Title of Invention	MEDICAL CONTAINER
Abstract	A medical cntainer produced from a film or sheet having at least one resin layer comprising a polyolefin resin composition wherein the polyolefin resin composition comprises (A) at least one propylene-base polymer selected from the group consis1ing of (A1) a specfic propylene-base polymer and (A3) a specific propylene-base block copolymer composition, and (B) an ethylene-base copolymer comprising on elhylene and at least one a-plefin having 4 or more carbon atoms, and the refractive index of the xylene-soluble portion is from 1.480 to 1.405.

Title of Invention

MEDICAL CONTAINER

Abstract

A medical cntainer produced from a film or sheet having at least one resin layer comprising a polyolefin resin composition wherein the polyolefin resin composition comprises (A) at least one propylene-base polymer selected from the group consis1ing of (A1) a specfic propylene-base polymer and (A3) a specific propylene-base block copolymer composition, and (B) an ethylene-base copolymer comprising on elhylene and at least one a-plefin having 4 or more carbon atoms, and the refractive index of the xylene-soluble portion is from 1.480 to 1.405.

Full Text	MEDICAL CONTAINER TECHNICAL FIELD The present invention relates to a medical container, which is used by filling blood, medicament or the like in it. The application claims the benefit of U.S. provisional Application No. 60/455,564, filed on March 19, 2003, which is hereby incorporated by reference, and is based on Japanese Patent Application No. 2003-033440 filed on February 12, 2003, which is hereby incorporated by reference. BACKGROUND ART A medical container for filling blood, medicament or the like is demanded not only to be, needless to say, hygienic but also to have high heat resistance capable of enduring sterilization treatment at a high temperature, transparency to enable the check of mingling of a foreign material or visual inspection of the change by blending of a medicament, impact resistance sufficiently high. to prevent the bag from rupturing at falling on handling or at packaging and transportation, flexibility for facilitating the discharge of contents, and blocking resistance not to WO 2004/071375 PCT/JP2004/001411 2 readily cause separation of film or sheet at the production of a medical container or not to contact a medicament- containing medical container with its outer packaging bag. In particular, demands are increasing for a medical container which can be sterilized at a high temperature of 1210C or more having a strong sterilization power, can satisfy all of heat resistance, transparency, impact resistance, flexibility and .blocking resistance, and can be industrially produced. For the medical container, a soft polyvinyl chloride, a polyethylene base material such as high- pressure low-density polyethylene, linear low-density polyethylene, high-density polyethylene and ethylens-vinyl acetate copoiymer, and a polypropylene-bass material such as propylene homopolymer and random or block copolymer of propylene and other a-olefin have been heretofore used. The vinyl chloride-base resin is excellent in the balance of heat resistance, transparency, flexibility and impact resistance but this resin has a problem in that a plssticizer used for imparting the performance dissolves out into a medicament solution or food. Out of polyethylene-base materials, the high- pressure low-density polyethylene is deficient in that the heat resistance or impact strength is poor. As for the linear low-density polyethylene, a. .polyethylene. having a WO 2004/071375 PCT/JP2004/001411 3 low density is used so as to enhance the transparency or flexibility, but when the density is decreased, insufficient heat resistance is liable to result and furthermore, problems arise, for example, the low molecular weight component of the resin lowers the blocking resistance of the container or dissolves out into a medicament. The ethylene-vinyl acetate copolymer is excellent in the transparency but disadvantageously low in the heat resistance. The high-density polyethylene is deficient in that the transparency and impact resistance are poor. Thus, polyethylene-base materials cannot satisfy a good balance of heat resistance, transparency and impact resistance. Out of polypropylene-base materials, the propylene homopolymer and propylene random copolyiner are excellent in the transparency but inferior in the blocking resistance, and the propylene block copolymer is poor in the balance of flexibility, impact resistance and transparency. For solving these problems, with respect to the medical container using a polyethylene-base material, a multilayer container having a layer mainly comprising a high-density polyethylene and a layer mainly comprising a linear low-density polyethylene has been proposed (see, for example, JP-&-5-293160 (the term "JP-A" as used herein means an "unexamined published Japanese patent WO 2004/071375 PCT/JP2004/001411 4 application"). Furthermore, a polyethylene-base material produced by using a metallocene-base catalyst and having excellent Impact resistance and transparency has been recently developed and studies are being made to apply this material to a medical container. Also, a method of using these materials in combination and stacking two, three or more layers has been proposed (see, for example, JP-A-7-125738) . On the other hand, with respect to the medical container using a polypropylene-base material, a technique of using a resin composition comprising a propylene-base random copolymer having an a-olefin content of 5 to 8 mass% and a mixture of specific sthylene-propylene and fethylene— butene random copolymets to obtain a container excellent in. the heat resistance, transparency, impact resistance and the like has been disclosed, (see, for example, JF-A-B- 2317 97). Also, a container having a constitution such that a layer comprising a propylens homopolymer or propylene-a- olefin random capolymer containing from 0 to - 30% of a polyethylene-base resin is provided as the outer layer and a three-layer laminate comprising a mixture of a propylene - homopolymer or a propylene/a-olefin random copolymer and an olefin-base elastomer or the like is provided as the intermediate layer has been proposed (see, for ex ample, JP- WO 2004/071375 PCT/JP2004/001411 5 A-9-26294B). Furthermore, a technique of using a resin composition comprising a crystalline polypropylene and a propylene/a-olefin copolymer having a specific limiting viscosity ratio, and forming a specific morphology at the thermoforntatian has been proposed (see, for example, JP-A- 10-316810). However, the container described in JP-A-5-293160 cannot always hold a sufficient transparency after stetilization at a temperature of 121°C or more and fails in fully satisfying the requirement on the market that sterilination can be performed at a higher temperature in a shorter time. Also in the case of using the laminate described in JF-A-7-125738, the transparency after high-temperature stetilization of 121°C or more is not sufficiently high and moreover, the impact resistance is also insufficient to readily cause rupture at the heat-welded part on falling of the container, therefore, improvements are demanded. Furthermore, a film or sheet obtained by a water cooling inflation method, a T-die method or the like has particularly a smooth surface and readily causes blokcing of films or sheets with each other and when these are pulled apartr a whitened flaw remains on the surface and the outer appearance is seriously deteriorated in some WO 2004/071375 PCT/JP2004/001411 6 cases, The resin composition described in JP-A-8-2 31787 has a problem that the heat resistance and transparency are still insufficient. The container described In JP-A-9-262'948 does not have a sufficiently high impact resistance and particularly, in the case of a container having a volume of 1 L or more, the impact resistance is not satisfied from. the standpoint of preventing rupture on falling. The method described in JP-A-10-316810 has a problem in that not only the impact resistance or the thermal shrinkage percentage at the heat sterilization expresses strong anisotropy due to orientation of the domain but also stable production while keeping the quality can be hardly attained because the formation of specific morphology is sensitive to the molding conditions or the like. The present invention has been made under these circumstances and an object of the present invention is to provide a medical container having heat resistance high enough to enable sterilisation at a temperature of 121°C or more and exhibiting excellent properties in all of ths transparency, impact resistance, flexibility and blocking resistance. WO 2004/071375 PCT/JP2004/001411 7 DISCLOSURE OF INVENTION As a result of extensive investigations, the present inventors have found that the above-described object can be attained by a medical container using a polyalefin resin composition containing specific components, where the xylene-soluble portion has a refractive index within a specific range. Based on this finding, the following medical container has been accomplished. More specifically, the medical container of the present invention is produced from a film or sheet having at least one resin layer comprising a polyolefin reain composition, wherein the polyolefin resin composition comprises (A) at least one propylene-base polymer selected from the group consisting of (Al) a propylene-base polymer composition as a mixture of (All) a propylene polymer and (A12) an ethylene-propylene copolymer elastomer, (A2) a. propylene-base black copolymer, and (A3) a psropylene-bsse block copolymer composition as a mixture of (A2) a propylene-base block copolymar and (A12) an ethylene- propylene copolymer elastomer, and (B) an ethylene-base copolymer comprising an ethylene end at least one a-olefin having 4 or more carbon atoms, and the refractive index of the xylene-soluble portion is from 1.480 to 1.4 95. In the medical container of the present invention, WO 2004/071375 PCT/JP2004/001411 8 the polyolefin, resin composition preferably has a xylene- soluble portion content of 20 to 70 mass%. Furthermore, in the polyolefin resin composition, the ratio (MFRA/MFRg) of the melt flow rate (MFRA) of the propylene-base polymer (A) to the melt flow rate (MFRB) of ths ethylene-base copolymer (B) is pteferably front 0.3 to 3.0. The medical container of the present invention may also be produced such that the film or sheet has a first high-density polyethylene layer containing a high-density polyethylene and this first high-density polyethylene layer is disposed in the inner side. The medical container of the present invention may also be produced such that the film or sheet has a second high-density polyethylene layer containing high-density polyethylene and this second high-density polyethylene layer is disposed in the outer side. In the case where the film or sheet has a first high-density polyethylene layer, the first high-density polyethylene layer preferably contains 20 mass% or more of a high-density polyethylene having a density of 0.950 g/cm3 or. more. In the case where the film or sheet has a second high-density polyethylene layer, the second high-density polyethylene, layer preferably contains 20 mass% or more of WO 2004/071375 PCT/JP2004/001411 9 a high-density polyethylene having a density of 0.950 g/cm3 or more. In the medical container of the present invention, the thickness of the resin layer comprising a polyolefin resin composition preferably occupies 60% or more of the entire thickness of the film or sheet. In the present specification, unless otherwise indicated, MFR is a value measured at 230°C with a load of 21.18 N according to JIS K 7210. The medical container of the present invention is. presumed to have excellent properties because of the following reasons. That is, a resin component having high crystallinity is considered to impart heat resistance to the resin and a rubber-analogous resin component having low crystallinity is considered to impart the impact resistance. Usually, the refractive index greatly differs between a component having high crystallinity and a component having low crystallinity and therefore, a mixture of these components is decreased in the transparency, However, in the polyolefin resin composition for use in the medical container of the present invention, the component having low crystallinity has a specific refractive index. More specifically, the refractive index of the xylene- soluble portion presumed to contain a low crystallinity component is in a specific range and the difference in the WO 2004/071375 PCT/JP2004/001411 10 refractive index between the low crystallinity component and the high crystallinity component is considered to become small, so that heat resistance and impact resistance can be imparted without decreasing the transparency. By using a film or sheet having at least one layer comprising this polyolefin resin composition, a medical container excellent in the transparency, impact resistance, heat resistance, flexibility and blocking resistance can be obtained, BEST MODE FOR CARRYING OUT THE INVENTION The present invention is described in detail below. The medical container of the present invention is produced from a film or sheet having at least one resin layer comprising a polyolefin resin composition and has, for example, a bag form. The polyolefin composition contains (A) a propylene—base polymer and (B) an ethylene-base copolymer and the xylens-soluble portion thereof has a refractive index of 1.480 to 1.4 95. The propylene-base polymer (A) is at least one member selected from the group consisting of (A1) a propylane-base polymer composition as a mixture of (All) a propylane polymer and (Al2) an ethylene-propylene copolymer elastomer, (A2) a propylene-base block copolymer, and (A3) WO 2004/071375 PCT/JP2004/001411 11 a propylene-base block copolymer composition as a mixture of (A2) a propylene-base block copolymsr and (A12) an ethylene-propylene copolymer alastomer. The propylene polymer (All) (hereinafter, sometimes simply referred to as a component (All) contained in the propylene-base polymer composition (Al) is a propylene homopolymer or a propylene-ethylene random polymer. comprising propylene and ethylene and having an ethylene content of 5 mass% or less. The melt flow rate thereinafter referred to as "MFR") of the propylene polymer (All) is not particularly limited but this is preferably from 0.1 to 50 g/10 min, more preferably from 0.5 to 20 g/10 min, still more preferably from 0.5 to 5 g/l0 min, because the mold. processability, heat iresistance and impact resistance all can be enhanced. The ethylene-propylene copolymer elastomer (A12) (hereinafter, sometimes simply referred to as a componsnt (A12) contained in the propylene-base polymer composition (Al) is a copolymer elastomer substantially comprising only ethylene and propylene and having a propylene-originated unit content of 50 to 85 mass%. The MFR of the ethylene- propylene copolymer elastomer (A12) is not particularly limited but this is preferably from 0.1 to 50 g/10 min, more preferably from 0.5 to 20 g/10 min, still more WO 2004/071375 PCT/JP2004/001411 12 preferably from 0.5 to 5 g/10 min, because the mold processability, heat resistance and impact resistance all can be enhanced. The proportion of the propylene polymer (All) occupying in the propylene-base polymer composition (Al ) is, in view of high heat resistance, preferably from 90 to 30 mass%, more preferably from 85 to 50 mass%, still more preferably from 60 to 65 mass, per 100 mass% in total of components (All) and (A12). The propylerie-base block copolymer (A2) (hereinafter, sometimes simply referred to as a component (A2) is a propylene-ethylene block copolymer obtained by melt-kneading a polymer material mixture produced through a first step of polymerizing a propylene homopolymer or a propylene and ethylene copolymer having an ethylene content of less than 5 mass% and subsequently a second step of polymerizing a propylene and ethylene copolymer having an ethylene content of 10 to 70 mass% in a polymerization vessel consisting of at least two vessels, which may be the same as or different from that used in the polymerization of the first step. In the propylene-base block copolymer (A2), the proportion of the polymer produced in the first step is not particularly limited but this is preferably from 90 to 30 mass% and in view of profitability in the production, more WO 2004/071375 PCT/JP2004/001411 13 preferably from 85 to 50 mass%, still more preferably from 80 to 55 mass%. The ethylene content of the polymer obtained in the first step is usually less than 5 mass%, preferably less than 4 mass, more preferably less than 1.5 mass%. If the ethylene content of the polymer obtained in the first step is 5 mass% or more, the heat resistance at sterilization is liable to decrease. The ethylene content of the polymer obtained in the second step is usually from 10 to 70 mass%, preferably from 20 to 60 mass%. If the ethylene content of the polymer obtained in the second step is less than 10 mass%, the impact resistance readily decreases, where as if it exceeds 70 mass%, the transparency sometimes decreases. The catalyst used in the polymerization of the first and second steps is not particularly limited and, for example, a Ziegler Natta catalyst or a (netallocene catalyst is suitably used. The process for the polymerization may be any of a bulk method, a solution method, a slurry method, a vapor phase method and a combination thereof. The propylene-base block copolymer composition (A3) (herein after), sometimes simply preferred to as a component (A3) is a mixture of the above described propylene-base block copolymer (A2) and an ethylenie-propylene copolymer WO 2004/071375 PCT/JP2004/001411 14 elastomer (A12) The mixing ratio of (A2) and (A12) is, in view of high heat resistance, preferably from 90:10 to 50:50, more preferably from 80:20 to 50:50. Among those components (Al), (A2) and (A3), the propylene-base polymer (A) is preferably the component (A2) , namely, a propylane-base block copolymer, because this component expresses stable performance and is inexpensive. The MFR of the propylene-base polymer (A) is not particularly limited but this is preferably from 0.1 to 50 g/10 min, more preferably from 0.5 to 20 g/10 min, still more preferably from 0.5 to 5 g/10 min, because the mold. processability, heat resistance and impact resistance all can be enhanced. The ethylene-base copolymer (B) (hereinafter, sometimes simply referred to as component (B) is a copolymer consisting of an etnylene and at least one a- olefin having 4 or more carbon atoms and mainly comprising an ethylene-originated unit (50 mass% or more). Examples of the a-olefin include l-butene, 1-pentene, 4-methyl-1- pentene, 1-hexene and 1-octene. As the ethylene-base copolymer (B) one or more of these copolymers is (are ) used. The density (according to JIS K 7112 Method D) of the ethylene-base copolymer (B) is usually 0.915 g/cm3 or WO 2004/071375 PCT/JP2004/001411 15 less and in view of high transparency, preferably less than 0.905 g/cm3, more preferably less than 0,900 g/cm3. The MFR of the ethylene-base copolymer (B) is not particularly limited but this is preferably from 0.1 to 20 g/10 min, because the mold processability, heat resistanoe and impact resistance all can be enhanced. In the polyolofin resin composition containing these components (A) and (B) , the refractive index of the xylene-soluble portion which dissolves in xylene at ordinary temperature is from 1.480 to 1.495, preferably from 1.480 to 1,490. When the refractive index of the xylene-soluble portion falls in this range, both the impact resistance and the transparency can be satisfacrtorily high- If the refractive index of the xylene-saluble portion is less than 1.490 or exceeds 1.495, the transparency decreases. The refractive index at the xylene-soluble portion becomes higher as the density of the ethylene-base copolymer (B) increases, and becomes lower as the density of the ethylene-base copolymer (B) decreases. The proportion and re refractive index of the xylene- soluble portion are determined as follows. A specimen (10 g) of a polyolefin resin composition is added to 1 L of an orthoxylene and after the temperature is elevated to a boiling temperature (about 1350C) by WO 2004/071375 PCT/JP2004/001411 16 stirring the solution under heating, the specimen is completely dissolved over 30 minutes or more. After confirming the complete dissolution with an eye, the solution is left standing with stirring to cool to 100°C or less and held in a constant-temperature bath kept at 25°C for 2 hours. Thereafter, the precipitated component (xylene-insoluble portion xi) is separated by filtration through a filter paper to obtain a filtrate. The obtained filtrate is heated at a temperature of 1400C to distill out xylene in a nitrogen stream (about 1 L/min) and the residue is dried to obtain a xylene-soluble portion Xs . At this time, the drying of xylene-insoluble portion and xylene— soluble portion is performed at 60°C under reduced pressure for one day. The proportion of the xylene-soluble portion is determined by (mass of Xs/mass of specimen). The xylene-soluble portion is composed of a low molecular- material in the polyolefin resin composition, a non-crystalline molecule, and the like. In the measurement of refractive index of the. xylene-soluble portion, the xylene-solable portion is preheated at 230°C for 5 minutes in a press-molding machine, then degassed for 30 seconds, pressed at 6 MPa for 1 minute and cooled at 300C for 3 minutes to obtain a film. having a thickness of 50 to 80 pn. Subsequently, a WO 2004/071375 PCT/JP2004/001411 17 specimen comprising this film is left standing at ordinary temperature for 24 hours and then measured on the refractive index for sodium D line at 23°C by an Abbe refractive index meter (manufactured by Atago Co. Ltd.) using ethyl salicylate as the intermediate solution. The content of the xylene-soluble portion in the polyolefin resin composition, is preferably from 10 to 70 mass%, inore preferably from 20 to 70 mass%, if the xylene- soluble portion content is less than 10 mass% the impact strength at low temperatures is liable to be insufficient, whereas if it exceeds 70 mass%, the heat resistance is sometimes not satisfied. In the polyolefin resin composition, the ratio (MPRA/MFRB) of the MFR (MFRA) of the propylens-base polymer (A) to the MFR (MFRB) of the ethylene-bass copolymsr (B) is preferably from 0.3 to 3.0, more preferably from 0.3 to 2.5, still more preferably from 03 . to 2.0. If the MFR ratio is less than 0.3, the impact resistance at low temperatures is liable to he insufficient, whereas if it exceeds 3.0, fish eye is readily generated on the film to impair the outer appearance. The proportion of the component (A) in the polyolefin resin composition is not particularly limited as long as the refractive index of the xylene-soluble portion is in the rangs from 1.480 to 1.495, but in view of higher WO 2004/071375 PCT/JP2004/001411 18 heat resistance, this is-usually on the order of 40 to 90 mass%, preferably from 50 to 70 mass%. In the polyolefin resin composition, another polymer may be blended within the range of not impairing the object of the present invention. Specific examples of the another polymer which can be blended in the polyolefin resin composition include polyethylene-base resins such as high-pressure low-density polyethylene, linear low-density polyethylene and high-density polyethylene, various atyrene-base elastomer such as styrene-butadiene elastomer and hydrogenated product thereof, random copalymers of propylene and an a-olefin having 4 or more carbon atoms, an ethylene-vinyl acetate copolymer, copolymers of ethylene and a (meth) acrylic acid (ester), and olefln-base thernio- plastic elastomers. The proportion of this another polymer contained is preferably less than 40 mass% per 100 ruass% of the polyolefin resin composition. Examples of the method for producing the polyolefin resin composition include a melt-kneading method. In the case , of melt-kneading the components (Al), (A2) and (B), for example, the component (A2) may be meIt-mixed, after melt-mixing the components (All), (R12) and (B) . At this time, the order of melt-mixing the components (All), (A12) and (B) is not particularly limited and the component (B) may be melt-kneaded, after obtaining the component (Al) by WO 2004/071375 PCT/JP2004/001411 19 melt-kneading the components (All) and (A12) , or the components (All) , (A12) and (B) may be simultaneously melt- kneaded. For the melt-kneading, a single-screw or twin- screw extruder can be usually used. The thus-produced polyolefin resin composition contains (A) a propylene-base polymer and (B) an ethylene- base copolymer and the xylene-soluble portion in the polyolefin-base resin composition, which is presumed to be a low crystalline component, has a refractive index of 1.480 to 1.495, so that the resin composition can be excellent not only in the heat resistance but also in all of the transparency, impact assistance, flexibility and blocking resistance. The film ex sheet constituting ths medical container has at least one resin laysr comprising the above—described polyclefin resin composition. Such a film or sheet is formed by, for example, an air-cooling or water-cooling inflation molding method or a T-die method. This film or sheet may be a single-layer film or sheet composed o£ a resin layer comprising the polyolefin resin composition OJC may be a multilayer film or sheet including a resin layer comprising the polyolefin resin composition. The thickness of the film or sheet is usually from 30 to 1,000 pm and in view of flexibility and strength. WO 2004/071375 PCT/JP2004/001411 20 preferably from 50 to 100 pm more preferably from 100 to 500 pm. In the case where the film or sheet is composed of two or more layers, by taking account of transparency, impact resistance and heat resistance, the thickness of the resin layer comprising the polyolefin resin composition preferably occupies 60% or more of the entire thickness of the film or sheet. In the case of a multilayer film or sheet, the multilayer film can be produced by an extrusion lamination method of laminating a single layer or multilayer melt resin including at least one resin layer comprising the above-described polyolefin resin composition on a film fo rised of the same or different material, or by a dry lamination method of laminating a film formed of the same ot different material and a single layer or multilayer body including at least one resin layer comprising the above- described polyolefin resin composition, through an adhesive. The medical container is produced from a film or a sheet and has, for example, a bag form. This medical container may be a single chamber container or a container with multiple chambers divided by an easily separable partition part or a resin-made partition member. If desired, the medical container may be fixed with a mouth WO 2004/071375 PCT/JP2004/001411 21 member for injection or ejection or with another medicament container for the purpose of mixed infusion, by heat- sealing or the like. Examples of the method for producing the medical container include a method of cutting the above-described film or sheet and heat-sealing the marginal parts thereo to form a desired container shape. In this method, the order of cutting and heat-sealing may be reversed. The heat-sealing method at the formation of the film or sheet into a container shape is not particularly limited and, for example, welding methods such as hot-plate sealing method, high-frequency sealing method and ultrasonic wave sealing method can be employed. However, the heat-sealing conditions such as heat-sealing temperature and shape of the heat- sealed part are preferably set not to impair the performance of the medical container, such as outer appearance and impact resistance. The medical container can be easily produced when it is formed of a single layer film or sheet, and is more enhanced in the hygiene heat resistance and the like when, it is formed of a multilayer film or sheet. Particularly, when the film or sheet is a multilayer body having a first high-density pclyethylene layer containing a high-density polyethylene and the medical container is produced by disposing the first high- WO 2004/071375 PCT/JP2004/001411 22 density polyethylene layer in the inner side, a medicament comes into contact with this first high-density polyethylene layer and therefore, not only the hygiene is more improved but also the impact resistance at low temperatures, the appearance of heat-sealed part, the strength and the like are enhanced. Also, when the film or sheet is a multilayer body having a second high-density polyethylene layer containing a high-density polyethylene and the medical container is produced by disposing this second high-density polyethylene layer in the outer side, the impact resistance at low temperatures is enhanced. In particular, a medical container produced by disposing the second high-density polyethylene layer as the outermost layer is preferred, because blocking with the outer packaging material of the medical container hardly occurs. Accordingly, in a more preferred embodiment, the midical container has a high-density polyethylene layer in the inner and outer sides. Furthermore, when the film or sheet is a multilayer body having a layer containing a propylene-ethylene random copolymer and the medical container is produced by disposing this propylene-ethylene random copolymer- containing layer in the inner side and/or in the outer side, the heat resistance is more enhanced. WO 2004/071375 PCT/JP2004/001411 23 The high-density polyethylene contained in the first high-density polyethylene layer and the second high- density polyethylene layer is an ethylene homopolymer or an ethylene a—olefin copolymer of ethylene and a slight amount of a-olefin having from 3 to 12 carbon atoms. Examples of the a-olefin in the ethylene a-olefin copolymer include propylene, l-butene, 1-pentene, 1-hsxene, 4-methyl- 1-pentene, 1-octene, 1-decene and l-dodecene. These are used individually or in combination of two or more. Among these, 1-butene, 1-pentene, 1-hexene, 4-methyl-l-pentene and 1-octene are preferred. Such a high-density polyethylene is produced by various processes such as slurry method, vapor phase method and solution method, preferably using a ziegler Natta catalyst or a metallocene catalyst. The density (according to JIS K 7112 Method D) of this high-density polyethylene is usually 0.940 g/cam3 or mote, preferably 0.950 g/cm3 or more, more preferably 0.-955 g/cm3 or more. If the density is less than 0.940 g/cm3, insufficient heat resistance results in some cases and deformation, shrinkage or reduction of transparency may occur at the sterilization at a temperature exceeding 121°C. The HFR (at 1900C with a load of 21-18 N according to JIS K 7210) of the high-detisity polyethylene is WO 2004/071375 PCT/JP2004/001411 24 approximately from 0.1 to 50 g/10 min, preferably from 0.5 to 20 g/10 min. With an MFR of approximately from 0.1 to 50 g/10 min, an appropriate melt tension can be obtained at the molding and a film or sheet can be easily formed. In the first and second high-density polyethylene layers, another polymer may be blended within the range of not impairing the objet of the present invention. Specific examples of the another polymer include polyethylene resins such as high-pressure low-density polyethylene and linear low-density polyethylene, polypropylene resins such as propylene homopolymier, propylene a-olefin random copolymer and propylene a-olefin block copolymer, various styrene- base elastomers such as styrene-butadiene elastomer, ethylene -.propylene elastomer, an ethylene-vinyl acetate copolymer, copolymers of ethylene and (meth) acrylic acid (ester) , and olefin—base thermoplastic elastomers. The another polymer is blended for the purpose of, for example, adjusting the peel strength, at the marginal part of a medical container or at the easily separable partition part of a multiple chamber container. In the case of blending another polymer, the high- density polyethylene having a density of 0,950 g/cm3 or more is preferably contained in an amount of usually 20 mass% or more, preferably 30 mass% or more, more preferably 70 mass% or more, still more preferably 90 mass% or more in WO 2004/071375 PCT/JP2004/001411 25 each of the first and second high-density polyethylene layers. As long as the high-density polyethylene having a density of 0.950 g/cm3 or more is contained in an amount of 20 mass% or more, heat sterilization at 1210C or more can be performed even when the first or second high-density polyethylene layer is provided, and moreover, the blocking resistance of film is more enhanced. The preferred thickness of each of the first and second high-density polyethylene layers varies depending on the high-density polyethylene content but when the high- density polyethylene is contained in an amount of 90 mass% or more, the thickness is preferably from 5 to 40 pm. The finally obtained medical contained is used by filling a medicament and then subjecting it to steam sterilization under high pressure. The steam sterilisation temperature is not particularly limited but this is generally from 100 to 140°C. Other known sterilization methods such as ultraviolet ray and electron beam can also be used in combination with the high-temperature high- pressure heat sterilization. The thus-obtained medical container is produced from a film or sheet comprising the above-described polyolefin-base resin composition and therefore, exhibits excellent property not only in the heat resistance but also in all of the transparency, impact resistance, flexibility WO 2004/071375 PCT/JP2004/001411 26 and blocking resistance, in particular, even when sterilized at 121°C or more having a high sterilization effect, excellent property is exhibited in all of the transparency, impact resistance, flexibility and blocking resistance and therefore, this medical container is useful. In any of the resin materials for use in the medical container, commonly employed known, additives can be appropriately blended within the range of not impairing the effect of the present invention, if desired, such as antistatic agent, antioxidant, lubricant, anti-blocking agent, anti-clouding agent, nuelear agent, organic and inorganic pigments, ultraviolet absorbent, dispersing agent and reinforcing agent (e.g., talc, calcium carbonate). However, the blending amount thereof must be within, the range admitted in the medical field and in particular, these additives are preferably not blended in a layer which comes into direct contact with the contents. Examples The present invention is described in greater detail below by referring to Examples, however, the present invention is not limited to these Examples, In the following description, unless otherwise indicated, the percentage "%" is on a mass basis. WO 2004/071375 PCT/JP2004/001411 27 (Examples 1 to 9 and Comparative Examples 1 to 5) The resine used in Examples and Comparative Examples are as follows. [Propylene Polymer (All)] All-1: Propylene homopolymer (PL300A produced by SunAllomer Ltd.); MFR: 1.7 g/10 min, xylene-soluble content: 0.5%. All-2: Propylene-ethylene random copolymer having an ethylene content of 3 mass% (PB222A produced by SunAllomer Ltd.); MFR; 0.8 g/10 min, xylene -soluble content: 3.1%. [Ethylena-Propyleine Copolymer Elastomer [A12)] A12-1: Ethylene-propylene copolymer (Tafmer P0630 produced by Mitsui chemicals, Inc.); MFR: 0.7 g/10 min, density: 0-885 g/cm3. [Propylene-Base Block Copolymer (A2) ] A2-1: Propylene-sthylene block copolymer obtained through a first-step polymerization and a second-step polymerization, which is a propylene-ethylene block copolymer containing 75% of a propylene homopolymer obtained in the first step and 25% of a propylene-ethylene WO 2004/071375 PCT/JP2004/001411 28 copolymer having an ethylene Content of 35% obtained in the second step; MFR: 1-0 g/10 min, xylene—soluble content: 26%. This capolymer A2-1 was produced as follows. (1) Preparation of Solid Catalyst In a nitrogen atmosphere, 5 6.8 g anhydrous magnesium chloride was completely dissolved at 120"C in 100 g of absolute ethanol, 500 mL of petrolatum oil "CP15N" produced by Idemitsu Kosan Co, Ltd. and 500 mL of silicone oil "KF96" produced by Shin-Etsu Silicone Co, Ltd. The resulting solution was stirred at 120'C and 5,000 revolutions/min for 2 minutes by using TK Homomixer' manufactured by Tokushu Kika Kogyo Co. Ltd. While continuing the stirring, the solution was transferred to 2 liter of anhydrous heptane by taking care not to exceed 00C, thereby precipitating a white solid. The white solid obtained was thoroughly washed with anhydrous heptane, vacuum-dried at room temperature and then partially deprived of ethanol in nitrogen stream. Subsequently, 30 g of MgCl2 I.2C2H5OH obtained as a spherical solid was suspended in 200 mL of anhydrous heptane and thereto, 500 mL of titanium tetrachloride was added dropwise over 1 hour with stirring at 00C. Thereafter, the suspension was heated and when reached 40°C, 4.96 g of diisobutyl phthalate was added. Then, the temperature was elevated to 100°C over about 1 hour. After the reaction at 1000C for 2 WO 2004/071375 PCT/JP2004/001411 29 hours, the solid portion was sampled by hot filtration, 500 mL of titanium tetrachloride was added to this reaction product, and the resulting mixture was stirred and then reacted at 120°C for 1 house. After the completion of reaction, the solid portion was again removed by hot filtration and washed 7 times with 1.0 liter of hexane at 600C and then 3 times with 1.0 liter of hexane at room temperature to obtain a solid catalyst. The titanium content in the solid catalyst component obtained was measured and found to be 2.36. mass%. (2) Prepolymerization Into a 3-1iter autoclave, 500 mL of n-heptane, 6.0 g of triethylaluminum, 0.99 g of cyclohexylmethyldimethoxy- silane and 10 g of polymerization catalyst obtained above were charged in a nitrogen atmosphere and stirred at a temperature of 0 to 5ºC for 5 minutes. Subsequently, propylene was supplied to the autoclave such that 10 g of propylene was polymerized per 1 g of the polymerisation catalyst, and prepolynterization was performed at a temperature of 0 to 5°C for 1 hour. The prepolymerization catalyst obtained was washed 3 times with 500 mL of n- heptane and then used in the following main polymerization. (3) Main Polymerization (First Step: Production of Propylene Homopolymer) Into an autoclave equipped with a stirrer and WO 2004/071375 PCT/JP2004/001411 30 having an inner volume of 60 liter, 2.0 g of a prepolymerization solid catalyst prepared as above, 11.4 g of triethylaluminum and 1.88 g of cyclohexylmothy Idimethoxysilane were charged in a nitrogen atmosphere. Thereto, 18 kg of propylene and hydrogen in an amount of 5,000 mol ppm based on the propylene were charged and after elevating the temperature to 70°C, the polymerization was performed for 1 hour. After 1 hour, unreacted propylene was removed to complete the polymerization. (Second Step: Production of Propylene-Ethylene Copolymer) After the completion of first-step polymerization, liquid propylene was removed and subsequently, hydrogen and an ethylene/propylene (26/74 (by mass)) mixed gas of 2.2 Nm3/hour were supplied at 75°C to have a hydrogen concentration of 40,000 mol ppm based on the total amount of ethylene, propylene and hydrogen, and then the polymerization was performed for 60 minutes. Thereafter, unreacted gas was removed to complete the polymerization. As a result, 6.6 kg of a polymer material mixture was obtained. To 100 parts by mass of the polymer material mixture obtained above, 0.30 parts by mass of phenol-base antioxidant and 0.1 part by mass of calcium stearate were added and mixed by a Henschel mixer at room temperature for WO 2004/071375 PCT/JP2004/001411 31 3 minutes The resulting mixture was melt-kneaded by an extruder having a screw aperture of 40 mm (Nakatani Model VSK 40-mm Extruder) at a cylinder temperature set to 210°C to obtain propylene- ethylene block copolymer (A2-1) pellets. A2-2: propylene-ethylene block copolymer obtained through a first-step polymerization and a second-step polymerization, which is a propylene-ethylene block copolymer containing 80% of a propylene-ethylene random copolyrner having an ethylene content of 2% obtained in the first step and 20% of a propylene-ethylene copolymer having an ethylene content of 50% obtained in the second step. MFR: 1.0 g/10 min, xylene-soluble content: 26%. This copolymer A2-2 was produced as follows. (First Step: Production of Propylene-Ethylene Random Copolymer) Into an autoclave equipped with a stirrer and having an inner volume of 60 liter, 2.0 g of a prepolymerization solid catalyst prepared in the same manner as in Production of A2-1, 11.4 g of triethylaluminum and 1,88 g of cyclohexylmethyldimethoxysilane were charged in a nitrogen atmosphere. Thereto, 18 kg of propylene, 120 L of ethylene and hydrogen in an amount of 6,500 mol ppm based on the propylene were charged and after elevating the WO 2004/071375 PCT/JP2004/001411 32 temperature to 70°C, the polymerization was performed for 1 hour. After 1 hour, unreacted propylene was removed. (Second Step: Production of Propylene-Ethylene Copolymer) The polymerization was performed in the same manner as in Production of A2-1 except that an ethylene/propylene mixed gas at a mass ratio of 44/56 and hydrogen in an amount of giving a concentration of 40,000 mol ppm were supplied and after performing the polymerization for 40 minutes, unreacted gas was removed to complete the polymerization. By this production method, 5.7 kg of a polymer material mixture was obtained. From this polymer material mixture, propylene- ethylene block copolymer (A2-2) pellets were obtained in the same manner as in Production of A2-1. [Etlrylene-Base Copolymer (B) ] B-l: Ethylene-1-butene copolymer (EBM2021P produced by JSR) ; MFR: 2.6 g/10 min, density: 0.86 g/cm3. B-2: Ethylene-1-butene copolymer (Tafmer A4085 produced by Mitsui Chemicals, Inc.); MFR: 6.7 g/10 min, density: 0.8 9 g/cm3, B-3: Ethylene-l-butane copolymer (EBM3021P produced by JSR); MFR: 2.6 g/10 min, density: 0.86 g/cm3. WO 2004/071375 PCT/JP2004/001411 33 B-4: Sthylene-1-butene copolymer (Engage 8480 produced by DuPont Dow Elastomers Japan K.K.), MFR: 2 g/10 min, density: 0.902 g/cm3. [Other Component] High-density polyethylene, density: 0-955 g/cm3, MFR; 3.0 g/10 min. PE2: Linear low-density polyethylene, density: 0-905 g/cm3, MFR; 1.0 g/10 min. HFR: MFR of each component of paropylene-base polymer (A) and HFR of ethylene-base copolymer (B) were measured at 230ºC with a load of 21.18 N according to JIS K 7210. MFR of high-detisity polyethylene and linear low-density polyethylene was measured at 190ºC with a load of 21.18 N according to JIS K 7210. Density: This was measured according to JIS K 7112 Method D. Xylene-soluble content: This was treasured by the method described in Mode for Carrying out the Invention. WO 2004/071375 PCT/JP2004/001411 34 Refractive index: This was measured by the method described in Mode for Carrying Out the Invention. The resin materials described above were blended at the compositional ratio shown in Table 1, mixed by Henschel mixer for 3 minutes and then melt-kneaded at temperature of 230ºC by using a single screw extruder to obtain pellets of polyolefin resin composition. The physical properties of this polyolefin resin composition are shown in Table 2- The polyolefin resin composition pellets obtained above were molded into a tubular film having an entire thickness of 250 pm by a water cooling inflation three- layer molding machine at a temperature of 230°C- Incidentally, in the case where the tubular film was a two- layer film, the inner layer was formed to a thickness of 20 pm, and in the case of a three-layer film, the inner layer and the outer layer both were formed to a thickness of 20 pm. Separately a single layer film was molded to have a thickness of 250 pm by a water cooling inflation molding machine. WO 2004/071375 PCT/JP2004/001411 35 WO 2004/071375 PCT/JP2004/001411 36 1) MFR (at 230ºC) of propylene-base polymer (A)/MFR (at 230°C) of ethylene-base copolymer (B) Measurement > Tubular films in the state that respective inner surfaces were superposed were cut into a length of 20 cm and a width of 20 cm and then the length direction and the width direction each was heat-sealed in a seal width of 10 mm. In the inside thereof, 500 mL of water was filled to produce a bag-shaped medical container. At this time, the heat sealing was performed by using a hot-plate heat- sealing machine (a heat sealer manufactured by Tester Sangyo Co. Ltd,) under a pressure of 0,4 MPa at a seal temperature or 170ºC for a sealing time of 1 second. The WO 2004/071375 PCT/JP2004/001411 37 obtained medical container was subjected to a sterilization treatment at 121ºC for 30 minutes and used as a sample for measurement of the following various physical properties. However, the sample for the evaluation of blocking resistance only was subjected to a sterilization treatment at 121ºC in the state that respective inner layers were almost contacted by filling 2 mL of water into the inside and extracting the inner air by means of a vacuum pump. The measurement results of the following various physical properties are shown in Table 3. [Heat Resistance] The appearance of the container after sterilization treatment was evaluated with an eye and judged as follows. o: No deformation and no crinkling. x: Deformed and many crinkles. [Impact Resistance] The container after sterilization treatment was cooled at 4°C , and five containers held horizontally were dropped on a hard floor from a height of 100 cm. The number of ruptured containers was counted. [Transparency] The container after sterilization treatment was measured on the light transmittance by using u-3300 WO 2004/071375 PCT/JP2004/001411 38 manufactured by Hitachi Ltd. according to Transparency Test in Test Methods for Plastic Containers of The Japanese Pharmacopoeia, 14th ed- [Blocking Resistance] The container after sterilization treatment was left standing at 23ºC for 24 hours and then inner surfaces wera pulled apart. The degree of power necessary for the separation and the separated surface state were observed with an eye and judged as follows. o: Readily separated. x; Not separated. WO 2004/071375 PCT/JP2004/001411 39 WO 2004/071375 PCT/JP2004/001411 40 The medical containers of Examples 1 to 9 were produced from a film comprising a polyolefin resin composition containing (A) a propylene-base polymer and (B) an ethylene-base polymer and moreover, the xylene- soluble portion of the polyolefin resin composition had a refractive index of 1,480 to 1.495, therefore, these containers were excellent in tht heat resistance, impact resistance, transparency and blocking resistance. On the other hand, in the medical containers of Comparative Examples 1, 2 and 4, the xylene-soluble portion of the polyolefin resin composition had a refractive index out of the range from 1.480 to 1.495 and therefore, the transparency was low. Furthermore, the medical container of Comparative Example 3 was produced from a film comprising a polyolefin resin composition of only propylene-base polymer (A) and morerecover, the xylene-soluble portion of the polyolefin resin composition had a refractive index out of the range from 1.480 to 1.435, therefore, the transparency and impact resistance were low. In the medical container of Comparative Example 3, the xylene-soluble portion of the polyolefin resin composition had a refractive index out of the range from 1.480 to 1.495 and therefore, the transparency was low. Moreover, a layer comprising a linear low-density WO 2004/071375 PCT/JP2004/001411 41 polyethylene was provided in the inner and outer sides, therefore, the heat resistance and blocking resistance were insufficient. INDUSTRIAL APPLICABILITY The medical container of the present invention has heat resistance high enough to enable sterilization at a temperature of 121°C or more and at the same time, exhibits excellent properties in all of the transparency, impact resistance, flexibility and blocking resistance. WO 2004/071375 PCT/JP2004/001411 42 1- A radical container produced from a film or sheet having at least one resin layer comprising a polyolefin resin composition, where in said polyolefin resin composition comprises (A) at least one propylene-base polymer selected from the group consisting of (Al) a propylene-base polymer composition as a mixture of (All) a propylene polymer and (A12) an ethylene-propylene copolymer elastomer, (A2) a propylane-base block capolymer, and (A3) a propylene-base block copolymer composition as a mixture of (A2) a propylene-bass block copolymer and (A12) an ethylene-propylene copolymer elastomer, and (B) an ethylene-base copolymer comprising an ethylene and at least one a-olefin having 4 or more carbon atoms, and the refractive index of the xylene- solubla portion is from 1-480 to 1.495. 2. The medical container as claimed in claim 1, wherein said polyolefin resin composition has a xylene- soluble portion content of 20 to 70 mass%. . 3. The medical container as claimed in claim 1, wherein in said polyolefin resin composition, the ratio (MFRA/MFRB) of the melt flow rate (MFRA) of propylene-base WO 2004/071375 PCT/JP2004/001411 43 polymer (A) to the melt flow rate (MFRB) of ethylene-base copolymer (B) is from 0.3 to 3.0. 4 . The medical container as claimed in any one of claims 1, wherein said film or sheet has a first high- density polyethylene layer comprising a high-density polyethylene and said first high-density polyethylene layer is disposed in the inner side. 5. The medical container as claimed in any one of claims 1, wherein said film or sheet has a second high- density polyethylene layer comprising a high-density polyethylene and said second high-density polyethylene layer is disposed in the outer side. 6. The medical container as claimed in claim 4, wherein said first high-density polyethylene layer contains 20 mass% or more of a high-density polyethylene having a density of 0.950 g/cm3 or more. 7. The medical container as claimed in claim 5, Therein said second high-density polyethylene layer contains 2 0 mass% or more of a high-density polyethylene having a density of 0.950 g/cm3 or more. WO 2004/071375 PCT/JP2004/001411 44 8 . The medical container as claimed in any one of claims 1, wherein the thickness of the resin layer comprising a polyolefin resin composition occupies 60% or more of the entire thickness of the film or sheet. 45 A medical cntainer produced from a film or sheet having at least one resin layer comprising a polyolefin resin composition wherein the polyolefin resin composition comprises (A) at least one propylene-base polymer selected from the group consis1ing of (A1) a specfic propylene-base polymer and (A3) a specific propylene-base block copolymer composition, and (B) an ethylene-base copolymer comprising on elhylene and at least one a-plefin having 4 or more carbon atoms, and the refractive index of the xylene-soluble portion is from 1.480 to 1.405.

Full Text

MEDICAL CONTAINER
TECHNICAL FIELD
The present invention relates to a medical
container, which is used by filling blood, medicament or
the like in it. The application claims the benefit of U.S.
provisional Application No. 60/455,564, filed on March 19,
2003, which is hereby incorporated by reference, and is
based on Japanese Patent Application No. 2003-033440 filed
on February 12, 2003, which is hereby incorporated by
reference.
BACKGROUND ART
A medical container for filling blood, medicament
or the like is demanded not only to be, needless to say,
hygienic but also to have high heat resistance capable of
enduring sterilization treatment at a high temperature,
transparency to enable the check of mingling of a foreign
material or visual inspection of the change by blending of
a medicament, impact resistance sufficiently high. to
prevent the bag from rupturing at falling on handling or at
packaging and transportation, flexibility for facilitating
the discharge of contents, and blocking resistance not to

WO 2004/071375 PCT/JP2004/001411
2
readily cause separation of film or sheet at the production
of a medical container or not to contact a medicament-
containing medical container with its outer packaging bag.
In particular, demands are increasing for a medical
container which can be sterilized at a high temperature of
1210C or more having a strong sterilization power, can
satisfy all of heat resistance, transparency, impact
resistance, flexibility and .blocking resistance, and can be
industrially produced.
For the medical container, a soft polyvinyl
chloride, a polyethylene base material such as high-
pressure low-density polyethylene, linear low-density
polyethylene, high-density polyethylene and ethylens-vinyl
acetate copoiymer, and a polypropylene-bass material such
as propylene homopolymer and random or block copolymer of
propylene and other a-olefin have been heretofore used.
The vinyl chloride-base resin is excellent in the
balance of heat resistance, transparency, flexibility and
impact resistance but this resin has a problem in that a
plssticizer used for imparting the performance dissolves
out into a medicament solution or food.
Out of polyethylene-base materials, the high-
pressure low-density polyethylene is deficient in that the
heat resistance or impact strength is poor. As for the
linear low-density polyethylene, a. .polyethylene. having a

WO 2004/071375 PCT/JP2004/001411
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low density is used so as to enhance the transparency or
flexibility, but when the density is decreased,
insufficient heat resistance is liable to result and
furthermore, problems arise, for example, the low molecular
weight component of the resin lowers the blocking
resistance of the container or dissolves out into a
medicament. The ethylene-vinyl acetate copolymer is
excellent in the transparency but disadvantageously low in
the heat resistance. The high-density polyethylene is
deficient in that the transparency and impact resistance
are poor. Thus, polyethylene-base materials cannot satisfy
a good balance of heat resistance, transparency and impact
resistance.
Out of polypropylene-base materials, the propylene
homopolymer and propylene random copolyiner are excellent in
the transparency but inferior in the blocking resistance,
and the propylene block copolymer is poor in the balance of
flexibility, impact resistance and transparency.
For solving these problems, with respect to the
medical container using a polyethylene-base material, a
multilayer container having a layer mainly comprising a
high-density polyethylene and a layer mainly comprising a
linear low-density polyethylene has been proposed (see, for
example, JP-&-5-293160 (the term "JP-A" as used herein
means an "unexamined published Japanese patent

WO 2004/071375 PCT/JP2004/001411
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application").
Furthermore, a polyethylene-base material produced
by using a metallocene-base catalyst and having excellent
Impact resistance and transparency has been recently
developed and studies are being made to apply this material
to a medical container. Also, a method of using these
materials in combination and stacking two, three or more
layers has been proposed (see, for example, JP-A-7-125738) .
On the other hand, with respect to the medical
container using a polypropylene-base material, a technique
of using a resin composition comprising a propylene-base
random copolymer having an a-olefin content of 5 to 8 mass%
and a mixture of specific sthylene-propylene and fethylene—
butene random copolymets to obtain a container excellent in.
the heat resistance, transparency, impact resistance and
the like has been disclosed, (see, for example, JF-A-B-
2317 97).
Also, a container having a constitution such that a
layer comprising a propylens homopolymer or propylene-a-
olefin random capolymer containing from 0 to - 30% of a
polyethylene-base resin is provided as the outer layer and
a three-layer laminate comprising a mixture of a propylene -
homopolymer or a propylene/a-olefin random copolymer and an
olefin-base elastomer or the like is provided as the
intermediate layer has been proposed (see, for ex ample, JP-

WO 2004/071375 PCT/JP2004/001411
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A-9-26294B).
Furthermore, a technique of using a resin
composition comprising a crystalline polypropylene and a
propylene/a-olefin copolymer having a specific limiting
viscosity ratio, and forming a specific morphology at the
thermoforntatian has been proposed (see, for example, JP-A-
10-316810).
However, the container described in JP-A-5-293160
cannot always hold a sufficient transparency after
stetilization at a temperature of 121°C or more and fails
in fully satisfying the requirement on the market that
sterilination can be performed at a higher temperature in a
shorter time.
Also in the case of using the laminate described in
JF-A-7-125738, the transparency after high-temperature
stetilization of 121°C or more is not sufficiently high and
moreover, the impact resistance is also insufficient to
readily cause rupture at the heat-welded part on falling of
the container, therefore, improvements are demanded.
Furthermore, a film or sheet obtained by a water cooling
inflation method, a T-die method or the like has
particularly a smooth surface and readily causes blokcing
of films or sheets with each other and when these are
pulled apartr a whitened flaw remains on the surface and
the outer appearance is seriously deteriorated in some

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cases,
The resin composition described in JP-A-8-2 31787
has a problem that the heat resistance and transparency are
still insufficient.
The container described In JP-A-9-262'948 does not
have a sufficiently high impact resistance and
particularly, in the case of a container having a volume of
1 L or more, the impact resistance is not satisfied from.
the standpoint of preventing rupture on falling.
The method described in JP-A-10-316810 has a
problem in that not only the impact resistance or the
thermal shrinkage percentage at the heat sterilization
expresses strong anisotropy due to orientation of the
domain but also stable production while keeping the quality
can be hardly attained because the formation of specific
morphology is sensitive to the molding conditions or the
like.
The present invention has been made under these
circumstances and an object of the present invention is to
provide a medical container having heat resistance high
enough to enable sterilisation at a temperature of 121°C or
more and exhibiting excellent properties in all of ths
transparency, impact resistance, flexibility and blocking
resistance.

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DISCLOSURE OF INVENTION
As a result of extensive investigations, the
present inventors have found that the above-described
object can be attained by a medical container using a
polyalefin resin composition containing specific
components, where the xylene-soluble portion has a
refractive index within a specific range. Based on this
finding, the following medical container has been
accomplished.
More specifically, the medical container of the
present invention is produced from a film or sheet having
at least one resin layer comprising a polyolefin reain
composition, wherein the polyolefin resin composition
comprises (A) at least one propylene-base polymer selected
from the group consisting of (Al) a propylene-base polymer
composition as a mixture of (All) a propylene polymer and
(A12) an ethylene-propylene copolymer elastomer, (A2) a.
propylene-base black copolymer, and (A3) a psropylene-bsse
block copolymer composition as a mixture of (A2) a
propylene-base block copolymar and (A12) an ethylene-
propylene copolymer elastomer, and (B) an ethylene-base
copolymer comprising an ethylene end at least one a-olefin
having 4 or more carbon atoms, and the refractive index of
the xylene-soluble portion is from 1.480 to 1.4 95.
In the medical container of the present invention,

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8
the polyolefin, resin composition preferably has a xylene-
soluble portion content of 20 to 70 mass%.
Furthermore, in the polyolefin resin composition,
the ratio (MFRA/MFRg) of the melt flow rate (MFRA) of the
propylene-base polymer (A) to the melt flow rate (MFRB) of
ths ethylene-base copolymer (B) is pteferably front 0.3 to
3.0.
The medical container of the present invention may
also be produced such that the film or sheet has a first
high-density polyethylene layer containing a high-density
polyethylene and this first high-density polyethylene layer
is disposed in the inner side.
The medical container of the present invention may
also be produced such that the film or sheet has a second
high-density polyethylene layer containing high-density
polyethylene and this second high-density polyethylene
layer is disposed in the outer side.
In the case where the film or sheet has a first
high-density polyethylene layer, the first high-density
polyethylene layer preferably contains 20 mass% or more of
a high-density polyethylene having a density of 0.950 g/cm3
or. more.
In the case where the film or sheet has a second
high-density polyethylene layer, the second high-density
polyethylene, layer preferably contains 20 mass% or more of

WO 2004/071375 PCT/JP2004/001411
9
a high-density polyethylene having a density of 0.950 g/cm3
or more.
In the medical container of the present invention,
the thickness of the resin layer comprising a polyolefin
resin composition preferably occupies 60% or more of the
entire thickness of the film or sheet.
In the present specification, unless otherwise
indicated, MFR is a value measured at 230°C with a load of
21.18 N according to JIS K 7210.
The medical container of the present invention is.
presumed to have excellent properties because of the
following reasons. That is, a resin component having high
crystallinity is considered to impart heat resistance to
the resin and a rubber-analogous resin component having low
crystallinity is considered to impart the impact
resistance. Usually, the refractive index greatly differs
between a component having high crystallinity and a
component having low crystallinity and therefore, a mixture
of these components is decreased in the transparency,
However, in the polyolefin resin composition for use in the
medical container of the present invention, the component
having low crystallinity has a specific refractive index.
More specifically, the refractive index of the xylene-
soluble portion presumed to contain a low crystallinity
component is in a specific range and the difference in the

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refractive index between the low crystallinity component
and the high crystallinity component is considered to
become small, so that heat resistance and impact resistance
can be imparted without decreasing the transparency. By
using a film or sheet having at least one layer comprising
this polyolefin resin composition, a medical container
excellent in the transparency, impact resistance, heat
resistance, flexibility and blocking resistance can be
obtained,
BEST MODE FOR CARRYING OUT THE INVENTION
The present invention is described in detail below.
The medical container of the present invention is
produced from a film or sheet having at least one resin
layer comprising a polyolefin resin composition and has,
for example, a bag form.
The polyolefin composition contains (A) a
propylene—base polymer and (B) an ethylene-base copolymer
and the xylens-soluble portion thereof has a refractive
index of 1.480 to 1.4 95.
The propylene-base polymer (A) is at least one
member selected from the group consisting of (A1) a
propylane-base polymer composition as a mixture of (All) a
propylane polymer and (Al2) an ethylene-propylene copolymer
elastomer, (A2) a propylene-base block copolymer, and (A3)

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a propylene-base block copolymer composition as a mixture
of (A2) a propylene-base block copolymsr and (A12) an
ethylene-propylene copolymer alastomer.
The propylene polymer (All) (hereinafter, sometimes
simply referred to as a component (All) contained in the
propylene-base polymer composition (Al) is a propylene
homopolymer or a propylene-ethylene random polymer.
comprising propylene and ethylene and having an ethylene
content of 5 mass% or less.
The melt flow rate thereinafter referred to as
"MFR") of the propylene polymer (All) is not particularly
limited but this is preferably from 0.1 to 50 g/10 min,
more preferably from 0.5 to 20 g/10 min, still more
preferably from 0.5 to 5 g/l0 min, because the mold.
processability, heat iresistance and impact resistance all
can be enhanced.
The ethylene-propylene copolymer elastomer (A12)
(hereinafter, sometimes simply referred to as a componsnt
(A12) contained in the propylene-base polymer composition
(Al) is a copolymer elastomer substantially comprising only
ethylene and propylene and having a propylene-originated
unit content of 50 to 85 mass%. The MFR of the ethylene-
propylene copolymer elastomer (A12) is not particularly
limited but this is preferably from 0.1 to 50 g/10 min,
more preferably from 0.5 to 20 g/10 min, still more

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preferably from 0.5 to 5 g/10 min, because the mold
processability, heat resistance and impact resistance all
can be enhanced.
The proportion of the propylene polymer (All)
occupying in the propylene-base polymer composition (Al )
is, in view of high heat resistance, preferably from 90 to
30 mass%, more preferably from 85 to 50 mass%, still more
preferably from 60 to 65 mass, per 100 mass% in total of
components (All) and (A12).
The propylerie-base block copolymer (A2)
(hereinafter, sometimes simply referred to as a component
(A2) is a propylene-ethylene block copolymer obtained by
melt-kneading a polymer material mixture produced through a
first step of polymerizing a propylene homopolymer or a
propylene and ethylene copolymer having an ethylene content
of less than 5 mass% and subsequently a second step of
polymerizing a propylene and ethylene copolymer having an
ethylene content of 10 to 70 mass% in a polymerization
vessel consisting of at least two vessels, which may be the
same as or different from that used in the polymerization
of the first step.
In the propylene-base block copolymer (A2), the
proportion of the polymer produced in the first step is not
particularly limited but this is preferably from 90 to 30
mass% and in view of profitability in the production, more

WO 2004/071375 PCT/JP2004/001411
13
preferably from 85 to 50 mass%, still more preferably from
80 to 55 mass%.
The ethylene content of the polymer obtained in the
first step is usually less than 5 mass%, preferably less
than 4 mass, more preferably less than 1.5 mass%. If the
ethylene content of the polymer obtained in the first step
is 5 mass% or more, the heat resistance at sterilization is
liable to decrease.
The ethylene content of the polymer obtained in the
second step is usually from 10 to 70 mass%, preferably from
20 to 60 mass%. If the ethylene content of the polymer
obtained in the second step is less than 10 mass%, the
impact resistance readily decreases, where as if it exceeds
70 mass%, the transparency sometimes decreases.
The catalyst used in the polymerization of the
first and second steps is not particularly limited and, for
example, a Ziegler Natta catalyst or a (netallocene
catalyst is suitably used. The process for the
polymerization may be any of a bulk method, a solution
method, a slurry method, a vapor phase method and a
combination thereof.
The propylene-base block copolymer composition (A3)
(herein after), sometimes simply preferred to as a component
(A3) is a mixture of the above described propylene-base
block copolymer (A2) and an ethylenie-propylene copolymer

WO 2004/071375 PCT/JP2004/001411
14
elastomer (A12) The mixing ratio of (A2) and (A12) is, in
view of high heat resistance, preferably from 90:10 to
50:50, more preferably from 80:20 to 50:50.
Among those components (Al), (A2) and (A3), the
propylene-base polymer (A) is preferably the component
(A2) , namely, a propylane-base block copolymer, because
this component expresses stable performance and is
inexpensive.
The MFR of the propylene-base polymer (A) is not
particularly limited but this is preferably from 0.1 to 50
g/10 min, more preferably from 0.5 to 20 g/10 min, still
more preferably from 0.5 to 5 g/10 min, because the mold.
processability, heat resistance and impact resistance all
can be enhanced.
The ethylene-base copolymer (B) (hereinafter,
sometimes simply referred to as component (B) is a
copolymer consisting of an etnylene and at least one a-
olefin having 4 or more carbon atoms and mainly comprising
an ethylene-originated unit (50 mass% or more). Examples
of the a-olefin include l-butene, 1-pentene, 4-methyl-1-
pentene, 1-hexene and 1-octene. As the ethylene-base
copolymer (B) one or more of these copolymers is (are )
used.
The density (according to JIS K 7112 Method D) of
the ethylene-base copolymer (B) is usually 0.915 g/cm3 or

WO 2004/071375 PCT/JP2004/001411

15
less and in view of high transparency, preferably less than
0.905 g/cm3, more preferably less than 0,900 g/cm3.
The MFR of the ethylene-base copolymer (B) is not
particularly limited but this is preferably from 0.1 to 20
g/10 min, because the mold processability, heat resistanoe
and impact resistance all can be enhanced.
In the polyolofin resin composition containing
these components (A) and (B) , the refractive index of the
xylene-soluble portion which dissolves in xylene at
ordinary temperature is from 1.480 to 1.495, preferably
from 1.480 to 1,490. When the refractive index of the
xylene-soluble portion falls in this range, both the impact
resistance and the transparency can be satisfacrtorily high-
If the refractive index of the xylene-saluble portion is
less than 1.490 or exceeds 1.495, the transparency
decreases.
The refractive index at the xylene-soluble portion
becomes higher as the density of the ethylene-base
copolymer (B) increases, and becomes lower as the density
of the ethylene-base copolymer (B) decreases.
The proportion and re refractive index of the xylene-
soluble portion are determined as follows.
A specimen (10 g) of a polyolefin resin composition
is added to 1 L of an orthoxylene and after the temperature
is elevated to a boiling temperature (about 1350C) by

WO 2004/071375 PCT/JP2004/001411
16
stirring the solution under heating, the specimen is
completely dissolved over 30 minutes or more. After
confirming the complete dissolution with an eye, the
solution is left standing with stirring to cool to 100°C or
less and held in a constant-temperature bath kept at 25°C
for 2 hours. Thereafter, the precipitated component
(xylene-insoluble portion xi) is separated by filtration
through a filter paper to obtain a filtrate. The obtained
filtrate is heated at a temperature of 1400C to distill out
xylene in a nitrogen stream (about 1 L/min) and the residue
is dried to obtain a xylene-soluble portion Xs . At this
time, the drying of xylene-insoluble portion and xylene—
soluble portion is performed at 60°C under reduced pressure
for one day.
The proportion of the xylene-soluble portion is
determined by (mass of Xs/mass of specimen).
The xylene-soluble portion is composed of a low
molecular- material in the polyolefin resin composition, a
non-crystalline molecule, and the like.
In the measurement of refractive index of the.
xylene-soluble portion, the xylene-solable portion is
preheated at 230°C for 5 minutes in a press-molding
machine, then degassed for 30 seconds, pressed at 6 MPa for
1 minute and cooled at 300C for 3 minutes to obtain a film.
having a thickness of 50 to 80 pn. Subsequently, a

WO 2004/071375 PCT/JP2004/001411
17
specimen comprising this film is left standing at ordinary
temperature for 24 hours and then measured on the
refractive index for sodium D line at 23°C by an Abbe
refractive index meter (manufactured by Atago Co. Ltd.)
using ethyl salicylate as the intermediate solution.
The content of the xylene-soluble portion in the
polyolefin resin composition, is preferably from 10 to 70
mass%, inore preferably from 20 to 70 mass%, if the xylene-
soluble portion content is less than 10 mass% the impact
strength at low temperatures is liable to be insufficient,
whereas if it exceeds 70 mass%, the heat resistance is
sometimes not satisfied.
In the polyolefin resin composition, the ratio
(MPRA/MFRB) of the MFR (MFRA) of the propylens-base polymer
(A) to the MFR (MFRB) of the ethylene-bass copolymsr (B) is
preferably from 0.3 to 3.0, more preferably from 0.3 to
2.5, still more preferably from 03 . to 2.0. If the MFR
ratio is less than 0.3, the impact resistance at low
temperatures is liable to he insufficient, whereas if it
exceeds 3.0, fish eye is readily generated on the film to
impair the outer appearance.
The proportion of the component (A) in the
polyolefin resin composition is not particularly limited as
long as the refractive index of the xylene-soluble portion
is in the rangs from 1.480 to 1.495, but in view of higher

WO 2004/071375 PCT/JP2004/001411
18
heat resistance, this is-usually on the order of 40 to 90
mass%, preferably from 50 to 70 mass%.
In the polyolefin resin composition, another
polymer may be blended within the range of not impairing
the object of the present invention. Specific examples of
the another polymer which can be blended in the polyolefin
resin composition include polyethylene-base resins such as
high-pressure low-density polyethylene, linear low-density
polyethylene and high-density polyethylene, various
atyrene-base elastomer such as styrene-butadiene elastomer
and hydrogenated product thereof, random copalymers of
propylene and an a-olefin having 4 or more carbon atoms, an
ethylene-vinyl acetate copolymer, copolymers of ethylene
and a (meth) acrylic acid (ester), and olefln-base thernio-
plastic elastomers. The proportion of this another polymer
contained is preferably less than 40 mass% per 100 ruass% of
the polyolefin resin composition.
Examples of the method for producing the polyolefin
resin composition include a melt-kneading method. In the
case , of melt-kneading the components (Al), (A2) and (B),
for example, the component (A2) may be meIt-mixed, after
melt-mixing the components (All), (R12) and (B) . At this
time, the order of melt-mixing the components (All), (A12)
and (B) is not particularly limited and the component (B)
may be melt-kneaded, after obtaining the component (Al) by

WO 2004/071375 PCT/JP2004/001411
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melt-kneading the components (All) and (A12) , or the
components (All) , (A12) and (B) may be simultaneously melt-
kneaded. For the melt-kneading, a single-screw or twin-
screw extruder can be usually used.
The thus-produced polyolefin resin composition
contains (A) a propylene-base polymer and (B) an ethylene-
base copolymer and the xylene-soluble portion in the
polyolefin-base resin composition, which is presumed to be
a low crystalline component, has a refractive index of
1.480 to 1.495, so that the resin composition can be
excellent not only in the heat resistance but also in all
of the transparency, impact assistance, flexibility and
blocking resistance.
The film ex sheet constituting ths medical
container has at least one resin laysr comprising the
above—described polyclefin resin composition. Such a film
or sheet is formed by, for example, an air-cooling or
water-cooling inflation molding method or a T-die method.
This film or sheet may be a single-layer film or
sheet composed o£ a resin layer comprising the polyolefin
resin composition OJC may be a multilayer film or sheet
including a resin layer comprising the polyolefin resin
composition.
The thickness of the film or sheet is usually from
30 to 1,000 pm and in view of flexibility and strength.

WO 2004/071375 PCT/JP2004/001411
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preferably from 50 to 100 pm more preferably from 100 to
500 pm.
In the case where the film or sheet is composed of
two or more layers, by taking account of transparency,
impact resistance and heat resistance, the thickness of the
resin layer comprising the polyolefin resin composition
preferably occupies 60% or more of the entire thickness of
the film or sheet.
In the case of a multilayer film or sheet, the
multilayer film can be produced by an extrusion lamination
method of laminating a single layer or multilayer melt
resin including at least one resin layer comprising the
above-described polyolefin resin composition on a film
fo rised of the same or different material, or by a dry
lamination method of laminating a film formed of the same
ot different material and a single layer or multilayer body
including at least one resin layer comprising the above-
described polyolefin resin composition, through an
adhesive.
The medical container is produced from a film or a
sheet and has, for example, a bag form. This medical
container may be a single chamber container or a container
with multiple chambers divided by an easily separable
partition part or a resin-made partition member. If
desired, the medical container may be fixed with a mouth

WO 2004/071375 PCT/JP2004/001411
21
member for injection or ejection or with another medicament
container for the purpose of mixed infusion, by heat-
sealing or the like.
Examples of the method for producing the medical
container include a method of cutting the above-described
film or sheet and heat-sealing the marginal parts thereo
to form a desired container shape. In this method, the
order of cutting and heat-sealing may be reversed.
The heat-sealing method at the formation of the
film or sheet into a container shape is not particularly
limited and, for example, welding methods such as hot-plate
sealing method, high-frequency sealing method and
ultrasonic wave sealing method can be employed. However,
the heat-sealing conditions such as heat-sealing
temperature and shape of the heat- sealed part are
preferably set not to impair the performance of the medical
container, such as outer appearance and impact resistance.
The medical container can be easily produced when
it is formed of a single layer film or sheet, and is more
enhanced in the hygiene heat resistance and the like when,
it is formed of a multilayer film or sheet.
Particularly, when the film or sheet is a
multilayer body having a first high-density pclyethylene
layer containing a high-density polyethylene and the
medical container is produced by disposing the first high-

WO 2004/071375 PCT/JP2004/001411
22
density polyethylene layer in the inner side, a medicament
comes into contact with this first high-density
polyethylene layer and therefore, not only the hygiene is
more improved but also the impact resistance at low
temperatures, the appearance of heat-sealed part, the
strength and the like are enhanced.
Also, when the film or sheet is a multilayer body
having a second high-density polyethylene layer containing
a high-density polyethylene and the medical container is
produced by disposing this second high-density polyethylene
layer in the outer side, the impact resistance at low
temperatures is enhanced. In particular, a medical
container produced by disposing the second high-density
polyethylene layer as the outermost layer is preferred,
because blocking with the outer packaging material of the
medical container hardly occurs.
Accordingly, in a more preferred embodiment, the
midical container has a high-density polyethylene layer in
the inner and outer sides.
Furthermore, when the film or sheet is a multilayer
body having a layer containing a propylene-ethylene random
copolymer and the medical container is produced by
disposing this propylene-ethylene random copolymer-
containing layer in the inner side and/or in the outer
side, the heat resistance is more enhanced.

WO 2004/071375 PCT/JP2004/001411
23
The high-density polyethylene contained in the
first high-density polyethylene layer and the second high-
density polyethylene layer is an ethylene homopolymer or an
ethylene a—olefin copolymer of ethylene and a slight
amount of a-olefin having from 3 to 12 carbon atoms.
Examples of the a-olefin in the ethylene a-olefin copolymer
include propylene, l-butene, 1-pentene, 1-hsxene, 4-methyl-
1-pentene, 1-octene, 1-decene and l-dodecene. These are
used individually or in combination of two or more. Among
these, 1-butene, 1-pentene, 1-hexene, 4-methyl-l-pentene
and 1-octene are preferred.
Such a high-density polyethylene is produced by
various processes such as slurry method, vapor phase method
and solution method, preferably using a ziegler Natta
catalyst or a metallocene catalyst.
The density (according to JIS K 7112 Method D) of
this high-density polyethylene is usually 0.940 g/cam3 or
mote, preferably 0.950 g/cm3 or more, more preferably 0.-955
g/cm3 or more. If the density is less than 0.940 g/cm3,
insufficient heat resistance results in some cases and
deformation, shrinkage or reduction of transparency may
occur at the sterilization at a temperature exceeding
121°C.
The HFR (at 1900C with a load of 21-18 N according
to JIS K 7210) of the high-detisity polyethylene is

WO 2004/071375 PCT/JP2004/001411
24
approximately from 0.1 to 50 g/10 min, preferably from 0.5
to 20 g/10 min. With an MFR of approximately from 0.1 to
50 g/10 min, an appropriate melt tension can be obtained at
the molding and a film or sheet can be easily formed.
In the first and second high-density polyethylene
layers, another polymer may be blended within the range of
not impairing the objet of the present invention. Specific
examples of the another polymer include polyethylene resins
such as high-pressure low-density polyethylene and linear
low-density polyethylene, polypropylene resins such as
propylene homopolymier, propylene a-olefin random copolymer
and propylene a-olefin block copolymer, various styrene-
base elastomers such as styrene-butadiene elastomer,
ethylene -.propylene elastomer, an ethylene-vinyl acetate
copolymer, copolymers of ethylene and (meth) acrylic acid
(ester) , and olefin—base thermoplastic elastomers. The
another polymer is blended for the purpose of, for example,
adjusting the peel strength, at the marginal part of a
medical container or at the easily separable partition part
of a multiple chamber container.
In the case of blending another polymer, the high-
density polyethylene having a density of 0,950 g/cm3 or
more is preferably contained in an amount of usually 20
mass% or more, preferably 30 mass% or more, more preferably
70 mass% or more, still more preferably 90 mass% or more in

WO 2004/071375 PCT/JP2004/001411
25
each of the first and second high-density polyethylene
layers. As long as the high-density polyethylene having a
density of 0.950 g/cm3 or more is contained in an amount of
20 mass% or more, heat sterilization at 1210C or more can
be performed even when the first or second high-density
polyethylene layer is provided, and moreover, the blocking
resistance of film is more enhanced.
The preferred thickness of each of the first and
second high-density polyethylene layers varies depending on
the high-density polyethylene content but when the high-
density polyethylene is contained in an amount of 90 mass%
or more, the thickness is preferably from 5 to 40 pm.
The finally obtained medical contained is used by
filling a medicament and then subjecting it to steam
sterilization under high pressure. The steam sterilisation
temperature is not particularly limited but this is
generally from 100 to 140°C. Other known sterilization
methods such as ultraviolet ray and electron beam can also
be used in combination with the high-temperature high-
pressure heat sterilization.
The thus-obtained medical container is produced
from a film or sheet comprising the above-described
polyolefin-base resin composition and therefore, exhibits
excellent property not only in the heat resistance but also
in all of the transparency, impact resistance, flexibility

WO 2004/071375 PCT/JP2004/001411
26
and blocking resistance, in particular, even when
sterilized at 121°C or more having a high sterilization
effect, excellent property is exhibited in all of the
transparency, impact resistance, flexibility and blocking
resistance and therefore, this medical container is useful.
In any of the resin materials for use in the
medical container, commonly employed known, additives can be
appropriately blended within the range of not impairing the
effect of the present invention, if desired, such as
antistatic agent, antioxidant, lubricant, anti-blocking
agent, anti-clouding agent, nuelear agent, organic and
inorganic pigments, ultraviolet absorbent, dispersing agent
and reinforcing agent (e.g., talc, calcium carbonate).
However, the blending amount thereof must be within, the
range admitted in the medical field and in particular,
these additives are preferably not blended in a layer which
comes into direct contact with the contents.
Examples
The present invention is described in greater
detail below by referring to Examples, however, the present
invention is not limited to these Examples, In the
following description, unless otherwise indicated, the
percentage "%" is on a mass basis.

WO 2004/071375 PCT/JP2004/001411
27

(Examples 1 to 9 and Comparative Examples 1 to 5)
The resine used in Examples and Comparative
Examples are as follows.
[Propylene Polymer (All)]
All-1:
Propylene homopolymer (PL300A produced by
SunAllomer Ltd.); MFR: 1.7 g/10 min, xylene-soluble
content: 0.5%.
All-2:
Propylene-ethylene random copolymer having an
ethylene content of 3 mass% (PB222A produced by SunAllomer
Ltd.); MFR; 0.8 g/10 min, xylene -soluble content: 3.1%.
[Ethylena-Propyleine Copolymer Elastomer [A12)]
A12-1:
Ethylene-propylene copolymer (Tafmer P0630 produced
by Mitsui chemicals, Inc.); MFR: 0.7 g/10 min, density:
0-885 g/cm3.
[Propylene-Base Block Copolymer (A2) ]
A2-1:
Propylene-sthylene block copolymer obtained through
a first-step polymerization and a second-step
polymerization, which is a propylene-ethylene block
copolymer containing 75% of a propylene homopolymer
obtained in the first step and 25% of a propylene-ethylene

WO 2004/071375 PCT/JP2004/001411
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copolymer having an ethylene Content of 35% obtained in the
second step; MFR: 1-0 g/10 min, xylene—soluble content:
26%. This capolymer A2-1 was produced as follows.
(1) Preparation of Solid Catalyst
In a nitrogen atmosphere, 5 6.8 g anhydrous
magnesium chloride was completely dissolved at 120"C in 100
g of absolute ethanol, 500 mL of petrolatum oil "CP15N"
produced by Idemitsu Kosan Co, Ltd. and 500 mL of silicone
oil "KF96" produced by Shin-Etsu Silicone Co, Ltd. The
resulting solution was stirred at 120'C and 5,000
revolutions/min for 2 minutes by using TK Homomixer'
manufactured by Tokushu Kika Kogyo Co. Ltd. While
continuing the stirring, the solution was transferred to 2
liter of anhydrous heptane by taking care not to exceed
00C, thereby precipitating a white solid. The white solid
obtained was thoroughly washed with anhydrous heptane,
vacuum-dried at room temperature and then partially
deprived of ethanol in nitrogen stream. Subsequently, 30 g
of MgCl2 I.2C2H5OH obtained as a spherical solid was
suspended in 200 mL of anhydrous heptane and thereto,
500 mL of titanium tetrachloride was added dropwise over 1
hour with stirring at 00C. Thereafter, the suspension was
heated and when reached 40°C, 4.96 g of diisobutyl
phthalate was added. Then, the temperature was elevated to
100°C over about 1 hour. After the reaction at 1000C for 2

WO 2004/071375 PCT/JP2004/001411

29
hours, the solid portion was sampled by hot filtration,
500 mL of titanium tetrachloride was added to this reaction
product, and the resulting mixture was stirred and then
reacted at 120°C for 1 house. After the completion of
reaction, the solid portion was again removed by hot
filtration and washed 7 times with 1.0 liter of hexane at
600C and then 3 times with 1.0 liter of hexane at room
temperature to obtain a solid catalyst. The titanium
content in the solid catalyst component obtained was
measured and found to be 2.36. mass%.
(2) Prepolymerization
Into a 3-1iter autoclave, 500 mL of n-heptane, 6.0
g of triethylaluminum, 0.99 g of cyclohexylmethyldimethoxy-
silane and 10 g of polymerization catalyst obtained above
were charged in a nitrogen atmosphere and stirred at a
temperature of 0 to 5ºC for 5 minutes. Subsequently,
propylene was supplied to the autoclave such that 10 g of
propylene was polymerized per 1 g of the polymerisation
catalyst, and prepolynterization was performed at a
temperature of 0 to 5°C for 1 hour. The prepolymerization
catalyst obtained was washed 3 times with 500 mL of n-
heptane and then used in the following main polymerization.
(3) Main Polymerization
(First Step: Production of Propylene Homopolymer)
Into an autoclave equipped with a stirrer and

WO 2004/071375 PCT/JP2004/001411
30
having an inner volume of 60 liter, 2.0 g of a
prepolymerization solid catalyst prepared as above, 11.4 g
of triethylaluminum and 1.88 g of
cyclohexylmothy Idimethoxysilane were charged in a nitrogen
atmosphere. Thereto, 18 kg of propylene and hydrogen in an
amount of 5,000 mol ppm based on the propylene were charged
and after elevating the temperature to 70°C, the
polymerization was performed for 1 hour. After 1 hour,
unreacted propylene was removed to complete the
polymerization.
(Second Step: Production of Propylene-Ethylene Copolymer)
After the completion of first-step polymerization,
liquid propylene was removed and subsequently, hydrogen and
an ethylene/propylene (26/74 (by mass)) mixed gas of
2.2 Nm3/hour were supplied at 75°C to have a hydrogen
concentration of 40,000 mol ppm based on the total amount
of ethylene, propylene and hydrogen, and then the
polymerization was performed for 60 minutes. Thereafter,
unreacted gas was removed to complete the polymerization.
As a result, 6.6 kg of a polymer material mixture was
obtained.
To 100 parts by mass of the polymer material
mixture obtained above, 0.30 parts by mass of phenol-base
antioxidant and 0.1 part by mass of calcium stearate were
added and mixed by a Henschel mixer at room temperature for

WO 2004/071375 PCT/JP2004/001411

31
3 minutes The resulting mixture was melt-kneaded by an
extruder having a screw aperture of 40 mm (Nakatani Model
VSK 40-mm Extruder) at a cylinder temperature set to 210°C
to obtain propylene- ethylene block copolymer (A2-1)
pellets.
A2-2:
propylene-ethylene block copolymer obtained through
a first-step polymerization and a second-step
polymerization, which is a propylene-ethylene block
copolymer containing 80% of a propylene-ethylene random
copolyrner having an ethylene content of 2% obtained in the
first step and 20% of a propylene-ethylene copolymer having
an ethylene content of 50% obtained in the second step.
MFR: 1.0 g/10 min, xylene-soluble content: 26%. This
copolymer A2-2 was produced as follows.
(First Step: Production of Propylene-Ethylene Random
Copolymer)
Into an autoclave equipped with a stirrer and
having an inner volume of 60 liter, 2.0 g of a
prepolymerization solid catalyst prepared in the same
manner as in Production of A2-1, 11.4 g of triethylaluminum
and 1,88 g of cyclohexylmethyldimethoxysilane were charged
in a nitrogen atmosphere. Thereto, 18 kg of propylene, 120
L of ethylene and hydrogen in an amount of 6,500 mol ppm
based on the propylene were charged and after elevating the

WO 2004/071375 PCT/JP2004/001411
32
temperature to 70°C, the polymerization was performed for 1
hour. After 1 hour, unreacted propylene was removed.
(Second Step: Production of Propylene-Ethylene Copolymer)
The polymerization was performed in the same manner
as in Production of A2-1 except that an ethylene/propylene
mixed gas at a mass ratio of 44/56 and hydrogen in an
amount of giving a concentration of 40,000 mol ppm were
supplied and after performing the polymerization for 40
minutes, unreacted gas was removed to complete the
polymerization. By this production method, 5.7 kg of a
polymer material mixture was obtained.
From this polymer material mixture, propylene-
ethylene block copolymer (A2-2) pellets were obtained in
the same manner as in Production of A2-1.
[Etlrylene-Base Copolymer (B) ]
B-l:
Ethylene-1-butene copolymer (EBM2021P produced by
JSR) ; MFR: 2.6 g/10 min, density: 0.86 g/cm3.
B-2:
Ethylene-1-butene copolymer (Tafmer A4085 produced
by Mitsui Chemicals, Inc.); MFR: 6.7 g/10 min, density:
0.8 9 g/cm3,
B-3:
Ethylene-l-butane copolymer (EBM3021P produced by
JSR); MFR: 2.6 g/10 min, density: 0.86 g/cm3.

WO 2004/071375 PCT/JP2004/001411
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B-4:
Sthylene-1-butene copolymer (Engage 8480 produced
by DuPont Dow Elastomers Japan K.K.), MFR: 2 g/10 min,
density: 0.902 g/cm3.
[Other Component]
High-density polyethylene, density: 0-955 g/cm3,
MFR; 3.0 g/10 min.
PE2:
Linear low-density polyethylene, density: 0-905
g/cm3, MFR; 1.0 g/10 min.

HFR:
MFR of each component of paropylene-base polymer (A)
and HFR of ethylene-base copolymer (B) were measured at
230ºC with a load of 21.18 N according to JIS K 7210. MFR
of high-detisity polyethylene and linear low-density
polyethylene was measured at 190ºC with a load of 21.18 N
according to JIS K 7210.
Density:
This was measured according to JIS K 7112 Method D.
Xylene-soluble content:
This was treasured by the method described in Mode
for Carrying out the Invention.

WO 2004/071375 PCT/JP2004/001411
34
Refractive index:
This was measured by the method described in Mode
for Carrying Out the Invention.

The resin materials described above were blended at
the compositional ratio shown in Table 1, mixed by Henschel
mixer for 3 minutes and then melt-kneaded at temperature of
230ºC by using a single screw extruder to obtain pellets of
polyolefin resin composition. The physical properties of
this polyolefin resin composition are shown in Table 2-

The polyolefin resin composition pellets obtained
above were molded into a tubular film having an entire
thickness of 250 pm by a water cooling inflation three-
layer molding machine at a temperature of 230°C-
Incidentally, in the case where the tubular film was a two-
layer film, the inner layer was formed to a thickness of
20 pm, and in the case of a three-layer film, the inner
layer and the outer layer both were formed to a thickness
of 20 pm.
Separately a single layer film was molded to have
a thickness of 250 pm by a water cooling inflation molding
machine.

WO 2004/071375 PCT/JP2004/001411
35

WO 2004/071375 PCT/JP2004/001411
36

1) MFR (at 230ºC) of propylene-base polymer (A)/MFR (at
230°C) of ethylene-base copolymer (B)
Measurement >
Tubular films in the state that respective inner
surfaces were superposed were cut into a length of 20 cm
and a width of 20 cm and then the length direction and the
width direction each was heat-sealed in a seal width of
10 mm. In the inside thereof, 500 mL of water was filled
to produce a bag-shaped medical container. At this time,
the heat sealing was performed by using a hot-plate heat-
sealing machine (a heat sealer manufactured by Tester
Sangyo Co. Ltd,) under a pressure of 0,4 MPa at a seal
temperature or 170ºC for a sealing time of 1 second. The

WO 2004/071375 PCT/JP2004/001411
37
obtained medical container was subjected to a
sterilization treatment at 121ºC for 30 minutes and used
as a sample for measurement of the following various
physical properties. However, the sample for the
evaluation of blocking resistance only was subjected to a
sterilization treatment at 121ºC in the state that
respective inner layers were almost contacted by filling 2
mL of water into the inside and extracting the inner air
by means of a vacuum pump.

The measurement results of the following various
physical properties are shown in Table 3.
[Heat Resistance]
The appearance of the container after sterilization
treatment was evaluated with an eye and judged as follows.
o: No deformation and no crinkling.
x: Deformed and many crinkles.
[Impact Resistance]
The container after sterilization treatment was
cooled at 4°C , and five containers held horizontally were
dropped on a hard floor from a height of 100 cm. The
number of ruptured containers was counted.
[Transparency]
The container after sterilization treatment was
measured on the light transmittance by using u-3300

WO 2004/071375 PCT/JP2004/001411
38
manufactured by Hitachi Ltd. according to Transparency
Test in Test Methods for Plastic Containers of The
Japanese Pharmacopoeia, 14th ed-
[Blocking Resistance]
The container after sterilization treatment was
left standing at 23ºC for 24 hours and then inner surfaces
wera pulled apart. The degree of power necessary for the
separation and the separated surface state were observed
with an eye and judged as follows.
o: Readily separated.
x; Not separated.

WO 2004/071375 PCT/JP2004/001411
39

WO 2004/071375 PCT/JP2004/001411
40
The medical containers of Examples 1 to 9 were
produced from a film comprising a polyolefin resin
composition containing (A) a propylene-base polymer and
(B) an ethylene-base polymer and moreover, the xylene-
soluble portion of the polyolefin resin composition had a
refractive index of 1,480 to 1.495, therefore, these
containers were excellent in tht heat resistance, impact
resistance, transparency and blocking resistance.
On the other hand, in the medical containers of
Comparative Examples 1, 2 and 4, the xylene-soluble
portion of the polyolefin resin composition had a
refractive index out of the range from 1.480 to 1.495 and
therefore, the transparency was low.
Furthermore, the medical container of Comparative
Example 3 was produced from a film comprising a polyolefin
resin composition of only propylene-base polymer (A) and
morerecover, the xylene-soluble portion of the polyolefin
resin composition had a refractive index out of the range
from 1.480 to 1.435, therefore, the transparency and
impact resistance were low.
In the medical container of Comparative Example 3,
the xylene-soluble portion of the polyolefin resin
composition had a refractive index out of the range from
1.480 to 1.495 and therefore, the transparency was low.
Moreover, a layer comprising a linear low-density

WO 2004/071375 PCT/JP2004/001411
41
polyethylene was provided in the inner and outer sides,
therefore, the heat resistance and blocking resistance
were insufficient.
INDUSTRIAL APPLICABILITY
The medical container of the present invention has
heat resistance high enough to enable sterilization at a
temperature of 121°C or more and at the same time,
exhibits excellent properties in all of the transparency,
impact resistance, flexibility and blocking resistance.

WO 2004/071375 PCT/JP2004/001411
42
1- A radical container produced from a film or sheet
having at least one resin layer comprising a polyolefin
resin composition, where in said polyolefin resin
composition comprises (A) at least one propylene-base
polymer selected from the group consisting of (Al) a
propylene-base polymer composition as a mixture of (All) a
propylene polymer and (A12) an ethylene-propylene
copolymer elastomer, (A2) a propylane-base block
capolymer, and (A3) a propylene-base block copolymer
composition as a mixture of (A2) a propylene-bass block
copolymer and (A12) an ethylene-propylene copolymer
elastomer, and (B) an ethylene-base copolymer comprising
an ethylene and at least one a-olefin having 4 or more
carbon atoms, and the refractive index of the xylene-
solubla portion is from 1-480 to 1.495.
2. The medical container as claimed in claim 1,
wherein said polyolefin resin composition has a xylene-
soluble portion content of 20 to 70 mass%. .
3. The medical container as claimed in claim 1,
wherein in said polyolefin resin composition, the ratio
(MFRA/MFRB) of the melt flow rate (MFRA) of propylene-base

WO 2004/071375 PCT/JP2004/001411
43
polymer (A) to the melt flow rate (MFRB) of ethylene-base
copolymer (B) is from 0.3 to 3.0.
4 . The medical container as claimed in any one of
claims 1, wherein said film or sheet has a first high-
density polyethylene layer comprising a high-density
polyethylene and said first high-density polyethylene
layer is disposed in the inner side.
5. The medical container as claimed in any one of
claims 1, wherein said film or sheet has a second high-
density polyethylene layer comprising a high-density
polyethylene and said second high-density polyethylene
layer is disposed in the outer side.
6. The medical container as claimed in claim 4,
wherein said first high-density polyethylene layer
contains 20 mass% or more of a high-density polyethylene
having a density of 0.950 g/cm3 or more.
7. The medical container as claimed in claim 5,
Therein said second high-density polyethylene layer
contains 2 0 mass% or more of a high-density polyethylene
having a density of 0.950 g/cm3 or more.

WO 2004/071375 PCT/JP2004/001411
44
8 . The medical container as claimed in any one of
claims 1, wherein the thickness of the resin layer
comprising a polyolefin resin composition occupies 60% or
more of the entire thickness of the film or sheet.

45

A medical cntainer produced from a film or sheet having at least one resin layer comprising a polyolefin resin
composition wherein the polyolefin resin composition comprises (A) at least one propylene-base polymer selected from the group
consis1ing of (A1) a specfic propylene-base polymer and (A3) a specific propylene-base block copolymer composition, and (B) an
ethylene-base copolymer comprising on elhylene and at least one a-plefin having 4 or more carbon atoms, and the refractive index
of the xylene-soluble portion is from 1.480 to 1.405.

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Patent Number

217427

Indian Patent Application Number

01153/KOLNP/2005

PG Journal Number

13/2008

Publication Date

28-Mar-2008

Grant Date

26-Mar-2008

Date of Filing

15-Jun-2005

Name of Patentee

HOSOKAWA YOKO CO. LTD.

Applicant Address

11-5,NIBAN-CHO,CHIYODA,KU,TOKYO, JAPAN.

Inventors:

#	Inventor's Name	Inventor's Address
1	IWASAKI, TOSHIHARU	C/O SHOWA DENKO PLASTIC PRODUCTS CO., TLD., KAWASAKI RESEARCH LABORATORY, 5-1, OKAWASAKI-CHO, KAWASAKI-KU, KAWASAKI-SHI, KANAGAWA 210-0858 JAPAN
2	KOTANI, MASATAKA	C/O SHOWA DENKO PLASTIC PRODUCTS CO., LTD., KAWASAKI RESEARCH LABORATORY, 5-1, OKAWA-CHO, KAWASAKI-KU, KAWASAKI-SHI, KANAGAWA 210-0858 JAPAN

PCT International Classification Number

A61J 1/00

PCT International Application Number

PCT/JP2004/001411

PCT International Filing date

2004-02-10

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	2003-033440	2003-02-12	Japan
2	60/455,564	2003-03-19	Japan