JP6822167B2 - Polyolefin resin laminated film and medical packaging - Google Patents

Description

The present invention relates to medical packaging such as blood bags, platelet storage bags, infusion (drug) bags, artificial dialysis bags, medical tubes, etc., and is particularly excellent in flexibility, transparency, adhesiveness, and autoclave sterilization. It relates to a laminated film that can be preferably used, especially for a blood component storage container (plasma bag) and the like.

Blood used for blood transfusion in the medical field is usually used for blood transfusion after blood obtained by donating blood from a donor is separated into each component and stored. For example, whole blood is placed in a blood collection bag and centrifuged to separate it into a low-density (low specific gravity) component and a high-density (high specific gravity) red blood cell component, and the blood collection bag is pressurized to release plasma, which is a supernatant component. , Transferred to the blood bag via the tube, and each fractionated component is utilized as a plasma preparation and a red blood cell preparation. Here, the blood bag (plasma bag) used for collecting plasma has been sterilized at high temperature in advance.
Plasma preparations fractionated into blood bags are cryopreserved and thawed in a thermostat or thaw device before use.

For these reasons, blood bags are required to have low-temperature impact resistance that can withstand the freezing treatment temperature, and blocking resistance, heat resistance, and hygiene when sterilized at high temperature without containing contents. In addition, blood bags are usually made by heat-sealing the peripheral edges of single-wafer films cut into a predetermined shape and molding them into a bag shape, so that the inner layer during bag making is used. , Heat sealability for bag making is also required.

Conventionally, as a material constituting a blood bag, a soft vinyl chloride resin composition is generally used because of its excellent flexibility and blood storage stability (Non-Patent Document 1). However, blood bags made of a soft vinyl chloride resin composition have poor low-temperature impact resistance, and chronic cracking at low temperatures has become a problem. Furthermore, hydrogen chloride during elution of plasticizers and waste combustion. -Since there are problems such as the generation of dioxins, those using a polyolefin resin composition such as polyethylene or polypropylene are desired.
However, those mainly using a polyethylene-based resin composition are excellent in flexibility and cold resistance, but are poor in heat resistance (Patent Document 1), and electron beam cross-linking is required to improve the heat resistance, which is very difficult to maintain the device. There is a problem that energy and cost are required (Patent Document 2).
On the other hand, those mainly using polypropylene-based resin have excellent heat resistance, but have problems of poor flexibility and cold resistance (Patent Document 3).

Japanese Unexamined Patent Publication No. 2002-136572 Japanese Unexamined Patent Publication No. 2001-029432 Japanese Unexamined Patent Publication No. 09-085913

Journal of the Japan Society of Blood Transfusion 26 (5): 301-360, 1980

The problem to be solved by the present invention is to obtain a laminated film which is excellent in both cold resistance and heat resistance, mainly composed of a polyolefin resin composition, and which can be suitably used for medical packaging, with good productivity. is there.

As a result of diligent studies to achieve the above problems, the present inventors have laminated three or more layers of polyolefin resin compositions, and at least the intermediate layer contains a certain amount of a polyethylene-based copolymer having a specific composition. The present invention has been completed by focusing on solving such a problem by squeezing. That is, the gist of the present invention is as follows.

[1] A laminated film composed of at least three layers of a surface layer, an intermediate layer, and a back layer, and at least the intermediate layer of the laminated film contains a block copolymer having an ethylene block and an α-olefin block. A polyolefin-based resin laminated film characterized by having 4 or more and 20 or less carbon atoms of the α-olefin.

[2] Both the surface layer and the back layer of the laminated film are made of a polyolefin-based resin composition containing a polyolefin-based resin, and the mass ratio of the block copolymer in all the layers is 50% by mass or more and 99% by mass or less. The polyolefin-based resin laminated film according to [1].

[3] The polyolefin-based resin laminated film according to [1] or [2], wherein the copolymerization ratio of α-olefin in the block copolymer is 30% by mass or more and 50% by mass or less.

[4] The polyolefin-based resin film according to [2] or [3], wherein the polyolefin-based resin composition of the surface layer and the back layer has a tensile storage elastic modulus of 1 MPa or more and 80 MPa or less at 121 ° C.

[5] The polyolefin-based resin laminated film according to any one of [1] to [4], wherein the laminated film has a heat shrinkage rate of 1% or less at 121 ° C.

[6] A medical packaging using the polyolefin-based resin laminated film according to any one of [1] to [5].

The laminated film proposed by the present invention makes it possible to produce medical packaging such as a blood bag and a chemical solution bag having good cold resistance and good heat resistance with high productivity.

Hereinafter, embodiments of the present invention will be described in detail. However, the content of the present invention is not limited to the embodiments described below.

In the present invention, when expressed as "X to Y" (X, Y are arbitrary numbers), unless otherwise specified, it means "X or more and Y or less", and "preferably larger than X" and "preferably Y". Includes the meaning of "smaller".
Further, in the present invention, when expressed as "X or more" (X is an arbitrary number), it includes the meaning of "preferably larger than X" unless otherwise specified, and "Y or less" (Y is an arbitrary number). ) Includes the meaning of "preferably smaller than Y" unless otherwise specified.

<Polyolefin-based resin laminated film>
It is important that the polyolefin-based resin laminated film of the present invention (hereinafter, may be simply referred to as “laminated film”) is composed of at least three layers, a surface layer, an intermediate layer, and a back layer. If the number of layers is three or more, it is preferable because both the flexibility of the intermediate layer and the heat resistance of the front and back layers can be provided. Further, from the viewpoint of interlayer adhesion and further imparting functionality, a configuration of four or more layers may be used. The upper limit is not particularly limited, but 20 layers or less is preferable because the production equipment may become complicated and the productivity may deteriorate.

<Front and back layers>
In the polyolefin-based resin laminated film of the present invention, it is preferable that both the front and back layers are made of a polyolefin-based resin composition. The polyolefin-based resin composition is a composition containing a polyolefin-based resin. Examples of the polyolefin resin include polyethylene, polypropylene, polybutene, poly-4-methylpentene, and copolymers thereof. From the viewpoint of elution, polyethylene, polypropylene, and poly (ethylene-propylene) copolymers are used. preferable. The proportion of the polyolefin-based resin in the polyolefin-based resin composition constituting each layer is preferably 50% by mass or more and 100% by mass or less, and 60% by mass or more and 100% by mass or less, from the viewpoint of interlayer adhesion. More preferably, it is more preferably 70% by mass or more and 100% by mass or less.

The tensile storage elastic modulus of the polyolefin resin composition constituting the front and back layers at 121 ° C. is preferably 1 MPa or more and 80 MPa or less, more preferably 1.5 MPa or more and 75 MPa or less, and preferably 2 MPa or more and 70 MPa. More preferred. When the tensile storage elastic modulus at 121 ° C. is 1 MPa or more, there is an effect of suppressing deformation during heat sterilization when the medical package is used. On the other hand, when it is 80 MPa or less, it is possible to impart suitable flexibility to the medical packaging.

The tensile storage elastic modulus of the polyolefin resin composition constituting the front and back layers at 121 ° C. is measured based on JIS K 7244-4, and is determined as the tensile storage elastic modulus of 121 ° C. at a measurement frequency of 1 Hz.

Additives such as lubricants, antifogging agents, antioxidants, stabilizers, and antiblocking agents are added to the polyolefin resin composition constituting the front and back layers as necessary without departing from the gist of the present invention. You may.

The thickness of each of the front and back layers is preferably 1 μm or more and 100 μm or less, more preferably 2 μm or more and 80 μm or less, and further preferably 3 μm or more and 70 μm or less. When it is 1 μm or more, there is an effect of maintaining the heat resistance of the polyolefin-based resin laminated film of the present invention. When it is 100 μm or less, there is an effect of imparting flexibility to the polyolefin-based resin laminated film of the present invention. The thickness of each layer can be measured by cross-sectional observation by SEM.

<Ethylene-α-olefin block copolymer (bEOP)>
The polyolefin-based resin laminated film of the present invention is a block copolymer composed of at least three layers, a surface layer, an intermediate layer, and a back layer, and having an ethylene block and an α-olefin block in at least the intermediate layer of the laminated film (hereinafter, It is important to include (sometimes referred to as bEOP). When at least the intermediate layer of the laminated film contains the above-mentioned block copolymer, the film is imparted with good flexibility and heat resistance.

The content of bEOP contained in the intermediate layer is not particularly limited, but is preferably 50% by mass or more, more preferably 60% by mass or more, based on 100% by mass of the resin composition constituting the intermediate layer. It is preferably 70% by mass or more, and more preferably 70% by mass or more. When it is 50% by mass or more, there is an effect that good flexibility and heat resistance are imparted to the laminated film. On the other hand, the upper limit is not particularly limited and is 100% by mass.
It is most preferable that bEOP is contained only in the intermediate layer of the laminated film.

The intermediate layer of the laminated film may be at least one layer, and a plurality of intermediate layers may be present. The thickness of the intermediate layer (in the case of a plurality of existing forms, the total thickness) is preferably 30 μm or more and 500 μm or less, more preferably 40 μm or more and 400 μm or less, and further preferably 50 μm or more and 300 μm or less. When the thickness of the intermediate layer is 30 μm or more, there is an effect of imparting flexibility to the laminated film of the present invention. On the other hand, when it is 500 μm or less, there is an effect of imparting heat resistance to the laminated film of the present invention. The thickness of the intermediate layer can be measured by cross-sectional observation by SEM.

In the form in which bEOP is contained in the surface layer and / or the back layer of the laminated film, the content of bEOP is preferably 30% by mass or less with respect to 100% by mass of the polyolefin resin composition constituting each layer. It is more preferably mass% or less, further preferably 10 mass% or less, and most preferably 0 mass%. If the content of bEOP contained in the polyolefin resin composition constituting the surface layer and / or the back layer exceeds 30% by mass, the films are likely to block each other when the films are wound, which may cause a problem in the manufacturing process. There is.

In the bEOP used in the present invention, it is important that the α-olefin has 4 or more carbon atoms, preferably 6 or more, and further preferably 8 or more.
When the number of carbon atoms of the α-olefin is 4 or more, the flexibility and heat resistance of the bEOP are improved, and there is an effect that the flexibility of the film is imparted. The upper limit is preferably 20 or less because it makes it difficult to produce a copolymer.
As such bEOP, in addition to mixing ethylene and α-olefin, respectively, and polymerizing using a polymerization catalyst, it is commercially available as “INFUSE” manufactured by Dow Chemical Co., Ltd. and can be obtained.

(Copolymerization ratio)
In the bEOP used in the present invention, the copolymerization ratio of α-olefin is preferably 30% by mass or more and 50% by mass or less. When it is 30% by mass or more, there is an effect that flexibility when made into a film is exhibited. When it is 50% by mass or less, there is an effect that heat resistance when made into a film is exhibited. It is more preferably 32% by mass or more and 48% by mass or less, and further preferably 34% by mass or more and 46% by mass or less.

The copolymerization ratio of bEOP used in the present invention was measured by ¹³ C-NMR under the following conditions.
About 200 mg of the sample was weighed into an NMR sample tube having an outer diameter of 10 mm, 2.7 mL of a mixed solution of heavy orthodichlorobenzene and heavy paradichlorobenzene having a mass ratio of 7/1 was added, and the mixture was dissolved at 130 ° C. Measured at a frequency of 100 MHz, a flip angle of 900 °, a pulse repetition time of 20 s, an integration frequency of 3200 times, and a temperature of 130 ° C. using a Unity 400 manufactured by Variant, and assigning a ¹³ C-NMR spectrum with the ethylene main chain signal as 30.0 ppm. Then, the content of α-olefin was determined.

<Other layers>
The polyolefin-based resin laminated film of the present invention may have a further layer laminated in addition to the above-mentioned three layers as long as the gist of the present invention is not deviated. Examples of the further layer include an adhesive layer for improving the interlayer strength, a barrier layer for inhibiting the permeability of the film, a colored layer for improving the visibility of the film, and the like. The additional layers may be laminated in any order.

Additives such as lubricants, antifogging agents, antioxidants, and stabilizers may be added to each layer of the polyolefin resin-based laminated film of the present invention as necessary without departing from the gist of the present invention.

Generally, a "film" is a thin, flat product that is extremely small in thickness relative to its length and width and whose maximum thickness is arbitrarily limited, and is usually supplied in the form of rolls. (Japanese Industrial Standard JIS K 6900), in general, "sheet" means a product that is thin by definition in JIS and whose thickness is generally small and flat for its length and width. However, since the boundary between the sheet and the film is not clear and it is not necessary to distinguish between the two in the present invention, the term "film" is used to include the "sheet" and is referred to as the "sheet" in the present invention. Even if it is, it shall include "film".

The polyolefin-based resin laminated film of the present invention preferably has a heat shrinkage rate at 121 ° C. of 1% or less, more preferably 0.8% or less, and even more preferably 0.5% or less. When the heat shrinkage rate is 1% or less, there is an effect that processing defects during processing as a medical packaging can be reduced. On the other hand, the lower limit is not particularly limited, but is preferably 0% or more. The heat shrinkage rate is measured by the method described later.

The cold resistance of the polyolefin-based resin laminated film of the present invention can be quantified by measuring the embrittlement temperature. The embrittlement temperature is measured by the method described below. The embrittlement temperature of the polyolefin-based resin laminated film of the present invention is preferably −55 ° C. or lower, more preferably −60 ° C. or lower. When the embrittlement temperature is −55 ° C. or lower, it has an effect of reducing damage when stored frozen as a medical package. The lower limit is not particularly limited, but is preferably −200 ° C.

<Manufacturing method of polyolefin resin laminated film>
The polyolefin-based resin laminated film of the present invention can be produced by a production method such as a T-die method, a water-cooled inflation method, an air-cooled inflation method, or a lamination method. Among these, the T-die method and the water-cooled inflation method are preferable from the viewpoint of hygiene.

In the production of the polyolefin-based resin laminated film of the present invention, the extrusion processing temperature in extrusion molding is appropriately adjusted depending on the flow characteristics, moldability, etc. of the resin composition, but is generally preferably 180 to 300 ° C, more preferably 190 to 250 ° C. It is preferable, and more preferably 200 to 220 ° C. When the temperature is 180 ° C. or higher, the viscosity of the molten resin is sufficiently low, the moldability is excellent, and the productivity is improved, which is preferable. On the other hand, when the temperature is set to 300 ° C. or lower, deterioration of the resin composition and eventually deterioration of the mechanical strength of the obtained laminated film can be suppressed.

Examples will be shown below and the present invention will be described in more detail. However, the present invention is not limited thereto, and various applications are possible without departing from the technical idea of the present invention.

<Measurement and evaluation method>
First, a method for measuring and evaluating various physical property values of the samples obtained in Examples and Comparative Examples will be described.

(1) With a dial gauge having a thickness of 1/1000 mm of the polyolefin-based resin laminated film, the in-plane of the portion coated with the thermistor component was unspecifiedly measured at 5 points, and the average value was measured at 5 points of the polyolefin-based resin laminated film. It was made thick.

(2) Thickness of front and back layers In the produced polyolefin-based resin laminated film, the thickness of each of the front and back layers was measured by measuring the cross-sectional SEM. In this embodiment, for convenience, the front and back layers on the cast surface side are used as the back layer, and the front and back layers on the non-cast surface side are used as the surface layer.

(3) Thickness of Intermediate Layer The thickness of the intermediate layer was measured by measuring the cross-sectional SEM of the produced polyolefin-based resin laminated film.

(4) Cold resistance The cold resistance of the produced polyolefin resin laminated film and the existing polyvinyl chloride film was evaluated according to the following criteria.
The embrittlement temperature was measured according to JIS K 7216.
⊚: The embrittlement temperature of the film is lower than -60 ° C.
◯: The embrittlement temperature of the film is −60 ° C. or higher and −55 ° C. or lower.
Δ: The embrittlement temperature of the film is −55 ° C. or higher and lower than −50 ° C.
X: The embrittlement temperature of the film exceeds −50 ° C.

(5) Heat resistance The produced polyolefin-based resin laminated film and the existing polyvinyl chloride film are cut into a size of 50 mm × 100 mm, placed on a wire mesh having a square 20 mm pitch, and heat-treated in a heat treatment oven at 121 ° C. for 1 hour. After that, the appearance of the film was evaluated according to the following criteria, and the heat resistance was evaluated.
⊚: The film is not deformed in appearance.
◯: The film is slightly deformed in appearance.
Δ: Deformation marks remain on the film along the pitch of the wire mesh.
X: The film clearly does not maintain its shape.

(6) Heat Shrinkage The produced polyolefin-based resin laminated film and the existing polyvinyl chloride film were cut into strips of 10 mm × 200 mm in the longitudinal direction and the width direction, respectively, and heat-treated in a heat treatment oven at 121 ° C. for 1 hour. Later, the heat shrinkage of the strips in the longitudinal direction and the width direction was measured by the following formula, and the additive average was used as the heat shrinkage of the film.
Heat shrinkage rate [%] = {(length before heat treatment)-(length after heat treatment)} / (length before heat treatment) x 100

(7) Windability The produced polyolefin-based resin laminated film was wound around a plastic core having a diameter of 3 inches, and the winding property was judged based on the following criteria.
◯: The films do not adhere to each other and can be easily unwound.
X: The films adhere to each other and cannot be easily unwound. Alternatively, even if the film is unwound, the film remains deformed.

<Example 1>
Two 32 mm single-screw extruders manufactured by Mitsubishi Heavy Industries, Ltd. are connected to a T-die with a two-kind, three-layer structure that has a layer structure of A / B / A (called A extruder and B extruder, respectively). From the extruder, linear low-density polyethylene "FY-13 (manufactured by Toso Co., Ltd.)" (specific gravity 0.950) having a tensile storage elasticity of 66 MPa at 121 ° C. was introduced, and from the B extruder, α-olefin (8 carbon atoms). Ethylene-α olefin block copolymer (bEOP) "INFUSE 9000 (manufactured by Dow Chemical Co., Ltd.)" (specific gravity 0.877) having a copolymerization ratio of 36% by mass, each having a thickness ratio of A: B: A = 1: 8. The laminated film according to Example 1 having a width of 400 mm and a thickness of 300 μm having a two-kind, three-layer structure was obtained by extruding at 200 ° C. at 1: 1 and quenching and winding with a cooling roll at 40 ° C. The evaluation results are shown in Table 1.

<Example 2>
From the A extruder, polypropylene resin "Zeras 7025 (manufactured by Mitsubishi Chemical Corporation)" (specific gravity 0.890) with a tensile storage elasticity of 59 MPa at 121 ° C. was used, and from the B extruder, α-olefin (8 carbon atoms). Ethylene-α olefin block copolymer (bEOP) "INFUSE 9000 (manufactured by Dow Chemical Co., Ltd.)" (specific gravity 0.877) with a copolymerization ratio of 36% by mass and linear low-density polyethylene "FY-12 (manufactured by Toso Co., Ltd.)" ) ”(Specific gravity 0.915) was extruded at a mass ratio of 7: 3, and the laminated film according to Example 2 was obtained in the same manner as in Example 1. The evaluation results are shown in Table 1.

<Example 3>
From the A extruder, a polypropylene resin "Zeras 7025 (manufactured by Mitsubishi Chemical Corporation)" (specific gravity 0.890) having a tensile storage elasticity of 59 MPa at 121 ° C. was used, and from the B extruder, α-olefin (8 carbon atoms). The same as in Example 1 except that the ethylene-α olefin block copolymer (bEOP) "INFUSE 9000 (manufactured by Dow Chemical Co., Ltd.)" (specific gravity 0.877) having a copolymerization ratio of 36% by mass was extruded. , A laminated film according to Example 3 was obtained. The evaluation results are shown in Table 1.

<Example 4>
From the A extruder, a polypropylene resin "Zeras 7025 (manufactured by Mitsubishi Chemical Corporation)" (specific gravity 0.890) having a tensile storage elasticity of 59 MPa at 121 ° C. was used, and from the B extruder, α-olefin (8 carbon atoms). The same as in Example 1 except that the ethylene-α olefin block copolymer (bEOP) "INFUSE 9107 (manufactured by Dow Chemical Co., Ltd.)" (specific gravity 0.866) having a copolymerization ratio of 48% by mass was extruded. , A laminated film according to Example 4 was obtained. The evaluation results are shown in Table 1.

<Example 5>
From the A extruder, linear low-density polyethylene "FY-13 (manufactured by Toso Co., Ltd.)" (specific gravity 0.950) having a tensile storage elastic coefficient of 66 MPa at 121 ° C. was introduced, and from the B extruder, α-olefin (8 carbon atoms). ) Is an ethylene-α olefin block copolymer (bEOP) "INFUSE 9000 (manufactured by Dow Chemical Co., Ltd.)" (specific gravity 0.877) having a copolymerization ratio of 36% by mass, each having a thickness ratio of A: B: A = 1: A laminated film according to Example 5 was obtained in the same manner as in Example 1 except that it was extruded at a ratio of 3: 1. The evaluation results are shown in Table 1.

<Comparative example 1>
An ethylene-α-olefin block copolymer (bEOP) "INFUSE 9000 (manufactured by Dow Chemical Co., Ltd.)" (specific gravity 0.877) having a copolymerization ratio of α-olefin (8 carbon atoms) of 36% by mass was extruded from the A extruder. Example 1 and Example 1 except that linear low-density polyethylene "FY-13 (manufactured by Toso Co., Ltd.)" (specific gravity 0.950) having a tensile storage elastic coefficient of 66 MPa at 121 ° C. was extruded from the B extruder. Similarly, the laminated film according to Comparative Example 1 was obtained, but blocking occurred due to winding, which caused a problem in production. The evaluation results are shown in Table 1.

<Comparative example 2>
An ethylene-α-olefin random copolymer (rEOP) "AFFINITY PL1880G (manufactured by Dow Chemical Co., Ltd.)" (specific gravity 0.902) having a copolymerization ratio of α-olefin (8 carbon atoms) of 36% by mass was extruded from a B extruder. A laminated film according to Comparative Example 2 was obtained in the same manner as in Example 1 except for the above. The evaluation results are shown in Table 1.

<Comparative example 3>
Except for extruding an ethylene-propylene block copolymer "Prime TPO T310E (manufactured by Prime Polymer Co., Ltd.)" (specific gravity 0.890) having a copolymerization ratio of α-olefin (3 carbon atoms) of 36% by mass from a B extruder. A laminated film according to Comparative Example 3 was obtained in the same manner as in Example 1. The evaluation results are shown in Table 1.

<Comparative example 4>
From the A extruder, the polypropylene resin "Zeras 7025 (manufactured by Mitsubishi Chemical Corporation)" (manufactured by Mitsubishi Chemical Corporation) with a tensile storage elasticity of 66 MPa at 121 ° C., and from the B extruder, the polypropylene resin "Zeras 7025 (Mitsubishi)" A laminated film according to Comparative Example 4 was obtained in the same manner as in Example 1 except that "(manufactured by Chemical Corporation)" (specific gravity 0.890) was extruded. The evaluation results are shown in Table 1.

<Comparative example 5>
Table 1 shows the evaluation results of the existing polyvinyl chloride film.

In Examples 1 to 5, laminated films having excellent cold resistance and heat resistance and which can be suitably used for medical packaging were obtained.
On the other hand, in Comparative Example 1, since the front and back layers and the intermediate layer are opposite to each other and the ethylene-α-olefin block copolymer (bEOP) having a low room temperature elastic modulus is present in the outer layer, there is a problem in winding property. In Comparative Example 2, since an ethylene-α-olefin random copolymer (rEOP) was used, the heat resistance was not sufficient. In Comparative Example 3, since the α-olefin was polypropylene having 3 carbon atoms, the heat resistance was not sufficient. Since the laminated film according to Comparative Example 4 was made of polypropylene only, the cold resistance was not sufficient. The existing polyvinyl chloride film according to Comparative Example 5 did not have good cold resistance.

Claims (4)

A laminated film composed of at least three layers of a surface layer, an intermediate layer, and a back layer, and at least the intermediate layer of the laminated film contains a block copolymer having an ethylene block and an α-olefin block, and the said the number of carbon atoms of the α- olefin Ri der 4 to 20, and none of the surface layer and the backing layer of the laminated film is made of a polyolefin resin composition, the mass of the block copolymer to the total layer during A polyolefin-based resin having a ratio of 50% by mass or more and 99% by mass or less, and having a tensile storage elasticity of the polyolefin-based resin composition of the surface layer and the back layer at 121 ° C. of 1 MPa or more and 80 MPa or less. Laminated film. The polyolefin-based resin laminated film according to claim 1, wherein the copolymerization ratio of α-olefin in the block copolymer is 30% by mass or more and 50% by mass or less. The polyolefin-based resin laminated film according to claim 1 or 2 , wherein the laminated film has a heat shrinkage rate of 1% or less at 121 ° C. A medical packaging body using the polyolefin-based resin laminated film according to any one of claims 1 to 3 .