Production of biopolymer particles

Abstract

The present disclosure provides a method for producing biopolymer particles, the method comprising: (a) passing a dispersed phase containing the biopolymer in a solvent through a membrane to form an emulsion of the biopolymer in the continuous phase, thereby membrane-emulsifying the dispersed phase in the continuous phase, and (b) forming particles of the biopolymer by phase inversion with an antisolvent; and (b) cooling the emulsion to a temperature T1. Also provided are biopolymer particles obtained by this method.

Description

[Technical Field]

[0001] The present invention relates to a method for producing biopolymer particles, in particular to a method that results in an improved yield of said biopolymer particles, where yield is defined herein. The present invention also provides biopolymer particles obtainable by the method of the present invention. [Background technology]

[0002] The development of biopolymers is important for reducing the environmental impact of consumer products. Polymeric materials are widely used due to their adaptability, durability, and affordability, to the point that it is difficult to identify consumer products that do not contain polymeric materials. However, many of the synthetic polymers developed are primarily derived from petroleum and coal, which means they are environmentally incompatible and rely on unsustainable resources. Polymer microparticles, in particular, pose serious environmental problems because they often persist in ecosystems even after consumers discard the products. Therefore, biopolymers and biopolymer particles play a major role in addressing these issues, as they are not only derived from renewable and sustainable raw materials but are also often biodegradable. However, the production of biopolymer particles is considered to be a challenging task.

[0003] One method that has been used to produce biopolymer particles is membrane emulsification followed by phase inversion. In the membrane emulsification process, a dispersed phase of biopolymer is forced through the pores of a microporous membrane directly into a continuous phase, forming an emulsion from which particles can be extracted. However, this process can present various challenges, including coalescence and aggregation of particles in the continuous phase. Phase inversion involves exposing the emulsion to a poor solvent, for example, by immersing the emulsion in the poor solvent, which can cause deformation upon exposure / immersion and further aggregation and coalescence.

[0004] Overall, there remains a need in the art for a method for producing biopolymer particles that does not suffer from the above-mentioned problems, and in particular, a method that prevents coalescence, aggregation, and / or deformation of the biopolymer particles, thereby improving yield. Summary of the Invention

[0005] An object of the present invention is to provide a method for producing biopolymer particles, the method comprising: (a) membrane emulsifying a dispersed phase in a continuous phase, the dispersed phase comprising the biopolymer in a solvent, by passing the dispersed phase through a membrane to form an emulsion of the biopolymer in the continuous phase; and (b) forming particles of the biopolymer by phase inversion with an antisolvent. The method further comprises, prior to (b), cooling the emulsion to a temperature T1, where T1 is the pour point (T) of the continuous phase. cont ) but is higher than the transition temperature (T disp The transition temperature of the dispersed phase is selected from the group consisting of a freezing point, a glass transition temperature, and a pour point.

[0006] T1 is defined as follows: T cont <T1≦T disp ; In the formula, T disp >T cont is.

[0007] In various embodiments of the present invention, the anti-solvent is aqueous, i.e., comprises water. In various embodiments of the present invention, the anti-solvent comprises an organic solvent, such as an alcohol, acetone, etc. In various embodiments, the anti-solvent comprises an organic solvent and water. In various embodiments of the present invention, the anti-solvent is cooled. For example, the anti-solvent can be cooled to a temperature T2 for phase inversion (b), where T2 is equal to or less than T disp Preferably, T2 is substantially equal to T1, and more preferably, T2 is equal to T1.

[0008] In various embodiments of the present invention, the membrane emulsification is selected from the group consisting of cross-flow membrane emulsification, rotating membrane emulsification, vibrating membrane emulsification, and combinations thereof. Preferably, the membrane emulsification comprises cross-flow membrane emulsification.

[0009] In various embodiments of the invention, cooling of the emulsion occurs at the outlet of the membrane, for example, because an emulsion of the dispersed phase in the continuous phase is formed. In various embodiments of the invention, the continuous phase comprises a non-polar solvent. In various embodiments of the invention, the dispersed phase comprises a polar solvent.

[0010] In various embodiments of the present invention, the phase inversion is carried out under shear. In various embodiments, the phase inversion comprises a filtration step. In various embodiments, the phase inversion is carried out under shear and comprises a filtration step.

[0011] In various embodiments of the present invention, the method is continuous.

[0012] In various embodiments of the present invention, after phase inversion (b), the antisolvent / continuous phase mixture is removed from the particles.

[0013] In various embodiments of the present invention, the biopolymer is a polysaccharide. Preferably, the biopolymer is cellulose.

[0014] It is another object of the present invention to provide biopolymer particles obtainable by the methods described herein. Accordingly, the features described herein in the context of the methods are also applicable to the biopolymer particles obtainable by the methods described herein. The biopolymer particles obtainable by the methods described herein are distinguishable from the prior art due to increased yield and regularity of size and shape. Such regularity can be seen, for example, in Figure 5(b).

[0015] These objects and embodiments are set forth in the accompanying independent and dependent claims. It will be understood that features of the dependent claims may be combined with each other and with features of the independent claims in combinations other than those explicitly set forth in the claims. Furthermore, the approach described herein is not limited to the specific embodiments set forth below, but rather includes and contemplates any combination of features provided herein.

[0016] The above and other objects, features and advantages of the present invention will become more fully apparent from the following detailed description considered in conjunction with the accompanying drawings, although it should be clearly understood that the drawings are for illustrative purposes only and are not to be construed as defining the scope of the invention. [Brief explanation of the drawings]

[0017] [Figure 1] FIG. 1 is a schematic diagram of membrane emulsification. [Figure 2] An example of the desired particle size (<50 μm) and shape (spherical) (FIG. 2(a)) and four photographs of particles showing the deformation and aggregation problems encountered in the prior art (FIGS. 2(b)-2(d)). [Figure 3] 3(a) includes a schematic diagram of a prior art process (FIG. 3(a)) and a diagram of one embodiment of emulsion cooling according to the present invention (FIG. 3(b)). [Figure 4] 1 is a diagrammatic representation of one embodiment of a method according to the present invention. [Figure 5] It includes two photographs, Figure 5(a) is a photograph of cellulose particles obtained from a comparative example in which emulsion cooling according to the present invention was not performed, and Figure 5(b) is a photograph of cellulose particles obtained according to an example according to the present invention described below. DETAILED DESCRIPTION OF THE INVENTION

[0018] Although various exemplary embodiments have been described or suggested herein, other exemplary embodiments utilizing various methods and materials similar or equivalent to those described or suggested herein are encompassed by the general inventive concept. Aspects and features of conventionally practiced embodiments may not be discussed or described in detail in the interest of brevity. Accordingly, it will be understood that aspects and features of the apparatus and methods described herein that are not described in detail can be implemented in accordance with any conventional techniques for implementing such aspects and features.

[0019] The general inventive concept centers around increasing the yield of biopolymer particles from membrane emulsification and phase inversion processes, where the term "yield" refers to the mass of spherical particles or beads within a defined particle size distribution. Membrane emulsification is known in the art and is a technique in which a dispersed phase is forced directly into a continuous phase through the pores of a microporous membrane, where emulsified droplets form and break off at the edges of the pores in a drop-by-drop mechanism. A schematic diagram of the membrane emulsification process is shown in Figure 1, with arrows indicating the direction of flow.

[0020] The dispersed phase generally contains a first liquid, which contains a biopolymer dissolved in a solvent, and the continuous phase contains a second liquid that is immiscible with the first liquid. The interaction of the two liquids when the dispersed phase is transported, such as by being pushed through a membrane, is called the dispersion process, and their heterogeneous mixture is called an emulsion: droplets of the dispersed phase surrounded by the continuous phase.

[0021] The advantages of membrane emulsification compared to conventional emulsification are recognized in the art, including the ability to obtain very fine emulsions with controlled droplet size and narrow droplet size distribution. Furthermore, successful emulsification can be achieved with significantly less emulsifier and energy consumption. And, due to the reduced impact of shear stress, membrane emulsification allows the use of shear-sensitive raw materials, such as starch and proteins. However, it is recognized that the productivity of membrane emulsification needs to be improved in order to expand its industrial application.

[0022] Biopolymer production has been successfully achieved by phase inversion of dispersed droplets in a continuous phase. For cellulose, this is described in ACS Sustainable Chem. Eng. 2017, 5, 7, 5931-5939, incorporated herein by reference. Phase inversion is a chemical phenomenon used to create artificial membranes and is achieved by removing the solvent from a liquid-polymer solution. Various phase inversion methods exist, such as immersing the polymer solution in a third liquid, called an antisolvent. The use of antisolvent-based phase inversion has proven particularly effective for precipitating biopolymer droplets into particles from dispersed / continuous emulsions.

[0023] Unfortunately, however, dispersed phase droplets in emulsions are at risk of engaging in undesirable processes that reduce yield, where yield as referred to herein refers to the mass of spherical particles or beads within a defined particle size distribution. The droplets may irreversibly interact with each other (otherwise referred to herein as coalescence or aggregation) and / or may irreversibly deform, for example, during phase inversion.

[0024] Four biopolymer particle shapes are shown in Figures 2(a)-2(d). Figure 2(a) shows exemplary particle shapes and sizes that may be desirable in certain applications, with individual spherical beads having diameters <50 μm; Figure 2(b) shows undesirable shape deformation, with individual teardrop-shaped particles; Figure 2(c) shows undesirable coalescence of multiple spherical particles with diameters >200 μm; and Figure 2(d) shows undesirable asymmetric aggregation of multiple beads. Deformation and aggregation affect both the size and shape distribution of the biopolymer particles, which negatively impacts biopolymer particle yield.

[0025] Because it is difficult to examine forming particles in situ, only theoretical explanations can be offered for where and how deformed shapes, coalesced structures, aggregated structures, etc. form. While not wishing to be bound by any one theory, the inventors believe that dispersed-phase droplets may undesirably interact with one another as they flow through equipment typically used in membrane emulsification or subsequent process piping, fittings, and equipment. These droplets may coalesce when there is a change in the fluid transport flow regime, such as a transition from laminar to turbulent flow, a recirculation zone, or a change in flow direction. Another theory is that dispersed-phase droplets may be deformed by shear forces, for example, during the phase inversion process (e.g., as the emulsion flows through the antisolvent), and these deformed shapes (e.g., teardrops) may be preserved by the antisolvent. Dispersed-phase droplets may also interact during the phase inversion process before or upon contact with the antisolvent, potentially coalescing to form larger droplets or grouping together to form larger structures that are preserved by the antisolvent. There may also be other mechanisms, such as the entrapment of smaller phase-transition particles by larger droplets during the phase-transition process, followed by the preservation of their structure by the antisolvent.

[0026] The present invention surprisingly avoids these distortion and coagulation problems, thereby improving overall yield. This yield improvement is achieved by cooling the emulsion formed by membrane emulsification to a temperature T1 before phase inversion. Specifically, T1 is greater than (i.e., higher than) the pour point of the continuous phase and less than (i.e., lower than) the transition temperature of the dispersed phase, as defined herein, provided that the transition temperature of the dispersed phase is greater than / higher than the pour point of the continuous phase. Because distortion and coagulation are believed to occur when the dispersed phase droplets are in a liquid state, cooling the emulsion below the pour point of the dispersed phase is believed to temporarily (at least partially) change the "colloid class" of the emulsion from an emulsion (i.e., liquid-in-liquid) to a sol (solid-in-liquid), thereby making the dispersed phase easier to handle in downstream processes.

[0027] Furthermore, the fact that the dispersed phase has a transition temperature (the transition temperature being selected from the group consisting of freezing point, glass transition temperature, and pour point) higher than the pour point of the continuous phase means that the continuous phase surrounding the solidified dispersed phase can still function as a transport medium. A schematic diagram of an emulsion being cooled and temporarily converted to a sol in a cooling coil heat exchanger is shown in Figure 3(b).

[0028] Figure 3(a) represents the prior art, where the continuous phase forms an emulsion with dispersed phase droplets (in this example, microdroplets; see definition below), resulting in flow stagnation and turbulence, leading to undesirable coalescence and yield loss. Figure 3(b) then illustrates an example where the emulsion is cooled in a coil heat exchanger to a temperature below the transition temperature of the dispersed phase but above the pour point of the continuous phase, allowing the continuous phase to remain mobile and transport the transitioned droplets. The exemplary embodiment of Figure 3(b) avoids the particle coalescence, deformation, and aggregation, and resulting yield loss, encountered in the prior art process of Figure 3(a).

[0029] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0030] The term "biopolymer" refers to a macromolecule produced by an organism. In other words, a polymeric biomolecule. There are three main classes of biopolymers, classified according to the monomer units used and the structure of the biopolymer formed: polynucleotides (RNA and DNA), which are polymers of 13 or more nucleotide monomers; polypeptides, which are polymers of amino acids; and polysaccharides, which are typically polymeric carbohydrate structures. Other examples of biopolymers include rubber, suberin, melanin, chitin, and lignin, preferably chitin and lignin.

[0031] In various embodiments of the present invention, the biopolymer is selected from the group consisting of polynucleotides, polypeptides, and polysaccharides. Preferably, the biopolymer is selected from the group consisting of polypeptides and polysaccharides. More preferably, the biopolymer is a polysaccharide, such as starch, cellulose, chitin, chitosan, or glycogen. Most preferably, the biopolymer is starch or cellulose.

[0032] The term "particle" is used interchangeably with "bead" herein and refers to a solid formed following phase inversion of dispersed phase droplets. In various embodiments of the present invention, the particles or beads are microparticles or microbeads. As will be understood by those skilled in the art, microparticles or microbeads are particles / beads having a diameter of 1 to 1000 microns (μm). Such particles can be readily identified by those skilled in the art using, for example, optical microscope images and image analysis software with an appropriate detection algorithm (e.g., ImageJ using an edge detection algorithm), laser diffraction using commercially available equipment such as a Mastersizer (e.g., Mastersizer 3000) from Malvern Panalytical, or appropriately sized sieves.

[0033] The membrane emulsification step of the method of the present invention involves passing a dispersed phase through a continuous phase through a membrane to form an emulsion. The membrane is not limited and can be any porous structure suitable for the membrane emulsification process. For example, the membrane can be a plate with holes that function as pores (e.g., micron-sized holes), a perforated metal tube, or sintered porous glass.

[0034] The term "emulsion" refers to a class of two-phase systems of matter in which both phases are liquids. Emulsions are a type of colloid and generally consist of two immiscible liquids. In various embodiments of the present invention, the emulsion may be a macroemulsion, which is an emulsion in which the particles of the dispersed phase have diameters of about 1 to 1000 microns. The term "sol" refers to a general class of two-phase systems of matter in which the continuous phase is a liquid and the dispersed phase is a solid.

[0035] The term "agglomerate" refers to a structure made up of primary particles that can typically be redispersed, and the term "aggregate" refers to a structure made up of primary particles that cannot be redispersed.

[0036] The term "pour point" refers to the temperature below which a substance (e.g., a liquid) loses its flow properties. It is typically defined as the lowest temperature at which a liquid (e.g., an oil) can pour from a beaker. Pour point can be measured by standard methods known in the art. For example, ASTM D7346 "Standard Test Method for No-Pour and Pour Points of Petroleum Products and Liquid Fuels" can be used. For commercially available materials, pour points are often provided by the distributor or manufacturer.

[0037] The term "freezing point" refers to the temperature at which a substance changes state from a liquid to a solid at standard atmospheric pressure (1 atm). Freezing point can be measured by standard methods known in the art. For example, ASTM E794 "Standard Test Method for Thermal Analysis Melting and Crystallization Temperatures" can be used. For commercially available materials, the freezing point may be provided by the distributor or manufacturer.

[0038] The term "glass transition point" or "glass transition temperature" refers to the temperature at which a polymer structure transitions from a hard or glassy material to a soft, rubbery material. This temperature can be measured by a differential scanning calorimeter according to the standard test method: ASTM E1356 "Standard Test Method for Assignment of Glass Transition Temperatures by Differential Scanning Calorimetry." For commercially available materials, the glass transition temperature may be provided by the supplier or manufacturer.

[0039] For ease of reference, these and further features of the present invention are discussed herein under appropriate section headings, however, the teachings under each section are not limited to the section in which they are described.

[0040] Membrane emulsification As described above, membrane emulsification is not limited and can be any membrane emulsification process known in the art. For example, the membrane emulsification process can be cross-flow membrane emulsification, rotating membrane emulsification, vibrating membrane emulsification, or a combination thereof. As understood in the art, the terms "cross-flow," "rotating," and "vibrating" refer to methods used to generate shear on the membrane surface. For example, the continuous phase can be moved relative to a stationary membrane to generate shear, or the membrane can be moved relative to the stationary phase. Alternatively, the dispersed phase can be injected into a stationary continuous phase. Known process parameters, such as membrane type, average pore size and porosity, cross-flow velocity, transmembrane pressure, and emulsifier, can also be used. In various embodiments of the present invention, membrane emulsification can include cross-flow systems, stirred cell tube membranes, stirred cell flat membranes, rotating flat membranes, vibrating / rotating tube membranes, and / or premix membrane emulsification.

[0041] International Patent Application No. WO01 / 45830 describes an example of rotating membrane emulsification. International Patent Application No. WO2012 / 094595 describes an example of cross-flow membrane emulsification. Pedro S. Silva et al. "Azimuthally Oscillating Membrane Emulsification for Controlled Droplet Production", AIChE Journal 2015 Vol. 00, No. 00 describes oscillating membrane emulsification: specifically, a membrane emulsification system including a tubular metal membrane that periodically oscillates azimuthally in a gently cross-flowing continuous phase. WO2019 / 092461 describes cross-flow membrane emulsification. Each of these method descriptions is incorporated herein by reference.

[0042] In various embodiments of the present invention, the membrane emulsification is cross-flow membrane emulsification, preferably an emulsification process in which the continuous phase moves relative to a stationary membrane.

[0043] As will be appreciated by those skilled in the art, the dispersed and continuous phases will depend on the biopolymer being produced. The dispersed phase will comprise a solvent that disperses or dissolves the biopolymer, and the continuous phase will comprise a solvent that is immiscible with the dispersed phase such that an emulsion is formed when the dispersed phase is forced through a porous membrane.

[0044] The term "solvent" refers to any substance (e.g., a liquid) that disperses or dissolves a biopolymer. The term "solvent" also includes solvent mixtures.

[0045] The identification of suitable solvents for the dispersed and continuous phases is within the common general knowledge of those skilled in the art. As mentioned above, all that is required is that the two phases—i.e., the dispersed and continuous phases—be immiscible with each other. Therefore, the solvents for each phase must be immiscible with each other. The solvent can be, for example, an aqueous solvent, an ionic liquid (a salt that is liquid at temperatures between ambient temperature and 100°C, e.g., an imidazolium-based ionic liquid such as 1-ethyl-3-methylimidazolium acetate or 1-butyl-3-methylimidazolium chloride), an organic solvent, or an inorganic non-aqueous solvent.

[0046] In various embodiments of the present invention, the solvent of the dispersed phase comprises an ionic liquid, an inorganic non-aqueous solvent, an aqueous solvent, or a combination thereof. In various embodiments of the present invention, the solvent of the dispersed phase comprises an ionic liquid, an inorganic non-aqueous solvent, or a combination thereof. In various embodiments of the present invention, the solvent of the dispersed phase comprises one or more ionic liquids. In other embodiments, the solvent of the dispersed phase comprises an organic solvent.

[0047] Non-limiting examples of solvents include water, methanol, ethanol, ammonia, acetone, acetic acid, n-propanol, n-butanol, isopropyl alcohol, ethyl acetate, dimethyl sulfoxide, sulfuryl chloride, phosphorus chloride, carbon disulfide, morpholine, N-methylmorpholine, NaOH, unassociated and associated with urea and thiourea, bromine pentafluoride, hydrogen fluoride, sulfuryl chloride fluoride, acetonitrile, dimethylformamide, hydrocarbon oils and mixtures thereof, toluene, chloroform, carbon tetrachloride, benzene, hexane, pentane, cyclopentane, cyclohexane, 1,4-dioxane, dichloromethane, nitromethane. , propylene carbonate, formic acid, tetrahydrofuran, diethyl ether, phosphoric acid, 1-ethyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium chloride, 1-methoxymethyl-3-methylimidazolium bromide, N-ethylpyridinium chloride, N-methylmorpholine-N-oxide, 1-methylimidazole, N,N-dimethylformamide, N,N'-dimethylimidazolidin-2-one, N,N-dimethylacetamide, sulfolane, γ-valerolactone, γ-butyrolactone, N,N,N',N'-tetramethylurea, N-methylpyrrolidinone, and methylene chloride. Those skilled in the art will readily recognize whether exemplary solvents are ionic liquids, organic solvents, and / or inorganic non-aqueous solvents.

[0048] Preferably, the solvent used for at least one of the dispersed and continuous phases is environmentally friendly. More preferably, the solvent used for both the dispersed and continuous phases is environmentally friendly. The term "environmentally friendly" means that the solvent is not harmful to the environment, i.e., non-toxic, so that it can be disposed of without the need for specialized equipment or processes.

[0049] It is known in the art that polysaccharides are poorly soluble in most common solvents. It is also known in the art that solvents that dissolve polysaccharides are often toxic and / or highly selective. Therefore, when the biopolymer is a polysaccharide such as cellulose, starch, chitin, glycogen, and / or chitosan, the dispersed phase solvent can include an ionic liquid. The dissolution of cellulose with the ionic liquid 1-butyl-3-methylimidazolium chloride is described, for example, in Richard et al., J. Am. Chem. Soc. 2002, 124, 4974-4975. Similarly, Verma et al., Sustainable Chemistry and Pharmacy 13(2019), 100162, describes the solubility of cellulose in ionic liquids and cosolvents. Each of these disclosures is incorporated herein by reference.

[0050] The concentration of the biopolymer in the dispersed phase is not limited and can be any concentration suitable for membrane emulsification.

[0051] The dispersed phase and / or the continuous phase may further comprise optional ingredients, including, but not limited to, cosolvents, surfactants, porogens, active ingredients, bubbles, multiple emulsions, pigments and dyes. The level of any optional ingredient is not critical to the present invention. In various embodiments, the dispersed phase comprises a cosolvent.

[0052] The co-solvent can be any solvent known in the art, including, but not limited to, those described above for the continuous and / or dispersed phases. The co-solvent can also be a co-solvent mixture. Examples of possible co-solvents include water, 1-methylimidazole (1-MI); dimethyl sulfoxide (DMSO); N,N-dimethylformamide (DMF); N,N'-dimethylimidazolidin-2-one (DMI); N,N-dimethylacetamide (DMAc); sulfolane; γ-valerolactone (γ-val); γ-butyrolactone (γ-but); propylene carbonate (PC); N,N,N',N'-tetramethylurea (TMU); and N-methylpyrrolidinone (NMP). For example, 1-methylimidazole (1-MI); dimethyl sulfoxide (DMSO); N,N-dimethylformamide (DMF); N,N'-dimethylimidazolidin-2-one (DMI); N,N-dimethylacetamide (DMAc); sulfolane; γ-valerolactone (γ-val); γ-butyrolactone (γ-but); propylene carbonate (PC); N,N,N',N'-tetramethylurea (TMU); or N-methylpyrrolidinone (NMP).

[0053] The surfactant may be any suitable surfactant known in the art, for example, an ionic or nonionic surfactant. Ionic surfactants include sulfates, sulfonates, phosphates, and carboxylates, such as alkyl sulfates, ammonium lauryl sulfate, sodium lauryl sulfate, alkyl ether sulfates, sodium laureth sulfate, sodium myreth sulfate, dioctyl sodium sulfosuccinate, perfluorooctane sulfonate, perfluorobutane sulfonate, alkylbenzene sulfonate, alkylaryl ether phosphates, alkyl ether phosphates, and alkyl carboxylates. Nonionic surfactants may include polyethers, polyoxyalkylene derivatives of hexitols, partial long-chain fatty acid esters such as sorbitan oleate, ethylene oxide derivatives of long-chain alcohols, ethoxylated vegetable oils, polydimethylsiloxane, and ethylene oxide / propylene oxide copolymers.

[0054] Emulsion cooling The advantages of the present invention are primarily due to the cooling of the emulsion formed by membrane emulsification prior to phase inversion. The emulsion is cooled to a temperature T1, which is the pour point (T cont ) and a transition temperature (T) selected from the group consisting of the freezing point, glass transition temperature, and pour point of the dispersed phase. disp ) or less, and T disp >T cont However, the absolute value of T1 is not important to the present invention, but rather the relationship of T1 to the respective temperatures of the dispersed and continuous phases is important.

[0055] The cooling method is also not limited. The emulsion may be cooled by any means known in the art for removing heat (energy) from a system. The emulsion may also be cooled at any time before phase inversion. In various embodiments, this means that the emulsion is cooled simultaneously with or separately from the membrane emulsification process. The emulsion may, for example, be cooled as it is formed (e.g., by a cooling means disposed at the outlet of the membrane). Alternatively, the emulsion may be cooled in a step after membrane emulsification, for example, by a cooling device separate from the membrane emulsification device. Advantageously, cooling should be performed as soon as possible after emulsification to reduce the possibility of coalescence and / or coagulation of the dispersed phase droplets in the liquid state.

[0056] In various embodiments, the emulsion may be cooled by a cooling medium (e.g., water, ice, etc.) that at least partially surrounds the vessel in which the emulsion is formed. In a preferred embodiment, the vessel (e.g., a pipe) in which the emulsion is formed may have a cooling jacket containing a cooling medium. The cooling medium is not particularly limited and includes any medium that has a lower temperature than the emulsion.

[0057] In various embodiments, the emulsion may be cooled by a cooling device connected to the membrane emulsifier. The cooling device may be a heat exchanger, such as an immersion-type heat exchanger. In the exemplary embodiment described below, a coil heat exchanger is immersed in a cooling medium (e.g., a cold water bath), although the invention is not limited in this respect. It is contemplated that any type of heat exchanger may be used, such as a tube-and-shell heat exchanger, a plate-and-frame heat exchanger, or a jacketed tube. Furthermore, it is contemplated that an immersion-type heat exchanger may be used with another cooling medium, such as antifreeze, dry ice, etc., to cool the emulsion to T1.

[0058] Phase inversion The phase inversion can be any phase inversion process known in the art, including, but not limited to, the use of an anti-solvent. As noted above, the phase inversion is achieved in the present invention by removing the solvent from the continuous liquid-polymer solution containing the frozen dispersed phase.

[0059] The anti-solvent can be any suitable solvent or solvent mixture known in the art. In various embodiments of the present invention, the anti-solvent is aqueous. In various embodiments, the anti-solvent is non-aqueous. The anti-solvent may comprise an organic solvent, such as, for example, an alcohol or acetone, or any other organic solvent known in the art. Suitable alcohols include ethanol and / or methanol. In various embodiments, the anti-solvent comprises an organic solvent, water, or a mixture thereof, such as, for example, an alcohol, acetone, water, or a mixture thereof.

[0060] In various embodiments of the present invention, the phase inversion is carried out at ambient temperature, i.e., about 20-25°C. In such embodiments, the anti-solvent has a temperature of about 20-25°C. Alternatively and preferably, the anti-solvent is cooled to a temperature below ambient temperature, i.e., a temperature below about 20°C. In various embodiments of the present invention, the anti-solvent has a temperature T2 below the freezing point of the dispersed phase. An advantage of controlling the temperature of the anti-solvent (T2) is to prevent premature thawing of the frozen droplets. In various embodiments of the present invention, T2 is equal to T1, where T1 is defined above.

[0061] Without wishing to be bound by any one theory, the inventors believe that by cooling the antisolvent to T2, the droplets remain frozen (and therefore spherical and non-condensed) while the surrounding continuous phase is removed by phase inversion. The antisolvent can contact the droplet surface, which causes the biopolymer to precipitate and harden the surface of the precipitate. Furthermore, when the frozen dispersed phase droplets thaw, the antisolvent converts the dissolved biopolymer droplets into beads / particles of the antisolvent, leaching the solvent system into the antisolvent.

[0062] In various embodiments of the present invention, the phase inversion is carried out under shear. Those skilled in the art will be aware of suitable shear conditions for phase inversion. Shear can be achieved, for example, by using an agitated vessel (e.g., a mechanically agitated vessel) or a settling vessel (e.g., a gravity settling vessel). The term "shear" is used herein to refer to an external force acting on an object or surface parallel to the inclined or flat surface on which the object or surface lies, where the stress tends to cause distortion.

[0063] Shear is advantageous because it increases the rate at which the continuous phase is removed from the dispersed-phase droplets, thereby increasing the overall rate of phase inversion. Because the phase inversion process is diffusion-rate limited (Fickian diffusion), shear reduces the thickness of the continuous-phase layer surrounding the dispersed-phase droplets, shortening the travel distance of antisolvent molecules to the surface of the dispersed-phase droplets and thereby accelerating the phase inversion process. However, shear adversely affects particle shape and size, so it is not typically used in current phase inversion processes. Currently, a mild phase inversion step is used, in which emulsions can be precipitated with a non-flowing antisolvent (at room temperature). Surprisingly, the dispersed-phase droplets in their frozen state are relatively resistant to other methods of separation from the continuous phase, and this increased resistance increases the efficiency of such separations.

[0064] In various embodiments of the present invention, the phase inversion includes a filtration step. The filtration step can include, but is not limited to, mechanical or any other type of filtration (e.g., using a device known in the art, such as a hydrocyclone). The filtration step can also be performed when the phase inversion is performed under shear as described above. In various embodiments, a filtration medium (e.g., a filter) can be used to filter the emulsion through a poor solvent, thereby recovering the biopolymer particles. In such embodiments, the emulsion can gravitationally settle (shear) through the poor solvent into the filter, while the continuous phase passes through the filter (filtrate). The frozen droplets can then be collected in the filter as a filter cake.

[0065] If not recovered as part of the phase inversion (e.g., via filtration, etc.), the biopolymer particles may be separated from the anti-solvent / continuous phase mixture, or the anti-solvent / continuous phase mixture may be removed from the particles. The method of removal is not limited. However, in various embodiments, the method of removal will depend on whether the method of the present invention is operated in batch mode or continuous mode.

[0066] When the method of the present invention is carried out in batch mode, the phase inversion step can be carried out first in a closed vessel, and the resulting mixture can then be transferred to a decanter vessel to undergo the settling step. Once settled, the layers can be sequentially removed from the bottom of the vessel. Typically, the order of layers can be (1) a continuous phase, (2) an interfacial layer comprising wet biopolymer particles, and (3) the remaining antisolvent. However, the invention is not limited in this respect, and one skilled in the art will understand that the order of the layers will be determined by their respective densities.

[0067] In various embodiments of the present invention, the process is continuous and operates in a continuous mode, and the phase inversion step may be carried out with continuous input of emulsion and anti-solvent and continuous discharge of the multiphase mixture into a decanter. Within the decanter, there may be a steady-state partition of the mixture, and there may be continuous and preferably simultaneous removal from each phase. For example, there may be continuous and preferably simultaneous removal from (1) the continuous phase, (2) the anti-solvent, and (3) the wet biopolymer particles. Of course, the order of these layers may vary, and the present invention is not limited to any particular order.

[0068] Alternatively, multiphase (eg, three-phase) mixtures can be separated using techniques known in the art, such as disc stack separators (eg, Andritz centrifuges, etc.).

[0069] To provide continuous cooling with continuous phase inversion, the cooling medium (e.g., the medium surrounding the vessel containing the emulsion or the medium used with a heat exchanger connected to a membrane emulsification unit) may need to be recycled or recirculated in a suitable device. For example, a device such as a recirculating chiller (ThermoFlex available from ThermoFisher Scientific) can be used to maintain the cooling medium at the desired temperature.

[0070] Another advantage of the method of the present invention is the flexibility in the sequence of events. This flexibility arises from the ability to freeze dispersed phase droplets within the emulsion. Thus, in various embodiments of the present invention, the biopolymer particles are removed after the phase inversion, as described above, or during the phase inversion. The phase inversion can be followed by decantation, and then the biopolymer particles can be removed from the mixture, and / or the wet particles can be mechanically filtered from the antisolvent / continuous phase / particle mixture during the phase inversion.

[0071] Alternatively, the biopolymer particles can be removed from the continuous phase prior to phase inversion. In such embodiments, the wet, frozen droplets can be removed from the sol (e.g., using filtration) and then a phase inversion can be performed to precipitate the biopolymer and form its beads / particles.

[0072] Having described the present invention, a further understanding can be obtained by reference to the following specific illustrative embodiments, which are provided for illustrative purposes only and are not intended to be exhaustive or limiting unless expressly stated otherwise. [Example]

[0073] A dispersed phase containing 8 wt. % cellulose in 70 wt. % 1-ethyl-3-methylimidazolium acetate and 30 wt. % dimethyl sulfoxide was prepared according to conventional methods known in the art. This dispersed phase had a transition temperature (e.g., freezing point) of about 11° C. An aqueous continuous phase was also prepared according to conventional methods known in the art. This continuous phase had a pour point of −15° C.

[0074] The dispersed and continuous phases were fed into a membrane emulsifier as shown in Figure 4 to form an emulsion. The emulsion was then cooled to a temperature of 0-11°C and transferred to a phase inversion device using an ethanol antisolvent to form cellulose particles.

[0075] Cooling of the emulsion was performed using an immersed coil heat exchanger, as shown in the inset of Figure 4. The immersed coil heat exchanger was selected to maintain laminar flow and minimize flow disturbances associated with cooling the emulsion. The coil heat exchanger had a length (L) of coiled tubing with a diameter D and pitch P, immersed in a cold water bath at 0 °C, which was sufficient to cool 0.5 L / min of emulsion to below 11 °C. The temperature of the emulsion was monitored by a thermometer at the outlet of the coil heat exchanger.

[0076] A comparative example was also carried out in which cellulose particles were produced without a cooling step. Figure 5 shows two photographs (magnification 5x) of a comparative example (a) and an example according to the invention (b). These photographs show that the cooling step before the phase inversion significantly reduced the degree of coalescence and aggregation of the cellulose particles, which in turn led to an improved yield.

Claims

1. 1. A method for producing biopolymer particles, comprising: a. membrane-emulsifying a dispersed phase in a continuous phase, the dispersed phase comprising the biopolymer in a solvent, by passing the dispersed phase through a membrane to form an emulsion of the biopolymer in the continuous phase; and b. Phase inversion in an antisolvent to form particles of the biopolymer. Including, (b) before cooling the emulsion to a temperature T １ Then, T １ is the pour point (T ｃｏｎｔ ) higher than the transition temperature (T ｄｉｓｐ ) or less, i.e., T ｃｏｎｔ <T １ ≦T ｄｉｓｐ said transition temperature being selected from the group consisting of a freezing point, a glass transition temperature, and a pour point; T ｄｉｓｐ >T ｃｏｎｔ How to be.

2. The method of claim 1 , wherein the transition temperature of the dispersed phase is the freezing point.

3. The method of claim 1 , wherein the transition temperature of the dispersed phase is the pour point.

4. The method of claim 1 , wherein the transition temperature of the dispersed phase is a glass transition temperature.

5. For the phase inversion (b), the anti-solvent is heated to a temperature T ２ Cool to T ２ T ｄｉｓｐ The method according to any one of claims 1 to 4, wherein the temperature is lower than 100°C.

6. The method according to claim 1, wherein for the phase inversion (b), the anti-solvent is cooled to a temperature T 2 , where T 2 is equal to T 1 .

7. 7. The method according to claim 1, wherein the cooling of the emulsion is carried out at the outlet of the membrane.

8. 8. The method of claim 1, wherein the phase inversion is carried out under shear.

9. The method of any one of claims 1 to 8, wherein the phase inversion comprises a filtration step.

10. The method of any one of claims 1 to 9, wherein the membrane emulsification is selected from the group consisting of cross-flow membrane emulsification, spinning membrane emulsification, vibrating membrane emulsification, and combinations thereof.

11. The method of any one of claims 1 to 10, wherein the anti-solvent is aqueous and / or comprises an organic solvent.

12. The method according to any one of claims 1 to 11, wherein the method is continuous.

13. The method of any one of claims 1 to 12, wherein after the phase inversion (b), the anti-solvent / continuous phase mixture is removed from the particles.

14. The method of any one of claims 1 to 13, wherein the biopolymer is a polysaccharide.

15. The method of claim 14, wherein the biopolymer is cellulose.

16. 15. A biopolymer particle produced by the method of any one of claims 1 to 14, wherein the biopolymer is a polysaccharide selected from starch, cellulose, chitin, chitosan, or glycogen.

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