SQUEEZABLE AND AUTOCLAVABLE BOTTLES

Description

This application claims the benefit under 35 USC § 119(e) of U.S. provisional application No. 63/676,991, filed 30 Jul. 2024, herein incorporated by reference in its entirety.

INTRODUCTION

Aspects of the present disclosure generally relate to bottles, such as eye drop bottles, having (1) a thermoplastic elastomer and (2) a polypropylene (PP) such as a polypropylene homopolymer, a random polypropylene copolymer, a random, heterophasic polypropylene copolymer, or (3) combinations thereof.

Conventional small volume bottles (e.g., 5-10 ml (milliliters)) bottles for ophthalmic solutions) include a cap and body. The body is typically made of low-density polyethylene (LDPE). Sterilization of bottles and ophthalmic solutions is needed for regulatory compliance. Autoclaving, for example, is particularly suitable for ophthalmic drug products because more drug formulations can withstand the high temperatures of autoclave sterilization as compared to other sterilization methods such as gamma radiation or ethylene oxide (EtO).

Sterilization of bottles and ophthalmic formulations is currently performed as a complex process where the components of the bottle and formulation are sterilized individually prior to aseptic filling in a stringent Clean Zone A (ISO (International Organization for Standardization) Class 5 Cleanroom). Such a complex process involves investment, maintenance, and operational inconvenience for such stringent clean zone infrastructure and operation.

In particular, a counter-pressure autoclave process can be used for a sealed container, especially for a large volume sealed container. Indeed, autoclave sterilization (steam sterilization, also referred to as “terminal sterilization”) is recognized as one of the most effective terminal sterilization methods of bottles against a wide range of microorganisms. For example, terminal autoclaving allows for compounding formulations to be filled in a bottle in a lower ISO cleanroom class, such as Clean Zone B (ISO Class 7 cleanroom), improving compliance with European Pharmacopoeia and other regulations. However, bottles made of LDPE cannot be terminally autoclaved due to their low melting points (approximately 108-114° C. (Celsius)). For example, autoclaving is typically performed at least 121° C. for at least 15 minutes. Such low melting points of LDPEs further limit the size of bottles that can be manufactured for use with ophthalmic formulations by limiting any autoclaving process that may be performed. LDPE is also permeable to EtO, which can lead to undesired chemical reactions with the ophthalmic solution disposed in the body of the bottle. In addition, some ophthalmic solutions can at least partially degrade when exposed to such terminal autoclaving conditions. Nonetheless, an ability to be terminally autoclaved would provide compliance of the bottled ophthalmic formulation with European Pharmacopoeia 11th Edition (2023) and other regulatory thresholds.

In addition, other conventional small volume bottles have a body made of a polypropylene homopolymer or random polypropylene copolymer. Although the melting points of such polypropylenes is higher than the melting points of LDPEs, the squeezability of the body (to dispense drops of the ophthalmic solution from the bottle) is difficult, particularly for older populations. Difficulty with squeezing a bottle leads to overcompensation of squeezing by the user, dispensing too many drops which leads to waste of the ophthalmic solution.

There is a need for bottles for administering ophthalmic solutions, where the bottles are able to be terminally autoclaved without bottle deformation, such as with bottles having high volumes (e.g., 10 ml) of ophthalmic solution. There is also a need for bottles for administering ophthalmic solutions that, in addition to being terminally autoclaved, provide improved squeezability, as compared to LDPE bottles and conventional polypropylene bottles.

SUMMARY

In at least one embodiment, a bottle includes a cap, a nozzle tip, and a body. The cap is configured to engage a threaded portion of a neck of the body. The body includes a composition including (1) a thermoplastic elastomer and (2) a polypropylene homopolymer, a block or random polypropylene copolymer, a random, heterophasic polypropylene copolymer, or (3) combinations thereof.

In at least one embodiment, a bottle includes a cap, a nozzle tip, and a body. The cap is configured to engage a threaded portion of a neck of the body. The body includes (1) a first random, heterophasic polypropylene copolymer and (2) a second random, heterophasic polypropylene copolymer that is different than the first random, heterophasic polypropylene copolymer.

In at least one embodiment, a method includes sterilizing a bottle of the present disclosure. The method includes introducing an ophthalmic solution into the bottle. The method further includes fastening the cap to the body. The method also includes introducing the bottle to an autoclaving chamber. The method further includes introducing steam into the chamber. The method also includes maintaining the chamber at temperature of about 120° C. or greater for about 5 minutes or greater.

BRIEF DESCRIPTION OF THE DRAWINGS

So that the manner in which the above recited features of the present disclosure can be understood in detail, a more particular description of the disclosure, briefly summarized above, may be had by reference to embodiments, some of which are illustrated in the appended drawings. It is to be noted, however, that the appended drawings illustrate only exemplary embodiments and are therefore not to be considered limiting of its scope, may admit to other equally effective embodiments.

FIG. 1 shows a bottle, according to embodiments of the disclosure.

DETAILED DESCRIPTION

To facilitate understanding, identical reference numerals have been used, where possible, to designate identical elements that are common to the figures. It is contemplated that elements and features of one embodiment may be beneficially incorporated in other embodiments without further recitation.

Aspects of the present disclosure generally relate to bottles, such as eye drop bottles, having (1) a thermoplastic elastomer and (2) PP such as a polypropylene homopolymer, a random polypropylene copolymer, a random, heterophasic polypropylene copolymer, or (3) combinations thereof. Bottles of the present disclosure can provide administering ophthalmic solution where the bottles are able to be terminally autoclaved without bottle deformation, such as with bottles having high volumes (e.g., 10 ml) of a bottle for storing ophthalmic solution. In addition, bottles of the present disclosure for administering ophthalmic solution can provide improved squeezability, as compared to LDPE bottles and conventional polypropylene bottles.

For example, as provided by the present disclosure, using polymer(s) in bottles that provide a combination of low flexural modulus and low hardness (Shore D), while also having a high melting point, can provide an ability for autoclavability in addition to squeezability of a bottle, even at high volumes (e.g., 10 ml) of a bottle for storing ophthalmic solution.

In addition, as compared to LDPE for example, bottles of the present disclosure can have an improved (lower) moisture vapor transmission rate (MVTR). MVTR is a measure of the passage of water vapor through a substance. An improved MVTR provides reduced or eliminated weight loss of an ophthalmic solution from the bottle over time, improving product shelf life. In some embodiments, a bottle of the present disclosure can have an MVTR of about 1 cm³/m²/24 hr (cubic centimeters per square meters per 24 hours) to about 5 cm³/m²/24 hr, such as about 1 cm³/m²/24 hr to about 3 cm³/m²/24 hr, such as about 1 cm³/m²/24 hr to about 2 cm³/m²/24 hr.

In certain embodiments, bottles of the present disclosure can also have significantly lower flexural modulus and shore D hardness compared to bottles having only homopolymer polypropylenes and random copolymer polypropylenes. Such properties make it possible to achieve squeezability (dispensing force) similar to flexible LDPE bottles, while maintaining adequate bottle wall thickness and an increased melting point.

Bottles

Bottles of the present disclosure can have any shape or form suitable for dispensing a liquid (e.g., ophthalmic solution) therefrom. In some embodiments, the body of a bottle has a volume of about 5 ml to about 15 ml, such as about 8 ml to about 12 ml, such as about 10 ml.

Further, bottles of the present disclosure can have a squeezability of about 6 lbs (pounds) or less, such as about 1 lb to about 6 lbs, such as about 2 lbs to about 5 lbs, such as about 3 lbs to about 4 lbs. Squeezability can be measured by dispensing force either using Instron type instrument or pressure sensor on the fingers to capture the dispensing force and simulate the squeezability.

Bottles of the present disclosure can also have a wall thickness of about 0.3 mm (millimeters) to about 0.65 mm, such as about 0.56 mm to about 0.61 mm, alternatively about 0.3 mm to about 0.5 mm, such as about 0.4 mm to about 0.5 mm. A thinner wall thickness can provide reduced squeezability as compared to a thicker wall thickness. If the wall thickness is too thin, then the stability of the bottle decreases. However, if the wall thickness is too thick, then the squeezability of the bottle decreases and the bottle may become too rigid. Indeed, an example value of the wall thickness may be lower than in comparison with the prior art PE (polyethylene) bottles, so that there is lesser material necessary for molding the bottles, such as by an injection molding process.

Examples of bottles that can be utilized using compositions of the present disclosure include those typically used for DROP-TAINER® and Multi-Dose Preservative Free (MDPF) bottles. Bottles can include those for contact lens care solutions (e.g., CLEARCARE®, CLEARCARE PLUS®) and OPTI-FREE®. Bottles can also include Unit-Dose Preservative Free (UDPF) vials.

Bottles can be formed by melt blending polymers with one another and then conventional blow molding techniques or injection molding techniques to form the bottles (body, nozzle tip, cap, etc.).

As one example, FIG. 1 is a dropper bottle assembly 1 which comprises a body 2 having a nozzle tip 3 designed to snap fit within the neck portion 4 of the bottle 2, and a cap 5 designed to fit over the nozzle tip 3 and engage threaded portion 6 of the neck portion 4. The nozzle tip 3 has a passageway 7 for allowing fluid within the body 2 to be dispensed through outlet 8. Liquid is dispensed by first removing cap 5 and then squeezing the cylindrical sidewall 9 of body 2 with one's fingers which causes the liquid therein to pass through a passageway 7. For safety purposes the bottle assembly is further provided with either a shrink collar or with a tamper resistance ring 10.

The bottom 12 of body 2 has a concave configuration for avoiding deformation, e.g. shrinkage or blowing-up, of the bottle during the autoclaving processing. Due to the concave configuration, the degree of pressure necessary to cause deformation of the bottom is much higher than a body without a concave configuration. Other indentation, grooves, slits or slots can be designed at the bottom 12 or the sidewall 9 to give the body 2 a greater stability during the autoclaving processing. The nozzle tip 3 is also formed of a polypropylene homopolymer or polypropylene random copolymer of the present disclosure. Using a composition (resin blend) of the present disclosure for either or both of body 2 avoids problems of using polypropylene homopolymer or copolymer alone. For example, the softer material of the compositions provided herein allow for an easy snap fit of body 2 to the nozzle tip 3 into the neck portion 4 of the body 2, the nozzle tip 3 having a special configuration to ensure a good seal between the body 2 and the nozzle tip 3. The sealing part 13 of the nozzle tip 3 used for sticking the nozzle tip 3 into the neck portion 4 of the body 2 is formed in the upper part with a nearly cylindrical form, whereas the lower part has the form of a taper shank. As a stopping face, the sealing part 13 of the nozzle tip 3 is provided with a collar 14. The cap 5 is threaded on the neck portion 4 of the body 2 having external threads 6. In alternative embodiments (not shown), threads 6 are absent (or only a single thread 6 is present) and cap 5 is not threaded but has a snap portion for fitting to a lip of body 2, tamper resistance ring 10, or nozzle tip 3 to provide snap fit eye drop bottle instead of a screw-on lid eye drop bottle. The cap 5 as the closure of the bottle assembly is particularly formed of a high-density polyethylene (HDPE) (such as for an MDPF bottle) or a polypropylene (such as for a Drop-Tainer bottle).

Further, the body 2 is made of one or more of the compositions (resin blends) described below.

Compositions

Compositions (resin blends) of the present disclosure include (1) a thermoplastic elastomer and (2) a polypropylene homopolymer, a random polypropylene copolymer, a random, heterophasic polypropylene copolymer, or combinations thereof.

As used herein, a “composition” (also referred to as a “resin blend”) refers to a mixture or combination of different types of resin materials. Each polymer of a composition has its own properties. Resin blending or compounding involves mixing two or more types or grades of polymers (resins) to achieve properties, such as strength, durability, flexibility, or other performance attributes. The resulting composition combines the properties of the individual polymers, allowing for a tailored composition having particular properties. Resin blending is a versatile technique used in various industries and applications and as known in the art. For example, resin blending can be performed using a twin-screw extruder to form composition pellets. The pellets are then suitable for blow molding into bottles (body, cap, etc.).

In some embodiments, a composition includes about 5 wt % (percent by weight) to about 95 wt % of a random, heterophasic polypropylene copolymer and about 95 wt % to about 5 wt % of a thermoplastic elastomer, where wt % is based on the total weight of the random, heterophasic polypropylene copolymer plus the thermoplastic elastomer. For example, a composition can include about 5 wt % to about 95 wt % of a random, heterophasic polypropylene copolymer, such as about 10 wt % to about 80 wt %, such as about 10 wt % to about 20 wt %, alternatively about 20 wt % to about 30 wt %, alternatively about 30 wt % to about 40 wt %, alternatively about 40 wt % to about 50 wt %, alternatively about 50 wt % to about 60 wt %, alternatively about 60 wt % to about 70 wt %, alternatively about 70 wt % to about 80 wt %. A composition can include about 5 wt % to about 95 wt % of a thermoplastic elastomer, such as about 10 wt % to about 80 wt %, such as about 10 wt % to about 20 wt %, alternatively about 20 wt % to about 30 wt %, alternatively about 30 wt % to about 40 wt %, alternatively about 40 wt % to about 50 wt %, alternatively about 50 wt % to about 60 wt %, alternatively about 60 wt % to about 70 wt %, alternatively about 70 wt % to about 80 wt %.

In some embodiments, a composition includes about 5 wt % to about 95 wt % of a first random, heterophasic polypropylene copolymer and about 95 wt % to about 5 wt % of a second random, heterophasic polypropylene copolymer that is different than the first random, heterophasic polypropylene copolymer, where wt % is based on the total weight of the first random, heterophasic polypropylene copolymer plus the second random, heterophasic polypropylene copolymer. For example, a composition can include about 5 wt % to about 95 wt % of a first random, heterophasic polypropylene copolymer, such as about 10 wt % to about 80 wt %, such as about 10 wt % to about 20 wt %, alternatively about 20 wt % to about 30 wt %, alternatively about 30 wt % to about 40 wt %, alternatively about 40 wt % to about 50 wt %, alternatively about 50 wt % to about 60 wt %, alternatively about 60 wt % to about 70 wt %, alternatively about 70 wt % to about 80 wt %. A composition can include about 5 wt % to about 95 wt % of a second random, heterophasic polypropylene copolymer, such as about 10 wt % to about 80 wt %, such as about 10 wt % to about 20 wt %, alternatively about 20 wt % to about 30 wt %, alternatively about 30 wt % to about 40 wt %, alternatively about 40 wt % to about 50 wt %, alternatively about 50 wt % to about 60 wt %, alternatively about 60 wt % to about 70 wt %, alternatively about 70 wt % to about 80 wt %.

Compositions of the present disclosure can further include one or more polypropylene homopolymers and/or one or more random copolymer polypropylenes (in addition to random, heterophasic polypropylene copolymer content and/or thermoplastic elastomer content). For example, a composition can include about 1 wt % to about 50 wt % of a polypropylene homopolymer, such as about 5 wt % to about 10 wt %, alternatively about 10 wt % to about 20 wt %, alternatively about 20 wt % to about 30 wt %, alternatively about 30 wt % to about 40 wt %, alternatively about 40 wt % to about 50 wt %, where wt % is based on the total weight of the random, heterophasic polypropylene copolymer content plus the thermoplastic elastomer (TPE) content plus the polypropylene homopolymer content plus the random copolymer polypropylene content. A composition can include about 1 wt % to about 50 wt % of a random copolymer polypropylene, such as about 5 wt % to about 10 wt %, alternatively about 10 wt % to about 20 wt %, alternatively about 20 wt % to about 30 wt %, alternatively about 30 wt % to about 40 wt %, alternatively about 40 wt % to about 50 wt %, where wt % is based on the total weight of the random, heterophasic polypropylene copolymer content plus the thermoplastic elastomer content plus the polypropylene homopolymer content plus the random copolymer polypropylene content. Blending homopolymer polypropylene or random copolymer polypropylene with random, heterophasic polypropylene copolymer and/or thermoplastic elastomer provides balance between squeezability and increased dispensing force (provided by the homopolymer polypropylene or random copolymer polypropylene). Indeed, a fine balance of dispensing liquid from a bottle of the present disclosure can be achieved.

In at least one embodiment, a composition can have a hardness that is about 20 Shore D to about 70 Shore D, such as about 30 Shore D to about 50 Shore D. Shore D Hardness can be measured using a Zwick automated durometer according to ASTM (American Society for Testing and Materials) D2240.

In at least one embodiment, a composition can have a flexural modulus of about 100 MPa (megapascal) to about 2,000 MPa, such as about 200 MPa to about 1,000 MPa, such as about 200 MPa to about 500 MPa, such as about 200 MPa to about 350 MPa, alternatively about 350 MPa to about 500 MPa, as determined by ISO 178.

In at least one embodiment, a composition can have an ability to withstand temperatures of about 100° C. or more, such as about 110° C. to about 200° C., such as about 120° C. to about 180° C., such as about 130° C. to about 180° C. or about 150° C. to about 180° C.

As viscoelastic materials, polymers often undergo a time-dependent deformation under a certain load, also known as creep. Creep tests can be performed under a constant applied load (e.g., 40 N (Newtons)) at room temperature according to (ASTM BS 1178). PP has higher resistance to creep as compared with HDPE and LDPE or with their blends because of the differences in the structure of the polymers, e.g. low creep rate due to an effect of bulky side group (a methyl group) on every second atom of the PP main chain restricts rotation of the chain, producing a strong intermolecular force but less flexible material. In some embodiments, a composition can have a creep strain of 0.05 or less for greater than 200 minutes and about 400 minutes or less, such as about 600 minutes or less, such as about 800 minutes or less, such as about 1,000 minutes or less, such as about 1,200 minutes or less, such as about 1,400 minutes or less. In some embodiments, a composition can have a creep strain of 0.03 or less for greater than 200 minutes and about 400 minutes or less, such as about 600 minutes or less, such as about 800 minutes or less, such as about 1,000 minutes or less, such as about 1,200 minutes or less, such as about 1,400 minutes or less.

In some embodiments, a composition can have a density of about 0.89 g/cm³ (grams per cubic centimeters) or more, such as about 0.9 g/cm³ to about 0.94 g/cm³, such as about 0.9 g/cm³ to about 0.935 g/cm³, such as about 0.9 g/cm³ to about 0.92 g/cm³, alternatively about 0.92 g/cm³ to about 0.94 g/cm³.

In some embodiments, a composition can have a melting point of about 145° C. to about 210° C., such as about 150° C. to about 175° C., alternatively about 175° C. to about 210° C.

(A) Polypropylene Homopolymers and Copolymers

In at least one embodiment, a composition of the present disclosure includes one or more polymers that is a polypropylene homopolymer or a polypropylene copolymer (e.g., polypropylene having C₂ or C₄ to C₂₀ comonomer units (e.g., propylene-ethylene copolymers).

In at least one embodiment, the polypropylene copolymers have, for example, about 0.1 wt % to about 40 wt % (alternately about 5 wt % to about 40 wt %, such as about 10 wt % to about 35 wt %, such as about 10 wt % to about 20 wt %, alternatively about 20 wt % to about 30 wt %, of one or more C₂ or C₄ to C₂₀ olefin comonomer (such as C₃ to C₁₂ alpha-olefin, such as propylene, butene, hexene, octene, decene, dodecene, such as propylene, butene, hexene, octene). In at least one embodiment, the monomer is propylene and the comonomer is ethylene, such as about 5 wt % to about 40 wt % ethylene, such as about 10 wt % to about 35 wt % ethylene, such as about 15 wt % to about 25 wt % ethylene, based on the weight of the polymer.

In at least one embodiment, the polypropylene homopolymer or a polypropylene copolymer has a unimodal or multimodal molecular weight distribution as determined by Gel Permeation Chromatography (GPC). “Unimodal” refers to the GPC trace having one peak or inflection point. “Multimodal” refers to the GPC trace having at least two peaks or inflection points. An inflection point is the point where the second derivative of the GPC curve changes in sign (e.g., from negative to positive or vice versus).

In at least one embodiment, a polypropylene homopolymer or polypropylene copolymer of the present disclosure has an Mw (weight average molecular weight) of about 10,000 g/mol (grams per mole) to about 1,000,000 g/mol, such as about 10,000 g/mol to about 500,000 g/mol, such as about 100,000 g/mol to about 300,000 g/mol, such as about 100,000 g/mol to about 200,000 g/mol, alternatively about 200,000 g/mol to about 300,000 g/mol, such as about 250,000 g/mol to about 300,000 g/mol, alternatively about 300,000 g/mol to about 350,000 g/mol, alternatively about 100,000 g/mol to about 200,000 g/mol.

In at least one embodiment, a polypropylene homopolymer or polypropylene copolymer of the present disclosure has an Mn (number average molecular weight) of about 5,000 g/mol to about 200,000 g/mol, such as about 25,000 g/mol to about 100,000 g/mol, such as about 25,000 g/mol to about 50,000 g/mol, alternatively about 5,000 g/mol to about 25,000 g/mol, such as about 5,000 g/mol to about 15,000 g/mol, alternatively about 100,000 g/mol to about 200,000 g/mol.

In at least one embodiment, a polypropylene homopolymer or polypropylene copolymer of the present disclosure has an Mw/Mn (polydispersity index) value of about 1 to about 8, such as about 1.5 to about 8, such as about 1.5 to about 4, such as about 2 to about 3.5, such as about 2.5 to about 3.5.

In at least one embodiment, a polypropylene homopolymer or polypropylene copolymer of the present disclosure can have a melting point (Tm) (° C.) of about 120° C. to about 170° C., such as about 145° C. to about 165° C., such as about 150° C. to about 160° C., such as about 157° C. to about 162° C., alternatively about 150° C. to about 155° C.

The stereoregularity of isotactic polypropylene homopolymers can be determined by the catalyst, total monomer concentrations, and reactor temperature. The isotactic polypropylene homopolymers (or copolymers) made according to processes of the present disclosure may comprise up to 99.99% m-dyads based on the total number of dyads present in the polymer, such as a meso dyad (m-dyad) content (m %) of about 85% to about 99.99%, such as about 95% to about 99.95%, such as about 99% to about 99.9%, such as about 98% to about 99%, as determined by ¹³C Nuclear Magnetic Resonance (NMR), the remainder balance being r-dyad (racemic dyad) content (r %).

In some embodiments, an isotactic propylene homopolymer has an [mmmm] pentad content of about 95.0% to about 99.5%, such as about 95.0% to about 98.0%, such as about 95.0% to about 97.0%, as determined by ¹³C NMR. In some embodiments, an isotactic polypropylene homopolymer has an [rrrr] pentad content of about 0% to about 0.5%, such as about 0.0% to about 0.2%, such as about 0.01% to about 0.1%, as determined by ¹³C NMR.

In some embodiments, a polypropylene homopolymer or polypropylene copolymer has a Young's modulus (at 23° C.) of about 1700 MPa or more, such as about 1800 MPa or more, such as about 1900 MPa or more, according to ASTM D638. In some embodiments, a polypropylene homopolymer or polypropylene copolymer has a Young's modulus (at 23° C.) of about 1000 MPa to about 2300 MPa, such as about 1000 MPa to about 1300 MPa, alternatively about 1300 MPa to about 1800 MPa, alternatively about 1800 MPa to about 2200 MPa, such as about 1900 MPa to about 2200 MPa, such as about 2000 MPa to about 2200 MPa, alternatively about 1700 MPa to about 2000 MPa, such as about 1800 MPa to about 2000 MPa, according to ASTM D638.

In some embodiments, a propylene homopolymer or propylene copolymer has a tensile stress at yield at 23° C. of 20 MPa or more, such as about 25 MPa or more, such as about 30 MPa or more, such as about 35 MPa or more, according to ASTM D638. In some embodiments, a polypropylene homopolymer or polypropylene copolymer has a tensile stress at yield at 23° C. of about 20 MPa to about 50 MPa, such as about 25 MPa to about 30 MPa, alternatively about 30 MPa to 35 MPa, alternatively about 35 MPa to about 40 MPa, according to ASTM D638.

In some embodiments, a polymer is a polypropylene homopolymer. A polypropylene homopolymer of the present disclosure can have a flexural modulus of about 1,500 MPa to about 2,000 MPa, such as about 1,700 MPa to about 1,800 MPa, alternatively about 1,800 MPa to about 1,900 MPa, as determined by ISO 178 or ASTM D790. A polypropylene homopolymer can have a Shore D hardness of about 50 to about 90, such as about 60 to about 80, such as about 70 to about 75, alternatively about 65 to about 70, alternatively about 75 to about 80, as determined by ASTM D2240. A polypropylene homopolymer can have a melt mass-flow rate (MFR) (230° C.; 2.16 kg) of about 1 to about 60 g/10 min (grams per minute), such as about 8 to about 20 g/10 min, alternatively about 20 to about 35 g/10 min, as determined by ASTM D1238. A polypropylene homopolymer can have a melting point of about 150° C. to about 185° C., such as about 160° C. to about 170° C., such as about 160° C. to about 165° C., as determined by ISO 3146 or Differential Scanning calorimetry (DSC) method. In some embodiments, polypropylene homopolymers are obtained commercially, such as BOREALIS™ HC101BF.

In some embodiments, a polypropylene copolymer is a random or block polypropylene copolymer. Polypropylene heterophasic copolymers comprise a polymer matrix with a dispersed rubbery copolymer phase. The matrix is a homopolymer or random copolymer matrix. The rubbery copolymer phase is a reactor blend of an amorphous rubber, a rubber-like polymer which is normally an ethylene-propylene copolymer (rubber), and a semicrystalline ethylene copolymer. The heterophasic copolymers are produced in two or more reactors. The matrix homopolymer or random copolymer may be produced by standard polymerization with Ziegler-Natta catalyst system in one or more slurry or bulk (loop) reactors or gas phase reactors or combinations of both. In a second stage, the polymerization is continued, and the rubbery copolymer phase is produced in the matrix polymer using one or more gas phase reactors. The composition of the rubbery phase is controlled in the second stage by the ethylene/propylene ratio and the amount of hydrogen. A block or random polypropylene copolymer of the present disclosure can have a flexural modulus of about 800 MPa to about 1,400 MPa, such as about 850 MPa to about 1,000 MPa, alternatively about 1,000 MPa to about 1,300 MPa, as determined by ISO 178. A block or random polypropylene copolymer can have a Shore D hardness of about 60 to about 100, such as about 70 to about 90, such as about 75 to about 85, alternatively about 65 to about 75, alternatively about 85 to about 95, as determined by ASTM D2240. A block or random polypropylene copolymer can have a melt mass-flow rate (MFR) (230° C.; 2.16 kg (kilograms)) of about 2 to about 45 g/10 min, such as about 8 to about 20 g/10 min, as alternatively about 20 to about 35 g/10 min, as determined by ASTM 1238D. A block or random polypropylene copolymer can have a melting point of about 140° C. to about 155° C., such as about 145° C. to about 150° C., such as about 147° C. to about 150° C., as determined by DSC method. In some embodiments, block or random polypropylene copolymers are obtained commercially, such as TOTAL™ PPR 3020 SM3.

(A) (1) Polypropylene Random, Heterophasic Copolymers

In some embodiments, a propylene copolymer is a polypropylene random, heterophasic copolymer. A polypropylene random, heterophasic copolymer (also referred to herein as a “RAHECO”) is a type of polypropylene polymer that combines characteristics of both random copolymers and heterophasic copolymers. A polypropylene random, heterophasic copolymer combines random copolymer characteristics (due to the presence of ethylene) and heterophasic copolymer characteristics (with distinct phases within the material). This combination can result in a polymer with a unique set of properties, which may include improved flexibility, impact resistance, and optical performance compared to conventional homopolymer polypropylene or random copolymer polypropylene. A polypropylene random, heterophasic copolymer of the present disclosure can have a flexural modulus of about 250 MPa to about 500 MPa, such as about 300 MPa to about 475 MPa, such as about 275 MPa to about 350 MPa, alternatively about 350 MPa to about 500 MPa, such as about 400 MPa to about 450 MPa, as determined by ASTM D790. A polypropylene random, heterophasic copolymer can have a Shore D hardness of about 70 or less, such as about 10 to about 53, such as about 20 to about 50, such as about 20 to about 30, alternatively about 30 to about 40, alternatively about 40 to about 50, as determined by ASTM D2240. A polypropylene random, heterophasic copolymer can have a melt mass-flow rate (MFR) (230° C.; 2.16 kg) of about 2 to about 60 g/10 min, such as about 8 to about 35 g/10 min, such as about 10 to about 20 g/10 min, alternatively about 20 to about 30 g/10 min, as determined by ASTM 1238D. A polypropylene random, heterophasic copolymer can have a melting point of about 140° C. to about 155° C., such as about 145° C. to about 150° C., such as about 145° C. to about 148° C., as determined by ISO 3146. In some embodiments, polypropylene random, heterophasic copolymers are obtained commercially, such as the BORMED™ series of Borealis, in particular the polypropylene-ethylene copolymers BORMED™ RD808CF, BORMED™ SB815MO and BORMED™ SC876CF. Polypropylene random, heterophasic copolymers of the present disclosure can be synthesized according to any suitable polymerization, such as those described in U.S. Pat. No. 10,519,306, incorporated herein by reference.

Further, the RAHECO can have a toughness, such as a Charpy notched impact strength measured according to ISO 179-1eA: 2000 at 23° C. of about 10 to about 100.0 kJ/m² (kiloJoules per square meter), such as about 20 to about 90 kJ/m². In some embodiments, a RAHECO has a Charpy notched impact strength measured according to ISO 179-1eA: 2000 at −20° C. of about 2 to 20 kJ/m², such as about 2.5 to about 10 kJ/m².

With regard to the optical properties, a RAHECO can have a haze according to ASTM D 1003-00 measured on a 1 mm thick injection molded specimen below 80%, such as below 78%. Additionally or alternatively, a RAHECO has a haze before sterilization determined according to ASTM D 1003-00 measured on a 50 μm (micrometer) cast film of below 15%, such as below 12%, and/or a haze after sterilization determined according to ASTM D 1003-00 measured on a 50 μm cast film of below 20%, such as below 16%.

A RAHECO includes a matrix (M) being a random polypropylene copolymer (R-PP) and dispersed therein an elastomeric polypropylene copolymer (E). Thus the matrix (M) contains (finely) dispersed inclusions being not part of the matrix (M) and said inclusions contain the elastomeric polypropylene copolymer (E). The term inclusion indicates that the matrix (M) and the inclusion form different phases within the RAHECO. The presence of second phases or the so-called inclusions are for instance visible by high resolution microscopy, like electron microscopy or atomic force microscopy, or by dynamic mechanical thermal analysis (DMTA).

In some embodiments, a RAHECO includes as polymer components only the random polypropylene copolymer (R-PP) and the elastomeric polypropylene copolymer (E). In other words, the RAHECO may contain further additives but no other polymer in an amount exceeding 5 wt %, such as not exceeding 3 wt %, such as not exceeding 1 wt %, based on the total RAHECO. One additional polymer which may be present in such low amounts is a polyethylene which is a by-reaction product obtained by the preparation of the RAHECO. Accordingly, it is in particular appreciated that a RAHECO contains only the random polypropylene copolymer (R-PP), the elastomeric polypropylene copolymer (E) and optionally polyethylene in amounts as mentioned in this paragraph.

The RAHECO has a melt flow rate MFR2 (230° C./2.16 kg) of 2.5 to 12 g/10 min, such as about 3 to about 10 g/10 min, such as about 3.5 to about 8 g/10 min, such as about 3.5 to about 7 g/10 min.

A RAHECO is thermo mechanically stable. Accordingly, a RAHECO has a melting temperature of at least 140° C., such as about 140 to about 155° C., such as about 142 to about 152° C.

Typically, a RAHECO has a rather low crystallization temperature, i.e. of not more than 120° C., such as of about 95 to about 120° C., such as about 100 to about 118° C. These values are especially applicable in case the RAHECO is not α-nucleated.

A RAHECO includes apart from propylene also comonomers. For example, RAHECO includes apart from propylene ethylene and/or C₄ to C₈ α-olefins. Accordingly, the term “propylene copolymer” is understood as a polypropylene including units derivable from: (a) propylene and (b) ethylene and/or C₄ to C₈ α-olefins.

Thus, a RAHECO, i.e., the random polypropylene copolymer (R-PP) as well as the elastomeric polypropylene copolymer (E), comprises monomers copolymerizable with propylene, for example comonomers such as ethylene and/or C₄ to C₈ α-olefins, in particular ethylene and/or C₄ to C₈ α-olefins, e.g. 1-butene and/or 1-hexene. For example, a RAHECO includes monomers copolymerizable with propylene from the group of ethylene, 1-butene and 1-hexene. More specifically, the RAHECO comprises-apart from propylene-units derivable from ethylene and/or 1-butene. In at least one embodiment, a RAHECO comprises units derivable from ethylene and propylene only. In some embodiments, the random polypropylene copolymer (R-PP) as well as the elastomeric polypropylene copolymer (E) of the RAHECO contain the same comonomer, like ethylene.

Accordingly, the elastomeric polypropylene copolymer (E) can be an ethylene polypropylene rubber (EPR), whereas the random polypropylene copolymer (R-PP) is a random ethylene polypropylene copolymer (R-PP).

Additionally, it is appreciated that a RAHECO has a moderate total comonomer content which contributes to the softness of the material. Thus, the comonomer content of the RAHECO is about 12.5 to about 22.0 mol % (percentage of the total moles compound), such as about 13.9 to about 21 mol %, such as about 14 to about 20 mol %, such as about 14.3 to about 20.0 mol %.

The xylene cold soluble (XCS) fraction measured according to ISO 16152 (25° C.) of the RAHECO is about 38 to about 50 wt %, such as about 38 to about 45 wt %, such as about 39 to about 44 wt %, such as about 40 to about 43.5 wt %.

Further it is appreciated that the xylene cold soluble (XCS) fraction of the RAHECO is specified by its intrinsic viscosity. A low intrinsic viscosity (IV) value reflects a low weight average molecular weight. For example, the xylene cold soluble fraction (XCS) of the RAHECO has an intrinsic viscosity (IV) measured according to ISO 1628/1 (at 135° C. in decalin) of about 1.8 to about 3.5 dl/g, such as about 1.9 to about 3 dl/g, such as about 2 to below 2.8 dl/g, such as about 2.0 to below 2.6 dl/g.

Additionally, the comonomer content, such as the ethylene content, of the xylene cold soluble (XCS) fraction of the RAHECO is below about 36 mol %, such as about 28 to below 35.5 mol %, such as about 30 to below 34.5 mol. %. The comonomers present in the xylene cold soluble (XCS) fraction are those defined above for the random polypropylene copolymer (R-PP) and the elastomeric polypropylene copolymer (E), respectively. In some embodiments, the comonomer is ethylene only.

The RAHECO can be further defined by its individual components, i.e., the random polypropylene copolymer (R-PP) and the elastomeric polypropylene copolymer (E).

The random polypropylene copolymer (R-PP) comprises monomers copolymerizable with propylene, for example comonomers such as ethylene and/or C₄ to C₈ α-olefins, in particular ethylene and/or C₄ to C₆ α-olefins, e.g. 1-butene and/or 1-hexene. For example, the random polypropylene copolymer (R-PP) includes monomers copolymerizable with propylene from the group of ethylene, 1-butene and 1-hexene. More specifically the random polypropylene copolymer (R-PP) comprises-apart from polypropylene-units derivable from ethylene and/or 1-butene. In at least one embodiment, the random polypropylene copolymer (R-PP) comprises units derivable from ethylene and propylene only.

As mentioned above, the random polypropylene copolymer (R-PP) is featured by a moderate comonomer content. Accordingly, the comonomer content of the random polypropylene copolymer (R-PP) is in the range of about 5.1 to about 17 mol %, such as about 5.4 to about 10.5 mol %, such as about 5.7 to about 10 mol %, such as about 6 to about 9.8 mol %.

The random polypropylene copolymer (R-PP) may comprise at least two polymer fractions, like two or three polymer fractions, such as polypropylene copolymers. In some embodiments, the random polypropylene copolymer (R-PP) includes a first polypropylene copolymer fraction (R-PP1) and a second polypropylene copolymer fraction (R-PP2). In some embodiments, the first polypropylene copolymer fraction (R-PP1) is the comonomer lean fraction whereas the second polypropylene copolymer fraction (R-PP2) is the comonomer rich fraction.

Concerning the comonomers used for the first polypropylene copolymer fraction (R-PP1) and second polypropylene copolymer fraction (R-PP2), reference is made to the comonomers of the random polypropylene copolymer (R-PP). For example, the first polypropylene copolymer fraction (R-PP1) and the second polypropylene copolymer fraction (R-PP2) contain the same comonomers, like ethylene.

The term “random” indicates that the comonomers of the random polypropylene copolymer (R-PP), as well as of the first polypropylene copolymer fraction (R-PP1) and the second polypropylene copolymer fraction (R-PP2) are randomly distributed within the polypropylene copolymers.

In some embodiments, the random polypropylene copolymer (R-PP) is featured by its relative content of isolated to block ethylene sequences (I(E)). The isolated to block ethylene sequences (I(E)) of the random polypropylene copolymer (R-PP) is measured on the xylene cold insoluble fraction (XCI) of the RAHECO. Accordingly, the xylene cold insoluble fraction (XCI) of the RAHECO has an isolated to block ethylene sequences (I(E)) below 55%, such as about 40 to about 53%, such as about 42 to about 50%, such as about 43 to about 48%.

The I(E) content [%] is defined by in-equation (I):

I ⁡ ( E ) = fPEP ( fEEE + fPEE + fPEP ) × 100 ( I )

wherein

• • (E) is the relative content of isolated to block ethylene sequences [in %];
  • fPEP is the mol fraction of propylene/ethylene/propylene sequences (PEP) in the xylene cold insoluble fraction (XCI) of the RAHECO;
  • fPEE is the mol fraction of propylene/ethylene/ethylene sequences (PEE) and of ethylene/ethylene/propylene sequences (EEP) in the xylene cold insoluble fraction (XCI) of the RAHECO;
  • fEEE is the mol fraction of ethylene/ethylene/ethylene sequences (EEE) in the xylene cold insoluble fraction (XCI) of the RAHECO, wherein all sequence concentrations being based on a statistical triad analysis of ¹³C-NMR data.

The I(E) content is a value determined by the catalyst applied for the preparation of the RAHECO as well as the comonomer content of the xylene insoluble fraction (XCI). A low comonomer content leads to a higher I(E) content since the amount of propylene/ethylene/propylene sequences (PEP) in the xylene cold insoluble fraction (XCI) is statistically higher in case of a low overall amount of ethylene units.

In some embodiments, the RAHECO has a comonomer content of the xylene insoluble fraction (XCI) in the range of about 4 to about 15 mol %, such as about 6 to about 11 mol %, such as about 7 to about 9 mol %.

The random polypropylene copolymer (R-PP) has a melt flow rate MFR₂ (230° C./2.16 kg) before visbreaking measured according to ISO 1133 of about 1 to about 4 g/10 min, such as about 1.2 to about 3.5 g/10 min, such as about 1.4 to about 3 g/10 min.

In some embodiments, a RAHECO includes about 60 to about 85 wt %, such as about 65 to about 82 wt %, such as about 70 to about 80 wt % of the random polypropylene copolymer (R-PP), based on the total weight of the RAHECO.

Additionally, a RAHECO includes about 15 to about 40 wt %, such as about 18 to about 45 wt %, such as about 20 to about 40 wt % of the elastomeric polypropylene copolymer (E), based on the total weight of the RAHECO.

Thus, it is appreciated that a RAHECO can include about 60 to about 85 wt % of the random polypropylene copolymer (R-PP) and about 15 to about 40 wt % of the elastomeric polypropylene copolymer (E), based on the total weight of the RAHECO.

Accordingly, a further component of the RAHECO is the elastomeric polypropylene copolymer (E) dispersed in the matrix (M). Concerning the comonomers used in the elastomeric polypropylene copolymer (E) it is referred to the information provided for the RAHECO. Accordingly, the elastomeric polypropylene copolymer (E) comprises monomers copolymerizable with propylene, for example comonomers such as ethylene and/or C₄ to C₈ α-olefins, in particular ethylene and/or C₄ to C₆ α-olefins, e.g., 1-butene and/or 1-hexene. For example, the elastomeric polypropylene copolymer (E) includes monomers copolymerizable with propylene from the group of ethylene, 1-butene and 1-hexene. More specifically, the elastomeric polypropylene copolymer (E) includes—apart from propylene-units derivable from ethylene and/or 1-butene. Thus, in some embodiments, the elastomeric polypropylene copolymer (E) comprises units derivable from ethylene and propylene only.

The comonomer content, like ethylene content, of the elastomeric polypropylene copolymer (E) may be about 30 to about 65 mol %, such as about 55 to about 62 mol %, such as about 40 to about 60.0 mol %.

In some embodiments, a RAHECO may contain up to 5 wt % additives, like nucleating agents and antioxidants, as well as slip agents and antiblocking agents. In some embodiments, the additive content (without α-nucleating agents) is below 3 wt %, such as below 1 wt %.

(B) Thermoplastic Elastomers

Thermoplastic elastomers (TPEs) are a class of polymers that combine the properties of thermoplastics and elastomers and are known for their unique combination of elasticity, flexibility, and processability, making them versatile materials used in a wide range of applications, including medical device and pharmaceutical applications.

Example TPEs can include styrenic block copolymers, thermoplastic polyurethanes, thermoplastic olefins, thermoplastic vulcanizates, and thermoplastic copolyesters. Styrenic block copolymers (SBCs) include materials like styrene-butadien-styrene (SBS) and styrene-butylene-styrene (SEBS). For example, SEBS TPEs have versatility and ability to balance the mechanical properties of traditional rubber with the processability of thermoplastics. Thermoplastic polyurethanes (TPUs) are highly versatile and can promote flexibility and durability. Thermoplastic olefins (TPOs) can promote chemical resistance and impact strength. Thermoplastic vulcanizations (TPVs) combine properties of vulcanized rubber with thermoplastic processing characteristics. Thermoplastic copolyesters (TPE-E or TPEE) offer excellent chemical resistance and promote chemical resistance.

(B)(1) Styrenic Block Copolymers

A TPE can be a styrene-based elastomer, such as a styrene-isoprene-styrene (SIS) block copolymer, a styrene-butadiene-styrene (SBS) block copolymer or a styrene-isoprene-butadiene-styrene (SIBS) block copolymer, such as a styrene-isoprene-styrene (SIS) block copolymer, and has a styrene content of at least 5 wt %, such as at least 10 wt %, such as at least 15 wt %. The upper limit may be about 50 wt %, such as about 40 wt %, more such as about 35 wt %, such as about 30 wt %.

Further it is appreciated that the styrene-based elastomer, such as a styrene-isoprene-styrene (SIS) block copolymer, can have a melt flow rate MFR₂ (230° C., ISO 1133) of not more than 200 g/10 min, such as not more than 150 g/10 min, such as not more than 100 g/10 min.

On the other hand, the melt flow rate of the styrene-based elastomer, such as a styrene-isoprene-styrene (SIS) block copolymer or a styrene-butadiene-styrene block copolymer, does not fall below 2 g/10 min. Accordingly, a range is about 2 to about 200 g/10 min, such as about 8 to about 150 g/10 min, such as about 10 to about 100 g/10 min.

Further the styrene-based elastomer may be defined by its density. Thus, it is appreciated that the styrene-based elastomer has a density of about 0.900 g/cm³ (gram per cubic centimeter) to about 0.950 g/cm³, such as about 0.91 g/cm³ to about 0.95 g/cm³, such as about 0.915 to about 0.945 g/cm³.

Additionally or alternatively the styrene-based elastomer can be defined by the Shore A hardness. Thus, it is appreciated that the styrene-based elastomer (B) has a Shore A hardness measured according to ASTM D 2240 from 25 to 80, such as from 30 to 75.

Examples of styrene-based elastomer are the DEXCO™ TSRC—product line VECTOR for SIS and SBS, commercialized as VECTOR™ 4111A (SIS, Shore A hardness of 40, styrene content of 18 wt %, density 0.93 g/cm³), VECTOR™ 4211 (SIS, 29 wt % styrene, density 0.94 g/cm³, Shore A 68) or VECTOR™ 8508 (SBS, 29 wt % styrene, density 0.94 g/cm³, Shore A 67); or products from the KRATON™ D (SBS), KRATON™ D (SIS) or KRATON™ S (SIBS) product lines, like e.g. KRATON™ D1102 A (SBS, 29.5 wt % styrene, density 0.94 g/cm³, Shore A 70), KRATON™ D1111 K (SIS, 22 wt % styrene, density 0.93 g/cm³, Shore A 45) or KRATON™ D1119 B (SIS, 16 wt % styrene, density 0.94 g/cm³, Shore A 38) or from the VERSASLIS ENI™—product line “EUROPRENE™” for SIS and SBS, examples EUROPRENE™ SOL T 190 (SIS, 16 wt % styrene, density 0.92 g/cm³, Shore A 30) or EUROPRENE™ SOL T 6205 (SBS, 25 wt % styrene, density 0.93 g/cm³, Shore A 68).

(B)(2) Thermoplastic Polyurethanes (TPUs)

A thermoplastic elastomer can be a thermoplastic polyurethane. Thermoplastic polyurethanes are prepared by reacting (a) isocyanates with (b) compounds, also referred to as polyols, which are reactive toward isocyanates and have a number average molecular weight of from 0.5×10³ g/mol to 300×10³ g/mol, and optionally chain extenders having a molecular weight of 0.05×10³ g/mol to 0.499×10³ g/mol, optionally with the aid of catalysts and/or additives and/or auxiliaries.

The following components: (a) isocyanate, (b) compounds, also referred to as polyol, which are reactive toward isocyanates and (c) chain extenders are also referred to individually or collectively as formative components.

As organic isocyanates (a), preference can be given to using aliphatic, cycloaliphatic, araliphatic and/or aromatic isocyanates, such as diisocyanates, such as aliphatic diisocyanates, such as trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene and/or octamethylene diisocyanate, 1,6-hexamethylene diisocyanate (HDI), 2-methylpentamethylene 1,5-diisocyanate, 2-ethylbutylene 1,4-diisocyanate, pentamethylene 1,5-diisocyanate, butylene 1,4-diisocyanate, 1-isocyanato-3,3,5-trimethyl-5-isocyanatomethylcyclohexane (isophorone diisocyanate, IPDI), 1,4- and/or 1,3-bis(isocyanatomethyl)cyclohexane (HXDI), cyclohexane 1,4-diisocyanate, 1-methylcyclohexane 2,4- and/or 2,6-cyclohexane diisocyanate and/or dicyclohexylmethane 4,4′-, 2,4′- and 2,2′-diisocyanate (H12MDI), and/or 2,4-tetramethylenexylene diisocyante (TMXDI). The diisocyanate can be selected from: pentamethylene 1,5-diisocyanate, hexamethylene 1,6-diisocyanate (HDI), 1-isocyanato-3,3,5-trimethyl-5-isocyanatomethylcyclohexane (isophorone diisocyanate, IPDI), cyclohexane 1,4-diisocyanate, 1-methylcyclohexane 2,4- and 2,6-diisocyanate and dicyclohexylmethane 4,4′-, 2,4′- and 2,2′-diisocyanate (H12MDI). For example, hexamethylene diisocyanate can be used, such as 1,6-hexamethylene diisocyanate (HDI).

From compounds (b) which are reactive toward isocyanates, preference can be given to using polyesterols or polyetherols, which are also summarized under the term “polyols”. Polyetherols may be preferred. The number average molecular weights of these polyols are in the range from 0.5×10³ kg/mol to 8×10³ kg/mol, such as from 0.6×10³ g/mol to 5×10³ g/mol, in particular from 0.8×10³ g/mol to 3×10³ kg/mol. The polyols can have an average functionality in the range of 1.8 to 2.4, such as from 1.9 to 2.2, in particular from 1.95-2.05. The polyols (b) may have only primary hydroxyl groups.

In some embodiments, chain extenders are utilized in the thermoplastic polyurethane. These can be aliphatic, araliphatic, aromatic and/or cycloaliphatic compounds having a molecular weight of from 0.05×10³ kg/mol to 0.499×10³ g/mol. The chain extenders can be 2-functional compounds, i.e., they have two groups which are reactive toward isocyanates. Example chain extenders are diamines and/or alkanediols having from 2 to 10 carbon atoms in the alkylene radical, in particular 1,4-butanediol, 1,6-hexanediol and/or dialkylene, trialkylene, tetraalkylene, pentaalkylene, hexaalkylene, heptaalkylene, octaalkylene, nonaalkylene and/or decaalkylene glycols having from 3 to 8 carbon atoms, such as corresponding oligopropylene and/or polypropylene glycols, with mixtures of the chain extenders also being able to be used. The compounds (c) can have only primary hydroxyl groups. 1,3-propanediol, 1,4-butanediol or 1,6-hexanediol or any combination, i.e., 1,3-propanediol and 1,4-butanediol, or 1,3-propanediol and 1,6-hexanediol, or 1,4-butanediol and 1,6-hexanediol, or 1,6-hexanediol are used for preparing the thermoplastic polyurethane.

(B)(3) Thermoplastic Olefins (TPOs) and Thermoplastic Vulcanizates (TPVs)

A thermoplastic elastomer can include a thermoplastic olefin (TPO) or thermoplastic vulcanization (TPV).

TPVs include a rubber and a thermoplastic polyolefin. In at least one embodiment, the TPV (and/or TPO) can include an amount of a rubber that is about 80 wt % or less, such as about 70 wt % or less, such as about 50 wt % or less, such as about 40 wt % or less, such as about 30 wt % or less, such as about 25 wt % or less, such as about 20 wt % or less, such as about 15 wt % or less, such as about 10 wt % or less, such as about 5 wt %, based on a combined weight of the rubber and the thermoplastic polyolefin. In these or other embodiments, the amount of rubber within the TPV (and/or TPO) can be about 5 wt % to about 80 wt %, such as about 10 wt % to about 60 wt %, such as about 15 wt % to about 55 wt %, such as about 20 wt % to about 50 wt %, such as about 25 wt % to about 45 wt %, such as about 30 wt % to about 40 wt %, based on a combined weight of the rubber and the thermoplastic polyolefin. In at least one embodiment, the TPV (and/or TPO) can include one or more types of rubber.

In at least one embodiment, the TPV (and/or TPO) can include an amount of a thermoplastic phase (e.g., a thermoplastic polymer or a thermoplastic polyolefin) that is about 20 wt % or more, such as about 30 wt % or more, such as about 50 wt % or more, such as about 60 wt % or more, such as about 70 wt % or more, such as about 75 wt % or more, such as about 80 wt % or more, such as about 85 wt % or more, such as about 90 wt % or more, such as about 95 wt %, based on a combined weight of the rubber and the thermoplastic polyolefin phase. In these or other embodiments, the amount of thermoplastic phase within the TPV (and/or TPO) can be about 20 wt % to about 95 wt %, such as about 40 wt % to about 90 wt %, such as about 45 wt % to about 85 wt %, such as about 50 wt % to about 80 wt %, such as about 55 wt % to about 75 wt %, such as about 60 wt % to about 70 wt %, based on a combined weight of the rubber and the thermoplastic phase. In at least one embodiment, the TPV (and/or TPO) can include one or more types of thermoplastic phase.

In at least one embodiment, and where the thermoplastic phase includes a blend of propylene-based polymer and ethylene-based polymer, the thermoplastic phase may include about 51 wt % to about 100 wt % of propylene-based polymer (such as about 65 wt % to about 99.5 wt %, such as about 85 wt % to about 99 wt %, such as about 95 wt % to about 98 wt %) based on a total weight of the thermoplastic phase, with the balance of the thermoplastic phase including an ethylene-based polymer. For example, in some embodiments, the thermoplastic phase may include about 0 wt % to about 49 wt % of ethylene-based polymer (such as about 1 wt % to about 15 wt %, such as about 2 wt % to about 5 wt %) based on the total weight of the thermoplastic phase.

In at least one embodiment, fillers (such as calcium carbonate, clays, silica, talc, titanium dioxide, carbon black, a nucleating agent, mica, wood flour, and the like, and blends thereof, as well as inorganic and organic nanoscopic fillers) may be present in the TPV (and/or TPO) in an amount of about 0.1 wt % to about 10 wt % based on the total weight of the TPV (and/or TPO), such as about 1 wt % to about 7 wt %, such as about 2 wt % to about 5 wt %. The amount of filler that can be used may depend, at least in part, upon the type of filler and the amount of extender oil that is used.

In at least one embodiment, an oil (e.g., an extender oil) may be present in the TPV (and/or TPO) in an amount of about 10 wt % to about 40 wt % by weight of combined TPV (and/or TPO), such as about 12 wt % to about 35 wt %, such as about 14 wt % to about 32 wt %. The quantity of oil added can depend on the properties desired, with an upper limit that may depend on the compatibility of the particular oil and blend ingredients; and this limit can be exceeded when excessive exuding of oil occurs. The amount of oil can depend, at least in part, upon the type of rubber. High viscosity rubbers are more highly oil extendable. Where low molecular weight ester plasticizers are employed, the ester plasticizers are generally used in amounts of about 40 wt % or less, such as about 35 wt % or less based on total TPV (and/or TPO).

In at least one embodiment, the TPV (and/or TPO) can include a curative. Amounts and types of curatives that are useful for the TPVs (and/or TPO) described herein are discussed below.

In at least one embodiment, the TPV (and/or TPO) may include a processing additive (e.g., a polymeric processing additive) in an amount of about 0.1 wt % to about 20 wt % based on the total weight of the TPV (and/or TPO).

In at least one embodiment, the TPV (and/or TPO) may optionally include reinforcing and non-reinforcing fillers, colorants, antioxidants, nucleators, stabilizers, rubber processing oil, lubricants, antiblocking agents, anti-static agents, waxes, foaming agents, pigments, flame retardants, antistatic agents, slip masterbatches, siloxane based slip agents (e.g., Dow Corning™ HMB-0221 Masterbatch available from Dow Chemical Company) ultraviolet inhibitors, antioxidants, and other processing aids known in the rubber and TPV (or TPO) compounding art. These additives can be used in the TPVs (and/or TPOs) at an amount of up to about 20 wt % of the total weight of the TPV (and/or TPO).

In some embodiments, the TPV (or TPO) can be formed from an extremely low thermal conductivity rubber component and a high temperature resistant thermoplastic component having low thermal conductivity, high thermal softening point, high compressive strength, and/or high compressive creep resistance. In some embodiments, the rubber can be non-crosslinked, crosslinked, or partially crosslinked. In some embodiments, the outer surface of the conduit is provided with at least one layer of solid insulation comprising a high temperature resistant TPV (and/or TPO) composition having low thermal conductivity, high thermal softening point, high compressive strength, and high compressive creep resistance. In some embodiments, the thermoplastic phase of the TPV (and/or TPO) composition can include polypropylene, polyphenylene oxide blended with polypropylene, polybutylene terephthalate, polyethylene terephthalate, acrylonitrile butadiene styrene, acrylonitrile styrene acrylate, polyetherimide, polyamides (including polyamide 12 and 6), polymethylpentene (and blends thereof), cyclic olefin copolymers, and a combination thereof.

(B)(4) Rubber Phase of TPOs and/or TPVs

In at least one embodiment, the rubber phase can be non-crosslinked, crosslinked, or partially crosslinked. Reference to a rubber may include mixtures of more than one rubber. Rubbers that may be employed to form the rubber phase include those polymers that are capable of being cured or crosslinked by a phenolic resin or a hydrosilylation curative (e.g., silane-containing curative), a peroxide with a coagent, a moisture cure via silane grafting, or an azide.

Non-limiting examples of rubbers can include olefinic elastomeric terpolymers, nitrile rubbers, butyl rubbers (such as isobutylene-isoprene rubber (IIR), brominated isobutylene-isoprene rubber (BIIR), and isobutylene paramethyl styrene rubber (BIMSM), polyisobutylene rubber (PIB)), natural rubbers, ethylene polypropylene rubbers (EPR), acrylic rubbers such as alkyl acrylate copolymers (ACM), styrenic-block copolymers (SBC), styrene-butadiene-styrene (SBS) polymers, hydrogenated styrenic copolymers such as SEBS (styrene-ethylene/butylene-styrene), SEEPS (Styrene-[ethylene-(ethylene-propylene)]-styrene), fluoroelastomer rubbers (e.g., FKM), and mixtures thereof. In at least one embodiment, the olefinic elastomeric terpolymers can include ethylene-based elastomers such as ethylene-propylene-non-conjugated diene rubbers. In some embodiments, the polyisobutylene rubber can be liquid, solid bale, or masterbatch pellet form, can be oligomeric, polymeric, or a combination thereof. Non-limiting examples of rubber phases include ethylene based plastomer/elastomers such as ENGAGE™ and EXACT™, as well as propylene based plastomers/elastomers such as VISTAMAXX™ (including VISTAMAXX™ 6102) and VERSIFY™.

In some embodiments, the rubber can be highly cured. In some embodiments, the rubber can be advantageously partially or fully (completely) cured. In some embodiments, the rubber can be advantageously not cured or crosslinked. The degree of cure can be measured by determining the amount of rubber that is extractable from the TPV (and/or TPO) composition by using cyclohexane or boiling xylene as an extractant. This method is disclosed in U.S. Pat. No. 4,311,628, which is incorporated herein by reference. In some embodiments, the rubber can have a degree of cure where not more than about 5.9 wt %, such as not more than about 5 wt %, such as not more than about 4 wt %, such as not more than about 3 wt % is extractable by cyclohexane at 23° C. as described in U.S. Pat. Nos. 5,100,947 and 5,157,081, which are incorporated herein by reference. In these or other embodiments, the rubber can be cured to an extent where greater than about 94 wt %, such as greater than about 95 wt %, such as greater than about 96 wt %, such as greater than about 97 wt % by weight of the rubber is insoluble in cyclohexane at 23° C. Alternately, in some embodiments, the rubber can have a degree of cure such that the crosslink density is at least 4×10-5 moles per milliliter of rubber, such as at least 7×10-5 moles per milliliter of rubber, such as at least 10×10-5 moles per milliliter of rubber.

Despite the fact that the rubber may be partially or fully cured, the compositions of this disclosure can be processed and reprocessed by conventional plastic processing techniques such as extrusion, injection molding, blow molding, and compression molding. The rubber within these thermoplastic elastomers can be in the form of finely-divided and well-dispersed particles of vulcanized or cured rubber within a continuous thermoplastic phase or matrix. In some embodiments, a co-continuous morphology or a phase inversion can be achieved. In those embodiments where the cured rubber is in the form of finely-divided and well-dispersed particles within the thermoplastic medium, the rubber particles can have an average diameter that is about 50 μm or less, such as about 30 μm or less, such as about 10 μm or less, such as about 5 μm or less, such as about 1 μm or less. In some embodiments, at least about 50%, such as about 60%, such as about 75% of the particles can have an average diameter of about 5 μm or less, such as about 2 μm or less, such as about 1 μm or less.

(B)(5) Thermoplastic Phase of TPOs and/or TPVs

In some embodiments, the thermoplastic phase of the TPV (and/or TPO) can include a polymer with a high temperature Vicat softening point, such as about 100° C. to about 200° C., such as about 130° C. to about 180° C., and/or a thermal conductivity of about 0.2 W/m·K (Watts per meter per degree Kelvin) or less, such as about 0.10 W/m·K to about 0.20 W/m·K, such as about 0.15 W/m·K to about 0.18 W/m·K. In some embodiments, the thermoplastic phase of the TPV (and/or TPO) compositions include a polymer that can flow above its melting temperature.

In some embodiments, the thermoplastic phase (e.g., a thermoplastic polymer or a thermoplastic polyolefin) can include more than one thermoplastic polymers. Non-limiting examples of thermoplastic polymers can include polypropylene (e.g., homopolymer, random copolymer, ICP), polyethylene (homopolymer, random copolymer), syndiotactic polystyrene, cyclic olefin copolymer, polyphenylene oxide (PPO) blended with polypropylene, polybutylene terephthalate, polyethylene terephthalate, acrylonitrile butadiene styrene, acrylonitrile styrene acrylate, polyetherimide, polyamide, polymethylpentene polymethylpentene resin (such as a homopolymer or copolymer, e.g., a homopolymer or copolymer of 4-methyl-1-pentene), or a combination thereof.

In at least one embodiment, the thermoplastic phase can include polyphenylene oxide blended with homopolymers or copolymers of polypropylene, polystyrene, and/or polyamide. In these and other embodiments, this blend can be predominantly polyphenylene oxide, e.g., polyphenylene oxide is present in the blend in an amount of at least about 50 wt %. Examples of polyphenylene oxide-polypropylene blends useful for the TPVs (and/or TPOs) are commercially available under the trade name Noryl™, such as Noryl™ GTX.

In some embodiments, the major component of the thermoplastic phase can include at least one thermoplastic polyolefin such as a polypropylene (such as a homopolymer, random copolymer, or impact copolymer, or combination thereof), an ethylene-based polymer (e.g., a polyethylene), a butene-based polymer (e.g., a polybutene), or a combination thereof. In some embodiments, the thermoplastic phase may also include, as a minor constituent, at least one thermoplastic polyolefin such as an ethylene-based polymer (e.g., polyethylene), a propylene-based polymer (e.g., polypropylene), or a butene-based polymer (e.g., a polybutene or a polybutene-1).

In some embodiments, the polypropylene can include a homopolymer, random copolymer, or impact copolymer polypropylene or combination thereof. In some embodiments, the polypropylene can be a high melt strength (HMS) long chain branched (LCB) homopolymer polypropylene. The propylene-based polymers may be synthesized by using an appropriate polymerization technique known in the art such as the conventional Ziegler-Natta type polymerizations, and catalysis employing single-site organometallic catalysts including metallocene catalysts.

Examples of polypropylene useful for the TPVs (and/or TPOs) described herein can include ExxonMobil™ pp 5341 (available from ExxonMobil); Achieve™ pp 6282NE1 (available from ExxonMobil) and/or polypropylene resins with broad molecular weight distribution as described in U.S. Pat. Nos. 9,453,093 and 9,464,178; and other polypropylene resins described in US20180016414 and US20180051160; Waymax MFX6 (available from Japan Polypropylene Corp.); Borealis Daploy™ WB140 (available from Borealis AG); and Braskem Ampleo 1025MA, Braskem Ampleo 1020GA, Braskem F008F, Braskem F180A (available from Braskem Ampleo), and other suitable polypropylenes. Table B shows the characteristics of selected propylene-based polymers. g′_vis can be measured using GPC-4D. Techniques for determining the molecular properties are described below.

In one or more embodiments, the thermoplastic component can be or can include isotactic polypropylene. In some embodiments, the thermoplastic component can contain one or more crystalline polypropylene homopolymers or copolymers of propylene having a melting temperature of about 110° C. to about 170° C. or higher as measured by DSC. Example copolymers of propylene can include terpolymers of propylene, impact copolymers of propylene, random polypropylene, and mixtures thereof. Example comonomers can have about 2 carbon atoms or about 4 to about 12 carbon atoms. In some embodiments, the comonomer can be ethylene.

In one or more embodiments, the thermoplastic phase can be or include a “propylene-based copolymer.” A “propylene-based copolymer” includes at least two different types of monomer units, one of which is propylene. Suitable monomer units can include, but are not limited to, ethylene and higher alpha-olefins ranging from C₄ to C₂₀, such as, for example, 1-butene, 4-methyl-1-pentene, 1-hexene or 1-octene and 1-decene, or mixtures thereof, for example. In some embodiments, ethylene can be copolymerized with propylene, so that the propylene-based copolymer includes propylene-derived units (units on the polymer chain derived from propylene monomers) and ethylene-derived units (units on the polymer chain derived from ethylene monomers).

Ethylene-based polymers can include those solid, generally high-molecular weight plastic resins that primarily include units derived from the polymerization of ethylene. In some embodiments, at least 90%, or at least 95%, or at least 99% of the units of the ethylene-based polymer can derive from the polymerization of ethylene. In particular embodiments, these polymers can include homopolymers of ethylene.

In some embodiments, the ethylene-based polymers may also include units deriving from the polymerization of α-olefin comonomer such as propylene, 1-butene, 1-hexene, 1-octene, 2-methyl-1-propene, 3-methyl-1-pentene, 4-methyl-1-pentene, 5-methyl-1-hexene, and mixtures thereof.

The ethylene-based polymers may be synthesized by using an appropriate polymerization technique known in the art such as the conventional Ziegler-Natta type polymerizations, and catalysis employing single-site organometallic catalysts including metallocene catalysts. Some ethylene-based polymers are commercially available. Ethylene-based copolymers are commercially available under the trade name ExxonMobil™ Polyethylene (available from ExxonMobil of Houston, Tex.), which include metallocene produced linear low density polyethylene including Exceed™, Enable™, and Exceed™ XP. Examples of ethylene-based thermoplastic polymers useful for certain embodiments of the present TPVs (and/or TPOs) described herein can include ExxonMobil HD7800P, ExxonMobil HD6706.17, ExxonMobil HD7960.13, ExxonMobil HD9830, ExxonMobil AD60-007, Exceed XP 8318ML, Exceed™ XP 6056ML, Exceed 1018HA, Enable™ 2010 Series, Enable™ 2305 Series, and ExxonMobil™ LLDPE LL (e.g. 1001, 1002YB, 3003 Series), all available from ExxonMobil of Houston, Tex. Additional examples of ethylene-based thermoplastic polymers useful for certain embodiments of the present TPVs (and/or TPOs) described herein can include Innate™ ST50 and Dowlex™, available from The Dow Chemical Company of Midland, Mich.

In some embodiments, the ethylene-based polymer can include a low density polyethylene, a linear low density polyethylene, or a high density polyethylene. In some embodiments, the ethylene-based polymer can be a high melt strength (HMS) long chain branched (LCB) homopolymer polyethylene.

Butene-1-based polymers can include those solid, generally high molecular weight isotactic butene-1 resins that primarily include units deriving from a polymerization of butene-1.

In some embodiments, the butene-1-based polymers can include isotactic poly(butene-1) homopolymers. In some embodiments, the butene-1-based polymers may also include units deriving from the polymerization of α-olefin comonomer such as ethylene, propylene, 1-butene, 1-hexane, 1-octene, 4-methyl-1-pentene, 2-methyl-1-propene, 3-methyl-1-pentene, 4-methyl-1-pentene, 5-methyl-hexene, and mixtures thereof.

The butene-1-based polymers may be synthesized by using an appropriate polymerization technique known in the art such as the conventional Ziegler-Natta type polymerizations, and catalysis employing single-site organometallic catalysts including metallocene catalysts. Some butene-1-based polymers are commercially available. For example, some isotactic poly(1-butene) is commercially available under the tradename Polybutene Resins or PB (Basell).

In at least one embodiment, the thermoplastic phase can be a cyclic olefin polymer (COP) or cyclic olefin copolymer (COC). The COP is an amorphous polymer. COC can be about 98% amorphous and about 2% a semi-crystalline cyclic olefin copolymer of one or more residues of norbornene and ethylene, a bridged polycyclic hydrocarbon, a cyclo ethylene copolymer, a cyclic olefin polymer, ethylene norbornene copolymers, ethylene cyclopentene copolymers, poly norbornene, poly dicyclo pentadiene, and ring opened dicyclo pentadiene copolymers, or a combination thereof.

Useful COPs, COCs can be made using vanadium, Ziegler-Natta, and metallocene catalysts. Examples of suitable catalysts are disclosed in U.S. Pat. Nos. 4,614,778 and 5,087,677, for example. Presently, there exist numerous grades of commercially available cyclic olefin copolymers based on different types of cyclic monomers and polymerization methods. Cyclic olefin copolymers are typically produced by chain copolymerization of cyclic monomers such as 8,9,10-trinorborn-2-ene (norbornene) or 1,2,3,4,4a,5,8,8a-octahydro-1,4:5,8-dimethanonaphthalene (tetracyclododecene) with ethene.

Non-limiting examples of commercially available cyclic olefin polymers and copolymers can include those available from TOPAS Advanced Polymers under the designation TOPAS, Mitsui Chemical's APEL, or those formed by ring-opening metathesis polymerization of various cyclic monomers followed by hydrogenation, which are available from Japan Synthetic Rubber under the designation ARTON, and Zeon Chemical's ZEONEX and ZEONOR.

In at least one embodiment, the COC can include a copolymer of cyclic monomers such as norbornene in the range of about 60 wt % to about 90 wt % and ethylene. In some embodiments, the COC can have a glass transition of about 40° C. to about 200° C., such as about 60° C. to about 160° C.; and/or an MFR (260° C., 2.16 kg) of about 1 ml/10 min to about 60 ml/10 min, such as about 4 ml/10 min to about 50 ml/10 min.

In some embodiments, the TPVs (and/or TPOs) may include a polymeric processing additive. In some embodiments, the TPVs (and/or TPOs) of the present disclosure may optionally include reinforcing and non-reinforcing fillers, antioxidants, stabilizers, rubber processing oil, lubricants, antiblocking agents, anti-static agents, waxes, foaming agents, pigments, flame retardants, nucleating agents, and other processing aids known in the rubber compounding art. These additives can comprise up to about 50 weight percent of the total composition. Fillers and extenders that can be utilized include conventional inorganics such as calcium carbonate, clays, silica, talc, titanium dioxide, carbon black, a nucleating agent, mica, wood flour, and the like, and blends thereof, as well as inorganic and organic nanoscopic fillers.

TPVs and TPOs of the present disclosure can be prepared as follows: In some embodiments, the rubber can be partially or fully cured or crosslinked by dynamic vulcanization. The term dynamic vulcanization refers to a vulcanization or curing process for a rubber contained in a blend with a thermoplastic component, wherein the rubber is crosslinked or vulcanized under conditions of high shear at a temperature above the melting point of the thermoplastic component. The rubber can be cured by employing a variety of curatives. Exemplary curatives can include phenolic resin cure systems, peroxide cure systems, and silicon-containing cure systems, such as hydrosilylation and silane grafting/moisture cure. Dynamic vulcanization can occur in the presence of the polyolefin, or the polyolefin can be added after dynamic vulcanization (e.g., post added), or both (e.g., some polyolefin can be added prior to dynamic vulcanization and some polyolefin can be added after dynamic vulcanization).

TPVs and TPOs of the present disclosure can have one or more of the properties described in the following paragraphs.

In at least one embodiment, the TPV (and/or TPO) can have a hardness that is about 20 Shore D to about 70 Shore D, such as about 30 Shore D to about 50 Shore D. Shore D Hardness can be measured using a Zwick automated durometer according to ASTM D2240.

In at least one embodiment, the TPV (and/or TPO) can have an initial thermal conductivity of about 0.2 W/m·K or less, such as about 0.19 W/m·K or less, such as about 0.18 W/m·K or less, such as about 0.17 W/m·K or less, such as about 0.16 W/m·K or less, such as about 0.15 W/m·K or less, such as about 0.14 W/m·K or less. In at least one embodiment the TPV (and/or TPO) can have an initial thermal conductivity of about 0.13 W/m·K to about 0.20 W/m·K, such as about 0.14 W/m·K to about 0.19 W/m·K or about 0.15 W/m·K to about 0.18 W/m·K or about 0.14 W/m·K to about 0.16 W/m·K.

In at least one embodiment, the TPV (and/or TPO) can have a tensile modulus measured at 23° C. of about 50 MPa or more, such as about 100 MPa or more, such as about 125 MPa or more, such as about 140 MPa or more, such as about 300 or more.

In at least one embodiment, the TPV (and/or TPO) can have a high compressive strength measured at 23° C. The compressive strength can be about 10 MPa or more, such as about 25 MPa or more, such as about 100 MPa or more, such as about 10 MPa to about 1000 MPa, such as about 50 MPa to about 750 MPa, such as about 100 MPa to about 600 MPa, such as about 100 MPa to about 500 MPa.

In at least one embodiment, the TPV (and/or TPO) can have a high specific heat capacity at 110° C. The specific heat capacity can be about 1000 J/kg·K (Joules per Kilogram per Kelvin) or more, such as about 1300 J/kg·K or more, such as about 2000 J/kg·K or more, such as about 2300 J/kg·K or more, such as about 2500 J/kg·K or more, such as about 2600 J/kg·K or more, such as about 3000 J/kg·K or more. In at least one embodiment, the specific heat capacity can be about 1000 J/kg·K to about 5000 J/kg·K, such as about 1300 J/kg·K to about 4000 J/kg·K, such as about 1000 J/kg·K to about 3500 J/kg·K, such as about 2000 J/kg·K to about 3300 J/kg·K.

In at least one embodiment, the TPV (and/or TPO) can exhibit an ability to withstand temperatures of about 100° C. or more, such as about 100° C. to about 200° C., such as about 105° C. to about 160° C., such as about 110° C. to about 150° C. or about 150° C. to about 180° C.

In some embodiments, the TPV (and/or TPO) can exhibit a coefficient of linear thermal expansion (μm/m·° C.) (micrometer per meter per degree Celsius) of about 50 μm/m° C. or more, such as about 100 μm/m·° C. or more. In at least one embodiment, the TPV (and/or TPO) can exhibit a coefficient of linear thermal expansion (μm/m·° C.) of about 50 μm/m·° C. to about 250 μm/m·° C., such as about 100 μm/m·° C. to about 200 μm/m·° C., such as about 110 μm/m·° C. to about 150 μm/m·° C.

In some embodiments, the TPV (and/or TPO) can exhibit a water absorption (at room temperature for 28 days) of less than 5%, such as less than 3%, such as less than 2%, such as less than 1%.

In some embodiments, the TPV (and/or TPO) can exhibit a density of about 0.91 g/cm³ or more, such as about 0.91 g/cm³ to about 0.94 g/cm³, such as about 0.915 g/cm³ to about 0.935 g/cm³, such as about 0.92 g/cm³ to about 0.935 g/cm³, such as about 0.925 g/cm³ to about 0.93 g/cm³.

In some embodiments, the TPV (and/or TPO) can have a Tg (glass transition temperature) of about 0° C. or less, such as about −25° C. or less, such as about −35° C. or less, such as about −50° C. or less. In at least one embodiment, the TPV (and/or TPO) can have a Tg of about −100° C. to about 0° C., such as about −80° C. to about −25° C., such as about −70° C. to about −35° C., such as about −60° C. to about −50° C.

In at least one embodiment, the TPV (and/or TPO) can be made in-reactor, in an extruder, or a combination of the two.

Example TPVs (and/or TPOs) can include butyl based rubber TPV those described in U.S. Pat. No. 4,130,534, and nitrile rubber based TPVs described in, e.g., U.S. Pat. Nos. 4,355,139, 4,271,049, and 4,299,931, each of which are incorporated by reference herein.

(B)(6) Thermoplastic Copolyesters

A thermoplastic elastomer can include a thermoplastic copolyester. For example, in one embodiment, the elastomeric material may contain a segmented thermoplastic copolyester. The thermoplastic polyester elastomer, for example, may comprise a multi-block copolymer. Useful segmented thermoplastic copolyester elastomers include a multiplicity of recurring long chain ester units and short chain ester units joined head to tail through ester linkages. The long chain units can be represented by the formula:

and the short chain units can be represented by the formula:

where G is a divalent radical remaining after the removal of the terminal hydroxyl groups from a long chain polymeric glycol having a number average molecular weight in the range about 600 to 6,000 and a melting point below about 55° C., R is a hydrocarbon radical remaining after removal of the carboxyl groups from dicarboxylic acid having a molecular weight less than about 300, and D is a divalent radical remaining after removal of hydroxyl groups from low molecular weight diols having a molecular weight less than about 250.

The short chain ester units in the copolyetherester provide about 15 to 95% of the weight of the copolyetherester, and about 50 to 100% of the short chain ester units in the copolyetherester are identical.

The term “long chain ester units” refers to the reaction product of a long chain glycol with a dicarboxylic acid. The long chain glycols are polymeric glycols having terminal (or nearly terminal as possible) hydroxy groups, a molecular weight above about 600, such as about 600-6000, a melting point less than about 55° C. and a carbon to oxygen ratio about 2.0 or greater. The long chain glycols are generally poly(alkylene oxide) glycols or glycol esters of poly(alkylene oxide) dicarboxylic acids. Any substituent groups can be present which do not interfere with polymerization of the compound with glycol(s) or dicarboxylic acid(s), as the case may be. The hydroxy functional groups of the long chain glycols which react to form the copolyesters can be terminal groups to the extent possible. The terminal hydroxy groups can be placed on end capping glycol units different from the chain, e.g., ethylene oxide end groups on polypropylene oxide glycol).

The term “short chain ester units” refers to low molecular weight compounds or polymer chain units having molecular weights less than about 550 and are made by reacting a low molecular weight diol (below about 250) with a dicarboxylic acid.

The dicarboxylic acids may include the condensation polymerization equivalents of dicarboxylic acids, that is, their esters or ester-forming derivatives such as acid chlorides and anhydrides, or other derivatives which behave substantially like dicarboxylic acids in a polymerization reaction with a glycol.

The dicarboxylic acid monomers for the elastomer have a molecular weight less than about 300. They can be aromatic, aliphatic or cycloaliphatic. The dicarboxylic acids can contain any substituent groups or combination thereof which do not interfere with the polymerization reaction. Representative dicarboxylic acids include terephthalic and isophthalic acids, bibenzoic acid, substituted dicarboxy compounds with benzene nuclei such as bis(p-carboxyphenyl) methane, p-oxy-(p-carboxyphenyl)benzoic acid, ethylene-bis (p-oxybenzoic acid), 1,5-naphthalene dicarboxylic acid, 2,6-naphthalene dicarboxylic acid, 2,7-naphthalene dicarboxylic acid, phenanthralenedicarboxylic acid, anthralenedicarboxylic acid, 4,4′-sulfonyl dibenzoic acid, etc. and Ci-C10 alkyl and other ring substitution derivatives thereof such as halo, alkoxy or aryl derivatives. Hydroxy acids such as p (P-hydroxyethoxy)benzoic acid can also be used, providing an aromatic dicarboxylic acid is also present.

Representative aliphatic and cycloaliphatic acids are sebacic acid, 1,3- or 1,4-cyclohexane dicarboxylic acid, adipic acid, glutaric acid, succinic acid, carbonic acid, oxalic acid, itaconic acid, azelaic acid, diethylmalonic acid, fumaric acid, citraconic acid, allylmalonate acid, 4-cyclohexene-1,2-dicarboxylate acid, pimelic acid, suberic acid, 2,5-diethyladipic acid, 2-ethylsuberic acid, 2,2,3,3-tetramethylsuccinic acid, cyclopentanedicarboxylic acid, decahydro-1,5-(or 2,6-) naphthylenedicarboxylic acid, 4,4′-bicyclohexyl dicarboxylic acid, 4,4′-methylenebis(cyclohexyl carboxylic acid), 3,4-furan dicarboxylate, and 1,1-cyclobutane dicarboxylate.

The dicarboxylic acid may have a molecular weight less than about 300. In one embodiment, phenylene dicarboxylic acids are used such as terephthalic and isophthalic acid.

Included among the low molecular weight (less than about 250) diols which react to form short chain ester units of the copolyesters are acyclic, alicyclic and aromatic dihydroxy compounds. Included are diols with 2-15 carbon atoms such as ethylene, propylene, isobutylene, tetramethylene, pentamethylene, 2,2-dimethyltrimethylene, hexamethylene and decamethylene glycols, dihydroxy cyclohexane, cyclohexane dimethanol, resorcinol, hydroquinone, 1,5-dihydroxy naphthalene, etc. Also included are aliphatic diols containing 2-8 carbon atoms. Included among the bis-phenols which can be used are bis(p-hydroxy) diphenyl, bis(p-hydroxyphenyl) methane, and bis(p-hydroxyphenyl) propane. Equivalent ester-forming derivatives of diols are also useful (e.g., ethylene oxide or ethylene carbonate can be used in place of ethylene glycol). Low molecular weight diols also include such equivalent ester-forming derivatives.

Long chain glycols which can be used in preparing the polymers include the poly(alkylene oxide) glycols such as polyethylene glycol, poly(1,2- and 1,3-propylene oxide) glycol, poly(tetramethylene oxide) glycol, poly(pentamethylene oxide) glycol, poly(hexamethylene oxide) glycol, poly(heptamethylene oxide) glycol, poly(octamethylene oxide) glycol, poly(nonamethylene oxide) glycol and poly(1,2-butylene oxide) glycol; random and block copolymers of ethylene oxide and 1,2-propylene oxide and poly-formals prepared by reacting formaldehyde with glycols, such as pentamethylene glycol, or mixtures of glycols, such as a mixture of tetramethylene and pentamethylene glycols.

In addition, the dicarboxymethyl acids of poly(alkylene oxides) such as the one derived from polytetramethylene oxide can be used to form long chain glycols in situ. Polythioether glycols and polyester glycols also provide useful products. In using polyester glycols, care may be generally exercised to control a tendency to interchange during melt polymerization, but certain sterically hindered polyesters, e.g., poly(2,2-dimethyl-1,3-propylene adipate), poly(2,2-dimethyl-1,3-propylene/2-methyl-2-ethyl-1,3-propylene 2,5-dimethylterephthalate), poly(2,2-dimethyl-1,3-propylene/2,2-diethyl-1,3-propylene, 1,4 cyclohexanedicarboxylate) and poly(1,2-cyclohexylenedimethylene/2,2-dimethyl-1,3-propylene-1,4-cyclohexanedicarboxylate) can be utilized under normal reaction conditions and other more reactive polyester glycols can be used if a short residence time is employed. Either polybutadiene or polyisoprene glycols, copolymers of these and saturated hydrogenation products of these materials are also satisfactory long chain polymeric glycols. In addition, the glycol esters of dicarboxylic acids formed by oxidation of polyisobutylenediene copolymers are useful raw materials.

Although the long chain dicarboxylic acids above can be added to the polymerization reaction mixture as acids, they react with the low molecular weight diols(s) present, the diols being in excess, to form the corresponding poly(alkylene oxide) ester glycols which then polymerize to form the G units in the polymer chain, these particular G units having the structure

when only one low molecular weight diol (corresponding to D) is employed. When more than one diol is used, there can be a different diol cap at each end of the polymer chain units. Such dicarboxylic acids may also react with long chain glycols if they are present. The extent to which this reaction occurs is quite small, however, since the low molecular weight diol is present in considerable molar excess.

In place of a single low molecular weight diol, a mixture of such diols can be used. In place of a single long chain glycol or equivalent, a mixture of such compounds can be utilized, and in place of a single low molecular weight dicarboxylic acid or its equivalent, a mixture of two or more can be used in preparing the thermoplastic copolyester elastomers which can be employed in the compositions of the present disclosure. When an aliphatic acid is used which contains a mixture of geometric isomers, such as the cis-trans isomers of cyclohexane dicarboxylic acid, the different isomers should be considered as different compounds forming different short chain ester units with the same diol in the copolyesters. The copolyester elastomer can be made by conventional ester interchange reaction.

Copolyether esters with alternating, random-length sequences of either long chain or short chain oxyalkylene glycols can be used and contain repeating high melting blocks that are capable of crystallization and substantially amorphous blocks with a relatively low glass transition temperature. In at least one embodiment, the hard segments can be composed of tetramethylene terephthalate units and the soft segments may be derived from aliphatic polyether and polyester glycols. Of particular advantage, the above materials resist deformation at surface temperatures because of the presence of a network of microcrystallites formed by partial crystallization of the hard segments. The ratio of hard to soft segments determines the characteristics of the material. Thus, another advantage to thermoplastic polyester elastomers is that soft elastomers and hard elastoplastics can be produced by changing the ratio of the hard and soft segments.

In one particular embodiment, the polyester thermoplastic elastomer has the following formula: −[4GT]x[BT]y, wherein 4G is butylene glycol, such as 1,4-butane diol, B is poly(tetramethylene ether glycol) and T is terephthalate, and wherein x is about 0.60 to about 0.99 and y is about 0.01 to about 0.40. In at least one aspect, the thermoplastic polyester elastomer can be a block copolymer of polybutylene terephthalate and polyether segments and/or dimerdiol segments and can have a structure as follows:

wherein a and b are integers and can vary from 2 to 50,000, such as about 2 to about 10,000. The ratio between hard and soft segments in the block copolymer as described above can be varied in order to vary the properties of the elastomer.

In at least one aspect, the elastomeric material can contain a copolyester elastomer comprising a block copolymer having polybutylene terephthalate segments and polytetramethylene ether glycol terephthalate segments.

In at least one aspect, the density of the polyester elastomer can be about 1.05 g/cm³ to about 1.15 g/cm³, such as about 1.08 g/cm³ to about 1.2 g/cm³.

In at least one aspect, the copolyester elastomer can have a Shore D hardness of less than about 100, such as less than about 90, such as less than about 80, such as less than about 70, such as less than about 60, such as less than about 50, such as less than about 40. The Shore D hardness of the elastomer can generally be greater than about 10, such as greater than about 15, such as greater than about 20, such as greater than about 25.

(C) Ophthalmic Solutions

Bottles of the present disclosure can include any suitable ophthalmic solution disposed in the body of the bottle. For example, the ophthalmic pharmaceutical compositions of the present disclosure may contain various types of therapeutic agents. Examples of possible therapeutic agents include beta blockers (e.g., timolol, betaxolol, levobetaxolol, carteolol, levobunolol, and propranolol), carbonic anhydrase inhibitors (e.g., brinzolamide and dorzolamide), alpha-1 antagonists (e.g., nipradolol), alpha-2 agonists (e.g. apraclonidine, and brimonidine), miotics (e.g., pilocarpine and epinephrine), prostaglandin analogs (e.g., latanoprost, travoprost and unoprostone), hypotensive lipids (e.g., bimatoprost), neuroprotectants (e.g., memantine), serotonergics e.g., 5-HT agonists, such as S-(+)-1-(2-aminopropyl)-indazole-6-ol), anti-angiogenesis agents (e.g., anecortave acetate), anti-infective agents (e.g., quinolones, such as moxifloxacin and gatifloxacin, and aminoglycosides, such as tobramycin and gentamicin), non-steroidal and steroidal anti-inflammatory agents (e.g., prednisolone, dexamethasone, lotoprednol, suprofen, diclofenac and ketorolac), growth factors (e.g., EGF), immunosuppressant agents (e.g., cyclosporin), and anti-allergic agents (e.g., olopatadine). For example, the therapeutic agent can be apraclonidine or apraclonidine hydrochloride. As a further non-limiting example the therapeutic agent can be olopatadine or olopatadine hydrochloride.

The ophthalmic solution may be present in the form of a pharmaceutically acceptable free base, such as apraclonidine free base or olopatadine free base, or a pharmaceutically acceptable free salt, such as apraclonidine hydrochloride or olopatadine hydrochloride. The therapeutic agent can be anionic, cationic, or neutral. In the event the therapeutic agent selected is anionic in an aqueous solution at an ophthalmically acceptable pH (potential of Hydrogen) level, buffers described herein are be included.

The therapeutic agent can have a concentration of about 0.01% w/v (percent weight per volume) to about 1.0% w/v of therapeutic agent to ophthalmic solution. For example, the therapeutic agent has a concentration of about 0.06% w/v to about 0.8% w/v therapeutic agent to the ophthalmic solution, e.g., about 0.06% w/v, about 0.12 to about 0.13% w/v, or about 0.77% w/v to about 0.78% w/v, or the like. As a further non-limiting example, the therapeutic agent can be apraclonidine, in which the concentration is about 0.06% w/v to about 0.125% w/v, e.g., about 0.06% w/v, or about 0.125% w/v. As a further example, the therapeutic agent can be olopatadine, and the concentration is about 0.6% w/v to about 0.8% w/v, e.g., about 0.70% w/v.

The present disclosure is particularly directed to ophthalmic solutions in connection with the treatment of conditions wherein the cornea or adjacent ocular tissues are irritated, or conditions requiring frequent application of a composition, such as in the treatment of dry eye patients, red eye patients, or patients that have an ocular allergy. The ophthalmic solutions of the present disclosure are therefore particularly useful in the field of artificial tears, ocular lubricants, and other compositions used to treat dry eye conditions, as well as other conditions involving ocular inflammation or discomfort.

The ophthalmic solutions of the present disclosure may be formulated to include one or more viscosifying agents to enhance bioavailability of the therapeutic agent in the ophthalmic solution. Additionally, the viscosifying agent can provide ocular comfort and/or retention of the compositions on the eye following topical application. The types of viscosifying agents which may be utilized include: water soluble cellulose derivatives, such as cellulose ethers, such as hydroxypropyl guar referred to hereinafter as (“hp-guar”), hydroxypropyl methylcellulose (“HPMC”): Dextran 70, hydroxy methylcellulose (“HMC”), hydroxy ethylcellulose (“HEC”), or hydroxy propyl cellulose (“HPC”); polyethylene glycol; polyethylene oxide polymers; polyvinylpyrrolidone polymers, such as N-vinyl-2-pyrrolidone; propylene glycol; carboxy vinyl polymers; water soluble polyvinyl alcohol polymers or copolymers; copolymers having at least one vinyl lactam with one or more hydrophilic monomors, and polysaccharides. For example, the viscosifying agent can be hydroxypropyl methylcellulose, which provides enhanced bioavailability of the therapeutic agent compared to other viscosifying agents.

The viscosifying agent can include one or more copolymers of vinylpyrrolidone having one or more hydrophilic monomeric units. The viscosifying agent may include polyvinylpyrrolidone copolymers having a copolymer of vinylpyrrolidone and at least one amino containing vinylic monomer. An amino containing vinylic monomer can include alkylaminoalkylmethacrylate having 8-15 carbon atoms, alkylaminoalkylacrylate having 7-15 carbon atoms, dialkylaminoalkylmethacrylate having 8-20 carbon atoms, dialkylaminoalkylacrylate having 7-20 carbon atoms, N-vinylalkylamide having 3-10 carbon atoms. A copolymer of vinylpyrrolidone can be N-vinyl alkylamide, such as N-vinyl formaide, N-vinyl acetamide, N-vinyl isopropylamide, N-vinyl-N-methyl acetamide, or the like. For example, the viscosifying agent can be N-vinyl-2-pyrrolidone.

The viscosifying agent is present in the composition in an amount of about 0.01% w/v to about 5% w/v viscosifying agent to the ophthalmic solution, such as about 0.05% w/v to about 3% w/v, about 0.1% to about 1%, or about 0.01% w/v to about 5% w/v viscosifying agent, based on the total ophthalmic solution.

Ophthalmic solutions of the present disclosure can include a buffering agent. The buffering agent maintains the pH at a physiological acceptable range of about 6 to about 8. The buffering agent can include citric acid, citrates, boric acid, borates, e.g., sodium borate, bicarbonates, e.g., sodium bicarbonate, sodium hydroxide, hydrochloric acid, TRIS (2-amino-2-hydroxymethyl-1,3-propanediol), Bis-Tris (Bis-(2-hydroxyethyl)-imino-tris-(hydroxymethyl) methane), bis-aminopolyols, triethanolamine, ACES (N-(2-hydroxyethyl)-2-aminoethanesulfonic acid), BES (N,N-Bis (2-hydroxyethyl)-2-aminoethanesulfonic acid), HEPES (4-2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES (2-(N-morpholino) ethanesulfonic acid), MOPS (3-[N-morpholino]-propanesulfonic acid), PIPES (piperazine-N,N′-bis(2-ethanesulfonic acid), TES (N-[Tris (hydroxymethyl)methyl]-2-aminoethanesulfonic acid), phosphate buffers, e.g., NaHPO₄, NaH₂PO₄, NaH₂PO₄, and KH₂PO₄ or hydrates or mixtures thereof, or combinations of one or more buffer agent. For example, an ophthalmic solution may include a mixture of buffering agents including boric acid, sodium hydroxide, and hydrochloric acid. As a further non-limiting example, a buffering agent may include a mixture of buffering agents including sodium chloride, sodium citrate dehydrate, sodium hydroxide, and hydrochloric acid.

The buffering agent can have a concentration in the ophthalmic solution to maintain a pH of the composition of about 6.0 to about 8.5. The concentration of each buffering agent may be about 0.001% w/v to about 2% w/v of buffering agent to ophthalmic solution. For example, each buffering agent can have a concentration of about 0.01% w/v to 1% w/v, such as about 0.05% w/v to about 0.30% w/v.

The ophthalmic solution of the present disclosure can be isotonic with a lacrimal fluid. A solution which is isotonic with a lacrimal fluid is generally understood to be a solution whose concentration corresponds to the concentration of about 0.7% w/v to about 1.5% w/v of sodium chloride solution (308 mOsm/kg (milliosmoles per kilogram)), e.g., about 0.9% w/v. The tonicity of the ophthalmic solution can be adjusted by adding one or more tonicity agents, e.g., organic or inorganic substances, which affect the tonicity. Tonicity agents can include sodium chloride, potassium chloride, glycerol, propylene glycol, polyols, mannitol, sorbitol, xylitol and mixtures thereof. The tonicity of the solution is typically adjusted to be in the range about 200 to about 450 milliosmoles per kilogram (mOsm/kg), such as about 210 to 350 mOsm/kg.

An ophthalmic solution of the present disclosure can include a surfactant, including a mucin-like material, an ophthalmically beneficial materials. Mucin-like materials can include polyglycolic acid, polylactides, and the like. A mucin-like material causes continuous and slow release of the therapeutic agent to the ocular surface over extended period of time for treating dry eye syndrome. Ophthalmically beneficial materials can include 2-pyrrolidone-5-carboxylic acid (PCA), amino acids, e.g., taurine, glycine, or the like, linoleic and gamma linoleic acids, and vitamins, e.g., B5, A, B, and the like.

A surfactant can include a non-ionic, anionic, or amphoteric surfactants having at least one polyether alcohol moiety. A surfactant can include alkyl aryl polyether alcohols, e.g., tyloxapol, poloxamers, e.g., Pluronic® F108, F88, F68, F68LF, F127, F87, F77, P85, P75, P104, and P84, poloxamines, e.g., Tetronic 707, 1107 and 1307, polyethyleneglycol esters of fatty acids, e.g., Tween® 20 or Tween® 80, polyoxyethylene or polyoxypropylene ethers of C₁₂-C₁₈ alkanes, e.g., polyethylene glycol 400 or Brij® 35, polyoxyethyene stearates, e.g., Myrj® 52 or polyoxyl 40 stearate, sorbitol, sorbitan esters e.g., sorbitan monostearate, sorbitan tristearte, or sorbitan monolaurate, polyoxyethylene propylene glycol stearates, e.g., Atlas G2612, amphoteric surfactants under the trade names Mirataine® and Miranol®, or the like. The surfactant may include a combination of one or more mucin-like materials, ophthalmically beneficial materials, and/or surfactants. For example, a surfactant may include a combination of tyloxapol, polysorbate 80, and/or polyoxyl 40 stearate.

A surfactant can be present in the ophthalmic solution at a concentration of 7% w/v or less, e.g., about 0.001% w/v to about 7% w/v, or about 0.05% w/v to about 2% w/v, or about 0.1% w/v to about 1% w/v. As a non-limiting example, a surfactant including tyloxapol may have a concentration of about 0.05% w/v to about 0.3% w/v. As a further non-limiting example, a surfactant including polysorbate 80 may have a concentration of about 0.1% w/v to about 0.2% w/v. As a further non-limiting example, a surfactant including polyoxyl 40 stearate may have a concentration of about 0.1% w/v to about 7% w/v. The increased concentration of the surfactant in the ophthalmic solution allows for enhanced control of the dosing and promoted a stable drop size after each successive dose. Additionally, the reduced concentration of the surfactant allows for less overall ophthalmic solution needed to provide sufficient dosing amounts of therapeutic agent. Additionally, or alternatively, and without wishing to be bound by theory a surfactant comprising a polyether alcohol moiety can cause drop size to be reduced due to the interaction of the alcohol moiety with the surrounding diluents, in which a surface tension of the composition is reduced.

A surface tension of the ophthalmic solution may decrease as the surfactant concentration increases. The surface tension of the ophthalmic solution can be about 30 mN/m (millinewton per meter) to about 45 mN/m, e.g., about 30 mN/m to about 40 mN/m, about 35 mN/m to about 40 mN/m, about 37 mN/m to about 39 mN/m, or the like. Without wishing to be bound by theory, a lower surface tension may cause the drop size to be reduced in the ophthalmic solution, in which tyloxapol, polyoxyl 40 stearate, and polysorbate 80 each reduce the surface tension of the ophthalmic solutions described herein. For example, as the surfactant concentration increases from a first surfactant concentration to a second surfactant concentration, in which the second surfactant concentration is greater than the first surfactant concentration, a surface tension of the ophthalmic concentration may decrease from a first surface tension to a second surface tension, in which the second surface tension is lower than the first surface tension.

The ophthalmic solution of the present disclosure is generally formulated as a sterile solution having one or more diluents, such as water to form a sterile aqueous solution. The diluents can include any suitable diluent capable of acting as an ophthalmic solution, in which a suitable aqueous solvent is one that is compatible with an eye and/or other tissues to be treated with the ophthalmic solution. For example, a diluent of the ophthalmic solution described herein can include water.

The compositions of the present disclosure are formulated so as to be compatible with the eye and/or other tissues to be treated with the ophthalmic solutions. The ophthalmic solutions intended for direct application to the eye will be formulated so as to have a pH and tonicity which are compatible with the eye. The ophthalmic solution of the present disclosure does not include a conventional antimicrobial preservative, e.g., benzalkonium chloride, polyduaternium-1, hydrogen peroxides, such as sodium perborate, or chorine-containing agents, which can cause irritation to the eye and/or other tissues to be treated with the ophthalmic solutions described herein.

(D) Terminal Autoclaving

Autoclaving of bottles of the present disclosure can be performed. After filling the bottles with the ophthalmic solution, the closed bottles are introduced into an autoclaving chamber. In the context of the present application, filling of the bottles denotes typically a normal filling, such that for example some air will remain in the upper part of said bottle. As the whole bottle will be sterilized, it is not necessary for the filling and closing of the bottle to take place under aseptic conditions. Such an autoclaving chamber works with steam. The chamber comprises typically one or more nozzles for the steam entrance and typically several sensors for temperature monitoring. Advantageously the temperature can be adjusted very quickly if some corrections might be desired.

Further, particularly the chamber is provided with a pressure device for generating a counter pressure (e.g., 2700 mbar (millibar) to 3200 mbar) in the autoclaving chamber. Also, the pressure can be adjusted very quickly if some corrections might be desired. The counter pressure is regulated electronically via computer control. After introducing the bottles into the chamber, the temperature rises typically from room temperature to 121° C. and the pressure rises typically from atmospheric pressure to a maximum value which is characteristic for the sterilization process. Typically, the choice of the pressure value depends on the form of the bottles.

As 5 ml bottles are more rigid in comparison to 10 ml bottles, a lower pressure value is necessary to avoid blowing up of the bottles.

In the beginning of the autoclaving process, the increasing of the temperature is quite steep, whereas the gradient of the pressure remains nearly constant up to reaching the maximum value. During the sterilization, the values of the temperature and the pressure maintain constant. After the sterilization both the temperature and the pressure decrease continuously. The autoclaving processing takes as a whole nearly one hour. After reaching again room temperature and atmospheric pressure, the chamber will be opened for taking out the sterilized bottles.

Several test programs have shown that after an autoclaving procedure of a temperature of 121° C. during 20 minutes with an autoclaving procedure according to the above described diagrams, no deformation, e.g. shrinkage or blowing-up of the bottle assembly should be observed.

Further tests concerning the tightness of the bottles before and after the autoclaving procedure should show compliance with the regulations for pharmaceuticals. Tests concerning the O₂-barrier and the H₂O-barrier properties of the bottles after stress storage during 4 weeks at 80° C. should be compliant with desired MVTR.

Furthermore, tests in respect to bacteria toxicity should show that no toxicity is demonstrated for the bottles.

EMBODIMENTS LISTING

The present disclosure provides, among others, the following aspects, each of which can be considered as optionally including any alternate embodiments:

Clause 1. A bottle comprising:

• • a cap;
  • a nozzle tip; and
  • a body comprising a composition comprising (1) a thermoplastic elastomer and (2) a polypropylene homopolymer, a block or random polypropylene copolymer, a random, heterophasic polypropylene copolymer, or combinations thereof, wherein the cap is configured to engage a threaded portion of a neck of the body.

Clause 2. The bottle of Clause 1, further comprising an ophthalmic solution disposed within the body.

Clause 3. The bottle of Clauses 1 or 2, wherein the thermoplastic elastomer is selected from the group consisting of a styrenic block copolymer, a thermoplastic polyurethane, a thermoplastic olefin, thermoplastic vulcanizate, and a thermoplastic copolyester.

Clause 4. The bottle of any of Clauses 1 to 3, wherein the thermoplastic elastomer is a styrenic block copolymer selected from the group consisting of a styrene-butadien-styrene (SBS), styrene-butylene-styrene (SEBS), and combinations thereof.

Clause 5. The bottle of any of Clauses 1 to 4, wherein the body has an average wall thickness of about 0.3 mm to about 0.65 mm.

Clause 6. The bottle of any of Clauses 1 to 5, wherein the body has a volume of about 8 ml to about 15 ml.

Clause 7. The bottle of any of Clauses 1 to 6, wherein the composition has a hardness of about 20 Shore D to about 80 Shore D.

Clause 8. The bottle of any of Clauses 1 to 7, wherein the composition has a flexural modulus of about 200 MPa to about 500 MPa.

Clause 9. The bottle of any of Clauses 1 to 8, wherein the composition has a creep strain of 0.05 or less for greater than 200 minutes and about 400 minutes or less.

Clause 10. The bottle of any of Clauses 1 to 9, wherein the composition has a melting point of about 145° C. to about 210° C.

Clause 11. The bottle of any of Clauses 1 to 9, wherein the body has the following properties:

• • a hardness of about 20 Shore D to about 80 Shore D;
  • a flexural modulus of about 200 MPa to about 500 MPa; and
  • a melting point of about 145° C. to about 210° C.

Clause 12. The bottle of any of Clauses 1 to 11, wherein the body has a squeezability of about 6 lbs or less.

Clause 13. The bottle of any of Clauses 1 to 12, wherein the composition comprises: about 70 wt % to about 95 wt % of the random, heterophasic polypropylene copolymer; and about 5 wt % to about 30 wt % of the thermoplastic elastomer.

Clause 14. The bottle of any of Clauses 1 to 13, wherein the random, heterophasic polypropylene copolymer has:

• • a flexural modulus of about 200 MPa to about 500 MPa,
  • a Shore D hardness of about 70 or less, and
  • a melting point of about 140° C. to about 155° C.

Clause 15. The bottle of any of Clauses 1 to 14, wherein the composition comprises:

• • about 5 wt % to about 30 wt % of the thermoplastic elastomer; and about 70 wt % to about 95 wt % of the polypropylene homopolymer.

Clause 16. The bottle of any of Clauses 1 to 15, wherein the polypropylene homopolymer has:

• • a flexural modulus of about 1,500 MPa to about 2,000 MPa, and
  • a Shore D hardness of about 60 to about 90, and
  • a melting point of about 150° C. to about 185° C.

Clause 17. The bottle of any of Clauses 1 to 16, wherein the composition comprises:

• • about 50 wt % to about 90 wt % of the random polypropylene copolymer; and
  • about 50 wt % to about 10 wt % of the thermoplastic elastomer.

Clause 18. The bottle of any of Clauses 1 to 17, wherein the random polypropylene copolymer has:

• • a flexural modulus of about 800 MPa to about 1,300 MPa,
  • a Shore D hardness of about 70 to about 90, such as about 75 to about 85, and
  • a melting point of about 140° C. to about 155° C.

Clause 19. A bottle comprising:

• • a cap;
  • a nozzle tip; and
  • a body comprising a composition comprising (1) a first random, heterophasic polypropylene copolymer and (2) a second random, heterophasic polypropylene copolymer that is different than the first random, heterophasic polypropylene copolymer, wherein the cap is configured to engage a threaded portion of a neck of the body.

Clause 20. A method of sterilizing the bottle of any of Clauses 1 to 19, the method comprising:

• • introducing an ophthalmic solution into the bottle,
  • fastening the cap to the body;
  • introducing the bottle to an autoclaving chamber;
  • introducing steam into the chamber; and
  • maintaining the chamber at temperature of about 120° C. or greater for about 5 minutes or greater.

Overall, bottles of the present disclosure can be suitable for pharmaceutical products, such as for ophthalmic solutions, which can be sterilized as a whole after filling the solution into the bottle by a terminal autoclaving process even while having relatively thin walls of the bottle. For example, it has been discovered that bottles having polymer(s) that provide a combination of low flexural modulus and low hardness (Shore D), while also having a high melting point, can provide an ability for autoclavability in addition to squeezability of a bottle. After the autoclaving procedure, the bottles provided herein retain their improved squeezability which can be important for the consumer for dispensing a solution out of the bottle. Furthermore, no deformation is observed after having exposed the bottle to a terminal autoclaving process. This means that a bottle filled with an ophthalmic solution fulfills the European Pharmacopoeia 11th Edition (2023) and other regulatory thresholds, which ensure a high level of safety. Such advantages are provided even for bottles having high volumes (e.g., 10 mL) for storing ophthalmic solution. In addition, as compared to bottles made of LDPE, for example, bottles of the present disclosure can have an improved (lower) moisture vapor transmission rate (MVTR) for improved shelf life of bottles having ophthalmic solution disposed therein.

While the foregoing is directed to embodiments of the present disclosure, other and further embodiments of the disclosure may be devised without departing from the basic scope thereof, and the scope thereof is determined by the claims that follow.