Medical moldings and method for their preparation.

0001The present invention relates to a medical molding, for example a disposable medical instrument, comprising a γ-ray resistant material which has little deterioration of colour or physical properties even when irradiation by γ-rays is carried out for sterilization, as well as to a γ-ray resistant material.

0002Aromatic polycarbonate resins have excellent mechanical and thermal properties, and have been used in various applications. In addition, since they have excellent transparency and sanitary properties and are tough and highly heat-resistant, they have been used for various medical instruments such as container-like packages for putting into and packaging injectors, surgical tools, intravenous injectors and operation tools, as well as for various medical parts for an artificial lung, artificial kidney, anesthetic absorption device, intravene connectors and accessories, medical equipment such as a blood centrifugator, surgical instruments and operation instruments. They have particularly been used for parts of artificial dializers, artificial livers, artificial hearts and lungs, injectors and serum separators, which are disposable.

0003These medical parts are usually completely sterilized, for example by a contacting-treatment with ethylene oxide, heat-treatment in an autoclave or irradiation-treatment with ionizing radiation such as γ-rays.

0004Among these, use of ethylene oxide gas is not preferred in view of the toxicity and instability of ethylene oxide, as well as circumferential problems according to disposal-treatment. Use of an autoclave involves the problems that the resin may be deteriorated upon high-temperature treatment, the energy cost is expensive and drying before use is necessary since moisture remains in the parts after treatment.

0005Accordingly, a sterilizing-treatment using ionizing radiation, which can enable a low-temperature treatment and which is relatively inexpensive, is used instead of the above-mentioned methods.

0006Examples of ionizing radiation are α-rays, heavy electron-rays, proton-rays, β-rays, electron-rays, neutron-rays, γ-rays and X-rays, γ-rays being used preferably in industry.

0007However, when irradiated with γ-rays, an aromatic polycarbonate resin, which is optically transparent, turns yellow. Accordingly, there have been proposed a method of offsetting the yellow colour by, for example, previously mixing a blue colourant into the resin, blending in a boron compound [JP-A-61-215651 (1986)], and blending in a polyether or alkyl ether thereof [JP-A-62-135556 (1987)].

0008Aromatic polycarbonate resins obtained by the above methods have various problems in that the prevention of yellowing is not sufficient. If a yellowing inhibitor is used in such an amount as to be sufficient to develop the desired effect, it remarkably deteriorates the strength of the resin itself, which cannot then be used in view of the poor strength thereof.

0009Accordingly, it has not yet been possible to obtain aromatic polycarbonate resins having little yellowing and still possessing sufficient strength and toughness after a sterilizing-treatment by γ-rays, or medical parts using such resins.

0010EP-A-296,473, published between the priorty dates and the filing date of the present application, discloses a molding composition which comprises an aromatic polycarbonate resin and a stabilizing agent which may contain, inter alia, a halogen atom.

0011The present invention provides a medical molding, for example a disposable medical instrument, suitable for contacting with blood or a physiological solution, comprising a γ-ray resistant material comprising an aromatic polycarbonate resin, which γ-ray resistant material contains from 0.1 to 10.0% by weight of bromine atoms.

0012The present invention also provides a method of sterilizing a medical molding which comprises irradiating a molding as defined above with γ-rays.

0013The present invention additionally provides a γ-ray resistant material as defined above.

0014The γ-ray resistant material comprising the bromine-containing aromatic polycarbonate resin or bromine-containing aromatic polycarbonate resin further blended with propylene glycol shows less colour change and maintains its physical properties even after irradiation by the ionizing radiation.

0015The γ-ray resistant material may, for example, comprise an aromatic polycarbonate polymer, for example a copolymer, and an organic bromine-containing compound.

0016The γ-ray resistant material may also, for example comprise a brominated aromatic polycarbonate copolymer.

0017The γ-ray resistant material may additionally, for example, comprise an aromatic polycarbonate polymer, for example a copolymer, and a brominated aromatic polycarbonate copolymer.

0018The medical moldings of the present invention may be, for example, parts for artificial dialyzers, parts for artificial livers, parts for artificial kidneys, parts for artificial hearts and lungs, parts for injectors and serum separators.

0019The physiological solution is, for example, an artificial dialyzing solution, physiological saline water, Ringer's solution or a maintaining solution.

0020Examples of γ-ray resistant materials comprising aromatic polycarbonate resins are: <ul id="ul0001" list-style="none"><li>(1) Those obtained by blending a polymer prepared by a phosgene process of reacting a dihydroxydiaryl compound with phosgene, or an ester exchanging process of reacting a dihydroxydiaryl compound with a carbonate such as diphenyl carbonate, with an organic bromine-containing compound such that the γ-ray resistant material contains from 0.1 to 10% by weight of bromine atoms as a whole. Examples of typical polymers are those using 2,2-bis(4-hydroxyphenyl) propane (bisphenol A) as the dihydroxydiaryl compound comonomer.</li><li>(2) Those obtained by a phosgene process of reacting a dihydroxydiaryl compound and a brominated dihydroxydiaryl compound with phosgene, or an ester exchanging process of reacting a dihydroxydiaryl compound and a brominated dihydroxydiaryl compound with a carbonate such as diphenyl carbonate such that the γ-ray resistant material contains from 0.1 to 10.0% by weight of bromine atoms as a whole. Examples of the copolymer are those using 2,2-bis(4-hydroxyphenyl)propane (bisphenol A) and bromine derivative thereof (brominated bisphenol A) as the monomers. The process for producing a copolymer is known to those skilled in the art. There can be used, for example, a method as described in US-A-3,334,154 and JP-B-60-21691 (1985).</li><li>(3) Those obtained by blending a copolymer prepared by a phosgene process of reacting a dihydroxydiaryl compound and a brominated dihydroxydiaryl compound with phosgene, or an ester exchanging process of reacting a dihydroxydiaryl compound and a brominated dihydroxydiaryl compound with a carbonate such as diphenyl carbonate (the bromine content is not restricted to less than 10 wt%), with a polymer prepared by a phosgene process of reacting a dihydroxydiaryl compound with phosgene, or an ester exchanging process of reacting a dihydroxydiaryl compound with a carbonate such as diphenyl carbonate, such that the γ-ray resistant material contains from 0.1 to 10 wt% of bromine atoms as a whole.</li></ul>

0021As the dihydroxyaryl compound there can be mentioned, for example, bis(hydroxyaryl) alkanes such as 2,2-bis(4-hydroxyphenyl) propane (bisphenol A), bis(4-hydroxyphenyl) methane, 1,1-bis(4-hydroxyphenyl) ethane, 2,2-bis(4-hydroxyphenyl) butane, 2,2-bis(4-hydroxyphenyl) octane, bis(4-hydroxyphenyl) phenyl methane, 2,2-bis(4-hydroxyphenyl-3-methylphenyl) propane, 1,1-bis(4-hydroxy-3-tertiarybutylphenyl) propane, 2,2-bis(4-hydroxy-3-bromophenyl) propane, 2,2-bis(4-hydroxy-3,5-dibromophenyl) propane and 2,2-bis(4-hydroxy-3,5-dichlorophenyl) propane; bis(hydroxyaryl) cycloalkanes such as 1,1-bis(4-hydroxyphenyl) cyclopentane and 1,1-bis(4-hydroxyphenyl) cyclohexane; dihydroxydiaryl ethers such as 4,4'-dihydroxyphenyl ether and 4,4'-dihydroxy-3,3'-diethyldiphenyl ether; dihydroxydiaryl sulfides such as 4,4'-dihydroxydiphenyl sulfide and 4,4'-dihydroxy-3,3'-dimethyldiphenyl sulfide; dihydroxydiaryl sulfoxides such as 4,4'-dihydroxydiphenyl sulfoxide and 4,4'-dihydroxy-3,3'-dimethyldiphenyl sulfoxide; and dihydroxydiaryl sulfones such as 4,4'-dihydroxydiphenyl sulfone, and 4,4'-dihydroxy-3,3'-dimethyldiphenyl sulfone.

0022These compounds may be used singly or as a mixture of two or more. In addition, at least one of, for example, piperadine, dipiperidyl hydroquinone, resorcine and 4,4'-dihydroxydiphenyl may be mixed therewith.

0023The brominated dihydroxydiaryl compound is a compound prepared by partially or entirely substituting a hydrogen atom(s) on the phenyl group in a dihydroxydiaryl compound with bromine. There can be mentioned, for example: 2,2-bis(4-hydroxy-3,5-dibromophenyl) propane (tetrabromobisphenol A), 2,2-bis(4-hydroxy-3-bromophenyl) propane, and 2,2-bis(4-hydroxy-2,3,5,6-tetrabromophenyl) propane.

0024The organic bromine compound contains bromine atoms. As such a compound, there can be mentioned, for example, brominated benzenes such as hexabromobenzene and pentabromotoluene; brominated diphenyls such as tetrabromodiphenyl, decabromodiphenyl, tetrabromodiphenyl ether, decabromodiphenyl ether and decabromodiphenyl sulfone; brominated bisphenol A or the derivatives thereof such as 2,2-bis(4-hydroxy-3,5-dibromophenyl) propane (tetrabromobisphenol A), 2,2-bis(4-glycidoxy-3,5-dibromophenyl) propane or low polymers thereof (brominated bisphenol A-type epoxy resin), 2,2-bis(4-hydroxyethoxy-3,5-dibromophenyl) propane, 2,2-bis(4-acetoxy-3,5-dibromophenyl) propane and a polycarbonate oligomer of tetrabromobisphenol A; tetrabromophthalic acid anhydride; tribromophenyl condensates; polypentabromobenzyl acrylate; brominated polystyrene; and condensates of tetrabromobisphenol A, cyanuric acid and tribromophenol. A polycarbonate oligomer prepared from brominated bisphenol A such as a polycarbonate oligomer of tetrabromobisphenol A is particularly preferred.

0025The bromine atom content of the γ-ray resistant material of the present invention is from 0.1 to 10% by weight, preferably, 0.5 to 8% by weight.

0026If the amount of the bromine atoms is less than 0.1% by weight, the effect of improving the γ-ray resistance is poor, whereas the mechanical property of the composition is deteriorated or the heat-stability on melt-molding is poor if it is more than 10% by weight.

0027If polypropylene glycol is blended with the aromatic polycarbonate resins the γ-ray resistance can further be improved.

0028The molecular weight of polypropylene glycol used in the present invention is preferably not greater than 8,000, more preferably 1,000 to 8,000. If the molecular weight exceeds 8,000, the transparency tends to be deteriorated. The blending amount of polypropylene glycol is from 0.1 to 5% by weight, preferably from 0.5 to 2% by weight, based on the weight of the γ-ray resistant material. If it is less than 0.1% by weight, a sufficient effect cannot be developed. On the other hand, if it exceeds 5% by weight, it tends to deteriorate the transparency and mechanical properties.

0029As a method of blending the organic bromine-containing compound or polypropylene glycol, various means well-known to those skilled in the art can be used at any stage before the molding of the final molded product.

0030In the γ-ray resistant materials other resins, for example, polyethylene terephthalate, polybutylene terephthalate, polyester polycarbonate, polyarylate, polycondensate of cyclohexane dimethanol and terephthalic acid and/or isophthalic acid, or a copolymer of them with polyethylene terephthalate may be contained in a small amount such that the effect of the present invention is not impaired.

0031The γ-ray resistant materials may also contain various well-known additives, for example, a hydrolysis inhibitor such as an epoxy compound, lubricant such as paraffin wax and fatty acid ester, anti-oxidant such as a hindered phenol, phosphoric acid ester or phosphorous acid ester, weather proofness improver such as triazine compound or colourant such as a pigment or dye.

0032Medical moldings, such as medical instruments, of the present invention are obtained by molding the γ-ray resistant materials by methods well known to those skilled in the art, with no particular restriction. For example, injection molding, extrusion molding, blow molding or press molding can be used.

0033The medical moldings of the present invention can be subjected to irradiation by γ-rays for sterilization. They show little yellowing even after undergoing such sterilizing treatment.

0034The sterilized medical molding of the present invention is obtained by irradiating γ-rays to a medical molding comprising a γ-ray resistant material comprising an aromatic polycarbonate resin, which γ-ray resistant material contains from 0.1 to 10% by weight of bromine atoms.

0035The irradiation dose of γ-rays is usually 2 to 5 Mrad. The irradiating time and strength of γ-rays may be adjusted so that the dose is within the above-mentioned dose range.

0036It is possible to produce medical moldings which are fully sterilized until they are used for medical treatment, and which have little yellowing even having undergone the sterilizing treatment, by the above method. It is thus possible to provide medical parts which are highly resistant to ionizing radiation.

0037The present invention is now further explained specifically in the following Examples.

Examples 1 - 7 and Comparative Examples 1 - 2

:

0038As the aromatic polycarbonate resin, a bisphenol A polycarbonate resin having a viscosity average molecular weight of 22,000 (NOVAREX 7022A: trade name of Mitsubishi Kasei Corp.) was blended with a polycarbonate oligomer of tetrabromobisphenol A (BC-58, trade name of Great Lakes Co.), decabromodiphenyl ether (DE-83P : trade name of Great Lakes Co.) and polypropylene glycol having a molecular weight of 4,500 (E-4500 : trade name of Dow Chemical Co.) in a composition as shown in Table 1 and pelletized by an extruder having a bent with a screw diameter of 40 mmφ at a resin temperature of from 270 to 290°C. After drying the pellets, test specimens (each of 50 mmφ x 3 mm thickness) were prepared by using an injection molding machine with a mold clamping pressure of 75 ton at a resin temperature range of from 280 to 300°C.

0039The yellowness index of the resultant test specimen was measured in accordance with JIS K-7103 and, furthermore, the test specimen was subjected to sterilization by the irradiation of γ-rays at 2.5 Mrad in an air and oxygen-free atomosphere with the aid of the Nippon Isotope Association. Then yellowness index was again measured after two days. The results are shown in Table 1. The oxygen-free atmosphere was obtained by tightly sealing the specimen together with an oxygen remover (Ageless: trade name of Mitsubishi Gas Chemical Company, Inc.). <tables id="tabl0001" num="0001"><img file="EP0359366B1_D0001.tif" /></tables>

Reference Examples 1 - 3

:

0040Copolymerized polycarbonate resins comprising bisphenol A and tetrabromobisphenol A was obtained by a method as described in JP-B-60-21691 (1985). The properties of the resins are:

Reference Example 1 :

0041<tables id="tabl0002" num="0002"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Molecular weight</entry><entry namest="col2" nameend="col2" align="left">21,500</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Bromine-content</entry><entry namest="col2" nameend="col2" align="left">0.5 wt%</entry></row></tbody></tgroup></table></tables>

Reference Example 2 :

0042<tables id="tabl0003" num="0003"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Molecular weight</entry><entry namest="col2" nameend="col2" align="left">21,900</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Bromine-content</entry><entry namest="col2" nameend="col2" align="left">2.5 wt%</entry></row></tbody></tgroup></table></tables>

Reference Example 3 :

0043<tables id="tabl0004" num="0004"><table frame="all"><tgroup cols="2" colsep="1" rowsep="0"><colspec colnum="1" colname="col1" colwidth="78.75mm" /><colspec colnum="2" colname="col2" colwidth="78.75mm" /><tbody valign="top"><row><entry namest="col1" nameend="col1" align="left">Molecular weight</entry><entry namest="col2" nameend="col2" align="left">21,300</entry></row><row rowsep="1"><entry namest="col1" nameend="col1" align="left">Bromine-content</entry><entry namest="col2" nameend="col2" align="left">7.5 wt%</entry></row></tbody></tgroup></table></tables>

Reference Example 4

:

0044Commercially available bisphenol A polycarbonate resin having a molecular weight of 22,000 not containing halogen (NOVAREX 7022A, trade mark of Mitsubishi Kasei Corp.)

Examples 8 - 13

:

0045The brominated aromatic polycarbonate resins in Reference Examples 1 to 3, alone or blended with commercially available polypropylene glycol having a molecular weight of 4,500 (E-4500 : manufactured by Dow Chemical Co.) each in the composition as shown in Table 2, were pelletized using an extruder with a bent with screw diameter of 40 mmφ at a resin temperature of from 270 to 290°C. After drying the pellets, test specimens (each of 50 mmφ x 3 mm thickness) were prepared using an injection molding machine with a mold clamping pressure of 75 ton at a resin temperature range of from 280 to 300°C.

0046The yellowness index of the thus obtained test specimens was measured in accordance with JIS K-7103 and, furthermore, the specimens were sterilized by the irradiation of γ-rays at 2.5 Mrad in air with the aid of the Nippon Isotope Association. Then the yellowness index was measured again after two days. The results obtained are shown in Table 2.

Comparative Examples 3 - 4

:

0047The same procedures as those in Examples 8 - 13 were conducted except for using the polycarbonate resin not containing halogen in Reference Example 4. <tables id="tabl0005" num="0005"><img file="EP0359366B1_D0002.tif" /></tables>

Example 14

:

0048100 parts by weight of the copolymerized polycarbonate resin of Reference Example 1 was blended with 1.0 part by weight of polypropylene glycol (E-4500; trade name of Dow Chemical Co.) and pelletized using an extruder with a bent with screw diameter of 40 mmφ at a resin temperature range of from 270 to 290°C. After drying the pellets, ten dialyzer outer-cylinders each having an inner diameter of 40 mmφ, an outer diameter of 45 mmφ and length of 225 mm disposed with an introduction/discharge port of 12 mmφ each at the upper end and the lower end were molded using an injection molding machine with a mold clamping pressure of 160 ton at a resin temperature range of from 290 to 310°C. Pieces of 30 mm x 30 mm were cut out from the middle portion (2 mm thickness) of five of the ten outer-cylinders, and the yellowness index was measured in accordance with JIS K-7103. The remaining five outer-cylinders were sterilized under irradiation of Co-60 γ-rays at 2.5 Mrad in air with the aid of the Nippon Isotope Association. Then, two days after, specimens of 30 mm x 30 mm were cut out from the middle portions thereof in the same manner as described above and the yellowness index was measured. The results obtained are shown in Table 3.

Comparative Example 5

:

0049The procedures were conducted in the same as those in Example 14 except for using the polycarbonate not containing halogen in Reference Example 4 and not blending polypropylene glycol. The results are shown in Table 3. <tables id="tabl0006" num="0006"><img file="EP0359366B1_D0003.tif" /></tables>