Patent Application
20240132270
The present disclosure generally relates to systems and methods to store and transport 1,1-disubstituted alkene compositions.
Polymerizable monomers are useful components in a number of applications and products. For example, polymerizable monomers can be used in adhesives, coatings, sealants, moldings, films, articles, composite binders, and numerous other applications. 1,1-disubstituted alkene monomers are particularly suitable polymerizable monomers for such applications and demonstrate excellent mechanical, physical, and chemical properties. Additionally, 1,1-disubstituted alkene monomers can be readily polymerizable upon contact with a variety of initiators and can exhibit favorable adhesion properties and cure times.
According to one embodiment, a method of handling a 1,1-disubstituted alkene composition includes providing a storage container and filling the storage container a 1,1-disubstituted alkene composition. The storage container includes a barrier layer. The barrier layer decreases the water vapor transmission rate of the storage container.
According to another embodiment, a method of handing a 1,1-disubstituted alkene composition includes providing a storage container and filling the storage container with a 1,1-disubstituted alkene composition. The storage container is substantially entirely formed of plastic containing fluorine, nitryl, polyamide, or a composite of polyamide or is entirely formed of high-density polyethylene or fluorinated high-density polyethylene.
According to another embodiment, a container comprises a storage container and a 1,1-disubstituted alkene composition stored in the storage container. The storage container comprises a barrier layer. The barrier layer decreases the water vapor transmission rate of the storage container.
As used herein, 1,1-disubstituted alkene monomers refer to monomers having two carbonyl groups bonded to the carbon on the alkenyl group and a hydrocarbyl group bonded to each of the carbonyl groups. In such 1,1-disubstituted alkene monomers, the hydrocarbyl groups can be bonded to the carbonyl groups forming ketone directly or through an oxygen atom forming ester.
As can be appreciated, 1,1-disubstituted alkene monomers exhibit a number of desirable properties in both monomeric and polymerized forms. As a monomer, 1,1-disubstituted alkene monomers are readily polymerizable and can be provided in optically-clear, solvent-free compositions. The monomers can be tailored for specific applications by modifications to the size and structure of the monomer (e.g., by modification of the hydrocarbyl groups), by modification of functional groups, and by forming monofunctional, difunctional, or multifunctional monomers.
In polymerized form, 1,1-disubstituted alkene monomers exhibit excellent physical and chemical properties including solvent and water resistance, excellent strength and adhesive properties, and excellent optical properties among numerous other tailorable properties.
Generally, 1,1-disubstituted alkene monomers can be polymerized by exposing the monomer to a suitable initiator or energy source. For example, 1,1-disubstituted alkene monomers can be anionically polymerized upon contact with a suitable anionic polymerization initiator or be free-radically polymerized using a suitable free-radical source (e.g., activation a heat- or photo-initiator).
To improve the usability of compositions containing 1,1-disubstituted alkene monomers, it would be useful to provide systems and methods that can store, transport, and increase the shelf life of the monomers. As can be appreciated, this will obviate the need to synthesize the monomers during, or just prior to, usage and increase the number of applications and users of 1,1-disubstituted alkene monomers.
In certain embodiments, the systems and methods described herein can improve the shelf life and storage of 1,1-disubstituted alkene compositions through use of a storage container. The storage containers described herein can generally be capable of storing 1,1-disubstituted alkene monomers or any compositions containing 1,1-disubstituted alkene monomers alone or with other components (both used herein as “1,1-disubstituted alkene compositions”). For example, the storage containers described herein can be suitable to store and transport substantially pure 1,1-disubstituted alkene monomer or store compositions which further contain one or more additional components such as inactivated initiators, stabilizers, fillers, etc. As used herein, substantially pure means a purity of about 85% or greater, about 90% or greater, about 95% or greater, or about 99% or greater.
As can be appreciated, 1,1-disubstituted alkene monomers can vary greatly in structure. For example, 1,1-disubstituted alkene monomers can have different hydrocarbyl groups, different substituent or functional groups, and can be monofunctional, difunctional, or multifunctional.
According to certain embodiments, suitable hydrocarbyl groups can include at least straight or branched chain alkyl groups, straight or branched chain alkyl alkenyl groups, straight or branched chain alkynyl groups, cycloalkyl groups, alkyl substituted cycloalkyl groups, aryl groups, aralkyl groups, and alkaryl groups. Additionally, suitable hydrocarbyl groups can also contain one or more heteroatoms in the backbone of the hydrocarbyl group.
In certain embodiments, a suitable hydrocarbyl group can also, or alternatively, be functionalized with a substituent group. Non-limiting examples of substituent groups can include one or more halo, alkoxy, alkylthio, hydroxyl, nitro, cyano, azido, carboxy, acyloxy, and sulfonyl groups. In certain embodiments, substituent groups can be selected from one or more halo, alkoxy, alkylthio, and hydroxyl groups. In certain embodiments, substituent groups can be selected from one or more halo and alkoxy groups.
In certain embodiments, suitable hydrocarbyl groups can be C1-20 hydrocarbyl groups. For example, the hydrocarbyl group can be functionalized by an ether group. Suitable ether groups can include, without limitation, ethoxy, propoxy, and butoxy groups.
Suitable examples of more specific hydrocarbyl groups can include, in certain embodiments, C1-15 straight or branched chain alkyl groups, C1-15 straight or branched chain alkenyl groups, C5-18 cycloalkyl groups, C6-24 alkyl substituted cycloalkyl groups, C4-18 aryl groups, C4-20 aralkyl groups, and C4-20 alkaryl groups. In certain embodiments, the hydrocarbyl group can more preferably be C1-8 straight or branched chain alkyl groups, C5-12cycloalkyl groups, C6-12 alkyl substituted cycloalkyl groups, C4-18 aryl groups, C4-20 aralkyl groups, or C4-20 alkaryl groups.
As used herein, alkaryl can include an alkyl group bonded to an aryl group. Aralkyl can include an aryl group bonded to an alkyl group. Aralkyl can also include alkylene bridged aryl groups such as diphenyl methyl or propyl groups. As used herein, aryl can include groups containing more than one aromatic ring. Cycloalkyl can include groups containing one or more rings including bridged or fused rings. Alkyl substituted cycloalkyl can include a cycloalkyl group having one or more alkyl groups bonded to the cycloalkyl ring.
In certain embodiments, suitable alkyl groups can include methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl, pentyl, hexyl, and ethyl hexyl. Similarly, examples of suitable cycloalkyl groups can include cyclohexyl and fenchyl and examples of suitable alkyl substituted groups can include menthyl and isobornyl.
According to certain embodiments, suitable hydrocarbyl groups can include methyl, ethyl, propyl, isopropyl, butyl, tertiary butyl, ethyl pentyl, hexyl, ethyl hexyl, fenchyl, menthyl, and isobornyl groups.
In certain embodiments, illustrative examples of 1,1-disubstituted alkene compounds can include methylene malonate compounds, methylene β-ketoester compounds, methylene β-di-ketone compounds, and any monofunctional, difunctional, or multifunctional monomers, oligomers, or polymers thereof. Compositions having one or more of such illustrative example compounds can be used as a suitable composition according to certain embodiments.
As can be appreciated, 1,1-disubstituted alkene compounds can be monofunctional, difunctional, or multifunctional. As used herein, monofunctional monomers can refer to monomers that have a single addition polymerizable group. Difunctional monomers can refer to monomers, oligomers, resins, or polymers that contain two addition polymerizable groups. Multifunctional compounds can refer to any monomer, oligomer, resin, or polymer that contains three or more addition polymerizable groups. In contrast to monofunctional compounds, difunctional compounds and multifunctional compounds can undergo additional crosslinking, chain-extension, or both, when polymerized. As can be appreciated, chain extension and crosslinking can provide for enhanced functionality and improved durability, strength, and longevity compared to monofunctional monomers.
An illustrative example of a monofunctional 1,1-disubstituted alkene compound is depicted by general formula I:
wherein each X can independently be O or a direct bond and R1 and R2 can be the same or different and can each represent a hydrocarbyl group.
An illustrative example of a multifunctional monomer having more than one methylene group connected by a multi-functionalized hydrocarbyl group can be depicted by general formula II:
wherein each X can independently be O or a direct bond; R3 and R5 can be the same or different and can each represent a hydrocarbyl group; R4 can be a hydrocarbyl group having n+1 functionalities; and n is an integer of 1 or greater. In certain embodiments, n can be 3 or fewer; and in certain embodiments, n can be 2 or fewer or n can be 2 to 20 or 4 to 7.
An additional example of a multifunctional monomer (methylene malonate polyester) having more than one methylene group connected by a di-functionalized hydrocarbyl group can be depicted by general formula III:
wherein each X is O bond; R6 and R8 can be the same or different and can each represent a hydrocarbyl group; R7 is a diol and n is an integer of 1 or greater. In certain embodiments, n can be 1 or more; and in certain embodiments, n can be 2 or more or n can be 1 to 100.
According to certain embodiments, more specific examples of 1,1-disubstituted alkene compounds can include methylene malonate compounds having general formula IV:
wherein R9 and R10 can be the same or different and can each represent a hydrocarbyl group. For example, methylene malonate compounds can include diethyl methylene malonate (“DEMM”), dimethyl methylene malonate (“DMMM” or “D3M”), hexyl methyl methylene malonate (“HMMM”), ethyl ethoxyethyl methylene malonate (“EEOEMM”), fenchyl methyl methylene malonate (“FMMM”), dibutyl methylene malonate (“DBMM”), dihexyl methylene malonate (“DHMM”), dicyclohexyl methylene malonate (“DCHMM”), di-n-propyl methylene malonate, di-isopropyl methylene malonate, and dibenzyl methylene malonate. Additionally, in certain embodiments, certain transesterification reaction products formed from the reaction of methylene malonate compounds with acetates, diacetates, alcohols, diols, and polyols can also be used to form 1,1-disubstituted alkene macromers.
According to certain embodiments, examples of methylene beta ketoesters can be represented by general formula V:
wherein R11 and R12 can be the same or different and can each represent a hydrocarbyl group.
According to certain embodiments, examples of methylene beta diketones can be represented by general formula VI:
wherein R13 and R14 can be the same or different and can each represent a hydrocarbyl group.
Additional details and methods of making suitable 1,1-disubstituted alkene compounds as well as other suitable compositions are disclosed in U.S. Pat. Nos. 8,609,885; 8,884,051; 9,221,739; 9,512,058; 9,527,795; WO 2013/059473; WO 2013/066629; and WO 2014/110388 each of which are hereby incorporated by reference.
In certain embodiments, 1,1-disubstituted alkene compounds can also, or additionally, include polyester macromers. As can be appreciated, compositions containing polyester macromers can undergo polymerization when exposed to basic initiators. Polyester macromers are disclosed in U.S. Pat. Nos. 9,617,377 and 9,745,413 each incorporated herein by reference. An example of a suitable methylene malonate polyester includes the transesterification, and partial Michael addition, product formed from the reaction of diethyl methylene malonate with 1,4-butanediol (hereinafter, “methylene malonate polyester”).
As will be appreciated, the systems and methods described herein can facilitate the long-term storage and transport of 1,1-disubstituted alkene monomers without any premature degradation of the monomers through, for example, premature polymerization of the monomer or other chemical reactions between the 1,1-disubstituted alkene monomers with the storage container or surrounding environment.
Generally, the storage containers described herein can be formed of materials which are non-reactive to 1,1-disubstituted alkene monomers. As used herein, non-reactive means that the storage container material, or the 1,1-disubstituted alkene composition, does not substantially change in either appearance or weight when placed in contact with each other.
It has been discovered that the reactivity of plastics to 1,1-disubstituted alkene monomers varies, in part, upon the specific chemistry of a 1,1-disubstituted alkene monomer. For example, monomers with larger hydrocarbyl groups, such as dicyclohexyl methylene malonate with bulky ring structures, exhibit less reactivity to certain plastics than similar methylene malonates with smaller hydrocarbyl groups such as diethyl methylene malonate. In certain embodiments, the storage containers described herein can be designed to store and transport only specific 1,1-disubstituted alkene monomers. For example, a storage container for storage and transport of dicyclohexyl methylene malonate can be formed of polypropylene, or polymethylpentene even though such storage containers would not necessarily be compatible with other 1,1-disubstituted alkene monomers such as diethyl methylene malonate or dihexyl methylene malonate.
As can be appreciated however, it can be useful to construct the storage containers described herein from materials which are non-reactive to substantially all 1,1-disubstituted alkene monomers. Unmodified plastic materials which have been discovered to be substantially non-reactive to 1,1-disubstituted alkene monomers generally include high-density polyethylene (“HDPE”), polyethylene terephthalate (“PET”) and polyacrylonitrile (“PAN”).
In certain embodiments, the storage containers described herein can alternatively be formed of reactive materials, such as reactive plastics, if the 1,1-disubstituted alkene monomer can be separated from the reactive materials. For example, a storage container formed of polypropylene can be suitable if it contains a non-reactive coating that is in contact with the 1,1-disubstituted alkene monomers.
In certain embodiments, examples of suitable non-reactive coatings for the storage containers described herein can include non-reactive plastics, plastics with surface modified properties, and certain metals. For example, a storage container made out of a laminated plastic having a PET or PAN layer in contact with the 1,1-disubstituted alkene monomer and another plastic such as polypropylene for strength can be a suitable storage container.
In certain embodiments, a halogenation process can be used to modify the surface of a plastic. In certain embodiments, the plastic can be a substantially non-reactive plastic such as HDPE while in other embodiments, a reactive plastic can be modified. Modification of a non-reactive plastic such as HDPE can be useful to further improve the shelf life of the 1,1-disubstituted alkene monomer or to improve resistance to harsher environments such as environments having a temperature of about 70° C. or greater or high relative humidity (e.g., about 75% relative humidity or greater).
As can be appreciated, other surface modification treatments are also possible for the storage containers described herein. For example, an acrylamide or metal coating can be formed using known processes (e.g., through surface activation followed by covalent bonding, sputtering or deposition processes, iCVD processes, electroplating processes, etc.). In certain embodiments, application of one or more of sulfur dioxide (SO2), methane sulfonic acid (“MSA”), trifluoromethane sulfonic acid (“TSA”), hydrochloric acid (HCl) and phosphoric acid (H3PO4) can be used to modify a plastic. As can be appreciated, such compounds can suppress undesired surface initiation and reduce the amount of anionic polymerization. As can be appreciated, the formation of a non-reactive layer can be beneficial to lower the cost of a storage container in addition to improving the shelf life of the 1,1-disubstituted alkene monomer composition contained therein.
It has been further discovered that moisture, including moisture present as atmospheric humidity, can impair the shelf life of a 1,1-disubstituted alkene monomer. To improve the shelf life, the storage containers described herein can include a barrier layer that prevents moisture migration through the storage container.
In certain embodiments, the barrier layer can be formed upon one or more surfaces of the storage container. Alternatively, the storage container can be partially, or entirely, formed of a material that inherently prevents moisture migration. For example, a storage container formed of HDPE can resist moisture migration without the formation of an additional barrier layer. As can be appreciated however, it can be useful even in certain such embodiments for the storage container to contain a barrier layer to further increase the shelf life of a 1,1-disubstituted monomers during storage. In certain embodiments, the barrier layer can be similar to, or substantially identical to, the nonreactive coating. In certain such embodiments, a non-reactive coating can also function as a moisture barrier layer and the storage container can include only layers that act as both a non-reactive coating and as a moisture barrier layer.
In certain embodiments, the storage containers described herein can have a moisture vapor transmission rate sufficient to ensure that a 1,1-disubstituted alkene monomer retains reactivity for at least about 60 days, at least about 90 days, or at least about 120 days even when subject to harsh conditions (e.g., temperature of about 50° C. to 70° C. or greater and humidity of about 75% relative humidity or greater). In certain embodiments, the storage containers can have a moisture vapor transmission rate of about 5.4×10−3 (g-mm/cm2/day) or less such as about 5.7×10−4 (g-mm/cm2/day), about 1×10−4 (g-mm/cm2/day), about 5×10−5 (g-mm/cm2/day), or less. In certain embodiments, the storage containers described herein can be substantially entirely formed out of a single material that exhibits such a moisture vapor transmission rate (e.g., HDPE) or include one or more non-reactive layers or moisture barrier layers to achieve such a moisture vapor transmission rate.
As can be appreciated, it can also be useful to form storage containers that exhibit multiple properties. For example, it can be useful for storage containers to exhibit a certain moisture vapor transmission rate to maintain reactivity of the 1,1-disubstituted alkene monomer while also including a halogenation layer to prevent swelling with certain 1,1-disubstituted alkene monomers and/or an acid treatment to suppress undesired surface initiation and/or reduce the amount of anionic polymerization particularly when acid stabilizers are not included in the 1,1-disubstituted alkene monomer.
Generally, the storage containers described herein can vary widely in size and shape. For example, the storage containers can be sized to store small samples (e.g., about 10 mL to about 50 mL) or can be larger for longer-term storage and bulk use (e.g., about 1 L to about 5 L or even greater such as a cubic meter (1 m3) or larger). As can be appreciated, the shelf life can vary depending on the size of the storage container with larger sizes generally having a greater volume to surface area ratio.
As can be appreciated, the storage containers described herein can differ from previous storage containers known to store 1,1-disubstituted alkene compounds. For example, known storage containers were often intended for use during production of 1,1-disubstituted alkene compounds and were not intended to store the monomers for long durations of time as contemplated by the presently described storage containers. Additionally, such previously known containers were often formed of laboratory glassware (e.g., borosilicate glass) or treated steel, and not designed to be repeatedly sealed or be transported. Other known storage containers include containers for cyanoacrylates. Such containers have not been evaluated with 1,1-disubstituted alkene compositions and may not be suitable and may exhibit, for example, swelling of the storage container when filled with a 1,1-disubstituted alkene composition or impair the quality of a 1,1-disubstituted alkene composition due to changes in viscosity or gelling of the composition due to premature polymerization.
The storage containers described herein can generally be formed as known in the art. For example, suitable storage containers can be formed through an injection molding process in certain embodiments. In embodiments including a non-reactive layer, the non-reactive layer can be formed after general shaping and formation of the storage container.
In certain embodiments, the storage containers can be filled by decanting a 1,1-disubstituted alkene composition into the storage container and then sealing the storage container. In certain embodiments, the storage containers can be filled under dry atmosphere, such as an atmosphere having a relative humidity of about 50% or less, about 20% or less, about 10% or less, about 5% or less, or about 1% or less. Filling a storage container under dry atmosphere can improve the shelf life by minimizing hydrolysis of the 1,1-disubstituted alkene monomers.
Generally, the storage containers described herein can be sealed in any suitable fashion. For example, small sample vials can be sealed by molding the storage container to a sealed end with heat and pressure. To open such small sample vials, the sealed end can be cut or punctured.
In certain embodiments, the storage containers can include a one-time use seal. Inclusion of a one-time use seal can allow end users to know that the 1,1-disubstituted alkene monomers have not been undesirably exposed to atmosphere or humidity. A sealing top can be located over the one-time use seal. As can be appreciated, in such embodiments, the sealing top can be reactive to 1,1-disubstituted alkene monomers because the one-time use seal acts as a barrier.
In certain embodiments, the storage containers can include a sealing top such as a screw top. In such embodiments, the storage container lids can be formed of a nonreactive material or can include a non-reactive coating as previously described herein. As can be appreciated, such storage containers can allow for long-term storage of 1,1-disubstituted alkene monomers and allow for multiple withdrawals of monomer or composition.
As can be appreciated, the storage containers described herein can be modified in a variety of ways. For example, the storage containers can be shaped and/or include additional packaging in certain embodiments to facilitate handling and transportation. For example, in certain embodiments, the storage containers can include handles.
In certain embodiments, the storage containers can include insulation. Insulation can allow the storage containers to maintain a stable temperature when exposed to either elevated or cold temperatures such as temperatures found during transportation. In certain embodiments, indicia can be included to identify the specific compositions contained within the container, a tare weight, or to allow for direct storage or shipping of the storage container. For example, in certain embodiments, the storage containers can comply with commercial and governmental regulations to be directly shipped and transported by mail, courier, and freight services.
In certain embodiments, the storage containers can be optically transparent to allow users to visually asses the amount of composition contained therein. In other alternative embodiments, the storage containers can be visually opaque to improve the shelf life such as in embodiments where a photoinitiator is present.
Generally, use of the methods and systems described herein can improve the shelf life of a 1,1-disubstituted alkene composition. For example, in certain embodiments, the systems and methods can enable a 1,1-disubstituted alkene composition to have a shelf life of about 3 months or greater, about 6 months or greater, about 9 months or greater, or even 12 months or greater when stored at ambient temperatures (e.g., between about 10° C. to about 35° C.).
As can be appreciated, the systems and methods described herein can also be used to store compositions formed of 1,1-disubstituted alkene monomers and other components. For example, in certain embodiments, the systems and methods described herein can be used to increase the shelf life of compositions which further include one or more additives. For example, the systems and methods can be used to store compositions further including, for example, one or more dyes, pigments, toughening agents, impact modifiers, rheology modifiers, plasticizing agents, natural or synthetic rubbers, filler agents, reinforcing agents, thickening agents, opacifiers, inhibitors, fluorescence markers, thermal degradation reducers, thermal resistance conferring agents, surfactants, wetting agents, conductive synergists, or stabilizers. For example, thickening agents and plasticizers such as vinyl chloride terpolymer and dimethyl sebacate respectively, can be used to modify the viscosity, elasticity, and robustness of a system. Additives can additionally, or alternatively, provide mechanical reinforcement to the polymerized system. Inclusion of such additives can be useful to provide a ready-to-use product or intermediate to end users.
In certain embodiments, the systems and methods described herein can alternatively, or further, store more than one 1,1-disubstituted alkene monomer. For example, the systems and methods can be useful for compositions including a blend of multiple 1,1-disubstituted alkene monomers. Storage of a blend of 1,1-disubstituted alkene monomers can facilitate additional uses such as, for example, in applications that require a blend of properties not possible when only a single 1,1-disubstituted alkene monomer is included. Generally, in such embodiments, the systems and methods (e.g., storage containers) can be compatible with each of the 1,1-disubstituted alkene monomers included in the blend. For example, a storage container for storing a blend of monomers including DEMM and DCHMM can be a storage container capable of storing either DEMM or DCHMM individually. As can be appreciated however, certain compositions can exhibit combined and/or synergistic effects and can be stored in storage containers that could not store each of the components individually. For example, a blend included a greater amount of DCHMM and a lesser amount of DEMM may be stored in a container that could not store solely DEMM.
According to certain embodiments, the systems, methods and containers described herein can also include additional stabilizers to increase and improve the shelf life of the compositions. For example, one or more anionic polymerization inhibitors such as liquid phase stabilizers (e.g., methanesulfonic acid (“MSA”)), vapor phase stabilizers (e.g., trifluoroacetic acid (“TFA”)), or free radical stabilizers (e.g., 4-methoxyphenol or mono methyl ether of hydroquinone (“MeHQ”)) or dibutylhydroxytoluene (“BHT”) can be used as a stabilizer package as disclosed in U.S. Pat. Nos. 8,609,885 and 8,884,051, each incorporated by reference. Additional free radical polymerization inhibitors are disclosed in U.S. Pat. No. 6,458,956, and are hereby incorporated by reference. Anionic polymerization stabilizers are generally electrophilic compounds that scavenge electrons from the composition or growing polymer chain. The use of anionic polymerization stabilizers can terminate additional polymer chain propagation. Generally, only minimal quantities of a stabilizer are needed and, in certain embodiments only about 1000 parts-per-million (“ppm”) or less can be included. In certain embodiments, a blend of multiple stabilizers can be included such as, for example, a blend of about 10 ppm MSA and 100 ppm MeHQ.
In certain embodiments, embodiments, the additional stabilizers can include antioxidants and acids. For example, suitable antioxidants can be included in a 1,1-disubstituted alkene composition between about 10 parts per million to about 1% by weight of the 1,1-disubstituted alkene composition. In certain embodiments, suitable antioxidants can include hindered phenol derivatives and thiol compounds free of nitrogen. In certain embodiments, the hindered phenol derivatives can be primary antioxidants and the thiol compounds can be secondary antioxidants. In certain embodiments, suitable acids can include acids having an H0 of about 3 or less. In such embodiments, acids can be included in concentrations between about 5 parts per million or more and about 1% by weight or less of the 1,1-disubstituted alkene composition.
Table 1 depicts the results of evaluating the compatibility of various plastic materials to methylene malonate monomers. Compatibility was determined by immersing example test strips formed from plastic sample containers in methylene malonate monomer and evaluating the weight change of the sample. Each of the example test strips was 15 mm wide by 60 mm long. Each example test strip was fully immersed in a glass screw vial containing diethyl methylene malonate (“DEMM”), dihexyl methylene malonate (“DHMM”), and dicyclohexyl methylene malonate (“DCHMM”). The sample vials were passivated methanesulfonic acid (“MSA”) in tetrahydrofuran (“THF”). The methylene malonate monomers included 2,000 parts-per-million (“ppm”) of butylated hydroxytoluene (“BHT”) stabilizer. Stability results of the example test strips after being held at 70° C. for 4 days, 5 days, and 8 days are depicted in Table 1. Evaluated plastics include high-density polyethylene (“HDPE”); fluorinated high-density polyethylene (“F-HDPE”); polypropylene (“PP”); polymethylpentene (“PMP”); polystyrene (“PS”); polycarbonate (“PC”); polyacrylonitrile (“PAN”); and polyethylene terephthalate (“PET”).
As depicted in Table 1, Examples 2, 7 and 8, formed of fluorinated high-density polyethylene, polyacrylonitrile and polyethylene terephthalate respectively, exhibited compatibility with each of the methylene malonate monomers. Examples 1, 3 and 4 (high-density polyethylene, polypropylene, and polymethylpentene) were not compatible with diethyl methylene malonate or dihexyl methylene malonate due to swelling but exhibited compatibility with dicyclohexyl methylene malonate. Examples 5 and 6 (polystyrene and polycarbonate) were not compatible with any of the methylene malonate monomers as they either dissolved the test piece (polystyrene) or turned the surface of the test strip white (polycarbonate).
HDPE containers were further evaluated by extending the limits of the test to 21 days and evaluating at 50° C. and 70° C. HDPE containers exhibited no visual change in appearance or weight after 21 days suggesting those materials are non-reactive and compatible with 1,1-disubstituted alkene monomers at temperatures of 50° C. or less. At temperatures of 70° C., HDPE exhibited swelling while F-HDPE showed better compatibility with 1,1-disubstituted alkene compositions.
In addition to the F-HDPE example depicted in Table 1, surface coating of high-density polyethylene was further evaluated by modifying the inside surfaces of a HDPE sample container with a deposited polyamide coating. The polyamide coated containers were then filled with each of diethyl methylene malonate (“DEMM”), dihexyl methylene malonate (“DHMM”), and dicyclohexyl methylene malonate (“DCHMM”).
The sample vials with surface coatings exhibited no change in appearance or weight after evaluation at 50° C. and 70° C. suggesting the efficacy of both fluorinated surfaces and polyamide coatings as a non-reactive coating.
Table 2 depicts the results of evaluating several example moisture barriers to improve the shelf life of a storage container. Specifically, Table 2 evaluates the effects of filling storage containers formed of fluorinated high-density polyethylene (“F-HDPE”) and Unified Numbering System (“UNS”) S30400 austenite stainless steel (SUS304 in Japan) with DHMM at 50° C. The example storage containers were filled, stored, and opened and reclosed under varying relative humidity (“RH”) conditions. Reactivity for anionic polymerization was measured weekly by counting the number of minutes until 1 g of DHMM was cured and became non-fluid after being mixed with 50 mg of 1%, by weight, ethyl 1-methyl-3-piperidine carboxylate in bis(2-ethylhexyl adipate) solvent.
Storage of DHMM under dry conditions of less than 1% relative humidity did not have a substantial impact upon reactivity of the monomer as indicated by Examples 9 and 11. Under high humidity conditions (Examples 10 and 12), stainless steel performed better than F-HDPE at preventing hydrolysis reactions.
Additional testing of HDPE, PET, Baritainer (Registered Trademark), and aluminum storage containers was performed over longer periods of time with a desiccant (dried anhydrous calcium chloride) to better understand moisture vapor transmission rates according to ASTM (D7709-12). Using these containers, the reactivity change of dihexyl methylene malonate and methylene malonate polyester over time was evaluated. Baritainer (Registered Trademark) is a multi-layer plastic material known for excellent oxygen barrier properties and includes HDPE and nylon layers. The HDPE was purchased from Nalgene. The storage containers were sealed with torques according to ASTM specifications (D7709) in a dried air atmosphere and stored in an oven set at 50° C. and 75% relative humidity. Table 3 depicts the volume of the evaluated storage containers as well as the volume of the samples used to evaluate the moisture vapor transmission rate and reactivity.
To determine moisture vapor transmission rates, the weight of the desiccant was measured after the first day and every seventh day thereafter for a period of 30 days. Three replicates were performed for each storage container and average weight was calculated to ensure statistical significance in the data. Results are depicted in Table 4 and plotted in
Based on the results of Table 4, the surface area and thickness of each evaluated storage container was used to generate a water vapor transmission rate (“WVTR”) using Formula 1 below:
WVTR (g-mm/cm2/day)=Water mass transfer per day (g/day)×wall thickness (mm)/surface area (cm2) [Math.1]
The calculated WVTRs are depicted in Table 5. PET had higher WVTR than either HDPE or Baritainer (Registered Trademark). Because the WVTR should be unmeasurably small for the aluminum container, the small amount of water absorbed by this container is theorized to have migrated through the plastic sealing top.
To determine the effect of the storage containers on anionic reactivity, three or four replicates were created and stored at 50° C. and 75% relative humidity for evaluation over 3 or 4 subsequent 7-day periods to obviate the need to open and then reseal the same container. Every seven days, a single container was removed for analysis and observation. In each observation, the storage container was emptied, and the monomer was evaluated for anionic reactivity using an initiator.
The anionic reactivity test for DHMM was performed by filling a 4 mL PP vial with 1 g of the DHMM sample from the evaluated storage container and placing a magnetic stir bar in the vial. While mixing with the stir bar at a speed of 500 rotations-per-minute (“rpm”), the temperature of the reaction mixture was measured as 0.5 g of a 0.025% 1,4-diazabicyclo [2.2.2]octane (“DABCO”) solution in DEGDEE was deposited into the reaction mixture. The timer was started at the moment the DABCO solution was added and continued until the observed temperature increment of the mixture was higher than 0.1° C. per second for two seconds in a row. The measured time was recorded as an indication of the reactivity of the DHMM. The anionic reactivity test for methylene malonate polyester was performed by filling a 4 mL polypropylene (“PP”) vial with 1 g of the methylene malonate polyester sample from the evaluated storage container and 0.5 g of diethyleneglycol diethyl ether (“DEGDEE”) and placing a stir bar in the vial. While mixing with the stir bar at a speed of 500 rpm, the temperature of the reaction mixture was measured as 0.5 g of a 1% dimethylbenzyl amine (“DMBA”) solution in DEGDEE was deposited into the middle of the reaction mixture. The timer was started at the moment the DMBA solution was added and continued until the observed temperature increment of the mixture was higher than 0.1° C. per second for two seconds in a row. The measured time was recorded as an indication of the reactivity of the methylene malonate polyester. The reactivity of DHMM over time in each of the storage containers is depicted in Table 6 while the reactivity changes of methylene malonate polyester are depicted in Table 7.
As depicted in Table 6 and 7, substantial differences in reactivity change were observed for the samples after storage in the storage containers. Aluminum containers showed the smallest degradation in reactivity over time while HDPE, Baritainer (Registered Trademark), and PET, in that order, exhibited greater losses in reactivity. DHMM samples contained in the PET container were unreactive by day 21 and could not be cured by the reactivity test. These results provide evidence that as WVTRs increase, loss in reactivity occurs.
However, in contrast to the change in reactivity, the viscosity of DHMM did not change even in the PET container. Viscosity of DHMM was 6.9 cP and 6.7 cP at the initial day of the test (day 0) and end of the test (day 21), respectively. This is a characteristic result for 1,1-disubstituted alkene such as methylene malonate and differs from other known anionically polymerizable compounds. As can be appreciated, most anionically polymerizable compounds, such as cyanoacrylates and isocyanates, instead exhibit changes in viscosity or exhibit gelation due to premature polymerization when they are in contact with water as explained in U.S. 2003/0039781 A1.
The amount of absorbed water (g) in the container at the time when anionic reactivity test was carried out can be determined by the following equation: “Water mass transfer per day (g/day) in Table 4”דthe number of days when reactivity test was carried out (days)”. The mole ratio between the absorbed water and methylene malonate was used to determine the degree of loss of reactivity for anionic polymerization due to hydrolysis. A correlation between the amount of absorbed water per the amount of methylene malonate (g/g) and increase in reactivity time (sec) of DHMM is depicted in
By defining the acceptable limit for the increase of the reactivity time, the acceptable amount of water to be absorbed in the container during storage per the amount of methylene malonate (g/g) can be determined. According to
Based on this acceptable water amount per methylene malonate (W g/g) as well as the quantity of the methylene malonate filled in the container (M g), the wall thickness of the container (T mm), the surface area of the container (A cm2) and the required storage period (S day), the acceptable WVTR (g-mm/cm2/day) can be determined using Formula 2:
WVTR (g-mm/cm2/day)=W (g/g)×M (g)×T (mm)/A (cm2)/S (day) [Math.2]
As can be appreciated, most applications cannot accept more than a quintupling of the cure time. For example, coating films or moldings produced on a production line using 1,1-disubstituted alkene would suffer from various issues if the cure time increased without compensating for the change in reactivity. Small differences in cure time can be compensated for by changing the line speed or by adding additional initiator to increase the reactivity rate and decrease the cure time. However, excessive initiator would be required to compensate for a quintupled reactivity rate with such amounts detrimentally impacting the quality of the coating films or moldings by causing yellowing or weather ability issues. According to eq. 1, the cure time of DHMM will be quintupled from 130 sec to 650 sec when 0.00095 (g/g) of water is absorbed per the amount of DHMM in the container. According to eq. 2, reactivity of methylene malonate polyester will be doubled from 80 sec to 400 sec when 0.0025 (g/g) of water is absorbed per the amount of methylene malonate polyester in the container. Therefore, to avoid the time to cure methylene malonate monomer or polyesters from being quintupled, acceptable amount of the absorbed water in the container per the amount of methylene malonate (W) can be set as 0.00095 (g/g). As can be appreciated, some specialized applications cannot accept more than a doubling in the reactivity rate. According to eq. 1, the reactivity of DHMM will double from 130 sec to 260 sec when 0.000099 (g/g) of water is absorbed per the amount of DHMM in the container. According to eq. 2, the reactivity of methylene malonate polyester will double from 80 sec to 160 sec when 0.00093 (g/g) of water is absorbed per amount of methylene malonate polyester in the container. Therefore, to avoid doubling of the reaction rate, the acceptable amount of absorbed water in the container per amount of methylene malonate (W) can be set as 0.000099 (g/g).
One of the most practical containers for shipping and storing reactive monomers, like methylene malonate, is a plastic tote. The volume of a plastic tote is 1 m3 and its full volume is typically filled with the material. Considering the density of DHMM is 1.03, the quantity of the methylene malonate filled in the tote container (M) is assumed to be 1.03×106 g. The wall thickness of the tote container (T) is usually around 30 mm and the surface area of the tote container (A) is 100×100×6=6×104 cm2. Water mass transfer rate can be measured according to the ASTM (D7709-12) for a given atmosphere condition (temperature and relative humidity). For example, 50° C. and 75% RH may represent harsh conditions representing the hot and humid climate areas in which the 1,1-disubstituted alkene monomers may need to withstand in a storage container. Assuming the required storage period (S) is 90 days for most applications, to avoid quintupling the time to cure methylene malonate monomer or polyesters, an acceptable WVTR (g-mm/cm2/day) can be calculated as 0.00095 (g/g)×1.03×106 (g)×30 (mm)/6×104 (cm2)/90 (days)=5.4×10−3 (g-mm/cm2/day). Similarly, to avoid doubling the time to cure methylene malonate monomer or polyesters, an acceptable WVTR (g-mm/cm2/day) can be calculated as 0.000099 (g/g)×1.03×106 (g)×30 (mm)/6×104 (cm2)/90 (days)=5.7×10−4 (g-mm/cm2/day).
A1. A method of handling a 1,1-disubstituted alkene composition comprising: providing a storage container, the storage container comprising a barrier layer, the barrier layer decreasing the water vapor transmission rate of the storage container; and filling the storage container with a 1,1-disubstituted alkene composition.
A2. The method according to paragraph A1, wherein the 1,1-disubstituted alkene composition comprises one or more of methylene malonate, methylene β-ketoester, methylene β-diketone, monofunctional, difunctional or multifunctional monomer, oligomer, or polymer thereof, and combinations thereof.
A3. The method according to paragraph A2, wherein the 1,1-disubstituted alkene composition comprises dialkyl methylene malonate or methylene malonate polyester.
A4. The method according to any preceding paragraph, wherein the dialkyl methylene malonate comprises dihexyl methylene malonate.
A5. The method according to any preceding paragraph, wherein the barrier layer is formed from a material compatible with a 1,1-disubstituted alkene composition.
A6. The method according to paragraph A5, wherein the material compatible with a 1,1-disubstituted alkene composition comprises one or more of high density polyethylene, nitryl, polyamide, or a composite of polyamide, polyethylene terephthalate, polytetrafluoroethylene, or metal.
A7. The method according to paragraph A5 or paragraph A6, wherein the material comprises high-density polyethylene.
A8. The method according to paragraph A7, wherein the material is modified by a halogenation process.
A9. The method according to paragraph A8, wherein the halogenation process comprises a fluorination process.
A10. The method according to paragraph A5, wherein the material comprises stainless steel or aluminum.
A11. The method according to any of paragraphs A5 to A10, wherein the barrier layer is an inner layer.
A12. The method according to any of paragraphs A5 to A10, wherein the barrier layer is a surface layer.
A13. The method according to any preceding paragraph, wherein the barrier layer is formed by application of one or more of sulfur dioxide (SO2), methane sulfonic acid (“MSA”), trifluoromethane sulfonic acid (“TSA”), hydrochloric acid (HCl) and phosphoric acid (H3PO4).
A14. The method according to any preceding paragraph, wherein the storage container exhibits a moisture vapor transmission rate of about 0.0054 g/cm2/mm/day or less at a temperature of about 50° C. and a relative humidity of about 75%.
A15. The method according to any preceding paragraph, wherein the storage container exhibits a moisture vapor transmission rate of about 0.00057 g/cm2/mm/day or less at a temperature of about 50° C. and a relative humidity of about 75%.
A16. The method according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition exhibits a shelf life of about 3 months or greater when the storage container is maintained at a temperature of about 50° C. and a relative humidity of about 75%.
A17. The method according to paragraph A16, wherein the 1,1-disubstituted alkene composition substantially maintains, over the course of the shelf life, one or more of viscosity and reactivity.
A18. The method according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition is filled at a relative humidity of about 50% or less.
A19. The method according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition is filled at a relative humidity of about 10% or less.
A20. The method according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition further comprises one or more antioxidants and acids.
A21. The method according to paragraph A20, wherein the one or more antioxidants comprise a primary antioxidant and wherein the 1,1-disubstituted alkene composition comprises between about 10 parts per million or more of the primary antioxidant and less than 1 percent by weight of the primary antioxidant.
A22. The method according to paragraph A21, wherein the primary antioxidant comprises a hindered phenol derivative.
A23. The method according to any of paragraphs A20 to A22, wherein the one or more antioxidants further comprise a secondary antioxidant and wherein the 1,1-disubstituted alkene composition comprises between about 10 parts per million or more of the secondary antioxidant and less than 1 percent by weight of the secondary antioxidant.
A24. The method according to paragraph A23, wherein the secondary antioxidant comprises a thiol and is substantially free of nitrogen.
A25. The method according to any of paragraphs A20 to A24, wherein the 1,1-disubstituted alkene composition comprises between about 5 parts per million or more of the acid and less than 1% by weight of the acid.
A26. The method according to paragraph A25, wherein the acid has an H0 of about 3 or less.
A27. The method according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition comprises one or more of methanesulfonic acid (“MSA”), mono methyl ether of hydroquinone (“MeHQ”), and dibutylhydroxytoluene (“BHT”).
A28. The method according to any preceding paragraph, wherein handling comprises storage and shipping.
A29. The method according to any preceding paragraph, wherein handling is performed at a temperature of about 50° C. or less.
A30. The method according to any preceding paragraph, wherein the storage container is substantially opaque to ultraviolet radiation.
A31. The method according to any preceding paragraph, wherein the barrier layer is applied with one or more of sulfur dioxide (SO2), methane sulfonic acid (“MSA”), trifluoromethane sulfonic acid (“TSA”), hydrochloric acid (HCl) and phosphoric acid (H3 PO4).
B1. A container comprising:
B2. The container according to paragraph B1, wherein the 1,1-disubstituted alkene composition comprises one or more of methylene malonate, methylene β-ketoester, methylene β-diketone, monofunctional, difunctional or multifunctional monomer, oligomer, or polymer thereof, and combinations thereof.
B3. The container according to paragraph B2, wherein the 1,1-disubstituted alkene composition comprises dialkyl methylene malonate or methylene malonate polyester.
B4. The container according to any preceding paragraph, wherein the dialkyl methylene malonate comprises dihexyl methylene malonate.
B5. The container according to any preceding paragraph, wherein the barrier layer is formed from a material compatible with a 1,1-disubstituted alkene composition.
B6. The container according to paragraph B5, wherein the material compatible with a 1,1-disubstituted alkene composition comprises one or more of high density polyethylene, nitryl, polyamide, or a composite of polyamide, polyethylene terephthalate, polytetrafluoroethylene, or metal.
B7. The container according to paragraph B5 or paragraph B6, wherein the material comprises high-density polyethylene.
B8. The container according to paragraph B7, wherein the surface of the material is modified by a halogenation process.
B9. The container according to paragraph B8, wherein the halogenation process comprises a fluorination process.
B10. The container according to paragraph B5, wherein the material comprises stainless steel or aluminum.
B11. The container according to any of paragraphs B5 to B10, wherein the barrier layer is an inner layer.
B12. The container according to any of paragraphs B5 to B10, wherein the barrier layer is a surface layer.
B13. The container according to any preceding paragraph, wherein the barrier layer is formed by application of one or more of sulfur dioxide (SO2), methane sulfonic acid (“MSA”), trifluoromethane sulfonic acid (“TSA”), hydrochloric acid (HCl) and phosphoric acid (H3PO4).
B14. The container according to any preceding paragraph, wherein the storage container exhibits a moisture vapor transmission rate of about 0.0054 g/cm2/mm/day or less at a temperature of about 50° C. and a relative humidity of about 75%.
B15. The container according to any preceding paragraph, wherein the storage container exhibits a moisture vapor transmission rate of about 0.00057 g/cm2/mm/day or less at a temperature of about 50° C. and a relative humidity of about 75%.
B16. The container according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition exhibits a shelf life of about 3 months or greater when the storage container is maintained at a temperature of about 50° C. and a relative humidity of about 75%.
B17. The container according to paragraph B16, wherein the 1,1-disubstituted alkene composition substantially maintains, over the course of the shelf life, one or more of viscosity and reactivity.
B18. The container according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition is filled at a relative humidity of about 50% or less.
B19. The container according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition is filled at a relative humidity of about 10% or less.
B20. The container according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition further comprises one or more antioxidants and acids.
B21. The container according to paragraph B20, wherein the one or more antioxidants comprise a primary antioxidant and wherein the 1,1-disubstituted alkene composition comprises between about 10 parts per million or more of the primary antioxidant and less than 1 percent by weight of the primary antioxidant.
B22. The container according to paragraph B21, wherein the primary antioxidant comprises a hindered phenol derivative.
B23. The container according to any of paragraphs B20 to B22, wherein the one or more antioxidants further comprise a secondary antioxidant and wherein the 1,1-disubstituted alkene composition comprises between about 10 parts per million or more of the secondary antioxidant and less than 1 percent by weight of the secondary antioxidant.
B24. The container according to paragraph B23, wherein the secondary antioxidant comprises a thiol and is substantially free of nitrogen.
B25. The container according to any of paragraphs B20 to B24, wherein the 1,1-disubstituted alkene composition comprises between about 5 parts per million or more of the acid and less than 1% by weight of the acid.
B26. The container according to paragraph B25, wherein the acid has an H0 of about 3 or less.
B27. The container according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition comprises one or more of methanesulfonic acid (“MSA”), mono methyl ether of hydroquinone (“MeHQ”), and dibutylhydroxytoluene (“BHT”).
B28. The container according to any preceding paragraph, wherein handling comprises storage and shipping.
B29. The container according to any preceding paragraph, wherein handling is performed at a temperature of about 50° C. or less.
B30. The container according to any preceding paragraph, wherein the storage container is substantially opaque to ultraviolet radiation.
B31. The container according to any preceding paragraph, wherein the storage container is entirely formed of the material.
B32. The container according to any preceding paragraph, wherein the storage container is sealed by one-time use seal.
B33. The container according to any preceding paragraph, wherein the storage container is sealed by a screw top.
B34. The container according to any preceding paragraph, wherein the storage container is filled with dry air having a relative humidity of about 50% or less, about 20% or less, about 10% or less, about 5% or less, or about 1% or less.
B35. The container according to any preceding paragraph, wherein the storage container is filled with the gas having oxygen concentration of 5 to 21% obtainable by diluting dry air having a relative humidity of about 50% or less, about 20% or less, about 10% or less, about 5% or less, or about 1% or less with inert gas selected from nitrogen gas, helium gas and argon gas.
B36. The container according to any preceding paragraph, wherein the storage container has gas or liquid inlet, and gas or liquid outlet.
B37. The container according to paragraph B36, wherein the inlet and/or outlet includes a valve.
B38. The container according to paragraph B36, wherein at least one of the outlets comprises a pipe that reaches a lower part of the interior of the storage container so that liquid can be discharged by insertion of gas.
B39. The container according to paragraph B38, wherein the pipe is formed from a material compatible with a 1,1-disubstituted alkene composition.
B40. The container according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition comprises preferably about 1000 ppm or lower, more preferably about 500 ppm or lower, further preferably about 100 ppm or lower, based on the amount of 1,1-disubstituted alkene, of an anionic polymerization inhibitor.
B41. The container according to any preceding paragraph, wherein the 1,1-disubstituted alkene composition comprises preferably about 5000 ppm or lower, more preferably about 2000 ppm or lower, further preferably about 1000 ppm or lower, based on the amount of 1,1-disubstituted alkene, of a radical polymerization inhibitor.
B42. The container according to any preceding paragraph, wherein the barrier layer is applied with one or more of sulfur dioxide (SO2), methane sulfonic acid (“MSA”), trifluoromethane sulfonic acid (“TSA”), hydrochloric acid (HCl) and phosphoric acid (H3 PO4).
The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Instead, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value.
It should be understood that every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this specification will include every higher numerical limitation, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this specification will include every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.
Every document cited herein, including any cross-referenced or related patent or application, is hereby incorporated herein by reference in its entirety unless expressly excluded or otherwise limited. The citation of any document is not an admission that it is prior art with respect to any invention disclosed or claimed herein or that it alone, or in any combination with any other reference or references, teaches, suggests, or discloses any such invention. Further, to the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in the document shall govern.
The foregoing description of embodiments and examples has been presented for purposes of description. It is not intended to be exhaustive or limiting to the forms described. Numerous modifications are possible in light of the above teachings. Some of those modifications have been discussed and others will be understood by those skilled in the art. The embodiments were chosen and described for illustration of various embodiments. The scope is, of course, not limited to the examples or embodiments set forth herein, but can be employed in any number of applications and equivalent articles by those of ordinary skill in the art. Rather it is hereby intended the scope be defined by the claims appended hereto.
It should be understood that certain embodiments, features, structures, or characteristics of the various embodiments can be interchanged in whole or in part. Reference to certain embodiments means that a particular aspect, feature, structure, or characteristic described in connection with certain embodiments can be included in at least one aspect and may be interchanged with certain other embodiments. The appearances of the phrase “in certain embodiments” in various places in specification are not necessarily all referring to the same aspect, nor are certain embodiments necessarily mutually exclusive of other certain embodiments. It should also be understood that the steps of the methods set forth herein are not necessarily required to be performed in the orders described, and the order of the steps of such methods should be understood to be merely exemplary. Likewise, additional steps can be included in such methods, and certain steps may be omitted or combined, in methods consistent with certain embodiments.
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2022/004075 | 2/2/2022 | WO |
| Number | Date | Country | |
|---|---|---|---|
| 63146427 | Feb 2021 | US |
