JPH09294929A - Porous hollow particles and method for producing the same - Google Patents

Abstract

(57) [Abstract] [PROBLEMS] To produce high-quality porous hollow particles. After gas is dissolved under pressure in the first continuous phase 11 of a primary emulsion 14 in which a first dispersed phase 13 is dispersed in a first continuous phase 11 containing a solidified component (FIG. 1). (A)), the primary emulsion 14 is used as the second dispersed phase 15 and is further dispersed in the second continuous phase 16 to obtain the secondary emulsion 17
(Fig. 1 (B)), and this secondary emulsion 1
After forming the hollow particles 18 under normal pressure (Fig. 1)
(C)), after solidifying the solidified component (FIG. 1 (D)), the first dispersed phase 13 of the primary emulsion 14
By removing the portion (FIG. 1 (E)), the traces of the removal of the portion of the first dispersed phase 13 become pores 19 to produce porous hollow particles 20.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for producing porous hollow particles through emulsion formation and a porous hollow particle produced by the method.

[0002]

2. Description of the Related Art As a method for producing porous fine particles, an in situ copolymerization method and other methods are known. For example, microcapsules of a copolymer containing isocyanate are prepared by the in situ copolymerization method, By heating and foaming it, hydrophilic porous fine particles can be produced (for example, JP-A-1-207133).

[0003]

However, since higher quality porous microcapsules are always required, it is necessary to improve the quality by improving the manufacturing method.

The present invention has been made in view of the above problems, and an object of the present invention is to provide a new and improved manufacturing method to provide higher-quality porous hollow particles.

[0005]

As described above, the method for producing porous hollow particles according to the present invention is a primary emulsion in which the first dispersed phase is dispersed in the first continuous phase containing the solidifying component. A secondary emulsion is produced by further dispersing the primer emulsion in which the gas is dissolved under pressure in the first continuous phase as a second dispersed phase in the second continuous phase. Is a normal pressure state to form hollow particles, and then the solidifying component is solidified, and then the first dispersed phase portion of the primary emulsion is removed to produce porous hollow particles.

Another method for producing porous hollow particles according to the present invention is to produce a primary emulsion in which a first dispersed phase is dispersed in a first continuous phase containing a solidifying component, As a second dispersed phase, a secondary emulsion is further dispersed in the secondary continuous phase to produce a secondary emulsion, and a gas is dissolved under pressure in the primary continuous phase in the secondary emulsion, and the secondary secondary phase is added. This is a method for producing porous hollow particles by forming the hollow particles under normal pressure in the emulsion, solidifying the solidifying component, and then removing the first dispersed phase portion of the primary emulsion.

Therefore, in any case, after the solidifying component of the hollow particles is solidified, the first dispersed phase portion is removed, so that pores are formed after the first dispersed phase portion is removed,
This produces porous hollow particles.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION As described above, claim 1 of the present application
In the method for producing porous hollow particles according to the described invention, a primary emulsion 14 in which a first disperse phase 13 is dispersed in a first continuous phase 11 containing a solidifying component is the first continuous phase 11 The secondary emulsion 17 is produced by dispersing the primary emulsion 14 (FIG. 1 (A)) in which gas is dissolved under pressure as the second dispersed phase 15 into the second continuous phase 16 ( 1 (B)), after the secondary emulsion 17 is under normal pressure to form hollow particles 18 (FIG. 1 (C)), the solidified component is solidified (FIG. 1 (D)), and then the primary emulsion is formed. The porous hollow particles 20 are manufactured by removing the portion of the first dispersed phase 13 of 14 (FIG. 1 (E)). The pressure dissolution of the gas may be performed before or after the production of the primary emulsion 14.
(See JP 5-228359).

In the method for producing porous hollow particles according to the eleventh aspect of the present invention, the primary emulsion 14 in which the first dispersed phase 13 is dispersed in the first continuous phase 11 containing the solidifying component is used. The primary emulsion 14 (Fig. 1 (A)) is produced and further dispersed in the second continuous phase 16 as the second dispersed phase 15 to produce a secondary emulsion 17 (Fig. 1 (B)).
After gas is dissolved under pressure in the first continuous phase 11 in the secondary emulsion 17 to make the secondary emulsion 17 under normal pressure to form hollow particles 18 (FIG. 1 (C)), The porous hollow particles 20 are manufactured by solidifying the solidifying component and then removing the first dispersed phase 13 portion of the primary emulsion 17 (FIG. 1 (D)).

In any of the first and the eleventh aspects, a gas soluble in the first continuous phase is selected according to the first continuous phase, as will be described later.

According to the method for producing porous hollow particles according to the present invention as described above, after the hollow particles 18 are hardened, the first dispersed phase 13 portion thereof is removed, whereby the first dispersed particles are removed. The traces of the removal of the portion of the phase 13 become pores 19 to produce porous hollow particles 20 (FIG. 1 (D) → FIG. 1 (E)).

The method according to claim 2 or 12, wherein the volume ratio of the first dispersed phase and the first continuous phase during the formation of the primary emulsion in the manufacturing method according to claim 1 or 11. Is adjusted to control the pore diameter and / or the number of pores of the porous hollow particles.

The pore size of the porous hollow particles can be adjusted by the volume ratio of the dispersed phase and the continuous phase in forming the primary emulsion. Generally, the larger the volume ratio of the dispersed phase, the larger the pore size of the resulting porous hollow particles.
Moreover, it is known from experiments that the number of pores of the porous hollow particles changes depending on the volume ratio of the dispersed phase and the continuous phase.

The method according to claim 3 or 13, wherein the concentration of the solidifying component dissolved in the first continuous phase in the production method according to claim 1 or 11, and the emulsification during the formation of the primary emulsion The volume of the first dispersed phase and the first continuous phase, the composition of the first continuous phase, or the type or concentration of the salt dissolved in the first dispersed phase, the porous hollow It is characterized by controlling the pore size and / or the number of pores of the particles.

In this case, the smaller the concentration of the solidified component dissolved in the continuous phase, the larger the pore size of the porous hollow particles. Further, the degree of emulsification, the volume ratio of the dispersed phase and the continuous phase, the composition of the continuous phase, or by adjusting the type or concentration of the salt dissolved in the first dispersed phase, the pore size of the resulting porous hollow particles and The number of pores can be controlled.

The method according to any one of claims 4 and 14 is the method according to any one of claims 1 to 3 or 11 to 13, wherein the first dispersed phase and the second continuous phase are aqueous phases. And the first continuous phase is an oil phase.

In this case, the primary emulsion is a w / o emulsion in which the first aqueous phase (hereinafter, the internal aqueous phase) is dispersed in the oil phase containing the solidified component. The secondary emulsion is a w / o / w prepared by dispersing this w / o emulsion in a second aqueous phase (hereinafter, external water phase).
It becomes an emulsion. Then, by solidifying the oil phase in a state in which this w / o / w emulsion is generated, and then removing the inner aqueous phase, the inner aqueous phase portion becomes pores to form porous hollow particles. To be done.

The method according to any one of claims 5 and 16 is the method according to any one of claims 1 to 4 or 11 to 14, wherein the first dispersed phase and the second continuous phase are oil phases. And the first continuous phase is an aqueous phase.

In this case, the phases of the emulsion are reversed from those of the methods according to claims 4 and 14, and the primary emulsion is such that the first oil phase (hereinafter, the internal oil phase) is added to the aqueous phase containing the solidified component. ) Is dispersed in the o / w emulsion. And the secondary emulsion is this o / w
It becomes an o / w / o emulsion in which the emulsion is dispersed in a second oil phase (hereinafter, the outer oil phase). And this o /
After the w / o emulsion has hardened, the internal oil phase is removed, whereby the portions where the internal oil phase has been removed become pores to form porous hollow particles.

In the method of claim 6, the emulsion 24 containing the solidified component and containing the dispersed phase 23 in which the gas is dissolved under pressure is brought to a normal pressure to form hollow particles 25 (FIG. 2 (A)). → (B)), after solidifying the hollow particles 24 to an intermediate degree (FIG. 2 (C)), the hollow particles 25 are impregnated with a solvent for the constituent components of the shell parts (FIG. 2).
(D)), the hollow particles impregnated with the solvent are further solidified, and then the solvent is removed to produce porous hollow particles (FIG. 2 (E)). The solidifying component used in the method of claim 6 includes, for example, a thermosetting resin monomer. When the monomer of the thermosetting resin is used, the "moderate" solidification means polymerization, and the "further solidification" after impregnation with the solvent means solidification by heat treatment. When other solidifying ingredients are used, "medium" solidification means
It means the solidification in the stage before the final solidification.

According to this method, when the hollow particles are solidified to an intermediate degree (FIG. 2 (C)) and then impregnated with a solvent,
The solvent enters between the constituent components of the shell, and the hollow particles expand by that amount (FIG. 2 (D)). Further solidification in this state solidifies in the state where the solvent is taken in. Therefore, when the solvent is removed therefrom, the traces 26 into which the solvent has entered become cavities 27 as they are, and porous hollow particles 28 are formed. Examples of solvents used in this method include styrene to polystyrene, ethyl acetate, and the like.

In the sixteenth aspect, after the gas is dissolved under pressure in the first continuous phase 11 in the secondary emulsion 17, the solidified components are solidified to an intermediate degree, and then the secondary emulsion 17 is subjected to normal pressure. After forming the hollow particles 18 in the state (FIG. 1 (C)), the solidified component is further solidified, and then the first dispersed phase 13 portion of the primary emulsion 17 is removed (FIG. 1 (D)). The porous hollow particles 20 are manufactured.

Here, the solidifying component may be, for example, a monomer of thermosetting resin. As a solidifying component,
When a thermosetting resin monomer is used, the above-mentioned "medium-level" solidification means polymerization, and the above-mentioned "further solidification".
Means solidification by heat treatment. When other solidifying components are used, "medium-level" solidifying means solidifying before the final solidifying.

Therefore, by solidifying the solidified component to a medium degree and then bringing the solidified component into a normal pressure state, the solidified component swells appropriately, and hollow particles having a uniform particle size and a uniform film can be produced.

In the method according to the seventh aspect, the emulsion 32 containing the dispersed phase 31 in which the phase-separating component is mixed and the gas is dissolved under pressure is brought to a normal pressure state to form hollow particles 34 (see FIG. ) → (B)), solidifying the hollow particles 34 (FIG. 3 (C)) and then dissolving the phase-separating component to produce the porous hollow particles 36 (FIG. 3 (D)). Characterize. The term "phase-separating component" as used in claim 7 means, for example, boric anhydride in the production of porous glass. Incidentally, when producing a porous glass, the boric anhydride portion is dissolved by sintering the glass component in a state in which boric anhydride is mixed and acid-treating it. When this is applied to the present invention, water glass mixed with boric anhydride is used to form hollow particles, which are then solidified into hollow glass particles. Then, the hollow glass particles are treated with an acid to produce porous hollow glass particles.

According to this method, when the phase separating component of the hollow particles 35 solidified with the phase separating component mixed therein is dissolved,
The traces of the mixture of the phase-separating components become the cavities 37 as they are, and the porous hollow particles 36 are formed. In the case of producing porous hollow glass particles, the traces of the mixed boric acid anhydride form hollows as they are, and porous hollow glass particles are formed.

According to the present invention, the porous hollow particles (claim 8, claim 17) produced by the method according to any one of claims 1 to 7 or 11 to 16, and claim 8 or claim 18. Slow-release hollow particles obtained by impregnating the above-mentioned particles with a substance to be sustained-released (claim 9, claim 18), and
A method of using the particles according to claim 8 or 18 as a carrier of a bioreactor (claims 10 and 19).
Is included.

In the present invention, the method described in Japanese Patent Application Laid-Open No. 5-228359 is used for producing the porous hollow particles. According to this method, the gas that has been pressure-dissolved in advance appears as bubbles in the particles due to the subsequent depressurization,
Balloon-shaped hollow particles are formed. In the present invention, after the hollow particles are formed, polymerization is carried out, and then the aqueous phase portion is removed by drying, and the removed aqueous phase portion becomes pores to form porous hollow particles. . In this case, when the dispersed phase at the time of forming the primary emulsion was the aqueous phase, the portion where the aqueous phase was removed becomes pores. On the other hand, when the dispersed phase of the primary emulsion is an oil phase, the oil phase portion becomes pores. Here, when an aqueous phase is used as the first continuous phase during the production of the primary emulsion, hollow particles are produced using a gas that is easily dissolved in the aqueous phase such as carbon dioxide and is difficult to be dissolved in the oil phase. To do. Conversely, when an oil phase is used as the first continuous phase in the primary emulsion, hollow particles are produced by using a gas that is easily dissolved in the oil phase, such as nitrogen gas, but is difficult to be dissolved in the water phase. be able to.

A vibromixer (trade name; for example, Japanese Examined Patent Publication No. 2-15247 and Japanese Patent Laid-Open No. 2-293035), which is based on vibrating a stirring blade, can be used to generate an emulsion. It is possible to use a mixing device whose basic principle is to use (for example, Japanese Patent Laid-Open No. 4-265137). Of course, it is also possible to use the mixing apparatus described in Japanese Patent Application No. 7-340335.

When the primary emulsion is produced, it is preferable to carry out ultrasonic emulsification. Ultrasonic emulsification in the production of the primary emulsion can make the particle size of the dispersed phase very small (about submicron). Since this dispersed phase finally constitutes the pores of the porous hollow particles, control of its size is one of the important issues. Can be reduced, and by extension, the pore diameter of the finally obtained porous hollow particles can be reduced.

The secondary emulsion can be produced by the same method as the primary emulsion.

In the production of the primary or secondary emulsion, an emulsifier or the like is appropriately added to form the emulsion.

The continuous phase during the formation of the primary emulsion contains the ingredients that eventually solidify it.
When the continuous phase is the oil phase, the styrene monomer and the like are dissolved (when the styrene monomer is polymerized, it becomes polystyrene and solidifies). As the solvent at that time, an organic solvent such as toluene which dissolves a monomer to be polymerized is used. When the continuous phase is an aqueous phase, water glass or the like is used as the solidified component to be dissolved. The solidified body finally obtained in this case is silica. The polymerization is
It can be carried out by adding a polymerization initiator or the like to the system.

As shown in FIG. 4, the obtained hollow particles 20 are composed of a shell portion 21 constituting an outer shell and a hollow portion 22 formed inside thereof. As a matter of course,
The holes 19 are present in the shell of the hollow particles obtained in the present invention. As shown in FIG. 5, the hole 19 is buried in the shell portion 21, appears only on the surface of the shell portion 21, appears only at the hollow portion 22, and the shell portion 21. Various forms such as a case where the hollow portion 22 is connected to the outside by penetrating 21 are adopted.

As is apparent from FIG. 5, the holes 19 may be independent of each other, or may be hollow (sponge-like) by overlapping the holes 19 with each other. You can also As a matter of course, it is possible to set the condition to an intermediate state by appropriately setting the condition. Which of these is selected is determined in consideration of the mode of sustained release and the like. For example, if the holes 19 are made independent of each other, the sustained release substance is released through the shell substance of the hollow particles.
In the case of a hollow shape, the sustained release substance is mainly diffused through the hollow.

The finally obtained porous hollow particles may be those in which the hollow portions or pores are impregnated with a drug, an agricultural chemical, a perfume or the like, and these are gradually released.

The porous hollow particles according to the present invention can also be used as a carrier for immobilized enzyme in a bioreactor. Further, it can be used as a matrix (or carrier) for affinity chromatography. When it is composed of biodegradable plastic, it can be used as a pesticide or a fertilizer and does not adversely affect the environment.

The particle size mainly depends on the amount of gas dissolved in the first continuous phase, and can be freely set between several microns and several millimeters (diameter). Since this can be freely controlled by adjusting the emulsion preparation method and the pressure of the gas, it is possible to exceed this range.

[0039]

INDUSTRIAL APPLICABILITY As described above, the present invention provides a novel method for producing porous hollow particles, and the porous hollow particles obtained by this method are of good quality and applied to the pharmaceutical field. It is expected to be applied in various fields.

[Brief description of drawings]

FIG. 1 is a diagram for explaining a step of producing porous hollow particles according to the present invention via a primary emulsion and a secondary emulsion.

FIG. 2 is a diagram for explaining a step of producing porous hollow particles according to the present invention by impregnating solidified hollow particles with a solvent.

FIG. 3 is a diagram illustrating a step of producing porous hollow particles according to the present invention using a phase separation method.

FIG. 4 is a partial cutaway view of porous hollow particles according to the present invention.

FIG. 5 is an enlarged cross-sectional view of a shell portion of the porous hollow particle according to the present invention.

[Explanation of symbols]

11 1st continuous phase, 13 1st dispersed phase, 14 primary emulsion, 15 2nd dispersed phase, 16 2nd continuous phase, 17 secondary emulsion, 18
Hollow particles, 19 pores, 20 Porous hollow particles, 21 Shell portion, 22 Hollow portion, 23 Dispersed phase containing solidified component and gas dissolved under pressure, 24 Emulsion containing dispersed phase 23, 25 Hollow particles, 26 Traces, 27 cavities,
28 porous hollow particles, 31 dispersed phase in which phase separating component is mixed and gas is dissolved under pressure, 32 emulsion containing dispersed phase 31, 34 hollow particles, 35 hollow particles, 36 porous hollow particles, 37 cavities.

Claims (19)

[Claims] 1. A primary emulsion in which a first disperse phase is dispersed in a first continuous phase containing a solidifying component, wherein a gas is dissolved under pressure in the first continuous phase. A secondary emulsion is produced by further dispersing it in the second continuous phase as the second dispersed phase, and the secondary emulsion is formed into hollow particles under normal pressure, and then the solidifying component is solidified before the solidified component is solidified. A method for producing porous hollow particles by removing the first dispersed phase portion of the primary emulsion. 2. The production method according to claim 1, wherein the volume ratio of the first dispersed phase and the first continuous phase at the time of forming the primary emulsion is adjusted to adjust the pore diameter and / or the pore diameter of the porous hollow particles. A method for producing porous hollow particles, which comprises controlling the number of pores. 3. The production method according to claim 1, wherein the concentration of the solidifying component dissolved in the first continuous phase, the degree of emulsification during the formation of the primary emulsion, the first dispersed phase and the first continuous phase. The pore diameter and / or the number of pores of the porous hollow particles are adjusted by adjusting the volume ratio, the composition of the first continuous phase, or the type or concentration of the salt dissolved in the first dispersed phase. A method for producing porous hollow particles. 4. The production method according to claim 1, wherein the first dispersed phase and the second continuous phase are an aqueous phase, and the first continuous phase is an oil phase. A method for producing a porous hollow particle, which is characterized. 5. The production method according to claim 1, wherein the first dispersed phase and the second continuous phase are an oil phase, and the first continuous phase is an aqueous phase. A method for producing a porous hollow particle, which is characterized. 6. A hollow particle is formed by bringing an emulsion containing a solidifying component and containing a dispersed phase in which a gas is dissolved under pressure into a normal pressure state to solidify the hollow particle to an intermediate level, and then the hollow particle. A method for producing porous hollow particles by impregnating the shell portion with a solvent for the constituent components of the shell portion, further solidifying the hollow particles impregnated with the solvent, and then removing the solvent. 7. A hollow particle is formed by bringing an emulsion containing a dispersed phase in which a phase-separating component is mixed and a gas is dissolved under pressure into a normal pressure state to solidify the hollow particle, and then the phase-separating component is removed. A method for producing porous hollow particles by dissolving. 8. A porous hollow particle produced by the method according to claim 1. 9. Sustained-release hollow particles obtained by impregnating the particles according to claim 8 with a substance to be sustained-released. 10. A method of using the particles according to claim 8 as a carrier for a bioreactor. 11. A primary emulsion in which a first dispersed phase is dispersed in a first continuous phase containing a solidifying component, and the primary emulsion is further dispersed in a second continuous phase as a second dispersed phase. A secondary emulsion is produced by allowing to dissolve a gas under pressure in the first continuous phase in the secondary emulsion to form hollow particles in a normal pressure state of the secondary emulsion, and A method for producing porous hollow particles, which comprises solidifying a solidified component and then removing the first dispersed phase portion of the primary emulsion. 12. The production method according to claim 11, wherein the volume ratio of the first dispersed phase and the first continuous phase at the time of forming the primary emulsion is adjusted to adjust the pore diameter and the pore diameter of the porous hollow particles. The method for producing porous hollow particles is characterized by adjusting the number of pores. 13. The production method according to claim 11, wherein the concentration of the solidifying component dissolved or solidified in the first continuous phase, the degree of emulsification during the formation of the primary emulsion, the first dispersed phase and the first continuous phase. Volume ratio of phases, composition of first continuous phase,
Alternatively, the method for producing porous hollow particles is characterized in that the pore diameter and / or the number of pores of the porous hollow particles are adjusted by adjusting the type or concentration of the salt dissolved in the first dispersed phase. 14. The manufacturing method according to claim 11, wherein the first dispersed phase and the second continuous phase are an aqueous phase, and the first continuous phase is an oil phase. A method for producing porous hollow particles, characterized by being present. 15. The manufacturing method according to claim 11, wherein the first dispersed phase and the second continuous phase are oil phases, and the first continuous phase is an aqueous phase. A method for producing porous hollow particles, characterized by being present. 16. The manufacturing method according to claim 11, wherein the gas is dissolved under pressure in the first continuous phase in the secondary emulsion, and then solidified to an intermediate degree. Characterized in that the components are solidified, and then the secondary emulsion is subjected to normal pressure to form hollow particles, and then the solidified component is further solidified, and then the first dispersed phase portion of the primary emulsion is removed. Method for producing porous hollow particles. 17. A porous hollow particle produced by the production method according to any one of claims 11 to 16. 18. A sustained-release hollow particle obtained by impregnating the porous hollow particle according to claim 17 with a substance to be released. 19. A method of using the porous hollow particles according to claim 17 as a carrier for a bioreactor.