POLYOLEFIN ARTICLES STERILISABLE BY GAMMA-IRRADIATION

Abstract: Polyolefin articles, especially polypropylene hypodermic syringes are made more resistant to the yellow discolouration and embrittlement which accompanies sterilisation by gamma-irradiation by the addition to the polyolefin of a heterocyclic hindered amine, e.g. di-(2,2,6,6-tetra-methyl-4-­ piperidyl)sebacate, to the amount from 0.01 to 2% by weight of the polymer.

Description: POLYOLEFIN ARTICLES STERILISABLE BY GAMMA-IRRADIATION This invention relates to polyolefin articles, especially polypropylene hypodermic syringe components which are suitable for sterilisation by gamma-irradiation from a cobalt-60 source. Polypropylene syringes have been in use for many years (see British patent specification 1 050 802 published in 1966) and have been sterilised by gammairradiation even though this causes yellow discolouration and/or embrittlement of the syringe. Plester reports (see Bio-Medical Engineering* September 1970, pages 443 to 447) that polypropylene is of only "borderline'. suitability for such use and accordingly many attempts have been made to alleviate the problem. Nevertheless, the problem has persisted and was discussed and left unsolved by Williams et al in "Radiation Physics and Chemistry", Volume 9, pages 445 to 454, published in 1977. It has now been discovered that polyolefins containing certain hindered amines are more resistant to the discolouration which occurs as a result of gammairradiation. Typical hindered amines are described in West German patent specifications 2 204 659 and 2 319 816, published in 1972 and 1973 respectively. Accordingly, this invention provides an article of medical (including hospital) ware sterilisable by gamma-irradiation from a cobalt-60 source and made from a composition comprising a crystalline polymer of an aliphatic alpha-olefin characterised in that the composition comprises from 0.01 to 2 (preferably 0.08 to 0.3)% by weight of the polymer of a hindered amine or its salt, N-oxide, N-hydroxide or N-nitroxide wherein the amine nitrogen is contained in a carbon-nitrogen-carbon chain which forms part of a non-aromatic heterocyclic ring and wherein each of the two carbon atoms of the chain is bonded to two same or different lower alkyl groups each containing 1 to 12 carbon atoms or to an alicyclic group containing 4 to 9 carbon atoms which groups sterically hinder the amine. In general, the articles can receive a radiation dose of 5.0 Mrad from a cobalt-60 source and then have a discolouration factor (as hereinafter defined) of better than 0.750 (often better than 0.800) two weeks after irradiation and an oven life in air at 15o0C of at least 6 and often over 10 days in sections 3.17 mm thick. The hindered amines preferably comprise a 5- or 6membered heterocyclic ring containing the hindered amine nitrogen and optionally another hetero atom preferably nitrogen or oxygen. If the hindered amine is a tertiary amine, the tertiary group may be, for example, an optionally substituted alkyl, aralkyl, alkaryl or alicyclic group containing 1 to 12 carbon atoms and one or more of the substituents may be hindered amines so that the tertiary group may be used to link a plurality of hindered amines. The e hindering groups are preferably alkyl groups containing 1 to 4 carbon atoms and most preferably all four groups are methyl. The most preferred hindered amines comprise 2,2,4,4-tetramethyl piperidine derivatives. The hindered amine is preferably bonded to a carrier moiety which should have little if any inhibiting effect on the chemical activity of the hindered amine. Reasonably inert carriers include aromatic compounds (for example those based on the benzene, imidazole or triazine rings), saturated hydrocarbon compounds, esters or amides of carboxylic acids, ketones and ether, thioether, sulphinyl or sulphone groups. Preferably, in order to reduce the extractability of the hindered amines from polyolefins, the carriers can be used to link together a plurality of hindered amines and hence the tertiary groups may be regarded as carriers too. - Examples of hindered amines linked by diesters or ketones include: : a) di-(2,2,6,6-tetramethyl-4-piperidyl) sebacate (see formula I) where it is the sebacate which is the carrier, b) di-(2,2,6,6-tetramethyl-4-piperidyl) 1-(3,5 ditertiarybutyl-4-hydroxyphenylmethyl )-l,l- pentanedicarboxylate (see formula II) where it is the pentanedicarboxylate which is the carrier, c) the condensate of succinic acid and N-(2 hydroxypropyl)-2,2,6,6-tetramethyl-4- hydroxypiperidine (see formula III) where both the succinate moiety and the tertiary propoxy groups combine to form carriers. The condensate preferably contains 6 to 20 hindered amine groups, and d) l,4-di-(2,2,6,6-tetramethyl-4-piperidyl)-2,3- butanedione (see formula IV) where it is the butanedione which is the carrier. The polyolefin can be, for example, a homopolymer of ethylene (low or high density polyethylene), propylene, butene-l or 4-methyl-pentene-1 or a copolymer of two or more of these monomers. Preferred copolymers are copolymers of propylene and either from 7 to 20% (by weight of the copolymer) of ethylene when made by injecting ethylene into the latter stages of an otherwise homopolymerisation of propylene or from 0.5 to 10% of ethylene when made by random copolymerisation. Copolymers of ethylene with up to 30% of vinyl acetate, methyl, ethyl or butyl (including tertiary butyl) acrylates or methacrylates or acrylic or methacrylic acids may also be used. Preferably, the polyolefins have melt flow indexes of from 0.1 to 25 g/10 minutes when measured according to British Standard 2782 Part 1/105C of 1970 using a 2.16 kg load at 2300C in the case of polymers containing a major amount of polymerised propylene and at 1900C in all other cases. Added rubbers improve inipact strength. The composition may contain stabilising amounts (e.g. 0.01 to 2% by weight of the polymer) of light stablisers (e.g. benzotriazoles) and/or phenolic antioxidants of the kind used in polyolefins, for example, n-octadecyl 3-(3,5ditertiarybutyl-4-hydroxyphenyl) propionate. However, phenolic antioxidants may aggravate discolouration so their use may entail sacrifice of some of the improvement in discolouration. The compositions may also contain stabilising amounts of sulphur compounds of the type known to synergise with phenolic antioxidants in polyolefins, for example, long chain (e.g. C10 td C22) mercaptans and sulphides but the preferred compounds are dialkyl thiodialkanoates especially when the alkyl groups contain from 10 to 22 carbon atoms and the alkanoic acids contain from 2 to 6 carbon atoms. Specific examples are dilauryl and distearyl thiodipropionate. The compositions preferably contain from 0.01 to 10% (usually 0.1 to 0.5%) by weight of organic sulphur compound. Other conventional additives such as pigments or moulding aids may be used. Articles of sterilisable medical ware according to this invention include syringe components (such as barrels, plungers and needle hubs), catheters, cannulae and prosthetic devices and also wrappings for such articles. The invention is illustrated by the following examples of which A to I are comparative. EXAMPLES A TO I AND 1 to 3 Using a high speed powder mixer, powdered propylene homopolymer having a melt flow index of 8 g/10 minutes was mixed with 0.2% by weight of powdered calcium stearate and various amounts of various powdered additives as specified in Table 1. (The percentages specified in Table 1 and of calcium stearate are based on the weight of the polymer). Each mixture of powders was heated to 225 0C to melt the polymer and the melt was converted to granules. Each batch of granules was injection moulded into discs 3.17 z thick and 11.4 cm in diameter. Sample discs were retained as controls and the rest were irradiated at 2.5 or 5.0 Mrad using a cobalt-60 source. The irradiated discs were divided into three groups. The first group were kept under ambient conditions for 2 weeks and then their discolouration factors were measured. They were then kept under ambient conditions for a period of three months after irradiation and then their discolouration factors were measured again. The second group of discs were kept under ambient conditions for 4 weeks and then placed in an aircirculating oven maintained at 1000C for three days. On removal from the oven and cooling to ambient temperature, the discolouration factors of the discs were measured. The third group of discs were put into an aircirculating oven maintained at 1500C and the time taken for them to embrittle (i.e. for surface cracking to appear) was noted. All the results are shown in Table 2. "Discolouration factor" is measured using a 'Colormaster' differential colorimeter as supplied by the Manufacturers, Engineering and Equipment Corporation of Warrington, Pennsylvania, USA. A beam of blue light from the 'Colormaster' was shone onto a white surface at an angle of incidence of 450 so as to illuminate an area of the surface. The intensity of light leaving the illuminated area in a direction normal to the surface was registered by the 'Colormaster'. A disc 3.17 mm thick was then placed over the illuminated area and was compared by the 'Colormaster'. The procedure was repeated using red light and the ratio of loss of intensity of blue light to loss of intensity of red light as compared by the 'Colormaster' was calculated. This ratio is defined as the "discolouration factor". The higher the discolouration factor, the lower is the yellow discolouration of the sample. Therefore, it will be seen that in general the least yellow discolouration occurred in Examples 1, 2, 3 and A, but in the case of A, the brittleness of the sample was unacceptable. TABLE 1 EMI6.1 <tb> Example <SEP> % <SEP> by <SEP> weight <SEP> % <SEP> by <SEP> weight <SEP> % <SEP> by <SEP> weight <tb> <SEP> antioxidant <SEP> thioester <SEP> other <SEP> *additive <SEP> <tb> <SEP> A <tb> <SEP> B <SEP> - <SEP> 0.3 <tb> <SEP> C <SEP> 0.1 <SEP> 0.3 <tb> <SEP> D <SEP> 0.2 <SEP> 0.5 <SEP> <SEP> 4 <SEP> <tb> <SEP> E <SEP> 0.1 <SEP> 0.3 <SEP> 0.3a <tb> <SEP> F <SEP> 0.1 <SEP> 0.3 <SEP> 0.1b <SEP> <tb> <SEP> G <SEP> 0.1 <SEP> 0.3 <SEP> 0.lc <SEP> <tb> <SEP> H <SEP> 0.1 <SEP> 0.3 <SEP> 0.ld <SEP> <tb> <SEP> I <SEP> Proprietry <SEP> Composition <tb> <SEP> 1 <SEP> 0.1 <SEP> 0.2e <tb> <SEP> 2 <SEP> - <SEP> - <SEP> 0.2f <tb> <SEP> 3 <SEP> 0.1 <SEP> - <SEP> 0.2g <SEP> <tb> *Additives a = di-benzylidene sorbitol. b = a mixture of tri-mono and tri-di-nonyl phenyl phosphite containing 1% by weight (of the weight of the phosphite) of tri isopropanol amine. c = tris-(2,4-ditertiary butyl phenyl) phosphite. d = a proprietry organic phosphonite. e = as formula III. f = as formula II. g = as formula I. TABLE 2 Irradiation dose Megarads EMI7.1 0 <SEP> 2.5 <SEP> 5.0 <tb> Ex. <SEP> Discolouration <SEP> factor <SEP> Discolouration <SEP> factor <tb> Discolouration <SEP> Oven <SEP> Oven <SEP> Oven <tb> factor <SEP> life <SEP> life <SEP> life <tb> days <SEP> After <SEP> After <SEP> 4 <SEP> weeks <SEP> days <SEP> After <SEP> After <SEP> 4 <SEP> weeks <SEP> days <tb> 2 <SEP> weeks <SEP> + <SEP> 3 <SEP> days <SEP> 3 <SEP> months <SEP> 2 <SEP> weeks <SEP> + <SEP> 3 <SEP> days <tb> at <SEP> 100 C <SEP> at <SEP> 100 C <tb> A <SEP> 0.941 <SEP> 3 <SEP> 0.940 <SEP> Brittle <SEP> - <SEP> #3 <SEP> 0.847 <SEP> Brittle <SEP> #3 <tb> B <SEP> 0.949 <SEP> 6 <SEP> 0.918 <SEP> 0.473 <SEP> - <SEP> #3 <SEP> 0.713 <SEP> 0.488 <SEP> #3 <tb> C <SEP> 0.940 <SEP> 49 <SEP> 0.813 <SEP> 0.740 <SEP> - <SEP> 17 <SEP> 0.679 <SEP> 0.593 <SEP> #3 <tb> D <SEP> 0.927 <SEP> - <SEP> 0.766 <SEP> 0.730 <SEP> - <SEP> 31 <SEP> 0.593 <SEP> 0.535 <SEP> #3 <tb> E <SEP> 0.935 <SEP> 54 <SEP> 0.786 <SEP> 0.737 <SEP> - <SEP> 21 <SEP> 0.648 <SEP> 0.555 <SEP> #3 <tb> F <SEP> 0.913 <SEP> 46 <SEP> 0.760 <SEP> 0.691 <SEP> - <SEP> 18 <SEP> 0.596 <SEP> 0.546 <SEP> #3 <tb> G <SEP> 0.939 <SEP> - <SEP> 0.798 <SEP> 0.762 <SEP> - <SEP> 19 <SEP> 0.630 <SEP> 0.562 <SEP> #3 <tb> H <SEP> 0.944 <SEP> - <SEP> 0.798 <SEP> 0.742 <SEP> - <SEP> 18 <SEP> 0.672 <SEP> 0.581 <SEP> #3 <tb> I <SEP> 0.890 <SEP> 59 <SEP> 0.772 <SEP> 0.707 <SEP> - <SEP> 3 <SEP> 0.634 <SEP> 0.584 <SEP> #3 <tb> TABLE 2 (continued) Irradiation dose Megarads EMI8.1 0 <SEP> 2.5 <SEP> 5.0 <tb> Ex. <SEP> Discolouration <SEP> factor <SEP> Discolouration <SEP> factor <tb> Discolouration <SEP> Oven <SEP> Oven <SEP> Oven <tb> factor <SEP> life <SEP> life <SEP> life <tb> days <SEP> After <SEP> After <SEP> 4 <SEP> weeks <SEP> days <SEP> After <SEP> After <SEP> 4 <SEP> weeks <SEP> days <tb> 2 <SEP> weeks <SEP> + <SEP> 3 <SEP> days <SEP> 3 <SEP> months <SEP> 2 <SEP> weeks <SEP> + <SEP> 3 <SEP> days <tb> at <SEP> 100 C <SEP> at <SEP> 100 C <tb> 1 <SEP> 0.923 <SEP> 33 <SEP> 0.886 <SEP> 0.802 <SEP> 0.907 <SEP> 25 <SEP> 0.870 <SEP> 0.741 <SEP> 12 <tb> 2 <SEP> 0.899 <SEP> 31 <SEP> 0.855 <SEP> 0.786 <SEP> 0.900 <SEP> 25 <SEP> 0.827 <SEP> 0.736 <SEP> 19 <tb> 3 <SEP> 0.931 <SEP> 19 <SEP> 0.829 <SEP> 0.686 <SEP> 0.885 <SEP> 25 <SEP> 0.830 <SEP> 0.568 <SEP> > 20 <tb> EMI9.1 EMI10.1

Claims: CLAIMS 1. An article of medical ware sterilisable by gamma-irradiation from a cobalt-60 source and made from a composition comprising a crystalline polymer of an aliphatic alpha-olefin characterised in that the composition comprises from 0.01 to 2% by weight of the polymer of a hindered amine or its salt, N-oxide, N-hydroxide or N-nitroxide wherein the amine nitrogen is contained in a carbon-nitrogen-carbon chain which forms part of a non-aromatic heterocyclic ring and wherein each of the two carbon atoms of the chain is bonded to two same or different lower alkyl groups each containing 1 to 12 carbon atoms or to an alicyclic group containing 4 to 9 carbon atoms which groups sterically hinder the amine. 2. An article as claimed in claim 1 wherein the hindered amine comprises a 6-membered heterocyclic ring. 3. An article as claimed in claim 2 wherein the hindered amine is carried by a carrier comprising a d icarboxylate. 4. An article as claimed in claim 2 wherein the hindered amine is carried by a carrier comprising a triazine ring. 5. An article as claimed in claim 2 wherein the hindered amine is carried by a carrier comprising a dike tone. 6. An article as claimed in any one of the preceding claims wherein the article is a component for a hypodermic syringe.

Inventors: HARRIS, COLIN ANDREW, RAYNER, MARTIN GEOFFREY
Applicants: IMPERIAL CHEMICAL INDUSTRIES PLC
Application year: 1979
Main classification: C08L23
IPC codes: A61L31, C08K5, A61L29, A61M5