Method for producing acrylated and epoxidized vegetable oil particles

Abstract

The present invention relates to a method for producing acrylated epoxidized vegetable oil particles, comprising the following steps: a) mixing an acrylated epoxidized vegetable oil with at least one solvent in the presence of at least one photoinitiator; b) optionally, mixing the solution obtained after step a) with solution S1; c) mixing the solution obtained after step a) or, optionally, after step b) with an aqueous solution containing at least one surfactant to obtain droplets; d) exposing the above droplets to UV light; and e) recovering the acrylated epoxidized vegetable oil particles obtained after step d).

Description

Technical Field

[0001] The present invention relates to a method for producing acrylated epoxidized vegetable oil particles. The present invention also relates to acrylated epoxidized vegetable oil particles obtained by the method according to the present invention. The present invention also relates to the use of acrylated epoxidized vegetable oil particles obtained by the method according to the present invention for loading a fluorescent agent, or for releasing a biological molecule, or as an optical lens.

Background Art

[0002] The search for fossil fuels, particularly materials based on polymer materials, has greatly promoted the development of human society. Nevertheless, due to the continuous use of resources and the extensive use of petroleum-based polymers, a number of environmental problems such as energy crises and environmental pollution have gradually occurred in the past few decades.

[0003] In this regard, the concept of eco-materials was proposed in the early 1990s. The aforementioned eco-materials refer to materials that are environmentally friendly while maintaining their properties and performance.

[0004] Currently, more than 7% of oil, gas, and their derivatives are converted into polymer materials, most of which are not recyclable and are non-degradable, and can have a serious adverse impact on the environment.

[0005] As a result, there is a need to quickly find alternative raw materials derived from renewable resources to improve the environment and reduce excessive dependence on oil. Fortunately, abundant renewable resources can be found in nature and can be used, for example, to design and manufacture polymer materials derived from biological resources such as cellulose, chitosan, alginate, lignin, and vegetable oils.

[0006] Vegetable oils and their derivatives are the most promising candidates for natural sources of bio-derived materials and can offer a number of advantages such as easy access, low cost, wide sources of supply, renewability, and degradability.

[0007] They are mainly composed of unsaturated triglycerides, and the presence of unsaturated bonds in the molecule makes reaction modification and functionalization possible and easy.

[0008] In recent years, an increasing interest in research can be recognized in the development of strategies for the preparation and application of vegetable oil-based materials. Therefore, a large number of literatures have been carried out various studies on this topic.

[0009] However, it is still necessary to develop a new method for manufacturing vegetable oil-based materials. Summary of the Invention Problems to be Solved by the Invention

[0010] Therefore, an object of the present invention is to develop a new method for producing acrylated epoxidized vegetable oil particles. Means for Solving the Problems

[0011] Thus, the present invention is a method for producing acrylated epoxidized vegetable oil particles, comprising the following steps: a) mixing an acrylated epoxidized vegetable oil and at least one solvent in the presence of at least one photoinitiator; b) optionally, mixing the solution obtained after step a) with solution S1; c) mixing the solution obtained after step a) or optionally after step b) with an aqueous solution containing at least one surfactant to obtain droplets; d) exposing the above droplets to UV light; e) recovering the acrylated epoxidized vegetable oil particles obtained after step d) and relates to a method comprising.

[0012] The present invention also relates to acrylated epoxidized vegetable oil particles obtained by the method according to the present invention.

[0013] The present invention further relates to the use of acrylated epoxidized vegetable oil particles for loading fluorescent molecules, or for releasing biological molecules such as ibuprofen, or as optical lenses.

[0014] By the method according to the present invention, acrylated epoxidized vegetable oil particles can be obtained. The aforementioned particles can be particularly degradable in an aqueous phase in the presence of an enzyme, or in alcoholic and alkaline solutions.

[0015] In the description of the present invention, the expression “from... to...” shall be understood as including each of the recited boundaries.

[0016] The expression “at least one (kind)” is equivalent to “one (kind) or more”.

[0017] Further advantages and features of the present invention will become clearer upon examination of the detailed description and the accompanying drawings.

Brief Description of the Drawings

[0018]

Figure 1A

Figure 1B

Figure 2A

Figure 2B

Figure 3A

Figure 3B

Figure 4

Figure 5

Figure 6

[0019] As described above, in step a), the acrylated epoxidized vegetable oil is mixed with at least one solvent in the presence of at least one photoinitiator.

[0020] Preferably, the acrylated epoxidized vegetable oil is selected from acrylated epoxidized linseed oil, acrylated castor oil, acrylated epoxidized soybean oil, and mixtures thereof, and preferably, the acrylated epoxidized vegetable oil is acrylated epoxidized soybean oil.

[0021] Acrylated epoxidized soybean oil (AESO) is one of the most typical vegetable oil derivatives. Acrylated epoxidized soybean oil is obtained from the successive epoxidation and esterification of soybean oil, where the carbon-carbon double bonds are opened and modified by acrylate groups and hydroxyl groups.

[0022] Thus, in a preferred embodiment, the method according to the present invention is used to produce acrylated epoxidized soybean oil particles.

[0023] Obtaining acrylated epoxidized soybean oil in the form of particles represents a real technological advancement. In fact, acrylated epoxidized soybean oil has a very high viscosity in the range of 18,000 to 32,000 mPa·s. Due to this very high viscosity, the research conducted in this field has not described AESO in particle form for reasons of processability.

[0024] According to a preferred embodiment, the acrylated epoxidized vegetable oil particles are present in a content in the range of 40 to 90% by mass, preferably 50 to 90% by mass, more preferably 60 to 90% by mass, even more preferably 65 to 85% by mass, based on the total mass of the solution obtained after step a).

[0025] According to a preferred embodiment, the solvent is selected from alcohols, esters, and mixtures thereof, preferably from C6 to C 12 monohydric alcohols, C 12 ~C 36 esters, and mixtures thereof, more preferably from C6 to C 12 monohydric alcohols, C 12 ~C 24 esters, and mixtures thereof, even more preferably selected from 1-octanol, methyl oleate, and mixtures thereof, and even better, the solvent is 1-octanol.

[0026] According to one embodiment, the photoinitiator can be any photoinitiator suitable for acrylate monomers known to those skilled in the art.

[0027] Advantageously, the photoinitiator is selected from ketones such as 2-hydroxy-2-methyl-1-phenyl-propan-1-one, 1-hydroxy-cyclohexyl-phenyl-ketone, 2,2-dimethoxy-1,2-diphenylethane-1-one, 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, phosphine oxides such as phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, and mixtures thereof, more preferably selected from 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, and mixtures thereof, and even more preferably, the photoinitiator is phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide.

[0028] Advantageously, the photoinitiator is present in a content in the range of 0.05 to 5% by mass, preferably 0.05 to 3% by mass, more preferably 0.05 to 1% by mass, and even more preferably 0.1 to 0.5% by mass, based on the total mass of the solution obtained after step a).

[0029] According to one embodiment, the acrylated epoxidized vegetable oil can be further mixed with at least one surfactant. Preferably, the aforementioned surfactant can be a nonionic surfactant. Advantageously, the aforementioned surfactant can be sorbitan oleate (Span 80).

[0030] As described above, optionally by step b), the solution obtained after step b) can be mixed with solution S1.

[0031] Solution S1 can be any type of solution, such as a water-miscible solution or a water-immiscible solution and / or an oil-miscible solution or an oil-immiscible solution.

[0032] According to one embodiment, solution S1 can be a water-immiscible solution and an oil-immiscible solution.

[0033] According to another embodiment, solution S1 can be a water-miscible solution and an oil-immiscible solution.

[0034] Advantageously, solution S1 is selected from a solution containing water and a solution containing silicone oil.

[0035] According to one embodiment, solution S1 contains silicone oil, for example, polydimethylsiloxane, dimethicone, or dimethylpolysiloxane.

[0036] More preferably, solution S1 consists of a silicone oil such as polydimethylsiloxane. Suitable silicone oils can include polydimethylsiloxane having a viscosity in the range of 50 to 375 cSt. As the silicone oil, silicone oil (polydimethylsiloxane) sold by Sigma-Aldrich (viscosity of 350 cSt at 25°C, CAS n63148-62-9) and the like can be mentioned.

[0037] According to another embodiment, solution S1 contains water.

[0038] According to one embodiment, solution S1 can be an aqueous solution containing a thickener such as sodium alginate.

[0039] As described above, by step c), the solution obtained after step a) or after optional step b) is mixed with an aqueous solution containing at least one surfactant in order to obtain droplets.

[0040] The surfactant can be selected from anionic surfactants, nonionic surfactants, and mixtures thereof.

[0041] Advantageously, the surfactant is selected from poloxamer 188 (polyoxyethylene-polyoxypropylene block copolymer), sodium dodecyl sulfate, poloxamer 407, and mixtures thereof.

[0042] More preferably, the surfactant is a nonionic surfactant, and even more preferably, it is selected from poloxamer 188.

[0043] The surfactant may be present in a content in the range of 1 to 40% by mass, preferably 5 to 30% by mass, more preferably 10 to 20% by mass, based on the total mass of the aforementioned aqueous solution.

[0044] Preferably, the aqueous solution containing at least one surfactant further contains at least one viscous agent.

[0045] The viscous agent may be selected from sodium alginate.

[0046] When the viscous agent is present, the viscous agent may be present in a content in the range of 0.1 to 5% by mass, preferably 0.5 to 3% by mass, more preferably 0.5 to 2% by mass, based on the total mass of the aforementioned aqueous solution.

[0047] The aqueous solution may further contain polyethylene glycol sorbitan monolaurate (Tween 20).

[0048] Advantageously, both solutions can be mixed with a vortex mixer.

[0049] During step c), emulsification can be carried out.

[0050] As described above, in step d), the droplets are exposed to UV light. Thus, polymerization is carried out by this step of exposing to UV light.

[0051] Preferably, the UV light has a wavelength in the range of 315 to 380 nm.

[0052] Advantageously, step d) is carried out for a period in the range of 0.1 second to 30 minutes, preferably 0.5 second to 20 minutes, more preferably 0.5 second to 10 minutes.

[0053] According to a particular embodiment, a step of isolating and rinsing the droplets is carried out between step c) and step d).

[0054] The cleaning of the droplets makes it possible to remove the surfactant and, if present, any viscosity agent.

[0055] The droplets can be cleaned with a solution containing polyethylene glycol sorbitan monolaurate (Tween 20). The aforementioned solution can also contain a phosphate buffer.

[0056] According to another specific embodiment, the optional step b), as well as steps c) and d), are carried out in a microfluidic device comprising a glass substrate, a polydimethylsiloxane layer, and a polydimethylsiloxane chip, wherein the polydimethylsiloxane layer is located on the glass substrate, and the polydimethylsiloxane chip is located on the polydimethylsiloxane layer.

[0057] The polydimethylsiloxane chip can conventionally include a channel system. In these channels, a solution obtained from the steps as described above, an optional solution S1, and an aqueous solution containing at least one surfactant, which is a mixture of acrylated epoxidized vegetable oil and at least one solvent in the presence of at least one photoinitiator, can be circulated as described above.

[0058] Advantageously, the solution obtained from the step of mixing acrylated epoxidized vegetable oil and at least one solvent in the presence of at least one photoinitiator is added to the first end of the first channel, the aqueous solution containing at least one surfactant is added to the first end of the second channel, and the optional solution S1 can be added to the first end of the third channel.

[0059] In this specific embodiment, preferably, the added aqueous solution does not contain any viscosity agent.

[0060] Then, the aqueous solution can be mixed with the solution obtained from the step of mixing acrylated epoxidized vegetable oil and at least one solvent in the presence of at least one photoinitiator by the junction of the first and second channels.

[0061] Alternatively, a solution obtained from the step of mixing an acrylated and epoxidized vegetable oil with at least one solvent in the presence of at least one photoinitiator can be mixed with an optional solution S1 at the junction of the second and third channels. The aqueous solution can then be mixed with the mixture obtained above at the channel junction.

[0062] Thus, the polydimethylsiloxane chip can incorporate at least one transverse junction to converge the flow.

[0063] In this way, droplets can be formed.

[0064] The microfluidic device can be connected to a microfluidic flow controller well-known to those skilled in the art to regulate the fluid pressure circulating in different channels. An example of such a controller is sold under the trade name MFCS-EZ by Fluigent.

[0065] As is known to those skilled in the art, the pressure values for each channel can be set by software related to the controller.

[0066] By means of the aforementioned controller, several tubes connecting several reservoirs containing different solutions (for example, the aqueous solution, the optional solution S1, and the solution obtained from the step of mixing an acrylated and epoxidized vegetable oil with at least one solvent in the presence of at least one photoinitiator) and software, air can be pumped at a predetermined desired pressure. Then, the solutions contained in the aforementioned reservoirs can be flushed to the ends of the channels of the polydimethylsiloxane chip through several tubes connecting the reservoirs and the ends of the channels.

[0067] This pressure can be in the range of 80 - 290 mbar.

[0068] Next, the droplets can be flowed through a coiled fourth channel. This zone can be irradiated using UV light. In other words, the droplets are exposed to UV light.

[0069] Exposure to UV light can be carried out for a period in the range of 0.1 second to 1 minute, preferably 0.5 second to 30 seconds, more preferably 0.5 second to 10 seconds, and even more preferably 0.5 second to 5 seconds.

[0070] The exposure time of the UV light can be controlled, for example, by moving the above-mentioned UV light further away or closer, or by adjusting the range covered by the UV light area.

[0071] Acrylated epoxidized vegetable oil particles can be recovered at the outlet of the fourth channel.

[0072] Advantageously, the method includes step f) of dispersing the above-mentioned acrylated epoxidized vegetable oil particles obtained after step e) in a solution containing at least one photoinitiator and then exposing them to UV light.

[0073] According to a specific embodiment, the acrylated epoxidized vegetable oil particles obtained after step e) can be dispersed in a solution containing acetone and at least one photoinitiator.

[0074] Next, the above-mentioned particles can be exposed to UV light.

[0075] Preferably, the UV light has a wavelength in the range of 315 - 380 nm.

[0076] Advantageously, the photoinitiator is selected from ketones such as 2-hydroxy-2-methyl-1-phenyl-propan-1-one, 1-hydroxy-cyclohexyl-phenyl-ketone, 2,2-dimethoxy-1,2-diphenylethane-1-one, 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, phosphine oxides such as phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, and mixtures thereof, more preferably 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, and mixtures thereof, and even more preferably, the photoinitiator is phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide.

[0077] According to a particular embodiment, the exposure to UV light in step f) is carried out for a period in the range of 30 seconds to 30 minutes, preferably 1 minute to 10 minutes, more preferably 1 minute to 5 minutes.

[0078] A first embodiment of the method according to the invention can be described as follows.

[0079] In step a), the acrylated epoxidized soybean oil can be mixed with at least one solvent such as 1-octanol in the presence of at least one photoinitiator, for example, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure® 819). The content of the acrylated epoxidized soybean oil can be in the range of 40 to 90% by mass, for example, 85% by mass, based on the total mass of the solution obtained after step a). The content of the photoinitiator can be in the range of 0.05 to 5% by mass, for example, 0.4% by mass, based on the total mass of the solution obtained after step a).

[0080] Then, in step c), the solution obtained after step a) is mixed with an aqueous solution containing at least one surfactant to obtain droplets.

[0081] The surfactant can be, for example, a nonionic surfactant such as poloxamer 188 (Pluronic® F68). The aqueous solution can further contain at least one viscosity agent such as sodium alginate. The surfactant can be present in a content range of 1 to 40% by mass, for example, 15% by mass, based on the total mass of the aforementioned aqueous solution. The viscosity agent can be present in a content range of 0.1 to 5% by mass, for example, 2% by mass, based on the total mass of the aforementioned aqueous solution.

[0082] Both solutions can be mixed with a vortex mixer. Then, the obtained droplets can be collected, and then a step of isolating and washing the droplets can be performed.

[0083] Washing of these droplets enables removal of the surfactant and any viscosity agent.

[0084] In step d), the droplets are exposed to UV light. The UV light can have a wavelength in the range of 315 - 380 nm.

[0085] Exposure to the UV light can be carried out for a period in the range of 0.1 seconds to 30 minutes, more preferably 1 to 10 minutes, for example, 8 minutes.

[0086] Therefore, acrylated epoxidized soybean oil particles can be obtained by the method according to the present invention in the first embodiment.

[0087] Thus, the obtained particles can be spherical and can have a smooth appearance.

[0088] A second embodiment according to the present invention can be described as follows.

[0089] In this embodiment, a microfluidic device as shown in FIGS. 1A and 1B is used.

[0090] As shown in FIG. 1A, the device 1 may include a glass substrate 2, a polydimethylsiloxane layer 3, and a polydimethylsiloxane chip 4. The polydimethylsiloxane layer 3 is located on the glass substrate 2, and the polydimethylsiloxane chip 4 is located on the polydimethylsiloxane layer 3. As can be seen in FIG. 1B, the channel system (5, 5a, 5b, 6, 7, 8) can be found inside the polydimethylsiloxane chip 4.

[0091] In step a), acrylated epoxidized soybean oil can be mixed with at least one solvent such as 1-octanol in the presence of at least one photoinitiator, for example, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure® 819).

[0092] An aqueous solution containing at least one surfactant can be prepared. The surfactant can be, for example, a nonionic surfactant such as poloxamer 188 (Pluronic® F68).

[0093] Then, the aqueous solution can be poured into the reservoir 9, and the reservoir 9 can be connected to the first end of the channel 5 by the tube 10. The solution obtained after step a) can be poured into the reservoir 11, and the reservoir 11 can be connected to the first end of the channel 6 by the tube 12.

[0094] The reservoir 9 can be connected to a controller 13, such as those sold under the trade name MFCS-EZ by Fluigent, and the controller 13 can be connected to a computer 14 by the tube 15. The reservoir 11 can be connected to the controller 13 by the tube 16.

[0095] The controller 13 can pump air at a predetermined desired pressure through the tubes 15 and 16, respectively.

[0096] The aqueous solution containing at least one surfactant and stored in the reservoir 9 can be added to the first end of the channel 5 through the pipe 10, and as shown in Figure 1B, the solution obtained after step a) and stored in the reservoir 11 can be added to the first end of the channel 6 through the pipe 12. The channel 5 can be divided into two sub-channels, a first sub-channel 5a and a second sub-channel 5b.

[0097] Then, both solutions can be joined at the junction 7 of the first sub-channel 5a, the second sub-channel 5b, and the second channel 6. Therefore, the polydimethylsiloxane chip 4 can incorporate a transverse junction 7 to gather the flow.

[0098] In this way, droplets can be formed.

[0099] Then, as shown in Figure 1B, the droplets can flow through the coiled third channel 8. This zone can be irradiated using the UV light 17. In other words, the droplets can be exposed to the UV light 17. The aforementioned UV light 17 can be arranged outside the microfluidic device 1 and positioned to irradiate the coiled third channel 8.

[0100] The UV light can have a wavelength in the range of 315 - 380 nm. The exposure to the UV light can be carried out for a period in the range of 0.1 seconds to 30 minutes, more preferably 0.5 seconds to 5 seconds, for example, for 3 seconds.

[0101] At the outlet of the third channel 8 of the chip 4, acrylated epoxidized soybean oil particles can be recovered.

[0102] Then, the aforementioned acrylated epoxidized soybean oil particles can be dispersed in a solution containing at least one photoinitiator such as phenylbis(2,4,6 - trimethylbenzoyl)phosphine oxide (Irgacure® 819).

[0103] The aforementioned solution can further contain acetone.

[0104] Subsequently, the aforementioned particles can be exposed to UV light. The UV light can have a wavelength in the range of 315 - 380 nm.

[0105] Exposure to the UV light can be carried out for a period in the range of 30 seconds to 30 minutes, for example, 2 minutes.

[0106] Thus, by the method according to the invention of the second embodiment, acrylated epoxidized soybean oil particles can be obtained.

[0107] The particles thus obtained can be of different sizes depending on what is intended. In fact, the configuration of the first and second channels can be adapted to the pressure applied in the different channels to vary the size of the particles.

[0108] The obtained particles may further have a very narrow particle size distribution.

[0109] A third embodiment according to the invention can be described as follows.

[0110] In this embodiment, a microfluidic device as represented in FIG. 2A is used.

[0111] As can be seen in FIG. 2A, the device 1 can comprise a glass substrate 2, a polydimethylsiloxane layer 3, and a polydimethylsiloxane chip 4, the polydimethylsiloxane layer 3 being located on the glass substrate 2 and the polydimethylsiloxane chip 4 being located on the polydimethylsiloxane layer 3. A channel system (5, 5a, 5b, 18, 18a, 18b, 19, 20, 8) can be found inside the polydimethylsiloxane chip 4.

[0112] By step a), the acrylated epoxidized soybean oil can be mixed with at least one solvent, such as 1-octanol, in the presence of at least one photoinitiator, such as phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure® 819), etc.

[0113] An aqueous solution containing at least one surfactant can be prepared. The surfactant can be, for example, a nonionic surfactant such as poloxamer 188 (Pluronic® F68). The aqueous solution can further contain polyethylene glycol sorbitan monolaurate (Tween 20).

[0114] A solution S1, such as a solution consisting of a silicone oil such as polydimethylsiloxane, can be prepared.

[0115] As described in the previous embodiment, different solutions can be poured into the reservoir, and the reservoir can be connected to a controller, such as those sold under the MFCS-EZ trade name by Fluigent, etc.

[0116] The entire system (reservoir, tubes, controller, computer) is not shown in Figure 2A.

[0117] The aqueous solution containing at least one surfactant can be added to the first end of channel 5 through a tube. The solution obtained after step a) can be added to the first end of the first sub-channel 18a through a tube. Solution S1 can be added to the first end of the second sub-channel 18b through a tube.

[0118] Channel 5 can be divided into two sub-channels, a first sub-channel 5a and a second sub-channel 5b.

[0119] The first sub-channel 18a and the second sub-channel 18b can merge at the junction 19 to form channel 18.

[0120] Solution S1 and the solution obtained after step a) can merge at the junction 19 to form the solution obtained after step b) and can circulate into the channel 18.

[0121] Next, the solution obtained after step b) and an aqueous solution containing at least one surfactant can be merged by the junction 20 of the first sub-channel 5a, the second sub-channel 5b, and the channel 18. Therefore, the polydimethylsiloxane chip 4 can incorporate the transverse junction 20 to converge the flow.

[0122] In this way, droplets can be formed.

[0123] Next, the droplets can flow through the coiled third channel 8. This zone can be irradiated using the UV light 17. In other words, the droplets are exposed to the UV light 17. The UV light 17 can be arranged outside the microfluidic device 1 and can be positioned to irradiate the coiled third channel 8.

[0124] The UV light can have a wavelength in the range of 315 - 380 nm. The exposure to the UV light can be performed for a period in the range of 0.1 seconds to 30 minutes, more preferably 0.5 seconds to 5 seconds, for example, for 3 seconds.

[0125] At the outlet of the third channel 8 of the chip 4, acrylated epoxidized soybean oil particles can be recovered.

[0126] Next, the acrylated epoxidized soybean oil particles can be dispersed in a solution containing at least one photoinitiator such as phenylbis(2,4,6 - trimethylbenzoyl)phosphine oxide (Irgacure® 819).

[0127] The aforementioned solution can further contain acetone.

[0128] Next, the aforementioned particles can be exposed to UV light. The UV light can have a wavelength in the range of 315 - 380 nm.

[0129] Exposure to UV light can be carried out for a period in the range of 30 seconds to 30 minutes, for example, for 2 minutes.

[0130] Thus, crescent-shaped acrylated epoxidized soybean oil particles as represented in FIG. 2B can be obtained by the method according to the invention of the third embodiment.

[0131] A fourth embodiment according to the invention can be described as follows.

[0132] In this embodiment, a microfluidic device as represented in FIG. 3A is used.

[0133] As can be seen in FIG. 3A, the device 1 can comprise a glass substrate 2, a polydimethylsiloxane layer 3, and a polydimethylsiloxane chip 4, the polydimethylsiloxane layer 3 being located on the glass substrate 2, and the polydimethylsiloxane chip 4 being located on the polydimethylsiloxane layer 3. A channel system (5, 5a, 5b, 21, 21a, 21b, 22, 23, 24, 25, 8) can be found inside the polydimethylsiloxane chip 4.

[0134] In step a), the acrylated epoxidized soybean oil can be mixed with at least one solvent such as 1-octanol, etc. in the presence of at least one photoinitiator such as phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure® 819), etc.

[0135] An aqueous solution containing at least one surfactant can be prepared. The surfactant can be a nonionic surfactant such as poloxamer 188 (Pluronic® F68), etc. The aqueous solution can further contain polyethylene glycol sorbitan monolaurate (Tween 20).

[0136] For example, a solution S1 such as a solution S1 composed of a silicone oil such as polydimethylsiloxane can be prepared.

[0137] As described in the previous embodiment, different solutions can be poured into the reservoir, and the aforementioned reservoir can be connected to a controller such as those sold under the trade name MFCS-EZ by Fluigent.

[0138] The entire system (reservoir, tubes, controller, computer) is not shown in Figure 3A.

[0139] The aqueous solution containing at least one surfactant can be added to the first end of channel 5 through a tube. The solution obtained after step a) can be added to the first end of channel 21 through a tube. Solution S1 can be added to the first end of channel 22 through a tube.

[0140] The first channel 5 can be divided into two sub-channels: a first sub-channel 5a and a second sub-channel 5b.

[0141] Channel 21 can be divided into two sub-channels: a first sub-channel 21a and a second sub-channel 21b.

[0142] The first sub-channel 21a, the second sub-channel 21b, and channel 22 can merge at junction 23 to form channel 24.

[0143] Solution S1 and the solution obtained after step a) can merge at junction 23 to form the solution obtained after step b), which can circulate into channel 24.

[0144] Next, the solution obtained after step b) and the aqueous solution containing at least one surfactant can be merged by junction 25 of the first sub-channel 5a, the second sub-channel 5b, and channel 24. Therefore, the polydimethylsiloxane chip 4 can incorporate two cross-type junctions 23 and 25 to gather the flow.

[0145] In this way, droplets can be formed.

[0146] Subsequently, the droplets can flow through the coiled third channel 8. This zone can be irradiated using the UV light 17. In other words, the droplets are exposed to the UV light 17. The UV light 17 can be arranged outside the microfluidic device 1 and can be positioned to irradiate the coiled third channel 8.

[0147] The UV light can have a wavelength in the range of 315 - 380 nm. The exposure to the UV light can be carried out for a period in the range of 0.1 seconds to 30 minutes, more preferably in the range of 0.5 seconds to 5 seconds, for example, for 3 seconds.

[0148] At the outlet of the third channel 8 of the chip 4, acrylated epoxidized soybean oil particles can be recovered.

[0149] Subsequently, the acrylated epoxidized soybean oil particles can be dispersed in a solution containing at least one photoinitiator such as phenylbis(2,4,6 - trimethylbenzoyl)phosphine oxide (Irgacure® 819).

[0150] The aforementioned solution can further contain acetone.

[0151] Subsequently, the particles can be exposed to the UV light. The UV light can have a wavelength in the range of 315 - 380 nm.

[0152] The exposure to the UV light can be carried out for a period in the range of 30 seconds to 30 minutes, for example, for 2 minutes.

[0153] In this way, by the method according to the invention of the fourth embodiment, acrylated epoxidized soybean oil particles having a core - shell structure as shown in Figure 3B can be obtained.

[0154] The fifth embodiment according to the invention can be described as follows.

[0155] In this embodiment, a microfluidic device as shown in FIG. 4 is used.

[0156] As can be seen in FIG. 4, the device 1 may include a glass substrate 2, a polydimethylsiloxane layer 3, and a first polydimethylsiloxane chip 4a and a second polydimethylsiloxane 4b connected in series. The polydimethylsiloxane layer 3 is located on the glass substrate 2, and the first and second polydimethylsiloxane chips 4a, 4b are located on the polydimethylsiloxane layer 3. The channel systems (26, 26a, 26b, 27, 28, 29, 30, 31, 31a, 31b, 32, 33, 8) can be found inside the polydimethylsiloxane chips 4a and 4b as can be seen in FIG. 4.

[0157] In step a), the acrylated epoxidized soybean oil can be mixed with at least one solvent such as 1-octanol or methyl oleate in the presence of at least one photoinitiator, for example, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure® 819), and optionally a surfactant such as span 80.

[0158] An aqueous solution containing at least one surfactant can be prepared. The surfactant can be, for example, a nonionic surfactant such as poloxamer 188 (Pluronic® F68). The aqueous solution can further contain polyethylene glycol sorbitan monolaurate (Tween 20).

[0159] For example, a solution S1 such as an aqueous solution S1 containing a thickener such as sodium alginate can be prepared.

[0160] As described in the previous embodiment, the different solutions can be poured into a reservoir, and the reservoir can be connected to a controller such as those sold under the trade name MFCS-EZ by Fluigent.

[0161] The entire system (reservoir, pipes, controller, computer) is not shown in Figure 4.

[0162] The solution obtained after step a) can be added to the first end of channel 26 through a pipe. The solution S1 can be added to the first end of channel 27 through a pipe.

[0163] Channel 26 can be divided into two sub-channels, a first sub-channel 26a and a second sub-channel 26b.

[0164] The first sub-channel 26a, the second sub-channel 26b, and channel 27 can merge at a junction 28 to form channel 29.

[0165] Solution S1 and the solution obtained after step a) can merge at junction 28 to form the solution obtained after step b) and can circulate into channel 29.

[0166] In this way, water-in-oil droplets can be formed.

[0167] The aqueous solution containing at least one surfactant can be added to the first end of channel 31 through a pipe.

[0168] Channel 29 is connected to the first end of channel 32 through channel 30.

[0169] Channel 31 can be divided into two sub-channels, a first sub-channel 31a and a second sub-channel 31b.

[0170] Next, the solution obtained after step b) and the aqueous solution containing at least one surfactant can be merged by a junction 33 of the first sub-channel 31a, the second sub-channel 31b, and channel 32. Therefore, the polydimethylsiloxane chip 4 can incorporate a transverse junction 33 to aggregate the flow.

[0171] In this way, oil-in-water-in-oil droplets can be formed.

[0172] Next, the droplets can flow through the coiled third channel 8. This zone can be irradiated using UV light 17. In other words, the droplets are exposed to UV light 17. The UV light 17 can be arranged outside the microfluidic device 1 and can be positioned to irradiate the coiled third channel 8.

[0173] The UV light can have a wavelength in the range of 315 - 380 nm. Exposure to the UV light can be carried out for a period in the range of 0.1 seconds to 30 minutes, more preferably in the range of 0.5 seconds to 5 seconds, for example, for 3 seconds.

[0174] At the outlet of the third channel 8 of the aforementioned chip 4b, acrylated epoxidized soybean oil particles can be recovered.

[0175] Next, the acrylated epoxidized soybean oil particles can be dispersed in a solution containing at least one photoinitiator such as phenylbis(2,4,6 - trimethylbenzoyl)phosphine oxide (Irgacure® 819).

[0176] The aforementioned solution can further contain acetone.

[0177] [[ID=2 + 2]] Next, the particles can be exposed to UV light. The UV light can have a wavelength in the range of 315 - 380 nm.

[0178] Exposure to the UV light can be carried out for a period in the range of 30 seconds to 30 minutes, for example, for 2 minutes.

[0179] As a result, by the method according to the invention of the fifth embodiment, acrylated epoxidized soybean oil microcapsule particles can be obtained. The microcapsules may have a shell portion and a core portion.

[0180] The present invention also relates to acrylated epoxidized vegetable oil particles obtained by the method according to the present invention.

[0181] Preferably, the acrylated epoxidized vegetable oil particles are epoxidized acrylated soybean oil particles.

[0182] The present invention also relates to the use of acrylated epoxidized vegetable oil particles obtained by the method according to the present invention for loading fluorescent molecules, or for releasing biological molecules such as ibuprofen, or for use as an optical lens.

[0183] The present invention is illustrated in a non-limiting manner by the following examples.

Example

[0184] (Example 1: Method for preparing acrylated epoxidized soybean oil particles) Acrylated epoxidized soybean oil was added to 1-octanol. Phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure® 819) was also added. The content of acrylated epoxidized soybean oil is 85% by mass based on the total mass of the solution. The content of phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide (Irgacure® 819) is 0.4% by mass based on the total mass of the solution.

[0185] The solution obtained above was mixed with an aqueous solution containing poloxamer 188 (Pluronic® F68) and sodium alginate. The content of poloxamer 188 (Pluronic® F68) is 15% by mass based on the total mass of the aqueous solution described above. The content of sodium alginate is 2% by mass based on the total mass of the aqueous solution described above.

[0186] Both solutions were mixed in a vortex mixer.

[0187] Next, the obtained droplets were collected and isolated, and then washed with a solution containing polyethylene glycol sorbitan monolaurate (Tween 20; 0.06 mmol / L, critical micelle concentration (CMC)) and phosphate buffer (20 mmol / L, pH of about 7). This washing step of the droplets enables the removal of surfactants and viscous agents.

[0188] Next, the droplets were exposed to UV light having a wavelength in the range of 315 - 380 nm with an output of 60 mW / cm 2 . The exposure to UV light was carried out for 2 minutes.

[0189] As a result, the obtained acrylated epoxidized soybean oil particles are spherical and have a smooth appearance. They have an average diameter (average Feret diameter) of 34.7 μm ± 10.1 μm.

[0190] (Example 2: Method for preparing acrylated epoxidized soybean oil particles) Acrylated epoxidized soybean oil was added to 1 - octanol. Phenylbis(2,4,6 - trimethylbenzoyl)phosphine oxide (Irgacure® 819) was also added. The content of acrylated epoxidized soybean oil is 65% by mass based on the total mass of the solution. The content of phenylbis(2,4,6 - trimethylbenzoyl)phosphine oxide (Irgacure® 819) is 0.4% by mass based on the total mass of the solution.

[0191] The obtained solution described above was mixed with an aqueous solution containing poloxamer 188 (Pluronic® F68). The content of poloxamer 188 (Pluronic® F68) is 15% by mass based on the total mass of the aforementioned aqueous solution.

[0192] In this example, a microfluidic device as shown in FIGS. 1A and 1B was used.

[0193] As shown in FIG. 1A, the device 1 includes a glass substrate 2, a polydimethylsiloxane layer 3, and a polydimethylsiloxane chip 4. The polydimethylsiloxane layer 3 is located on the glass substrate 2, and the polydimethylsiloxane chip 4 is located on the polydimethylsiloxane layer 3. As shown in FIG. 1B, a channel system (5, 5a, 5b, 6, 7, 8) is found inside the polydimethylsiloxane chip.

[0194] Then, the aqueous solution is poured into the reservoir 9, and the reservoir 9 is connected to the first end of the channel 5 through the tube 10. A solution containing acrylated epoxidized soybean oil is poured into the reservoir 11, and the reservoir 11 is connected to the first end of the channel 6 through the tube 12.

[0195] The reservoir 9 is connected to a controller 13 (sold under the trade name MFCS-EZ by Fluigent), and the controller 13 is connected to a computer 14 through a tube 15. The reservoir 11 is connected to the controller 13 through a tube 16. By the controller 13, air is sent through the tubes 15 and 16 by a pump respectively.

[0196] As shown in FIG. 1B, a solution containing acrylated epoxidized soybean oil is applied at a pressure of 133 mbar at the first end of the channel 5, and the aqueous solution is applied at a pressure of 138 mbar at the first end of the channel 6. The channel 5 is divided into two sub-channels, a first sub-channel 5a and a second sub-channel 5b.

[0197] Then, both solutions are merged by a junction 7 between the first sub-channel 5a, the second sub-channel 5b, and the channel 6. Therefore, the polydimethylsiloxane chip 4 incorporates a cross-type junction 7 to gather the flow.

[0198] As a result, droplets are formed.

[0199] Next, as shown in FIG. 1B, the droplets flowed through the coiled third channel 8. This zone was irradiated using UV light 17. As a result, the droplets were exposed to the UV light 17. The UV light 17 is disposed outside the microfluidic device 1 and is positioned to irradiate the coiled third channel 8.

[0200] The UV light has a wavelength in the range of 315 - 380 nm and an output of 424 mW / cm 2 Exposure to the UV light was performed for 1 second.

[0201] At the outlet of the third channel 8 of the chip 4 described above, acrylated epoxidized soybean oil particles were collected, collected in a microtube, then centrifuged at 3000 rad / min for 30 seconds, washed three times with acetone, and poloxamer 188 (Pluronic® F68) and excess 1 - octanol were removed.

[0202] Next, the acrylated epoxidized soybean oil particles described above were dispersed in a solution containing 0.4% by mass of phenylbis(2,4,6 - trimethylbenzoyl)phosphine oxide (Irgacure® 819) and acetone.

[0203] Next, the particles described above were exposed to UV light. The UV light has a wavelength in the range of 315 - 380 nm and an output of 60 mW / cm 2 Exposure to the UV light was performed for 2 minutes.

[0204] As a result, acrylated epoxidized soybean oil particles could be obtained by the method according to the present invention.

[0205] The particles obtained as a result have a very narrow particle size distribution with an average diameter (average Feret diameter) of 46.6 μm ± 1.2 μm.

[0206] (Example 3: Fluorescent Molecule) A specific modified fluorescent phospholipid (DOPE-CF (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(carboxyfluorescein), sold by Avanti Polar Lipids (Alabaster, AL, USA)) was added to the solution as prepared in step a) to a concentration of 0.1 mg / mL.

[0207] And the following protocol is in accordance with the protocol practiced in Example 2 above. Thus, the manufacturing method involves the use of a microfluidic device as described in Example 2.

[0208] Subsequently, the obtained particles were excited with a 488 nm laser.

[0209] It was observed that the obtained particles had a uniform green fluorescence that could be maintained during exposure to UV.

[0210] (Example 4: Degradability of Particles) The acrylated epoxidized soybean oil particles produced in Example 2 were contacted with different solutions A, B, C, D, and E.

[0211] Solution A is an aqueous solution containing 3% by mass of potassium hydroxide at room temperature.

[0212] Solution B is an ethanol solution containing 3% by mass of potassium hydroxide at room temperature.

[0213] Solution C is an ethanol solution containing 3% by mass of potassium hydroxide heated to 70 °C.

[0214] Solution D is an aqueous solution containing 150 units / mL of esterase solution at room temperature.

[0215] Solution E is an aqueous solution containing 700 units / mL of lipase solution at room temperature.

[0216] The aforementioned particles showed the highest degradation rate in Solution C. In fact, the particle suspension became transparent and the particles were completely hydrolyzed. After 1 hour of incubation, no particles were observed under the microscope.

[0217] On the other hand, 19 hours were required to observe complete particle degradation in Solution B.

[0218] Furthermore, even after 277 hours of incubation in Solution A, particle fragments were still observed.

[0219] As can be seen in Figure 5, the particles were observed to have good enzymatic degradability in a short period of time in both Solution D (Curve B) and Solution E (Curve A).

[0220] The particles had a faster hydrolysis rate under the effect of lipase in the initial phase (Curve A). Then, the hydrolysis rate of the particles in both solutions gradually decreased and stagnated after 6 days, at which point about 35% of the particles had been degraded (Curves A and B).

[0221] Therefore, the particles obtained by the method according to the present invention can be degraded in an aqueous phase in the presence of an enzyme, or in alcoholic and alkaline solutions.

[0222] This is a very advantageous property compared to materials that are not degradable and / or non-renewable and are currently widely used in various fields.

[0223] (Example 5: Release of Ibuprofen) The same method as used in Example 1 was used here. More specifically, 15 mg of ibuprofen ((RS)-2-(4-(2-methylpropyl)phenyl)propanoic acid) was added to 1 mL of an AESO / 1-octanol solution containing 85% by mass of AESO and 0.4% by mass of Irgacure 819 photoinitiator. Ibuprofen-added AESO particles were obtained.

[0224] Next, the particles were contacted with two different environments: simulated intestinal fluid [SIF, 6.8 g of KH2PO4 and 77 mL of aqueous NaOH solution (0.2 M), final pH = 6.8, 1000 mL] and simulated gastric fluid [SGF, 2.0 g of NaCl and 7.0 mL of aqueous HCl (37%) solution, final pH = 1.2, 1000 mL] (both without enzymes).

[0225] Release tests were performed by incubating ibuprofen-added AESO particles in a biomimetic environment. In each experiment, 50 mg of the dry added particles were placed in a sealed flask with 50 ml of SIF or SGF.

[0226] After immersing each sample in SIF and SGF, respectively, the system was maintained under constant shaking at 37 °C and 140 rpm in all tests. Aliquots (70 μL) were taken from each flask at different time intervals (0.5, 1, 2, 4, 8, 10, 24, 48, 120, 144 h), and the amount of drug released was quantified by UV-Vis spectroscopy. To avoid interference from the particles, the aliquots were centrifuged before UV-Vis analysis.

[0227] As seen in Figure 6, the progression of the concentration of ibuprofen in simulated intestinal fluid as a function of time (curve C) and the progression of the concentration of ibuprofen in simulated gastric fluid as a function of time (curve D) were observed.

[0228] It was found that ibuprofen-added AESO particles have a faster release rate in simulated intestinal fluid than in simulated gastric fluid.

[0229] The release rate of the particles in both environments gradually decreased and reached a stagnant region after 120 h, at which time the concentration of ibuprofen in the solution was 12.5 μg / mL (SIF) and 10.9 μg / mL (SGF), which corresponds to drug release rates of 83.7% and 73%, respectively.

Description of the symbols

[0230] 1 Microfluidic device 2 Glass substrate 3 Polydimethylsiloxane layer 4 Polydimethylsiloxane chip 4a First polydimethylsiloxane chip 4b Second polydimethylsiloxane chip 5, 5a, 5b, 6, 7, 8, 18, 18a, 18b, 19, 20, 21, 21a, 21b, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 31a, 31b, 32, 33 Channels 9, 11 Reservoirs 10, 12, 15, 16 Tubes 13 Controller 14 Computer 17 UV light 26a, 31a First sub-channel 26b, 31b Second sub-channel 28, 33 Junctions

Claims

1. A method for producing acrylated epoxidized vegetable oil particles, comprising the following steps: a) mixing an acrylated epoxidized vegetable oil and at least one solvent in the presence of at least one photoinitiator; b) optionally, mixing the solution obtained after step a) with solution S1; c) mixing the solution obtained after step a) or optionally after step b) with an aqueous solution containing at least one surfactant to obtain droplets; d) exposing the droplets to UV light; e) recovering the acrylated epoxidized vegetable oil particles obtained after step d). A method comprising the above steps.

2. The acrylated epoxidized vegetable oil is selected from acrylated epoxidized linseed oil, acrylated castor oil, acrylated epoxidized soybean oil, and mixtures thereof, preferably the acrylated epoxidized vegetable oil is acrylated epoxidized soybean oil. The method according to claim 1.

3. The acrylated epoxidized vegetable oil particles are present in a content in the range of 40 to 90% by mass, preferably 50 to 90% by mass, more preferably 60 to 90% by mass, still more preferably 65 to 85% by mass, based on the total mass of the solution obtained after step a). The method according to claim 1 or 2.

4. The solvent is selected from alcohols, esters, and mixtures thereof, preferably C 6 to C 12 monohydric alcohols, C 12 to C 36 esters, and mixtures thereof, more preferably C 6 to C 12 monohydric alcohols, C 12 to C 24 esters, and mixtures thereof, even more preferably selected from 1-octanol, methyl oleate, and mixtures thereof, and even more preferably, the method according to any one of claims 1 to 3, characterized in that the solvent is 1-octanol.

5. The photoinitiator is selected from ketones, phosphine oxides, and mixtures thereof, preferably selected from 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone, phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide, and mixtures thereof, still more preferably the photoinitiator is phenylbis(2,4,6-trimethylbenzoyl)phosphine oxide. The method according to any one of claims 1 to 4.

6. The photoinitiator is present in a content in the range of 0.05 to 5% by mass, preferably 0.05 to 3% by mass, more preferably 0.05 to 1% by mass, still more preferably 0.1 to 0.5% by mass, based on the total mass of the solution obtained after step a). The method according to any one of claims 1 to 5.

7. Solution S1 is selected from a solution containing water and a solution containing silicone oil. The method according to any one of claims 1 to 6.

8. The method according to any one of claims 1 to 7, characterized in that the surfactant is selected from an anionic surfactant, a nonionic surfactant, and a mixture thereof, preferably a nonionic surfactant, more preferably poloxamer 188.

9. The method according to any one of claims 1 to 8, characterized in that step d) is carried out for a period in the range of 0.1 second to 30 minutes, preferably 0.5 second to 20 minutes, more preferably 0.5 second to 10 minutes.

10. The method according to any one of claims 1 to 9, characterized in that the step of isolating and washing the droplets is carried out between step c) and step d).

11. The optional step b), and steps c) and d) are carried out in a microfluidic device comprising a glass substrate, a polydimethylsiloxane layer, and a polydimethylsiloxane chip, wherein the polydimethylsiloxane layer is located on the glass substrate, and the polydimethylsiloxane chip is located on the polydimethylsiloxane layer, the method according to any one of claims 1 to 9.

12. The method according to claim 11, characterized in that it includes step f) of dispersing the acrylated epoxidized vegetable oil particles obtained after step e) in a solution containing at least one photoinitiator and then exposing them to UV light.

13. The method according to claim 12, characterized in that the exposure to the UV light in step f) is carried out for a period in the range of 30 seconds to 30 minutes, preferably 1 minute to 10 minutes, more preferably 1 minute to 5 minutes.

14. Acrylated epoxidized vegetable oil particles obtained by the method as defined in any one of claims 1 to 13.

15. Use of the acrylated epoxidized vegetable oil particles obtained by the method as defined in claim 14 or as defined in any one of claims 1 to 13 for loading fluorescent molecules, or for releasing biological molecules such as ibuprofen, or as an optical lens.

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