracted with acetone, followed by drying at 120 ° C. for 12 hours. This sample was subjected to ¹ H-NMR measurement using DMSO-d ₆ as a solvent (“JNM-GX-500 type” manufactured by JEOL Ltd.), and an epoxy compound having a double bond was reacted in the obtained spectrum. The area of the double bond methine peak (5.9 ppm) or the double bond methylene peak (5.2 ppm) of the modified EVOH and the ethylene moiety peak (1.4 ppm) corresponding to the EVOH monomer unit. Calculated from the ratio.

(2) Melt flow rate (MFR) of EVOH and modified EVOH
Using a melt indexer L260 (manufactured by Techno Seven Co., Ltd.), the resin flow rate (g / 10 min) was measured at a load of 2.16 kg and a temperature of 190 ° C.

(3) Elution amount of allyl glycidyl ether (epoxy compound having a double bond) Prepare two standard solutions of allyl glycidyl ether: 0.02 g, solvent (methanol: chloroform = 50: 50): 20 mL, 100 mL, A calibration curve was prepared by gas chromatography (GC) under the following conditions. About 0.05 g of denatured EVOH used for measurement was precisely weighed into a 10 ml capacity vial, 1 ml of methanol was added and heated to 80 ° C. to dissolve. After cooling this solution to room temperature, 4 ml of chloroform was added little by little to precipitate a white precipitate. The solution part and the precipitate were separated by a centrifuge, the solution part was subjected to GC analysis, and the elution amount of allyl glycidyl ether was determined from the above calibration curve.
GC apparatus Agilent Technologies 6890, column: DB-5 (J & W Scientific, capillary column, length 30 m, φ0.25 mm, film sickness 1.0 μm)
Measurement conditions Inj. Temp. 150 ° C., carrier gas: helium, column flow rate: 3.0 ml / min, 50 ° C. (2 min hold) → temperature rise at 20 ° C./min→200° C. (0.5 min hold)
The limit value of detection in this measurement is 0.20 μg / g.

Synthesis example 1
28 parts by mass of zinc acetylacetonate monohydrate was mixed with 957 parts by mass of 1,2-dimethoxyethane to obtain a mixed solution. While stirring, 15 parts by mass of trifluoromethanesulfonic acid was added to the obtained mixed solution to obtain a catalyst solution.

  A TEM-35BS extruder (37 mmφ, L / D = 52.5) manufactured by Toshiba Machine Co., Ltd. was used, and a screw, three vents, and three pressure inlets were installed. The resin feed port was cooled with water, the temperature of the screw rotation portion was set to 200 ° C., and the operation was performed at a screw rotation speed of 300 rpm. EVOH (ethylene content 32 mol%, saponification degree 99 mol% or more, MFR 6.0 g / 10 min, potassium content 8 ppm, phosphate group content 20 ppm) is charged at a rate of 20.0 kg / hr from the resin feed port. Allyl glycidyl ether was added from the pressure inlet at a rate of 2.93 kg / hr and the catalyst solution at a rate of 0.5 kg / hr. Sodium acetate 0.82% aqueous solution was added at a rate of 0.6 kg / hr from the second pressure inlet. Excess allyl glycidyl ether was removed from the first vent under reduced pressure, water was added at a rate of 1 kg / hr from the third pressure inlet, and water and allyl glycidyl ether were removed from the second and third vents under reduced pressure. As a result, a modified EVOH (EVOH-1) having an allyl glycidyl ether modification amount of 1.7 mol%, an MFR of 2.0 g / 10 min, and a melting point of 166 ° C. was obtained. The AGE elution amount of the modified EVOH (EVOH-1) was 0.62 μg / g.

Synthesis example 2
Ratio of 60/40 mass ratio of modified EVOH (EVOH-1) obtained in Synthesis Example 1 and unmodified EVOH (ethylene content 27 mol%, saponification degree 99 mol% or more, MFR 4.0 g / 10 min) The mixture was dry-blended and extruded using a 25 mmφ twin screw extruder (LABO PLASTOMIL MODEL 15C300 manufactured by Toyo Seiki Co., Ltd.) at 220 ° C. under the conditions of a screw rotation speed of 100 rpm and an extrusion resin amount of 4.5 kg / hour to pelletize. Subsequently, drying was performed at 80 ° C. for 12 hours to obtain modified EVOH (EVOH-2) (the allyl glycidyl ether modified amount after blending was 1.0 mol% in calculation, and the AGE elution amount was 0.37 μg / g). Become).

Synthesis example 3
Ratio of 30/70 mass ratio of modified EVOH (EVOH-1) obtained in Synthesis Example 1 and unmodified EVOH (ethylene content 27 mol%, saponification degree 99 mol% or more, MFR 4.0 g / 10 min) The mixture was dry-blended and extruded into pellets using a 25 mmφ twin screw extruder (LABO PLASTOMIL MODEL 15C300 manufactured by Toyo Seiki Co., Ltd.) at 220 ° C. under the conditions of a screw rotation speed of 100 rpm and an extrusion resin amount of 4.5 kg / hour. Subsequently, drying was performed at 80 ° C. for 12 hours to obtain modified EVOH (EVOH-3) (the allyl glycidyl ether modified amount after blending was calculated to be 0.5 mol%, and the AGE elution amount was 0.18 μg / g). Becomes).

Example 1
Using the modified EVOH (EVOH-2) obtained in Synthesis Example 2 and polyamide “1022FD12” (trade name, manufactured by Ube Industries, Ltd., hereinafter referred to as PA) as raw materials, each was introduced into separate extruders. A PA / EVOH-2 / PA two-type three-layer multilayer tube was produced by coextrusion molding according to the conditions shown. The thickness structure of the obtained multilayer tube was 100/20/100 μm.

The configuration and operating conditions of the coextrusion molding machine are as follows.
Extruder 1 [PA]: Single screw extruder “GT-32-A type” manufactured by Plastic Engineering Laboratory Co., Ltd., screw diameter: 32 mmφ, screw rotation speed: 62 rpm, cylinder set temperature: 240 ° C.
Extruder 2 [modified EVOH]: single-screw extruder “Lab ME CO-NXT” manufactured by Toyo Seiki Seisakusho Co., Ltd., screw diameter: 20 mmφ, screw rotation speed: 18 rpm, cylinder set temperature: 220 ° C.
Die size: 300 mm, film take-up speed: 4 m / min, cooling roll temperature: 60 ° C.

  The obtained multilayer tube was irradiated with an electron beam of 100 kGy (acceleration voltage 250 kV) to be crosslinked. At this time, using a mixed solvent having a mass ratio of water to phenol (water / phenol) of 15/85, the content of the insoluble content of the modified EVOH layer when a heat dissolution test is performed at 60 ° C. for 12 hours, The gel fraction was 90.2%.

The multilayer tube was subjected to a retort sterilization treatment at 120 ° C. for 90 minutes. As a result, the tube form was satisfactory without delamination and whitening. As a result of measuring the oxygen permeation amount (OTR) of the multilayer tube before and after the retort sterilization treatment (120 ° C., 90 minutes) at 20 ° C. and 65% RH, 0.60 cc · 20 μm / m ² · day · Atm, after retorting, a good gas barrier property of 0.67 cc · 20 μm / m ² · day · atm was exhibited. The obtained results are summarized in Table 1.

Example 2
A multilayer tube was obtained in the same manner as in Example 1 except that the modified EVOH (EVOH-3) obtained in Synthesis Example 3 was used. At this time, the gel fraction was 70.8%. The multilayer tube was subjected to a retort sterilization treatment at 120 ° C. for 90 minutes. As a result, the multilayer tube form was satisfactory without delamination and whitening. As a result of measuring the oxygen permeation amount (OTR) of the multilayer tube before and after the retort sterilization treatment (120 ° C., 90 minutes) under 20 ° C. and 65% RH, 0.30 cc · 20 μm / m ² · day · Atm, after retorting, a good gas barrier property of 0.32 cc · 20 μm / m ² · day · atm was exhibited. The obtained results are summarized in Table 1.

Comparative Example 1
Instead of the modified EVOH (EVOH-2), “Eval” L171 (trade name, manufactured by Kuraray Co., Ltd.) having an ethylene content of 27 mol%, a saponification degree of 99 mol%, and an MFR of 4.0 g / 10 min was used. A multilayer tube was obtained in the same manner as in Example 1 except that was not irradiated. At this time, the gel fraction was 0%. As a result of the retort sterilization treatment at 120 ° C. for 90 minutes, the multilayer tube could not withstand high temperature and high pressure, and the multilayer tube was whitened and delamination occurred. The oxygen permeation amount (OTR) of the multilayer tube after the retort sterilization treatment (120 ° C., 90 minutes) could not be measured due to severe destruction of the tube. The obtained results are summarized in Table 1.

Comparative Example 2
A multilayer tube was obtained in the same manner as in Example 1 except that the modified EVOH (EVOH-3) obtained in Synthesis Example 3 was used and no electron beam was irradiated. At this time, the gel fraction was 1.7%. As a result of the retort sterilization treatment at 120 ° C. for 90 minutes, the multilayer tube could not withstand high temperature and high pressure, and the multilayer tube was whitened and delamination occurred. The oxygen permeation amount (OTR) of the multilayer tube after the retort sterilization treatment (120 ° C., 90 minutes) could not be measured due to severe destruction of the tube. The obtained results are summarized in Table 1.

Example 3
A multi-layer tube crosslinked with an electron beam was obtained in the same manner as in Example 1 except that the modified EVOH (EVOH-2) obtained in Synthesis Example 2 was used. At this time, the gel fraction was 90.2%. The multilayer tube was put into a blower dryer and heated to 120 ° C. to evaluate kink (the tube was bent or twisted so that the tube inner surfaces were in close contact with each other). There was no kink and good dimensional stability without any change in tube diameter. The obtained results are summarized in Table 2.

Example 4
A multi-layer tube cross-linked with an electron beam was obtained in the same manner as in Example 1 except that the modified EVOH (EVOH-3) obtained in Synthesis Example 3 was used. At this time, the gel fraction was 70.8%. The multilayer tube was put into a blower dryer and heated to 120 ° C. to evaluate kink. There was no kink and good dimensional stability without any change in tube diameter. The obtained results are summarized in Table 2.

Comparative Example 3
A multilayer tube was obtained in the same manner as in Example 1 except that the modified EVOH (EVOH-2) obtained in Synthesis Example 2 was used and no electron beam was irradiated. At this time, the gel fraction was 0%. The multilayer tube was put into a blower dryer and heated to 120 ° C. to evaluate kink. There was no kink and good dimensional stability without any change in tube diameter. The obtained results are summarized in Table 2.

Comparative Example 4
A multilayer tube was obtained in the same manner as in Example 1 except that “EVAL” L171 (trade name, manufactured by Kuraray Co., Ltd.) was used instead of modified EVOH (EVOH-2) and no electron beam was irradiated. At this time, the gel fraction was 1.7%. The multilayer tube was put into a blower dryer and heated to 120 ° C. to evaluate kink. There was no kink and good dimensional stability without any change in tube diameter. The obtained results are summarized in Table 2.

Claims (13)

  A medical tube comprising a modified ethylene-vinyl alcohol copolymer (C), wherein the modified ethylene-vinyl alcohol copolymer (C) is an unmodified ethylene-vinyl alcohol copolymer (A). The monomer unit of the ethylene-vinyl alcohol copolymer (A) is obtained by modification with an epoxy compound (B) having a double bond, and the amount of modification by the epoxy compound (B) having a double bond is The modified ethylene-vinyl alcohol copolymer (C) is at least partially crosslinked and the gel fraction thereof is 3% by mass or more. A characteristic medical tube.   A medical tube comprising a resin composition containing a modified ethylene-vinyl alcohol copolymer (C) and an unmodified ethylene-vinyl alcohol copolymer (D), the modified ethylene-vinyl alcohol copolymer The compound (C) was obtained by modifying an unmodified ethylene-vinyl alcohol copolymer (A) with an epoxy compound (B) having a double bond, and an epoxy compound having a double bond. The amount of modification by (B) is 0.1 to 10 mol% with respect to the monomer unit of the ethylene-vinyl alcohol copolymer (A), and at least a part of the resin composition is crosslinked, and A medical tube having a gel fraction of 3% by mass or more.   The medical tube according to claim 1 or 2, wherein the unmodified ethylene-vinyl alcohol copolymer (A) has an ethylene content of 5 to 55 mol% and a saponification degree of 90 mol% or more.   The medical tube according to any one of claims 1 to 3, wherein the epoxy compound (B) having a double bond is a monovalent epoxy compound having a molecular weight of 500 or less.   The medical tube according to claim 4, wherein the epoxy compound (B) having a double bond is allyl glycidyl ether.   2. The multilayer structure comprising a layer composed of a modified ethylene-vinyl alcohol copolymer (C) and a layer composed of a resin (F) other than the modified ethylene-vinyl alcohol copolymer (C). Medical tube.   Other than the layer composed of the resin composition containing the modified ethylene-vinyl alcohol copolymer (C) and the unmodified ethylene-vinyl alcohol copolymer (D) and the modified ethylene-vinyl alcohol copolymer (C) The medical tube according to claim 2, comprising a multilayer structure having a layer of the resin (F).   A method for producing a medical tube comprising a modified ethylene-vinyl alcohol copolymer (C), wherein an unmodified ethylene-vinyl alcohol copolymer (A) is an epoxy compound (B) having a double bond. The modified ethylene-vinyl alcohol copolymer (C) is produced, the modified ethylene-vinyl alcohol copolymer (C) is molded, and the modified ethylene-vinyl alcohol copolymer (C) is formed. A method for producing a medical tube, wherein at least a part is crosslinked and the gel fraction is 3% by mass or more.   A method for producing a medical tube comprising a resin composition comprising a modified ethylene-vinyl alcohol copolymer (C) and an unmodified ethylene-vinyl alcohol copolymer (D), wherein the unmodified ethylene- A modified ethylene-vinyl alcohol copolymer (C) is produced by modifying a vinyl alcohol copolymer (A) with an epoxy compound (B) having a double bond. (C) and an unmodified ethylene-vinyl alcohol copolymer (D) are mixed to produce a resin composition, the resin composition is molded, and at least a part of the resin composition is crosslinked. And the manufacturing method of the medical tube characterized by making the gel fraction into 3 mass% or more.   The method for producing a medical tube according to claim 8 or 9, wherein after the crosslinking, a heat sterilization treatment is performed at a pressure of 0.10 to 0.45 MPa.   The method for producing a medical tube according to claim 10, wherein the heat sterilization treatment is retort sterilization treatment or autoclave sterilization treatment.   12. The medical tube according to claim 8, wherein an elution amount of the epoxy compound (B) eluted from the modified ethylene-vinyl alcohol copolymer (C) before crosslinking is 0.50 μg / g or less. Production method. At least one part selected from the group consisting of electron beam, X-ray, γ-ray, ultraviolet ray and visible ray is irradiated or heated to at least partially crosslink the modified ethylene-vinyl alcohol copolymer (C). The method for producing a medical tube according to any one of claims 8 to 12.