Container containing barrier composition

Abstract

This disclosure provides a container. In one embodiment, the container includes a side wall. The side wall is made of a barrier composition. The barrier composition is made of (i) low-density polyethylene (LDPE) and (ii) a nucleating agent. The side wall is 100 cc-mil / 100 in 2 / day ~400cc-mil / 100in 2 It has an oxygen permeability of less than / day.

Description

[Technical Field]

[0001] Ampoules or bottles for medical use can be manufactured by blow molding or simultaneous filling (BFS) processes. Low-density polyethylene (LDPE) is known to be used in simultaneous filling (BFS) applications because it meets the requirements of low hexane extractability, compressibility, and suitable melt strength for processability. However, LDPE exhibits a high oxygen permeability that is detrimental to medical applications.

[0002] Therefore, it is recognized that there is a particular need in this technical field for LDPE with high barrier properties and low oxygen permeability. Specifically, there is a need for LDPE with low oxygen permeability suitable for medical applications, especially BFS containers. [Overview of the Initiative]

[0003] This disclosure provides a container. In one embodiment, the container includes a side wall. The side wall is made of a barrier composition. The barrier composition is made of (i) low-density polyethylene (LDPE) and (ii) a nucleating agent. The side wall is 100 cc-mil / 100 in 2 / day ~400cc-mil / 100in 2 It has an oxygen permeability of less than / day.

[0004] definition All references to the periodic table refer to the version published by CRC Press, Inc., 1990–1991. References to element groups in this table refer to a new notation used to number the groups.

[0005] For the purposes of U.S. patent practice, the content of any referenced patent, patent application, or publication, in particular with respect to the disclosure of definitions (to the extent that it does not conflict with any definitions specifically provided in this disclosure), is incorporated by reference in its entirety (or its corresponding U.S. version is incorporated by reference in this way).

[0006] Numerical ranges disclosed herein include all values ​​from the lower limit to the upper limit (including the lower and upper limits). In the case of ranges that include explicit values ​​(e.g., 1 or 2, or 3 to 5, or 6 or 7), any sub-ranges between any two explicit values ​​are included (e.g., the above range of 1 to 7 includes 1 to 2, 2 to 6, 5 to 7, 3 to 7, 5 to 6, etc.).

[0007] Unless otherwise stated, implied by the context, or customary in the art, all parts and percentages are based on weight, and all test methods are current as of the filing date of this disclosure.

[0008] Where used, the terms “blend” or “polymer blend” refer to a mixture of two or more polymers. A blend may or may not be miscible (not phase-separated at the molecular level). A blend may or may not be phase-separated. A blend may or may not contain one or more domain configurations as determined by transmission electron spectroscopy, light scattering, X-ray scattering, and other methods known in the art. A blend may be influenced by the physical mixing of two or more polymers at a macro level (e.g., melt blending or formulation of resins) or at a micro level (e.g., simultaneous formation in the same reactor).

[0009] The term "composition" refers to a mixture of materials that constitute a composition, as well as reaction products and decomposition products formed from the materials of the composition.

[0010] The terms “comprising,” “including,” and “having,” and their derivatives, are not intended to exclude the presence of any additional components, processes, or procedures, whether or not they are specifically disclosed. To avoid any doubt, all compositions claimed through the use of the term “comprising” may, unless otherwise stated, include any additional additives, adjuvants, or compounds, whether or not they are polymers. In contrast, the term “consisting essentially of” excludes any other components, processes, or procedures from the scope of any prior description, except those not essential for operability. The term “consisting of” excludes any components, processes, or procedures that are not specifically described or enumerated. The term “or” refers to the enumerated members individually and in any combination, unless otherwise stated. The use of the singular includes the use of the plural, and vice versa.

[0011] An "ethylene-based polymer" is a polymer containing more than 50 weight percent (wt%) of polymerizable ethylene monomers (based on the total amount of polymerizable monomers) and optionally containing at least one comonomer. Ethylene-based polymers include ethylene homopolymers and ethylene copolymers (meaning units derived from ethylene and one or more comonomers). The terms "ethylene-based polymer" and "polyethylene" may be used interchangeably.

[0012] As used herein, the terms "ethylene monomer" or "ethylene" refer to a chemical unit having two carbon atoms connected by a double bond, and each carbon atom being bonded to two hydrogen atoms, which polymerizes with other such chemical units.

[0013] "High-density polyethylene" (or "HDPE") is an ethylene homopolymer, or at least one C4-C 10An ethylene / α-olefin copolymer containing an α-olefin comonomer or at least one C4-C8 α-olefin comonomer, having a density of 0.940 g / cc, or 0.945 g / cc, or 0.950 g / cc, 0.953 g / cc to 0.955 g / cc, or 0.960 g / cc, or 0.965 g / cc, or 0.970 g / cc, or 0.975 g / cc, or 0.980 g / cc.

[0014] As used herein, the term "linear low density polyethylene" (or "LLDPE") refers to a linear ethylene / α-olefin copolymer containing units derived from ethylene and units derived from at least one C3-C 10 α-olefin or C4-C8 α-olefin comonomer, having a non-uniform short chain branch distribution. In contrast to conventional LDPE, LLDPE is characterized by having little to no long chain branching. LLDPE has a density of less than 0.910 g / cc to 0.940 g / cc. Non-limiting examples of LLDPE include TUFLIN (trademark) linear low density polyethylene resin (available from The Dow Chemical Company), DOWLEX (trademark) polyethylene resin (available from the Dow Chemical Company), and MARLEX (trademark) polyethylene (available from Chevron Phillips).

[0015] The term "low density polyethylene" (or "LDPE"), also sometimes referred to as "high pressure ethylene polymer" or "highly branched polyethylene", is an ethylene homopolymer typically produced by high pressure free radical polymerization (≥100 MPa (e.g., 100 - 400 MPa), using a free radical initiator in a tubular reactor or an autoclave reactor). LDPE resins typically have a density in the range of 0.915 - 0.935 g / cc. LDPE is different from LLDPE.

[0016] An "olefin" is an unsaturated aliphatic hydrocarbon having a carbon-carbon double bond.

[0017] As used herein, the terms "polymer" or "polymeric material" refer to compounds prepared by polymerizing monomers, whether of the same type or different types, and provide the multiple and / or repeating "units" or "mer units" constituting the polymer in polymerized form. Thus, the general term "polymer" encompasses both the term "homopolymer", which is commonly used to refer to a polymer prepared from only one type of monomer, and the term "copolymer", which is commonly used to refer to a polymer prepared from at least two types of monomers. It also encompasses all forms of copolymers, such as random, block, etc. The terms "ethylene / α-olefin polymer" and "propylene / α-olefin polymer" each denote the above-mentioned copolymers prepared by polymerizing ethylene or propylene with one or more additional polymerizable α-olefin monomers. Polymers are often referred to as being "made of", "based on", "containing" a specified monomer or type of monomer, etc. of one or more specified monomers. However, in this context, it should be noted that the term "monomer" is understood to refer to the specified monomer of the polymerization residue and not to non-polymerized species. Generally, polymers herein are referred to as being based on "units" that are the polymerized form of the corresponding monomers.

[0018] Test Methods Density. Density is measured by the substitution (Archimedes) method, ASTM Method D792 Method B. The sample is weighed in air (dry weight) and immersed in a fluid (wet weight). By knowing the density of the immersion fluid, the sample density can be calculated from the weight loss of the sample during immersion. A sheet of material is formed according to ASTM D4703, Annex A.1 Procedure C (cooling to 15°C). After removal from the press, three coupons (approximately 1.5 inches × approximately 0.5 inches × approximately 0.125 inches) are cut from the sheet and their density is measured. For Method B, the sample is weighed in air and then immersed in a fluid. The fluid (IPA, isopropyl alcohol) is contained in a double-walled container and the temperature is controlled to 23°C + / - 0.1°C. The sample is immersed in the fluid for 8 minutes to ensure that the sample equilibrates to the bath temperature. The sample is then weighed while still immersed in the fluid. Next, glass sinkers of known dry weight and volume are weighed while immersed in the fluid. The density of the immersed fluid is calculated from the known measurements of the glass sinkers (this corrects for small deviations in fluid density within the acceptable temperature range). Then, the density of the sample can be calculated from the known fluid density and the measured wet and dry sample weights.

[0019] The Triple Detector Gel Permeation Chromatography (TD-GPC) chromatography system consisted of a PolymerChar GPC-IR (Valencia, Spain) high-temperature GPC chromatograph equipped with an internal IR5 infrared detector (IR5), and a 4-capillary viscometer (DV) coupled to a Precision Detectors (now Agilent Technologies) Model 2040 two-angle laser light scattering (LS) detector. For all absolute light scattering measurements, a 15-degree angle was used. The autosampler oven compartment was set to 160°C, and the column and detector compartments were set to 150°C. The columns used were four Agilent "Mixed A" 30 cm, 20 micron linear mixed-bed columns. The chromatography solvent used was 1,2,4-trichlorobenzene (TCB), containing 200 ppm butylated hydroxytoluene (BHT). The solvent source was spurged with nitrogen. The injection volume used was 200 microliters, and the flow rate was 1.0 ml / min.

[0020] The GPC column set was calibrated using 21 polystyrene standards with narrow molecular weight distributions ranging from 580 to 8,400,000, placed in six "cocktail" mixtures with at least a 10-fold gap between individual molecular weights. The standards were purchased from Agilent Technologies. Polystyrene standards were prepared using 0.025 grams in 50 ml of solvent for molecular weights above 1,000,000, and 0.05 grams in 50 ml of solvent for molecular weights below 1,000,000. The polystyrene standards were pre-dissolved at 80°C with gentle stirring for 30 minutes, then cooled, and the room-temperature solution was transferred to an autosampler dissolution oven at 160°C for 30 minutes and cooled. The peak molecular weights of the polystyrene standards were converted to polyethylene molecular weights using Equation 1 (as described in Williams and Ward, J. Polym. Sci., Polym. Let., 6, 621 (1968)):

[0021]

number

[0022] A quintic polynomial was used to fit each polyethylene equivalent calibration point.

[0023] The total plate count of the GPC column set was performed using decane introduced into blank samples via a micropump controlled by the PolymerChar GPC-IR system. The plate count of the chromatography system should be greater than 18,000 for four Agilent "Mixed A" 30 cm² 20 micron linear mixed-bed columns.

[0024] The sample was prepared semi-automatically using PolymerChar's "Instrument Control" software, with a target weight of 2 mg / mL. The solvent (containing 200 ppm BHT) was added to a vial with a pre-nitrogen-spurged septum cap via a PolymerChar high-temperature autosampler. The sample was dissolved at 160°C for 3 hours under "low-speed" shaking.

[0025] Mn (cc) , Mw (cc) , and Mz (cc) The calculation was based on GPC results using the PolymerChar GPCOne® software, obtained from the IR chromatogram with the baseline subtracted at each equally spaced data retrieval point (i), and the narrow standard calibration curve of point (i) from Equation 1, using the internal IR5 detector (measurement channel) of the PolymerChar GPC-IR chromatograph and following Equations 2 to 4.

[0026]

number

[0027] To monitor deviations over time, a flow rate marker (decane) was introduced into each sample via a micropump controlled by the PolymerChar GPC-IR system. Using this flow rate marker (FM), the pump flow rate (nominal flow rate) for each sample was linearly corrected by matching the RV (RV(FM sample)) of each decane peak in the sample with the RV (RV(FM calibrated)) of the calibrated decane peak in the narrow standard material. It was assumed that any temporal change in the decane marker peak corresponds to a linear shift in the flow rate (effective flow rate) over the entire run. After calibrating the system based on the flow rate marker peaks, the effective flow rate (relative to the narrow standard calibration) was calculated using Equation 5. The processing of the flow rate marker peaks was performed via PolymerChar GPCOne® software. An acceptable flow rate correction is required so that the effective flow rate is within ±0.5% of the nominal flow rate. Effective flow rate = Nominal flow rate * (RV(FM calibrated) / RV(FM sample))(Equation 5)

[0028] Regarding the determination of viscometer and light scattering detector offsets from an IR5 detector, a systematic method for determining multiple detector offsets was developed by Balke, Mourey et al. (Mourey and Balke, Chromatography Polym. Chpt 12, (1992)) (Balke, Thitiratsakul, Lew, Cheung, Mourey, Chromatography Polym. Chpt 13, (1992)). Using PolymerChar GPCOne™ software, the results of triple detector log(MW and IV) obtained from linear homopolymer polyethylene standard materials (3.5>Mw / Mn>2.2) with molecular weights in the range of 115,000 to 125,000 g / mol were optimized to the results of narrow standard column calibration obtained from a narrow standard material calibration curve.

[0029] Absolute molecular weight data were obtained in a manner consistent with that published by Zimm (Zimm, B. H., J. Chem. Phys., 16, 1099 (1948)) and Kratochvil (Kratochvil, P., Classical Light Scattering from Polymer Solutions, Elsevier, Oxford, NY (1987)) using PolymerChar GPCOne™ software. The total injection concentration used in the determination of molecular weight was derived from the mass detector area and mass detector constant of one of a suitable linear polyethylene homopolymer or a polyethylene standard of known weight average molecular weight. The molecular weight calculated (using GPCOne™) was obtained using a light scattering constant derived from one or more of the polyethylene standards described below and a refractive index concentration coefficient, dn / dc, of -0.104. In general, the mass detector response (IR5) and light scattering constant (determined using GPCOne™) should be determined from linear standards having a molecular weight greater than about 50,000 g / mol. Calibration of the viscometer (determined using GPCOne™) can be accomplished using the method described by the manufacturer or, alternatively, using published values of a suitable linear standard such as Standard Reference Material (SRM) 1475a (available from the National Institute of Standards and Technology (NIST)). The specific viscosity area (DV) and injected mass for the calibration standard are used to calculate the viscometer constant (obtained using GPCOne™) associated with its intrinsic viscosity. The chromatographic concentration is presumed to be low enough to eliminate the second virial coefficient effect (concentration effect on molecular weight).

[0030] Absolute weight average molecular weight (MW (Abs)) is obtained (using GPCOne®) from a light scattering (LS) area integrated chromatogram (factored by the light scattering constant) divided by the mass reconstructed from the mass constant and mass detector (IR5) area. The molecular weight and intrinsic viscosity response are linearly extrapolated (using GPCOne®) at the edge of the chromatogram where signal-to-noise is low. The other respective moments are Mn (abs) , Mw (abs) and Mz (abs) This is calculated according to equations 6 through 8 below.

[0031]

number

[0032] Cumulative Detector Fraction (CDF) Calculation Method Cumulative detector fraction (CDF) from the internal infrared detector IR5 IR The calculation of ) is achieved using the following steps. 1) Linearly flow-correct the chromatogram based on the decane flow marker injection described above. 2) Calculate the molecular weight from the IR5 measurement channel described above. 3) According to Equation 9, for each data slice (j), the cumulative detector (CDF) of the IR5 chromatogram (measurement channel) is calculated based on the baseline subtracted peak height (H) of high to low molecular weight (low to high retention volume). IR Calculate ).

[0033]

number

[0034] gpcBR break-even point by TD-GPC The gpcBR branching index is determined, as described above, by first calibrating the light scattering, viscosity, and infrared IR5 detectors. Then, a baseline is subtracted from the light scattering, viscometer, and IR5 (measurement channel) chromatograms. Next, an integration window is set to ensure integration of all low molecular weight retention volume ranges of the light scattering and viscometer chromatograms that indicate the presence of detectable polymers from the infrared (IR5) chromatogram. Then, the Mark-Houwink constants for polyethylene and polystyrene are established using linear polyethylene standards. After obtaining the constants, a conventional calibration method using two linear references for polyethylene molecular weight and polyethylene intrinsic viscosity as a function of elution volume is constructed using the two values, as shown in equations (10) and (11).

[0035]

number

[0036] The gpcBR branching index is described in Yau, Wallace W., "Examples of Using 3D-GPC-TREF for Polyolefin Characterization," Macromol.Symp., 2007, 257, 29-45. This index is favorable to the entire polymer detector area and avoids the conventional "per-slice" TD-GPC calculation used in determining g' values ​​and calculating branching frequencies. From the TD-GPC data, the peak area method is used to determine the absolute weight-average molecular weight (Mw) of the sample bulk as measured by a light scattering (LS) detector. (Abs) This method allows us to obtain the following: This avoids the "slice-by-slice" ratio of the light scattering detector signal to the concentration detector signal, as required in conventional g' determination.

[0037] Using TD-GPC, the intrinsic viscosity of the sample is also obtained independently using equation (12). The area calculation in (12) provides higher accuracy because, as the overall sample area, it is less affected by the variations caused by detector noise and TD-GPC settings to the baseline and integration limit. More importantly, the peak area calculation is unaffected by the detector volume offset. Similarly, the high-precision sample intrinsic viscosity ([η]) is obtained by the area method shown in equation (12).

[0038]

number

[0039] To determine the gpcBR branching index, the light scattering elution area of ​​the sample polymer is used to determine the absolute molecular weight (MW) of the sample. (Abs) Determine the intrinsic viscosity ([η]) of the sample polymer. Determine the intrinsic viscosity ([η]) of the sample using the elution area of ​​the viscosity detector for the sample polymer.

[0040] First, the molecular weight and intrinsic viscosity of a linear polyethylene standard sample, such as SRM1475a or its equivalent, are determined using conventional calibration ("conventional calibration, cc"), both as functions of elution volume, according to equations (3) and (13).

[0041]

number

[0042] The GPCBR branch index is determined using equation (14).

[0043]

number

[0044] All statistical values ​​with the subscript "cc" represent the respective elution volume, the corresponding conventional calibration mentioned above, and the concentration (c i Determined using "MW". (Abs) The values ​​for '' and ''[h] are measurements based on the mass detector, LALLS, and viscometer area. PE The value of is adjusted iteratively until the linear reference sample has a gpcBR measurement of zero. For example, the final values ​​of α and Log K for determining the gpcBR in this particular case are 0.725 and -3.391 for polyethylene and 0.722 and -3.993 for polystyrene, respectively. These polyethylene coefficients (· and K) were then entered into Equation 14.

[0045] Once the K and α values ​​have been determined using the previously discussed procedure, the procedure is repeated using the branched sample. The branched sample is analyzed using the final Mark-Houwink constant obtained from the linear reference as the optimal "cc" calibration value.

[0046] Melt Index. As used herein, the term “Melt Index” or “MI” refers to a measure of how easily a thermoplastic polymer flows when in a molten state. The melt index, or I2, is measured according to ASTM D1238, conditions 190°C / 2.16 kg, method B, and reported as grams eluted every 10 minutes (g / 10 min).

[0047] Oxygen permeability. Oxygen permeability (OTR) is measured according to standard ASTM D3985. In this method, each test specimen in the form of a flat sheet is mounted in a diffusion cell and sealed tightly (using an O-ring and Apiezon T Grease). The diffusion cell consists of two chambers separated by the sample. A permeable (test) gas (i.e., O2) of the desired concentration and flow rate is piped to one side. An inert carrier gas (nitrogen (98% N2 and 2% H2)) is piped to the other side at the same flow rate. In that path, the carrier gas takes in oxygen molecules that have permeated the membrane. As the carrier gas exits the cell, it flows through a coulometric sensor designed to generate an electrical signal with an amplitude proportional to the oxygen content in the carrier gas. The result is given in terms of the volume of oxygen per unit area of ​​the sample per unit time. For OTR, the typical unit after normalization with respect to thickness (often called "permeability") is cc-mil / 100in. 2 The OTR of the test specimen is the equilibrium value read after several hours, where the difference from the last measurement is less than 1%. For the samples used in these experiments, a MOCON OX-TRAN2 / 22ML instrument was used, and two test specimens were used for each sample. The concentration of the test gas used was 10%, and the results were reported by correcting the measured value to 100% gas concentration by multiplying it by 10. The conditions used for both the test gas and carrier gas were 23°C and 0% relative humidity ("RH"). The test specimens were cut from blow-molded bottles, and their surface area (exposed to the gas) in a diffusion cell was 50 cm². 2 That was the case. [Brief explanation of the drawing]

[0048] [Figure 1] This is a perspective view of a BFS (Brewing-Filled Simultaneous Filling) ampoule according to one embodiment of the present disclosure. [Modes for carrying out the invention]

[0049] This disclosure relates to a container. In one embodiment, the container includes a side wall. The side wall is made of a barrier composition. The barrier composition is made of (i) low-density polyethylene (LDPE) and (ii) a nucleating agent. The side wall is 100 cc-mil / 100 in 2 / day ~400cc-mil / 100in 2 It has an oxygen permeability of less than / day.

[0050] The barrier composition comprises (A) low-density polyethylene (LDPE). LDPE is an ethylene homopolymer having one, some, or all of the following properties: (i) Density of 0.910 g / cc to 0.930 g / cc, and / or (ii) Melt index of 0.1g / 10 min to 2.4g / 10 min, or 0.5g / 10 min to 2.2g / 10 min, and / or (iii) Mw(abs) of 50,000 g / mol to 220,000 g / mol, or 100,000 g / mol to 220,000 g / mol, and / or (iv) CDF between 0.010 and less than 0.060 IR , and / or (v) gpcBR values ​​of 0.50~2.10, or 1.00~2.10, or 1.50~2.10, or 1.80~2.10, and / or (vi) The multivariance index (PDI) of Mw(cc) / Mn(cc) between 1.00 and less than 7.50.

[0051] The barrier composition contains a nucleating agent. Examples include metal carboxylates, metal aromatic carboxylates, metal hexahydrophthalates, stearates, organophosphates, sorbitol, bisamides, or mixtures thereof.

[0052] In one embodiment, the nucleating agent is 1,2-cyclohexanedicarboxylic acid.

[0053] In one embodiment, the nucleating agent is blended or melt-blended with LDPE by a nucleating agent masterbatch.

[0054] In one embodiment, the nucleating agent masterbatch comprises HPN-20E (HPN-20E is 67 wt% calcium salt of 1,2-cyclohexanedicarboxylic acid and 33 wt% zinc stearate, based on the total weight of HPN-20E). The nucleating agent masterbatch comprises 3 wt% HPN-20E, 1.5 wt% silica, 0.5 wt% hydrotalcite, 5 wt% antioxidant, and 90 wt% carrier resin. The carrier resin is a second ethylene-based polymer different from LDPE. In one embodiment, the second ethylene-based polymer is high-density polyethylene homopolymer (HDPE). In one embodiment, the second ethylene-based polymer is high-density polyethylene homopolymer (HDPE) having a narrow molecular weight distribution with a density of 0.945 g / cc to 0.970 g / cc and a melt index of 4 g / 10 min to 15 g / 10 min. In further embodiments, the sidewall (containing or not containing the second ethylene-based polymer) is either LLDPE-free or excludes LLDPE.

[0055] The barrier composition may contain one or more optional additives. Non-limiting examples of suitable additives include antioxidants, UV stabilizers, heat stabilizers, slip agents, anti-tack agents, pigments or colorants, processing aids, crosslinking catalysts, flame retardants, fillers, foaming agents, and combinations thereof. In one embodiment, the barrier composition contains 0% by weight, or 0.5% to 3% by weight, or 1.0% to 2.5% by weight, or 1.0% to 2.0% by weight, of the total amount of additives. The weight percentages are based on the total weight of the barrier composition.

[0056] In one embodiment, the side wall of the container is a single-layer structure composed solely of a barrier composition, and the barrier composition is (A) LDPE ethylene homopolymer in an amount of 94% to 99% by weight, or 95% to 98% by weight, having the following properties: (i) Density of 0.910 g / cc to 0.930 g / cc, and / or (ii) Melt index of 0.1g / 10 min to 2.4g / 10 min, or 0.5g / 10 min to 2.2g / 10 min, and / or (iii) Mw(abs) of 50,000 g / mol to 220,000 g / mol, or 100,000 g / mol to 220,000 g / mol, and / or (iv) CDF between 0.010 and less than 0.060 IR , and / or (v) gpcBR values ​​of 0.50~2.10, or 1.00~2.10, or 1.50~2.10, or 1.80~2.10, and / or (vi) Ethylene homopolymers having one, some, or all of the Mw(cc) / Mn(cc) polydispersity index (PDI) between 1.00 and less than 7.50; (B) A nucleating agent consisting of 1,2-cyclohexanedicarboxylic acid in an amount of 0.01% to 0.2% by weight, or 0.05% to 0.015% by weight; (C) Additives in amounts of 0% by weight, or 0.1% to 0.5% by weight, or 0.2% to 0.4% by weight; and (D) A second polymer which is HDPE in an amount of 0% by weight, or 1% to 5% by weight, or 1.5% to 4.5% by weight; comprising, essentially derived from, or consisting of (weight percentage is based on the total weight of the barrier composition), The sidewall can have a variable thickness, 100cc-mil / 100in 2 / day ~400cc-mil / 100in 2 It has an OTR of less than 1 / day (hereinafter referred to as sidewall 1).

[0057] In one embodiment, the side wall of the container is a single-layer structure composed solely of a barrier composition, and the barrier composition is (A) LDPE ethylene homopolymer in an amount of 94% to 99% by weight, or 95% to 98% by weight, having the following properties: (i) Densities of 0.91 g / cc to 0.93 g / cc, and / or (ii) Melt index of 0.1g / 10 min to 2.4g / 10 min, or 0.5g / 10 min to 2.2g / 10 min, and / or (iii) Mw(abs) of 50,000 g / mol to 220,000 g / mol, or 100,000 g / mol to 220,000 g / mol, and / or (iv) CDF between 0.010 and less than 0.060 IR , and / or (v) gpcBR values ​​of 0.50~2.10, or 1.00~2.10, or 1.50~2.10, or 1.80~2.10, and / or (vi) Ethylene homopolymers having one, some, or all of the Mw(cc) / Mn(cc) polydispersity index (PDI) between 1.00 and less than 7.50; (B) A nucleating agent consisting of 1,2-cyclohexanedicarboxylic acid in an amount of 0.01% to 0.2% by weight, or 0.05% to 0.15% by weight; (C) Additives consisting of silica (silicon dioxide) in a concentration of 75 ppm to 1500 ppm; and (D) A second polymer which is HDPE in an amount of 0% by weight, or 1% to 5% by weight, or 1.5% to 4.5% by weight; comprising, essentially derived from, or consisting of (weight percentage is based on the total weight of the barrier composition), The sidewall can have a variable thickness, and the sidewall is 100cc-mil / 100in 2 / day ~400cc-mil / 100in 2 It has an OTR of less than 1 / day (hereinafter referred to as sidewall 2).

[0058] The container may be a flexible package, a pouch, and / or an upright pouch.

[0059] In one embodiment, the container is a BFS container (a "BFS" ​​container). As used herein, a "BFS container" is a container manufactured in an automated manufacturing process by which polymer containers, such as bottles or ampoules, are blow-molded, filled, and sealed in a continuous operation. BFS containers are manufactured in a sterile, sealed area inside a machine. The advantage of the BFS manufacturing process is that the process is a closed, automated system. BFS containers are formed and filled with a sterile solution within a BFS machine, and the BFS containers are sealed with limited or no human intervention.

[0060] Figure 1 shows a BFS container 10. In the BFS container manufacturing process, the barrier composition of the present invention (i.e., LDPE, nucleating agent, and optional additives) is melted and extruded into a side wall 12 ("parison" or continuous side wall) formed into the shape of a cylindrical tube, and sterile air or nitrogen is blown into the cylindrical tube to form the barrier composition of the present invention (in its molten state) into the shape of the mold, thereby forming the container. Cooling of the container begins within seconds after it is formed, as the mold cools. Next, the drug 14 (typically liquid, semi-liquid, or gel) is filled into the newly formed polymer container while it is still inside the mold. The BFS machine then closes the side wall 12 on itself by sealing the upper and lower ends of the cylindrical tube, thereby forming a sealed BFS container 10 having a body portion 16, a top 18, a bottom 20, and a side wall 12 defining a closed chamber 22 containing the drug 14. In other words, the BFS container 10 is made from a single continuous side wall 12. The BFS container also includes a tab 24 (which is also made from the barrier composition of the present invention) for opening the container 10 and dispensing or releasing the drug 14 from the chamber 22.

[0061] Non-exclusive examples of drugs present in the chamber 22 and in direct contact with the side wall 12 include liquid eye drops (such as sterile eye drops), inhaled anesthetics, biological agents, cleaning agents, and vaccines.

[0062] The side wall 12 may have a uniform thickness, or its thickness may vary along the length of the BFS container 10 from the top 18 to the main body portion 16 and then to the bottom portion 20. In one embodiment, the continuous side wall 12 includes a closed top 18, a main body portion 16, and a bottom portion 20.

[0063] In one embodiment, the side wall 12 is a continuous side wall without seams and / or without sealing and / or heat fusion.

[0064] In one embodiment, the main body portion 16 is a continuous main body portion, has no seams, and / or the main body portion 16 is not heat-sealed.

[0065] Without limiting ourselves to any particular example, several embodiments of this disclosure will be described in detail in the following examples. [Examples]

[0066] The materials used in the examples (IE) and comparative samples (CS) of the present invention are shown in Table 1 below.

[0067] [Table 1]

[0068] [Table 2]

[0069] A blow-molded bottle (a 14-ounce "Boston Round" shaped bottle with a target bottle weight of 26 ± 0.5 grams) was fabricated using a Bekum H-111 continuous extrusion blow molding machine equipped with a 50 mm extruder and a MACO 6500 digital readout controller. A nucleating agent masterbatch pellet having the composition shown in Table 1a was added to the base LDPE in a bag to prepare a barrier composition containing 95 wt% LDPE and 5 wt% nucleating agent MB, based on the total weight of the barrier composition. The pellet bag was shaken by hand and then fed into the extruder. The blow molding machine was operated using parison programming to ensure a consistent and uniform sidewall thickness distribution was maintained in the manufactured bottles. The extruder barrel temperature was maintained at 350°F. The extrusion rate was 120 g / min to 140 g / min. The total weight of the parison was adjusted using head weight, which can be used to compensate for additional weight in bottle profiling. Higher head weight correlates with a wider die gap, and vice versa. The target bottle weight for each production bottle was 26 grams. The sidewall (and the entire bottle) consisted solely of a barrier composition, which, based on the total weight of the container sidewall, contained (i) 95% by weight of LDPE, (ii) 4.5% by weight of HDPE1, 0.15% by weight of HPN-20E, 0.075% by weight of Sylobloc45, 0.025% by weight of Hycite713, 0.05% by weight of Irganox1076, and 0.2% by weight of Irgafos168.

[0070] Blow-molded bottles with a chamber volume of 14 ounces and a sidewall thickness of 20 mil to 40 mil were formed from the barrier compositions shown in Table 2 below. The (i) initial LDPE (before blending with the nucleating agent MB) and (ii) OTR properties of the sidewalls of each sample container (Examples of the present invention ("IE") and comparative samples ("CS")) are provided in Table 2 below.

[0071] [Table 3] * OTR-cc-mil / 100in2 / day & LDPE properties before blending with nucleating agent MB

[0072] The applicant claims that the container sidewall, composed of unique LDPE (LDPE1~LDPE3) combined with a nucleating agent, has a low OTR (100cc-mil / 100in) 2 / day ~400cc-mil / 100in 2 We found that it exhibited less than / day. Although not bound by any particular theory, the specific structural features of the LDPEs in Examples IE1-IE3 of the present invention that enabled low OTR values ​​were found to be a lower level of high MW tail (CDF) compared to comparative samples LDPE4-LDPE6. IR Includes <0.055 (quantified), Mw(abs)(less than 220,000), gpcBr(less than 2.1), and PDI(less than 7.5). Each of LDPE4 to LDPE6 lacks at least one property, and each of LDPE4 to LDPE6 cannot provide a barrier composition for the container sidewall composition, and the sidewall is 100cc-mil / 100in 2 / day ~400cc-mil / 100in 2 It has an OTR of less than one day.

[0073] This disclosure is not limited to the embodiments and examples contained herein, but is specifically intended to include some embodiments and modified forms of those embodiments, including combinations of elements of different embodiments, to the extent that they fall within the scope of the following claims.

Claims

1. It is a container, A side wall, wherein the side wall is (i) Low-density polyethylene (LDPE), and (ii) It is composed of a barrier composition containing a nucleating agent, The aforementioned side wall is 100 cc-mil / 100 in ２ / day ~400cc-mil / 100in ２ A container with side walls having an oxygen permeability of less than one day.

2. The LDPE is an ethylene homopolymer, (i) Density of 0.91 g / cc to 0.93 g / cc, (ii) Melt index of 0.1 g / 10 min to 2.4 g / 10 min, (iii) Mw(abs) of 50,000 g / mol to 220,000 g / mol, (iv) CDF between 0.010 and less than 0.060 ＩＲ , (v) gpcBr values ​​of 0.50 to 2.10, (vi) Mw(cc) / Mn(cc) between 1.00 and less than 7.50, and (vii) The container according to claim 1, having properties selected from the group consisting of combinations of these.

3. The container according to claim 1 or 2, wherein the nucleating agent is a calcium salt of 1,2-cyclohexanedicarboxylic acid.

4. The barrier composition is The container according to any one of claims 1 to 3, further comprising a second ethylene-based polymer different from the LDPE.

5. The container according to any one of claims 1 to 4, wherein the barrier composition further comprises silica.

6. 94% to 99% by weight of the LDPE; The nucleating agent is 1,2-cyclohexanedicarboxylic acid in a concentration of 100 ppm to 2000 ppm; The second ethylene-based polymer, which is high-density polyethylene, in an amount of 1% to 5% by weight; and A container according to any one of claims 1 to 5, comprising 75 ppm to 1500 ppm of silica.

7. The aforementioned side wall defines the closed chamber, The container according to any one of claims 1 to 6, wherein the drug is present in the closed chamber.

8. The container according to any one of claims 1 to 7, wherein the side wall has a single-layer structure and a thickness of 0.3 mm to 1.5 mm.

9. The container according to any one of claims 7 to 8, wherein the closed chamber has a volume of 0.1 cc to 100 cc.

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