WO2010104173A1 - Microcapsule et procédé de production d'une microcapsule - Google Patents

Microcapsule et procédé de production d'une microcapsule Download PDF

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Publication number
WO2010104173A1
WO2010104173A1 PCT/JP2010/054220 JP2010054220W WO2010104173A1 WO 2010104173 A1 WO2010104173 A1 WO 2010104173A1 JP 2010054220 W JP2010054220 W JP 2010054220W WO 2010104173 A1 WO2010104173 A1 WO 2010104173A1
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WO
WIPO (PCT)
Prior art keywords
microcapsule
monomer
surfactant
emulsion
microcapsules
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Application number
PCT/JP2010/054220
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English (en)
Japanese (ja)
Inventor
努 小野
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国立大学法人岡山大学
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Publication of WO2010104173A1 publication Critical patent/WO2010104173A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F2/00—Processes of polymerisation
    • C08F2/12—Polymerisation in non-solvents
    • C08F2/16—Aqueous medium
    • C08F2/22—Emulsion polymerisation
    • C08F2/24—Emulsion polymerisation with the aid of emulsifying agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • B01J13/02—Making microcapsules or microballoons
    • B01J13/06—Making microcapsules or microballoons by phase separation
    • B01J13/14—Polymerisation; cross-linking
    • B01J13/18—In situ polymerisation with all reactants being present in the same phase
    • B01J13/185—In situ polymerisation with all reactants being present in the same phase in an organic phase

Definitions

  • the present invention provides a surfactant having a hydrophilic group at one end and a 2,2,6,6-tetramethyl-1-piperidinyloxyl radical group at the other end via an alkyl chain.
  • the present invention relates to a microcapsule composed of a polymer bonded to one end, and a method for producing the microcapsule.
  • microcapsules have been used in many applications such as pressure-sensitive copying paper, pharmaceuticals, agricultural chemicals, fragrances, liquid crystals, adhesives, inks, etc.
  • their production methods include interfacial polymerization, in-situ (in situ) In situ), coacervation, and phase separation methods have been proposed.
  • the in situ method is actively researched and developed because it can easily control the particle size of the microcapsules and the wall thickness of the microcapsules, and can easily cause the formation reaction of the microcapsules. It has been broken. So far, methods for producing microcapsules using various materials have been proposed.
  • a microcapsule wall is formed by polymerizing monomers dissolved in a dispersion medium or a dispersoid. Since the monomer is uniformly distributed in the dispersion medium or dispersoid, or both the dispersion medium and dispersoid, the concentration of the monomer tends to be low at the interface where the microcapsule wall is formed, and microcapsules can be generated efficiently. There was a risk of disappearing.
  • the monomers include incompatible monomers that phase separate into both oil-soluble solvents and water-soluble solvents such as acrylonitrile, and water-soluble monomers that do not phase separate from water-soluble solvents such as (meth) acrylic acid. It has been proposed to produce microcapsules by using (see, for example, Patent Document 1).
  • the thickness of the microcapsule wall is adjusted while polymerizing the water-soluble monomer around the microcapsule formed by polymerizing the incompatible monomer. It becomes. While the polymerization of the incompatible monomer occurs, the polymerization occurs relatively efficiently, but when the polymerization of the water-soluble monomer is started thereafter, the concentration of the water-soluble monomer is reduced as before, The decline in productivity was not completely eliminated.
  • microcapsule manufacturing methods other than the in-situ method use a variety of reagents to stabilize the core droplet, and delicate processes to improve the reactivity of the monomer polymerization reaction It is difficult to improve productivity because management is required.
  • the present inventor has achieved the present invention in the course of research and development to enable efficient production of microcapsules.
  • the microcapsule of the present invention has an interface having a hydrophilic group at one end and a 2,2,6,6-tetramethyl-1-piperidinyloxyl radical group at the other end via an alkyl chain. It is a microcapsule made of a polymer in which an active agent is bonded to one end.
  • the microcapsule of the present invention is an emulsion in which oil droplets are produced by mixing and emulsifying an oily monomer, water, and a surfactant, and the monomer is polymerized into a spherical shape. Generate.
  • a surfactant having a hydrophilic group at one end and having a 2,2,6,6-tetramethyl-1-piperidinyloxyl radical group at the other end via an alkyl chain is used. .
  • microcapsule of the present invention instead of the monomer, a polymer in which the surfactant is bonded to one end is used.
  • an emulsification step for producing an emulsion containing oil-in-water droplets by mixing and emulsifying an oily monomer, water, and a surfactant, and milk A method for producing a microcapsule having a polymerization step of polymerizing a monomer in a turbid liquid, comprising a surfactant having a hydrophilic group at one end, and 2, 2, at the other end via an alkyl chain. This is a surfactant having a 6,6-tetramethyl-1-piperidinyloxyl radical group.
  • the method for producing microcapsules of the present invention is also characterized by the following points.
  • the concentration of the surfactant in the emulsion should be below the critical micelle concentration.
  • the emulsion is heated to 125 ° C or higher to polymerize the monomer, while the polymerization is stopped at a temperature lower than 125 ° C.
  • a predetermined oil-soluble drug is dissolved in the emulsion.
  • a polymer in which the surfactant is bonded to one end is used instead of the monomer.
  • the present invention provides a surfactant having a hydrophilic group at one end and a 2,2,6,6-tetramethyl-1-piperidinyloxyl radical group at the other end via an alkyl chain.
  • a radical polymerization reaction promoted by a 2,2,6,6-tetramethyl-1-piperidinyloxyl radical group can cause a polymerization reaction without being greatly affected by the monomer concentration. Can do. Therefore, the manufacturing efficiency of microcapsules can be improved.
  • the microcapsules can be produced from a single monomer, the microcapsules can be made into a single-layer state, not only can the microcapsules of a simple structure be provided, but also the number of reagents used can be reduced, and the process control can be performed. Productivity can be easily improved by being easy.
  • a microcapsule when a microcapsule is produced by polymerizing a polymer instead of a monomer, a microcapsule having characteristics corresponding to the characteristics of the polymer can be produced, and a highly functional microcapsule can be produced.
  • FIG. 2 is an electron micrograph of microcapsules generated based on Example 1.
  • FIG. It is an electron micrograph of the cross section of the microcapsule shown in FIG. 4 is an electron micrograph of microcapsules generated based on Example 2.
  • FIG. 2 is an electron micrograph of microcapsules generated based on Example 1.
  • a hydrophilic group is present at one end, and the other end is referred to as a TEMPO derivative via an alkyl chain 2,2,6,
  • a surfactant having a 6-tetramethyl-1-piperidinyloxyl radical group is used.
  • the sulfonic acid group is used as the hydrophilic group, it is not limited to the sulfonic acid group, and any hydrophilic group may be used.
  • the 2,2,6,6-tetramethyl-1-piperidinyloxyl radical group is referred to as a TEMPO derivative.
  • the TEMPO derivative containing a nitroxide group can stably cap radicals, so that controlled radical polymerization can be realized, and polymerization reaction is generated without being greatly affected by the concentration of the monomer. be able to.
  • an emulsion containing oil-in-water droplets is produced by emulsifying an oily monomer and water using the surfactant of the above general formula (1), and the monomer is polymerized. Let them be microcapsules.
  • oil-in-water droplets are generated using the surfactant of the above general formula (1), and in the emulsion containing the oil-in-water droplets, the monomer is polymerized around the water droplets to form microcapsules.
  • the inside of the microcapsule is not filled with the monomer, and a hollow microcapsule can be reliably formed.
  • an appropriate polymer may be used in place of the monomer.
  • the polymer is produced from a mixed solution in which an appropriate monomer and the surfactant of the general formula (1) are mixed, and the general It is good also as a polymer with which the surfactant of Formula (1) was couple
  • aromatic vinyl monomers such as styrene, ⁇ -methylstyrene and vinyltoluene can be used, and a polymer may be formed using at least one aromatic vinyl monomer.
  • One type may be used as a comonomer to form a polymer.
  • the comonomer is preferably about 0 to 50 wt% as a comonomer component unit that can be copolymerized in the copolymer.
  • the polymer preferably has a molecular weight distribution Mw (weight average molecular weight) / Mn (number average molecular weight) of about 1.00 to 2.00.
  • the initiator for polymerizing the monomer may be added to the emulsion, but as shown in the following general formula (2), an alkoxyamine may be bonded as a polymerization initiating group to the TEMPO derivative of the surfactant. .
  • the microcapsule of the present invention has a feature that the surface has a stable charge derived from the initiator, and also has a feature that the surface potential can be controlled.
  • a TEMPO derivative in which the structure of the hydrophilic group is changed can be similarly used.
  • the surface charge can be made positive.
  • Any hydrophilic group having a positive charge may be used, and the functional group is not limited to the above.
  • the surface charge can be made almost zero.
  • Any nonionic hydrophilic group may be used, and it is not limited to a polyethylene glycol group.
  • the surface charge of the microcapsules of the present invention is usually preferably ⁇ 60 mV to +60 mV, more preferably ⁇ 40 mV to +40 mV.
  • the surface charge can be measured by a zeta potential measuring device.
  • microcapsules of the present invention can be used for applications such as DDS (drug delivery system), sustained-release drugs, sustained-release agricultural chemicals. Moreover, since the microcapsule of the present invention has a surface charge, it can be used for functional resin using a paint that does not bleed and does not bleed according to the coated surface, or a binder.
  • DDS drug delivery system
  • sustained-release drugs sustained-release agricultural chemicals.
  • the microcapsule of the present invention has a surface charge, it can be used for functional resin using a paint that does not bleed and does not bleed according to the coated surface, or a binder.
  • the crude product obtained by concentration under reduced pressure was adsorbed on silica gel and purified by column chromatography to obtain Br-TEMPO represented by the following general formula (3).
  • the developing solvent in column chromatography was hexane / ethyl acetate, 5 to 0.5 / 1, vol./vol.
  • the residue obtained by concentration under reduced pressure was adsorbed on silica gel and purified by column chromatography to obtain a surface active TEMPO derivative composed of NaSO 3 -TEMPO represented by the above general formula (1).
  • the developing solvent in column chromatography was chloroform / acetonitrile, 5 to 1/1, vol./vol.
  • the residue obtained by concentration under reduced pressure was adsorbed on silica gel and purified by column chromatography to obtain NaSO 3 -TEMPO-IBN represented by the above general formula (2).
  • the developing solvent in column chromatography was chloroform / acetonitrile, 5 to 1/1, vol./vol.
  • the surfactant represented by the general formula (2) can be synthesized by the above-described method.
  • the critical micelle concentration (CMC) before synthesis of alkoxyamine is 0.024 wt%. It was confirmed that the surface activity was higher than that of sodium dodecyl sulfate (SDS) having a CMC of 0.19 wt%.
  • evaluation of surface activity is a pendant drop (Pendant Drop) method.
  • CMC is 0.022 wt% after the synthesis of alkoxyamine, and the surfactant synthesized with alkoxyamine is hereinafter referred to as “15-SO3-TEMPO-IBN”.
  • Emulsification process 8 g of water, 1.6 mg of 15-SO3-TEMPO-IBN, 150 mg of styrene, and 7.5 mg of hexadecane are mixed, stirred at 10,000 rpm for 90 seconds with a homogenizer, and contain oil droplets in water An emulsion was produced. Hexadecane is a stabilizer for preventing the Ostwald dry-opening phenomenon.
  • styrene is used as a monomer, but methacrylic acid, divinylbenzene, or the like may be used, or an appropriate monomer may be used.
  • the mixing ratio of water and styrene is not particularly limited as long as oil-in-water droplets can be stably generated, and it is sufficient that at least water is more than styrene.
  • 15-SO3-TEMPO-IBN is CMC or less, and is 0.020 wt% in this embodiment.
  • a homogenizer was used for the production of the emulsion.
  • an appropriate stirring means such as a microreactor may be used.
  • the emulsion was rapidly cooled to 125 ° C. or lower in an ice bath to stop the polymerization reaction. If the emulsion can be cooled to 125 ° C. or lower, it is not necessary to use an ice bath, and it may be cooled by an appropriate method.
  • FIG. 1 is an electron micrograph of the collected microcapsules
  • FIG. 2 is an electron micrograph of a cross section of one of the microcapsules.
  • the produced microcapsules had a nanoscale to microscale particle size and were hollow as shown in FIG.
  • the molecular weight of the polymer constituting the produced microcapsule was about 1,000 to 100,000.
  • the surface charge of the microcapsule measured by a zeta potential measuring device was about ⁇ 40 mV.
  • the size of the microcapsule can be adjusted by adjusting the concentration of the surfactant or adjusting the output of the homogenizer.
  • the wall thickness of the microcapsules did not change greatly even when the polymerization time was increased, and was about 100 nm.
  • microcapsules can be generated in two steps, an emulsification step and a polymerization step, and the production efficiency of the microcapsules can be improved.
  • the microcapsules can be formed from a single monomer, the microcapsules can be made into a single layer state, not only can the microcapsules of a simple structure be provided, but also the number of reagents used can be reduced, and the process control can be performed. Productivity can be easily improved by being easy.
  • an emulsion in which a plurality of types of monomers are mixed may be generated to generate microcapsules.
  • the process management can be further facilitated.
  • a microcapsule containing an oil-soluble drug can be easily generated by dissolving a predetermined oil-soluble drug in advance in the emulsion or the oil used to generate the emulsion.
  • the oil-soluble drug must not decompose under the pressure and temperature conditions in the polymerization process.
  • FIG. 3 is an electron micrograph of the collected microcapsules.
  • the blending amount of 15-SO3-TEMPO-IBN is CMC or more, a large number of microcapsules having a particle size of 200 nm or less and not hollow but clogged inside may be generated. it can.
  • the surface charge of the microcapsule measured by a zeta potential measuring device was about -40 mV.
  • the blending amount of 15-SO3-TEMPO-IBN is CMC or less, it is a microcapsule having a relatively small diameter while suppressing the formation of particles with a small particle size inside, and having a particle shape. While it is possible to efficiently produce hollow microcapsules with small variations, when the blending amount of 15-SO3-TEMPO-IBN is set to CMC or more, the particle size is large together with the small particles inside the clogged particles. Hollow microcapsules can be produced simultaneously.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Polymers & Plastics (AREA)
  • Manufacturing Of Micro-Capsules (AREA)
  • Polymerisation Methods In General (AREA)
  • Polymerization Catalysts (AREA)

Abstract

Cette invention concerne une microcapsule pouvant être produite avec une grande efficacité de production. Cette invention concerne également un procédé de production de la microcapsule. L'invention concerne spécifiquement une microcapsule produite à partir d'un polymère comportant un tensioactif lié à une extrémité, le tensioactif contenant un groupe hydrophile à une extrémité et un groupe radical 2,2,6,6-tétraméthyl-1-pipéridinyloxy lié à l'autre extrémité au moyen d'un groupe alkyle. La microcapsule est produite en polymérisant un monomère huileux dans une émulsion qui est préparée en mélangeant et en émulsifiant le tensioactif, le monomère et l'eau et dans laquelle des gouttelettes huile dans l'eau se forment. En variante, un polymère comportant le tensioactif lié à une extrémité peut être utilisé à la place du monomère.
PCT/JP2010/054220 2009-03-12 2010-03-12 Microcapsule et procédé de production d'une microcapsule WO2010104173A1 (fr)

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JP2009-060057 2009-03-12
JP2009060057A JP2012106147A (ja) 2009-03-12 2009-03-12 界面活性剤、ポリマー、マイクロカプセル及びマイクロカプセルの製造方法

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111320713A (zh) * 2020-04-15 2020-06-23 山东京博中聚新材料有限公司 一种乳液聚合用调节剂及其制备方法
CN112316863A (zh) * 2020-10-16 2021-02-05 江苏君澄空间科技有限公司 一种纳米级微胶囊的制备方法

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
KOHEI OURA ET AL.: "Kaimen Kasseino o Yusuru TEMPO Yudotai no Gosei Oyobi Fukinso Jugo eno Oyo", ABSTRACTS OF 73TH ANNUAL MEETING OF THE SOCIETY OF CHEMICAL ENGINEERS, 2008, pages 614 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN111320713A (zh) * 2020-04-15 2020-06-23 山东京博中聚新材料有限公司 一种乳液聚合用调节剂及其制备方法
CN112316863A (zh) * 2020-10-16 2021-02-05 江苏君澄空间科技有限公司 一种纳米级微胶囊的制备方法

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