JP2012035179A - Temperature sensitive adsorbent and method of manufacturing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a temperature sensitive adsorbent in which the outer surface of porous silica is uniformly covered with a small amount of temperature sensitive polymer and which can control the pore entrance diameter of the porous silica by temperature control.SOLUTION: The temperature sensitive adsorbent is made by bonding the temperature sensitive polymer whose volume is changed according to a temperature change to the outer surface of the porous silica through a functional group.

Description

  The present invention relates to a thermosensitive adsorbent capable of reversibly changing the inlet diameter of pores by a change in external temperature and a method for producing the same.

  Porous silica has a high specific surface area and uniform pores, and is widely used as a catalyst or a separation / adsorption material. For example, porous silica whose organic functional group is modified inside the pores exhibits excellent adsorption ability for metal ions and organic molecules dissolved in water. One of the methods for modifying the organic functional group inside the pores of the porous silica is a so-called co-condensation method. The co-condensation method is a one-pot synthesis method by mixing a silane having an organic functional group together with a silica source. The removal of the surfactant is usually performed using an acidic solvent. According to this method, the organic functional group is uniformly dispersed in the pores, and the amount of the organic functional group immobilized can be easily controlled. In this case, the pore diameter can be changed by changing the amount of the organic functional group immobilized on the inner wall of the pore (Non-Patent Document 1). This indicates that the size of molecules that can be adsorbed can be controlled by the amount of the organic functional group, and it is considered possible to quickly and preferentially separate and adsorb molecules to be adsorbed. However, in this case, the pore diameter can only be changed by several units, and there is also a problem that the skeleton structure of porous silica is broken when a large amount of organic functional groups are introduced.

  On the other hand, stimuli-responsive polymers are expected as new adsorbing materials. The stimulus-responsive polymer changes its volume in response to external stimuli such as pH, light, and electric field. In particular, an acrylamide derivative such as poly (N-isopropylacrylamide), which is a kind of thermosensitive polymer, reversibly hydrates or dehydrates at a predetermined temperature (for example, 32 ° C.). Along with this, the polymer itself swells or contracts, and the volume changes. During this volume change, molecules can be taken into the network structure and adsorbed. However, when a stimuli-responsive polymer is used as an adsorbent, there are problems that the amount of adsorption is extremely small and the mechanical strength is not sufficient (Non-patent Document 2).

  In order to solve both the above-mentioned problems specific to porous silica and problems specific to stimuli-responsive polymers, research has been conducted on combining porous silica and stimuli-responsive polymers (Non-patent Document 3- 11). The purpose of this research is to control the pore inlet diameter by changing the volume of the stimulus-responsive polymer while taking advantage of the adsorption capacity, specific surface area, and mechanical strength of porous silica. However, when the stimulus-responsive polymer is coated on the porous silica, it is not easy to control the coating amount, and when the stimulus-responsive polymer is to be appropriately coated, the amount of the stimulus-responsive polymer on the outer surface of the porous silica. As a result, the stimulus-responsive polymer layer is thickly covered on the outer surface of the porous silica. As a result, it is difficult to control the pore inlet diameter of the porous silica.

K. Murakami, K. Fuda and M. Sugai, Geometrical Study on Change of Pore Volume of MCM-41 Functionalized with Aminopropyl Groups, Mater. Res. Soc. Symp. Proc., 1056E (2007) 1056-HH08-41 T. Oya, T. Enoki, AY Grosberg, S. Masamune, T. Sakiyama, Y. Takeoka, K. Tanaka, G. Wang, Y. Yilmaz, MS Feld, R. Dasari, and T. Tanaka, Reversible molecular adsorption based on multiple-point interaction by shrinkable gels, Science, 286 (1999) 1543-1545 Y. Zhu, J. Shi, W. Shen, X. Dong, J. Feng, M. Ran, and Y. Li, Stimuli-Responsive Controlled Drug Release from a Hollow Mesoporous Silica Sphere / Polyelectrolyte Multilayer Core-Shell Structure, Angew Chem. Int. Ed., 44 (2005) 5083-5087. S-W. Song, K. Hidajat, and S. Kawi, pH-Controllable drug release using hydrogel encapsulated mesoporous silica, Chem. Commn., 42 (2007) 4396-4398. W. Xu, Q. Gao, Y. Xu, D. Wu, Y. Sun, pH-Controlled drug release from mesoporous silica tablets coated with hydroxypropyl methylcellulose phthalate, Materials Research Bulletin 44 (2009) 606-612. H-J. Kim, H. Matsuda, H. Zhou, and I. Honma, Ultrasound-Triggered Smart Drug Release from a Poly (dimethylsiloxane) -Mesoporous Silica Composite, Adv. Mater. 18 (2006) 3083-3088. N. K. Mal, M. Fujiwara, and Y. Tanaka, Photocontrolled reversible release of guest molecules from coumarin-modified mesoporous silica, Nature, 421 (2003) 350-353. GV Rama Rao, ME Krug, S. Balamurugan, H. Xu, Q. Xu, and GP Lopez, Synthesis and Characterization of Silica-Poly (N-isopropylacylamide) Hybrid Membranes: Switchable Molecular Filters, Chem. Mater., 14 (2002 ) 5075-5080. Q. Fu, GV Rama Rao, LK Ista, Y. Wu, BP Andrzejewski, LA Sklar, TL Ward, and GP Lopez, Control of Molecular Transport Through Stimuli-Responsive Ordered Mesoporous Materials, Adv. Mater., 15 (2003) 1262 -1266. Q. Fu, G. V. Rama Rao, T. L. Ward, Y. Lu, and G. P. Lopez, Thermoresponsive Transport through Ordered Mesoporous Silica / PNIPAAm Copolymer Membranes and Microspheres, Langmuir, 23 (2007) 170-174. B.-S. Tian, and C. Yang, Temperature-Responsive Nanocomposites Based on Mesoporous SBA-15 Silica and PNIPAAm: Synthesis and Characterization, J. Phys. Chem. C., 113 (2009) 4925-4931.

  Accordingly, the present invention provides a temperature-sensitive adsorbent in which the outer surface of the porous silica is coated with a uniform and small amount of a temperature-sensitive polymer, and the pore inlet diameter of the porous silica can be controlled by temperature control. The task is to do.

In order to solve the above problems, the present invention adopts the following configuration. That is,
A first aspect of the present invention is a temperature-sensitive adsorbent in which a temperature-sensitive polymer whose volume changes in response to a temperature change is bonded to the outer surface of porous silica via a functional group. .

  In the present invention, the “outer surface of porous silica” refers to a surface other than the pore inner wall of the porous silica and is a surface exposed in appearance. In addition, “the thermosensitive polymer is bonded to the outer surface of the porous silica via a functional group” means that the thermosensitive polymer is chemically bonded to the functional group by a covalent bond or an ionic bond. In addition to the combined form, both forms formed by physical adsorption or entanglement between substances may be included. In particular, in the present invention, it is possible to chemically bond the thermosensitive polymer to the outer surface of the porous silica due to the presence of the functional group.

  In the first aspect of the present invention, the amount of the thermosensitive polymer can be 5% by mass or less based on the entire thermosensitive adsorbent (100% by mass). In the present invention, since the temperature-sensitive polymer is bonded to the outer surface of the silica via a functional group, the temperature-sensitive polymer is compared with the form in which the temperature-sensitive polymer simply covers the outer surface of the silica. The amount can be small. That is, even if the temperature-sensitive polymer is to be coated on the silica outer surface without using a functional group, if the amount of the temperature-sensitive polymer is small, the temperature-sensitive polymer cannot be coated well. For example, in the case of Tian et al. (Non-Patent Document 11), the amount of polymer is 21 to 28% by mass, or in the case of Fu et al. (Non-Patent Document 9), the amount of polymer is 24% by mass. Yes. That is, in the conventional form, the silica outer surface was coated with a very large number of polymers. In other words, when immobilizing a thermosensitive polymer without interposing a functional group, it can be said that immobilization could not be achieved unless the amount of the thermosensitive polymer was extremely large. On the other hand, in the present invention, even a very small amount of the functional high molecular weight of 5% by mass or less can be appropriately immobilized on the outer surface of the porous silica through the functional group.

  In the first aspect of the present invention, the functional group is preferably at least one selected from an amino group, a mono-substituted amino group, a di-substituted amino group, or a vinyl group, and among them, a dimethylamino group is particularly preferable. preferable. With these functional groups, the thermosensitive polymer can be more appropriately bonded to the outer surface of the silica.

  In the first aspect of the present invention, the thermosensitive polymer preferably comprises a monomer unit derived from a (meth) acrylamide derivative, and particularly preferably poly (N-isopropyl (meth) acrylamide). . Thereby, the precision of pore diameter control by temperature change further improves.

  In the first aspect of the present invention, the porous silica preferably has an ion exchange group inside the pore. In particular, the ion exchange group is preferably a primary to tertiary amino group, a quaternary ammonium group, a carboxyl group, or a sulfonic acid group. This makes it possible to use the temperature-sensitive adsorbent for ion exchange applications.

  In the second aspect of the present invention, a functional group addition step of adding a functional group to the outer surface of the porous silica skeleton, and a thermosensitive polymer whose volume changes in response to a temperature change are bonded to the functional group. And a temperature-sensitive polymer binding step.

  Here, the “porous silica skeleton” means a silica skeleton that can become porous silica. When forming a porous silica skeleton using a surfactant or the like as a template, the surfactant or the like may remain. “Binding the thermosensitive polymer to the functional group” means, for example, that the thermosensitive polymer is polymerized in the liquid in the vicinity of the functional group by polymerizing a monomer that forms the thermosensitive polymer. Any form can be applied as long as the thermosensitive polymer can be bonded to the functional group, such as a form chemically or physically bonded to the functional group.

  In the second aspect of the present invention, by using a solution containing a surfactant and a silica source, a porous silica skeleton is formed using the surfactant as a template, and then the surfactant is removed, whereby pores are obtained. It is good to form. In this case, it is preferable that the solution further contains an ion exchange group source. The “silica source” means a compound that is a raw material for porous silica. A conventionally known silica source can be used as the silica source, and specific examples thereof include silicic acid compounds such as tetraethoxysilane (TEOS). The “ion exchange group source” means a compound having an ion exchange group immobilized in the pores of porous silica. A conventionally well-known thing can be used as an ion exchange group source, For example, the silicic acid compound which has an organic functional group can be used.

  In the second aspect of the present invention, the thermosensitive polymer binding step is performed by polymerizing a monomer that forms the thermosensitive polymer in a liquid containing a porous silica skeleton to which a functional group is added. A step of bonding a thermosensitive polymer to the functional group.

  According to the present invention, the thermosensitive polymer is bonded to the outer surface of the porous silica via a functional group, so that the outer surface of the porous silica is uniformly coated with a small amount of the thermosensitive polymer. Thereby, the temperature sensitive adsorbent which can control the pore inlet diameter of porous silica by temperature control can be provided.

It is a figure which shows roughly the cross-section of the temperature sensitive adsorbent 100 of this invention which concerns on one Embodiment. It is the schematic for demonstrating the volume phase transition of a thermosensitive polymer. It is a figure for demonstrating the flow of the manufacturing method of the temperature sensitive adsorbent of this invention which concerns on one Embodiment. It is a figure for demonstrating the flow of the manufacturing method of the temperature sensitive adsorbent of this invention which concerns on one Embodiment. It is a figure which shows the form of a comparative example schematically. It is a figure which shows the form of a comparative example schematically. It is a figure which shows the XRD pattern about the composite_body | complex 300 which consists of the porous silica 10 to which only the functional group 20 was added. It is a figure which shows the FT-IR spectrum about the composite_body | complex 300 which consists of the porous silica 10 to which only the functional group 20 was added. It is a SEM photograph figure about the composite 400 which is not equipped with the thermosensitive adsorbent 100 and the thermosensitive polymer. It is a figure which shows the XRD pattern about the composite 400 which is not equipped with the thermosensitive adsorbent 100 and the thermosensitive polymer. It is a figure which shows the FT-IR spectrum about the composite 400 which is not equipped with the thermosensitive adsorbent 100 and the thermosensitive polymer. It is a figure which shows a thermogravimetric analysis result. It is a figure which shows the adsorption / desorption characteristic with respect to methyl orange about the composite_body | complex 400 which is not equipped with a temperature sensitive polymer. It is a figure which shows the adsorption / desorption characteristic with respect to methyl orange about the composite_body | complex 500 'produced by the conventional method. It is a figure which shows the adsorption / desorption characteristic with respect to methyl orange about the temperature sensitive adsorbent 100 of this invention.

1. FIG. 1 schematically shows a cross-sectional structure of a temperature-sensitive adsorbent 100 according to an embodiment of the present invention. As shown in FIG. 1, the thermosensitive adsorbent 100 has a thermosensitive polymer 30 bonded to the outer surface of porous silica 10 having pores 10a, 10a,. . Further, ion exchange groups 40, 40,... Are modified on the inner walls of the pores 10a, 10a,.

1.1. Porous silica The porous silica 10 has pores 10a, 10a,... And can adsorb specific substances on the inner walls of the pores 10a, 10a,. The diameters of the pores 10a, 10a,... Are not particularly limited, but are particularly preferably mesopores (pore diameter is about 2 to 50 nm). That is, mesoporous silica may be used as the porous silica 10. The specific surface area of the porous silica 10 is not particularly limited as long as it has a specific surface area that can be used as an adsorbent.

1.2. Functional group The functional group 20 is added to the outer surface of the porous silica 10 (the surface other than the inner walls of the pores 10a, 10a,... Of the porous silica 10 and exposed in appearance). The functional group 20 is not particularly limited as long as it can connect / bond the outer surface of the porous silica 10 and a thermosensitive polymer 30 described later. For example, it is preferably at least one selected from an amino group, a mono-substituted amino group, a di-substituted amino group, and a vinyl group, and more preferably a di-substituted amino group. In particular, a dimethylamino group may be used.

1.3. Temperature Sensitive Polymer The temperature sensitive polymer 30 is bonded to the outer surface of the porous silica 10 through the functional group 20. This is significantly different from the conventional configuration in which the temperature-sensitive polymer 30 simply covers the outer surface of the porous silica 10 (simply exists in the vicinity of the outer surface of the porous silica 10). The temperature-sensitive polymer 30 is not particularly limited as long as the volume is changed according to a temperature change. In particular, polymers comprising monomer units derived from N-alkyl (meth) acrylamide derivatives such as poly (N-isopropyl (meth) acrylamide), poly (N-acryloylpiperidine), poly (N-propylacrylamide), It is preferable to use a polymer having a monomer unit derived from N, N-dialkylacrylamide, such as (N, N-diethylacrylamide). For example, poly (N-isopropylacrylamide) has a volume phase transition temperature around 32 ° C., and the temperature-sensitive polymer 30 contracts on the higher temperature side and the temperature-sensitive polymer 30 swells on the lower temperature side. To do. That is, as shown in FIG. 2, on the higher temperature side than the volume phase transition temperature, the thermosensitive polymer 30 takes a dense network structure with small gaps, and thus does not allow the adsorbed substance X to pass through (FIG. 2). (A)). On the other hand, on the lower temperature side than the volume phase transition temperature, the temperature-sensitive polymer 30 has a sparse network structure with large gaps, and thus allows the adsorbed substance X to pass therethrough (FIG. 2B). In the present invention, the size of the gap of the temperature-sensitive polymer 30 is controlled by temperature control, and thereby the inlet diameter of the pores 10a, 10a,... Of the porous silica 10 is controlled.

  The amount of the temperature-sensitive polymer 30 is 5% by mass or less, preferably 3% by mass or less, more preferably 1% by mass or less, based on the temperature-sensitive adsorbent 100 as a whole (100% by mass). The lower limit is not particularly limited, and the effect of the present invention is exhibited as long as it exceeds 0% by mass. Especially 0.5 mass% or more is preferable. In the present invention, since the thermosensitive polymer 30 is bonded to the outer surface of the porous silica 10 via the functional group 20, the conventional thermosensitive polymer 30 simply covers the porous silica 10. Compared to the form, the outer surface of the porous silica 10 can be uniformly coated with a small amount of the thermosensitive polymer 30. That is, the thickness of the temperature-sensitive polymer 30 can be easily reduced, and the inlet diameter of the pores 10a, 10a,... Can be accurately controlled.

1.4. In the thermosensitive adsorbent 100 of the present invention, ion exchange groups 40, 40,... Are modified on the inner walls of the pores 10a of the porous silica 10. Thereby, it is possible not only to physically adsorb and desorb the substance to be adsorbed on the inner walls of the pores 10a of the temperature-sensitive adsorbent 100, but also to chemically adsorb and desorb it. That is, by modifying the ion exchange group 40, the thermosensitive adsorbent 100 of the present invention can function as an ion exchanger. As the ion exchange group 40, what is conventionally employ | adopted as an ion exchange group is applicable, without being specifically limited. Specific examples include a primary to tertiary amino group, a quaternary ammonium group, a carboxyl group, and a sulfonic acid group. For example, when an amino group is modified on the inner wall of the pore 10a, the temperature-sensitive adsorbent 100 of the present invention functions as an ion exchanger capable of adsorbing anions at low pH and desorbing anions at high pH. Can do.

  As described above, the temperature-sensitive adsorbent 100 of the present invention has a uniform and small amount of the temperature-sensitive polymer 30 bonded and coated on the outer surface of the porous silica 10 via the functional group 20. It becomes possible to control the inlet diameter of the pore 10a of the porous silica 10 by the control. Further, by modifying the inner wall of the pore 10a with the ion exchange group 40, it is possible to use a metal ion or the like in the liquid as an ion exchanger capable of ion exchange. The said ion exchanger can be utilized suitably as a column filler for ion exchange chromatography. In addition, it is considered possible to administer the temperature-sensitive adsorbent 100 holding a predetermined drug inside the pore 10a into the body, and desorb / release the drug by a temperature change at a predetermined position in the body. Application as a new drug delivery system is also possible.

2. Method for Producing Temperature Sensitive Adsorbent FIGS. 3 and 4 show an example of the method for producing the temperature sensitive adsorbent 100 of the present invention (production method S10). As shown in FIGS. 3 and 4, the production method S10 includes a step S1 for producing a solution containing the surfactant 50, a silica source and an ion exchange group source added to the produced solution, and the surfactant 50 as a template ( Step S2 for producing the composite 101 by forming a skeleton of porous silica 10 as a template), and a functional group addition step of adding a functional group 20 to the outer surface of the composite 101 to obtain a functional group-added composite 102 S3, a thermosensitive polymer binding step S4 for producing a thermosensitive polymer conjugate 103 in which the thermosensitive polymer 30 is bonded to the functional group 20 added in step S3, and obtained in step S4. Step S5 for obtaining the thermosensitive adsorbent 100 according to the present invention by removing the surfactant 50 from the thermosensitive polymer conjugate 103 obtained.

2.1. Step S1, Step S2
Step S1 is a step of producing a solution containing the surfactant 50, and step S2 is a step of producing a composite 101 by forming a skeleton of the porous silica 10 using the surfactant 50 as a template in the produced solution. It is. A technique for forming a skeleton of the porous silica 10 using the surfactant 50 as a template in the solution is a known technique, and a conventional method can be applied in the present invention. That is, a conventionally known surfactant (for example, one that can function as a template such as cetyltrimethylammonium bromide) is added to a solution (for example, an aqueous solution such as an aqueous ammonia solution), and heated and stirred using a hot stirrer or the like. As a result, a solution in which the surfactant 50 is dissolved is prepared (step S1). Thereafter, the temperature of the solution is lowered, a silica source (for example, a silicic acid compound such as tetraethyl orthosilicate) is added, and an ion exchange group source (for example, a silica having an ion exchange group such as 3-aminopropyltriethoxysilane) is added. The acid compound) is added, and after stirring, the suspension is filtered and washed, and the precipitate is dried, whereby the complex 101 can be obtained (step S2).

2.2. Functional group addition step S3
Step S3 is a step of adding the functional group 20 to the outer surface of the complex 101 obtained through the steps S1 and S2 to obtain the functional group-added complex 102. The step S3 is not particularly limited as long as the functional group-added complex 102 can be produced. For example, the complex 101 and the functional group source are added to a solvent and stirred, and the suspension is filtered and washed. Then, the precipitate can be dried to obtain the functional group-added complex 102. Examples of the solvent used in step S3 include organic solvents such as toluene. The functional group source used in step S3 is, for example, a predetermined group such as 3-dimethylaminopropyldiethoxymethylsilane, 3- (N-acryloylamino) propyltriethoxysilane, allyltrichlorosilane, or allyltriethoxysilane. Examples thereof include silicic acid compounds having a functional group.

2.3. Thermosensitive polymer binding step S4
Step S4 is a step of producing the thermosensitive polymer conjugate 103 in which the thermosensitive polymer 30 is bonded to the functional group 20 of the functional group-added complex 102 obtained through the step S3. The step S4 is not particularly limited as long as the temperature-sensitive polymer conjugate 103 can be produced. For example, the step S4 is functionalized in a solution in which a monomer capable of forming the temperature-sensitive polymer 30 is dissolved. The group addition complex 102 is added and suspended. If necessary, dissolved oxygen in the suspension is removed, and a known polymerization initiator is added to carry out a polymerization reaction, whereby the thermosensitive polymer 30 is obtained. A step of producing the thermosensitive polymer conjugate 103 by chemically or physically bonding the thermosensitive polymer 30 to the functional group 20 while generating the thermosensitive polymer conjugate 103 is possible. In particular, a form in which the thermosensitive polymer 30 is chemically bonded to the functional group 20 is preferable. Examples of the monomer used in step S4 include acrylamide derivatives such as N-isopropylacrylamide, N-acryloylpiperidine, N-propylacrylamide, N, N-diethylacrylamide, and methacrylamide derivatives. Examples of the solvent for dissolving the monomer in step S4 include water. As the polymerization initiator, conventionally known ones can be widely applied. For example, ammonium persulfate may be used.

2.4. Process S5
Step S5 is a step of removing the surfactant 50 from the temperature-sensitive polymer conjugate 103 obtained through step S4 to obtain the temperature-sensitive adsorbent 100 according to the present invention. The step S5 is not particularly limited as long as the surfactant 50 can be appropriately removed. For example, the temperature-sensitive polymer conjugate 103 is added to an acidic solution (for example, hydrochloric acid) and stirred. The step of obtaining the thermosensitive adsorbent 100 by eluting the surfactant 50 into the acidic solution, then filtering the solution, and washing and drying the extracted solid content can be performed. In step S5, the pores 10a are formed by removing the surfactant 50. The ion exchange groups 40, 40, ... are left on the inner wall of the pore 10a, and the ion exchange groups 40, 40, ... are uniformly modified on the inner wall of the pore 10a.

  Thus, in the method S10 for producing a thermosensitive adsorbent according to the present invention, the ion exchange group 40 is modified inside the pores 10a of the porous silica 10 using a so-called co-condensation method, A functional group 20 is added to the outer surface of the porous silica 10 by a predetermined method, and the thermosensitive polymer 30 is bonded through the functional group 20. As a result, the temperature-sensitive polymer 30 can be thinly coated and bonded, and the obtained temperature-sensitive adsorbent 100 can function as an ion exchanger.

  Hereinafter, based on an Example, the thermosensitive adsorbent of this invention is further explained in full detail. In the following description, the symbols used in FIG. 4 are appropriately used for the sake of easy understanding.

<Preparation of temperature-sensitive adsorbent 100>
The temperature-sensitive adsorbent 100 according to the example was manufactured in the following flow.

(Preparation of composite 101)
The composite 101 was prepared by the method of Grun et al. (M. Grun, KK Unger, A. Matsumoto, K. Tsutsumi, Novel pathways for the preparation of mesoporous MCM41 materials: control of porosity and morphology, Microporous and Mesoporous Mater., ( 1999) 207-216).
As the surfactant 50, cetyltrimethylammonium bromide (CTMBr) having 16 carbon atoms in the alkyl chain was used. To a mixed solution of 120 ml (6.66 mol) of distilled water and 9.5 ml (0.14 mol) of 28% aqueous ammonia, 6.6 mmol of CTMABr was added and stirred with a hot stirrer set at 80 ° C. until the CTMABr was dissolved. When the surfactant solution becomes colorless and transparent, the temperature of the solution is lowered to 25 ° C., 9.9 ml (47.5 mmol) of tetraethyl orthosilicate (TEOS) is added as a silica source, and 3-aminopropyltriethoxysilane (APTES) is further added. 0.5 ml (2.5 mmol) was added, and the mixture was stirred at 25 ° C. for 1 hour. After completion of the stirring, the suspension was filtered with suction and washed with water, and the solid was dried at 60 ° C. for 24 hours to obtain a complex 101 in which amino groups were modified as ion-exchange groups 40.

(Preparation of functional group-added complex 102)
0.1-1 ml of 1 g of the complex 101 and 3-dimethylaminopropyldiethoxymethylsilane (manufactured by Shin-Etsu Chemical Co., Ltd., LS-3675) was added to 120 ml of toluene, and the mixture was stirred at reflux at about 200 ° C. for 4 hours. . After completion of the stirring, the suspension was filtered with suction and washed with ethanol, and the solid was dried at 60 ° C. for 24 hours to obtain a functional group-added complex 102 having a dimethylamino group added as the functional group 20.

(Preparation of thermosensitive polymer conjugate 103)
3 g (26.5 mmol) of N-isopropylacrylamide (NIPAM) was dissolved in 30 ml of distilled water. Thereafter, 0.3 g of the functional group-added complex 102 was added to the NIPAM aqueous solution to prepare a suspension. Nitrogen was blown to remove dissolved oxygen in the suspension. Ten minutes later, 3 ml of an aqueous solution of ammonium persulfate (APS) (concentration: 20 mg / ml) was mixed with the suspension as a radical polymerization initiator to perform a polymerization reaction. During the reaction, the temperature of the solution was kept at 30 ° C., and nitrogen was continuously introduced. After stirring for 4 hours, the product is extracted by filtration and washing with water, dried at 60 ° C. for 24 hours, and the thermosensitive polymer conjugate 103 having poly (N-isopropylacrylamide) as the thermosensitive polymer 30. Got.

(Removal of surfactant 50, preparation of temperature-sensitive adsorbent 100)
In order to remove the surfactant 50 from the temperature-sensitive polymer conjugate 103, the temperature-sensitive polymer conjugate 103 is added to a mixed solution of 3.5 ml of concentrated hydrochloric acid and 150 ml of ethanol, and is kept in a constant temperature bath at 75 ° C. The mixture was stirred at reflux for 1 hour. After completion of the stirring, suction filtration and ethanol washing were performed, and the solid content was obtained by drying at 60 ° C. for 24 hours. Thereafter, the solid content was again added to a mixed liquid of concentrated hydrochloric acid and ethanol, stirred, suction filtered, washed with ethanol, and dried to completely remove the surfactant 50. As a result, an amino group is provided as an ion exchange group 40 on the inner wall of the pore 10a of the porous silica 10 and a dimethylamino group is provided as a functional group 20 on the outer surface, and a thermosensitive polymer is provided via the dimethylamino group. A temperature sensitive adsorbent 100 to which poly (N-isopropylacrylamide) was bound was obtained.

  In addition to the temperature-sensitive adsorbent 100 obtained as described above, as a comparative example, an amino group is provided as an ion exchange group 40 on the inner wall of the pore 10a of the porous silica 10 as shown in FIG. Only composite 200, composite 300 not including temperature-sensitive polymer 30 and ion-exchange group 40 as shown in FIG. 5B, temperature-sensitive polymer 30 as shown in FIG. 5C. A composite 400 that does not include the above was manufactured. That is, the outer surface of the porous silica skeleton obtained by removing the surfactant 50 from the complex 101 is the complex 200, and the surfactant 50 is used as a template and only the silica source is added without adding the ion exchange group source. The composite 300 was obtained by adding the functional group 20 and removing the surfactant 50, and the composite 400 was obtained by removing the surfactant 50 from the functional group-added complex 102.

  Furthermore, preparation was performed to produce a composite (for example, a composite 500 as shown in FIG. 5D) in which the porous silica 10 was coated with the thermosensitive polymer 30 without the functional group 20 interposed therebetween. . That is, the composite 101 produced in the same manner as described above was added to a NIPAM aqueous solution to form a suspension, and then NIPAM was polymerized using a polymerization initiator. Thereafter, the surfactant 50 was removed. The concentration of the NIPAM aqueous solution, the amount of the complex added, and the like were the same as described above. That is, the same operation as described above was performed except that no functional group was added. However, as will be described later, when the obtained composite was evaluated, in the above operation, the thermosensitive polymer 30 was not successfully coated on the outer surface of the porous silica 10, and the composite shown in FIG. It was thought to be in the form of 500 ′.

<Evaluation method of thermosensitive adsorbent 100>
The following evaluation was performed about the temperature sensitive adsorbent 100 which concerns on the said Example, and the composite_body | complex which concerns on a comparative example.

(characterization)
(1) The surface morphology was observed using a scanning electron microscope (manufactured by JEOL Ltd., JSM-6510LV). During the observation, the acceleration voltage was set to 30 kV.
(2) An X-ray diffraction pattern was obtained using an X-ray diffractometer (Rigaku RAD-C diffractometer, manufactured by Rigaku). The measurement conditions are CuKα ray, divergent slit 1.0 degree, light receiving slit 0.30 mm, scan speed 2.000 ° / min, 2θ = 1.500 ° to 10.000 °, and sampling width 0.20 °. did.
(3) An IR spectrum pattern was obtained using an FT-IR apparatus (Perkin Elmer, FT-IR2000). As measurement conditions, 99 mg of KBr was mixed with 1 mg of a sample to prepare a pellet having a diameter of 10 mm, the number of scans was 16 times by the transmission method, and the resolution was 4 cm ⁻¹ .
(4) Thermogravimetric analysis was performed using a thermogravimetric analyzer (manufactured by Bruker, TG-DTA 2000SA). The measurement conditions were an air atmosphere, a temperature increase rate of 10 ° C./min, and a temperature range from room temperature to 800 ° C.
(5) CHN elemental analysis was performed using a CHN elemental analyzer (manufactured by Yanaco Analytical Industrial Co., Ltd., HCN corder MT-700HCN).

(Methyl orange ion exchange capacity)
0.1 g of sample was added to 100 ml of 100 ppm methyl orange aqueous solution. The solution temperature was 25 ° C or 40 ° C. After the sample was added, aqueous ammonia or hydrochloric acid was added dropwise to adjust the pH of the solution to about 9.5 or 2.5. 2 ml of the solution was sampled every 30 minutes, and the pH adjustment was repeated. The sampled solution is centrifuged, and only 0.2 ml of the supernatant is collected. After adjusting the pH by diluting with hydrochloric acid, the absorbance at 510 nm is measured using a spectrophotometer (manufactured by JASCO Corporation, UV-Vis V630). Was measured to calculate the amount of methyl orange adsorbed. The suspension remaining after centrifugation was returned to the ion exchange experimental solution.

<Evaluation results>
(Quantification of amino group content and dimethylamino group content)
First, the amino group content of the composite 200 was calculated by elemental analysis. As a result of elemental analysis measurement, the amount of nitrogen in the composite 200 is 0.87 wt%, and assuming that this is all derived from amino groups, the amount of amino groups is 0.62 mmol / g. This amount corresponded to 78% of the amino group amount (0.80 mmol / g) calculated from the charged APTES amount. Further, the amount of dimethylamino groups in the composite 300 was calculated by elemental analysis. Table 1 shows the relationship between the charged amount of 3-dimethylaminopropyldiethoxymethylsilane (LS-3675) and the fixed amount of dimethylamino groups. When the addition amount of LS-3675 was 0.1 ml, the amount of immobilized dimethylamino groups was 0.65 mmol / g, and 92% of the charged value of 0.71 mmol / g was immobilized. Moreover, when the addition amount of LS-3675 was a small amount, when the addition amount was increased, the amount of dimethylamino groups immobilized was found to increase slightly. However, it was found that the amount of immobilized dimethylamino groups hardly increased even when 1 ml or more of LS-3675 was added.

(Structural analysis results)
7 and 8 show the XRD pattern and IR spectrum of the composite 300, respectively. In the figure, L (x) MS means the composite 300 in which the addition amount (preparation amount) of LS-3675 is x (ml). From the figure, it was found that the composite 300 had a structure belonging to the hexagonal system. In addition, four diffraction lines are seen in the XRD pattern, which correspond to the (100), (110), (200), and (210) planes, respectively. Large difference in the diffraction angles of these samples was not observed, (100) spacing d ₁₀₀ was found to be about 40Å in any of the samples. This result shows that the skeleton structure of the porous silica 10 is hardly affected even when the dimethylamino group is immobilized. On the other hand, from FIG. 8, no absorption related to C—N was observed even when the dimethylamino group was immobilized, but an absorption peak appeared in the vicinity of 1480 cm ⁻¹ , which is not found in mesoporous silica. . The absorption peak in the vicinity of 1480 cm ⁻¹ is considered to be caused by the C—H bending vibration of LS-3675. Further, the absorption peak near 1480 cm ⁻¹ hardly changes even when the amount of LS-3675 added is increased. As described above, this is consistent with the fact that the amount of dimethylamino groups immobilized is hardly changed even when the amount of LS-3675 added is increased.

  FIG. 9 shows SEM photographs of the composite 400 and the temperature-sensitive adsorbent 100. FIG. 9A shows the composite 400 and FIG. 9B shows the temperature-sensitive adsorbent 100. It can be seen that hexagonal particles having a particle diameter of about 1 μm are aggregated in both cases. Some rod-like particles were also observed. However, in terms of appearance, no difference in shape due to the presence or absence of the temperature-sensitive polymer 30 was observed. In the temperature-sensitive adsorbent 100, since the amount of binding / coating of the temperature-sensitive polymer 30 is extremely small, it is considered that the appearance is not affected.

  FIG. 10 shows XRD patterns of the composite 400 and the temperature-sensitive adsorbent 100. A slight decrease in diffraction intensity was observed due to bonding / coating of the thermosensitive polymer 30. Further, in the case of the temperature-sensitive adsorbent 100, (210) diffraction lines hardly appear. From this, it is considered that a slight disorder of the structural regularity is caused by bonding / coating the thermosensitive polymer 30.

FIG. 11 shows FT-IR spectra of the composite 400 and the temperature-sensitive adsorbent 100. Both spectra are very similar, and even if the thermosensitive polymer 30 is bonded and coated, the NH stretch characteristic absorption (1551 cm ⁻¹ ) and C═O stretch absorption characteristic of the thermosensitive polymer 30 are obtained. (1633 cm ⁻¹ ) was not recognized. This suggests that the amount of bonding / coating of the thermosensitive polymer 30 is extremely small.

(Thermogravimetric analysis results)
FIG. 12 shows thermogravimetric curves of the composite 400 and the thermosensitive adsorbent 100. In both cases, weight loss occurred from 100 ° C., and moderate weight loss was observed at temperatures of 500 ° C. or higher. Thermogravimetric analysis of the thermosensitive polymer 30 alone shows a large weight loss at 320 ° C. This indicates that the polymer has decomposed. In fact, the amount of weight reduction between the composite 400 and the temperature-sensitive adsorbent 100 has changed greatly from around 320 ° C. Therefore, it is considered that the difference in the weight reduction amount is the amount of the thermosensitive polymer 30 immobilized. From the figure, it was found that the immobilization amount of the temperature-sensitive polymer 30 in the temperature-sensitive adsorbent 100 was estimated to be 5% by mass. Moreover, when the nitrogen amount was measured by the elemental analysis about the composite 400 and the temperature sensitive adsorbent 100, and the immobilization amount of the temperature sensitive polymer 30 in the temperature sensitive adsorbent 100 was calculated from the nitrogen amount, it was 5% by mass. This was consistent with the results of thermogravimetric analysis.

(Results of adsorption / desorption experiments)
FIG. 13 shows the pH dependence of the methyl orange ion exchange adsorption amount when the complex 400 is used. Here, the solution temperature was 40 ° C. When all of the charged methyl orange is adsorbed, the ion exchange amount is about 0.3 mmol / g, which is about half of the amount of amino groups 0.62 mmol / g which is an ion exchange site. In the case of the composite 400, since the thermosensitive polymer 30 is not immobilized, it should exhibit a reversible adsorption / desorption behavior similar to that of a normal anion exchanger. Actually, it was confirmed from the figure that about 0.25 mmol / g of methyl orange was adsorbed at pH 2.5 and that methyl orange was almost completely desorbed at pH 9.5. On the other hand, all the methyl oranges present in the solution were not adsorbed because the ion exchange time was shortened to 30 minutes.

  FIG. 14 shows the pH dependence of the methyl orange ion exchange adsorption amount when the complex 500 ′ is used. Again, the solution temperature was 40 ° C. In the case of the composite 500 ′, there is no dimethylamino group, the temperature-sensitive polymer 30 is not chemically immobilized on the porous silica 10, and the temperature-sensitive high portion 30 is on the outer surface of the porous silica 10. It was thought to be simply in physical contact. At a solution temperature of 40 ° C., the thermosensitive polymer 30 has a dense structure and does not pass the adsorbed species, and therefore the thermosensitive polymer 30 is simply in physical contact with the porous silica 10. However, it was thought that the thermosensitive polymer 30 would be an obstacle and a large change in the adsorption behavior would appear. However, looking at the results, the composite 500 'showed the same reversible adsorption / desorption behavior as the composite 400. This means that in the composite 500 ′, the temperature-sensitive polymer 30 simply coexists with the porous silica 10, and the temperature-sensitive polymer 30 is almost present on the outer surface of the porous silica 10. 6 (FIG. 6), suggesting that the temperature-sensitive polymer 30 had little influence on the adsorption behavior. That is, since the concentration of the temperature-sensitive polymer 30 (the concentration of the NIPAM aqueous solution) is too low, the outer surface of the silica 10 is not well coated with the temperature-sensitive polymer 30, and the adsorption behavior causes the temperature-sensitive polymer 30. It is probable that the influence of No. did not appear. As a result, it was found that when the thermosensitive polymer 30 is simply physically coated on the outer surface of the silica 10 without the functional group 20, the amount of the thermosensitive polymer 30 must be extremely large. . On the other hand, the adsorption amount was about 0.2 mmol / g, which was slightly lower than that of the composite 400. This is because the temperature-sensitive polymer 30 coexists with the porous silica 10 to cause resistance to the diffusion of methyl orange in the liquid, so that the methyl orange sufficiently reaches the adsorption spot in a short time of 30 minutes. It is thought that it was not possible.

  FIG. 15 shows the pH dependence of the methyl orange ion exchange adsorption amount when the temperature sensitive adsorbent 100 is used. The phase transition temperature of poly (N-isopropylacrylamide) is about 32 ° C., but this temperature hardly changes even when it is combined with porous silica 10. Here, the adsorption / desorption experiment was performed by changing the solution temperature in the order of 40 ° C., 25 ° C., and 40 ° C. As a result, at 25 ° C., methyl orange repeatedly adsorbed and desorbed reversibly as the pH changed, as in the composites 400 and 500. On the other hand, at 40 ° C., the adsorption amount was 0.05 mmol / g at the maximum, and adsorption / desorption was not possible. This indicates that the temperature-sensitive polymer 30 is present near the entrance of the pore 10a of the porous silica 10 and closes the entrance of the pore 10a of the porous silica 10. That is, when the solution temperature is higher than the phase transition temperature of the temperature-sensitive polymer 30, the hydration water present in the temperature-sensitive polymer 30 is dehydrated, and the temperature-sensitive polymer contracts to form a dense network. As a result of adopting the structure, it is considered that methyl orange is prevented from entering the pores 10a. On the other hand, when the solution temperature is lower than the phase transition temperature of the temperature-sensitive polymer 30, the temperature-sensitive polymer 30 is hydrated again and swells, and as a result of taking a sparse network structure, methyl orange has pores 10a. It is considered that it can easily enter the inside and can be easily adsorbed to the ion exchange group 40. The fact that the thermosensitive polymer 30 is bonded to the outer surface of the porous silica 10 is also clear from the fact that the amount of methyl orange adsorbed is reduced to about 0.15 mmol / g. As described above, according to the present invention, the thermosensitive polymer 30 is bonded to the outer surface of the porous silica 10 via the functional group 20, so that even a small amount of the thermosensitive polymer 30 is porous. It can be uniformly fixed on the outer surface of the silica 10, and the adsorption / desorption behavior can be changed by changing the solution temperature.

  Although the present invention has been described with reference to the most practical and preferred embodiments at the present time, the invention is not limited to the embodiments disclosed herein. The temperature-sensitive adsorbent and the method for producing the same are also within the technical scope of the present invention without departing from the spirit or concept of the invention that can be read from the claims and the entire specification. It must be understood as included.

  For example, in the above description, in the temperature-sensitive adsorbent 100, the ion exchange group 40 has been described as an essential configuration, but the present invention is not limited to this form. Depending on the application of the temperature sensitive adsorbent 100, the inside of the pore 10a may or may not be modified with the ion exchange group 40. However, from the viewpoint of suitably functioning the temperature-sensitive adsorbent 100 as an ion exchanger, the temperature-sensitive adsorbent 100 including the ion-exchange group 40 is preferable.

  In the above description, in the manufacturing method S10 of the temperature-sensitive adsorbent 100, the so-called co-condensation method is used in steps S1 and S2, but the present invention is not limited to this embodiment. A so-called grafting method can also be used. However, from the viewpoint that the amount of the ion exchange groups 40 in the pores 10a can be easily controlled and the temperature-sensitive adsorbent 100 can be easily manufactured, a so-called co-condensation method is used in steps S1 and S2. Is preferred.

  In the above description, in the manufacturing method S10 of the temperature-sensitive adsorbent 100, the step S4 for bonding the temperature-sensitive polymer 30 is performed in the presence of the functional group-added complex 102 in the liquid. Although described as what polymerizes the monomer which forms the molecule | numerator 30, as long as the thermosensitive polymer 30 can be couple | bonded with the functional group 20, this invention may use any method.

  The temperature-sensitive adsorbent according to the present invention can control the pore inlet diameter of porous silica, and can efficiently perform selective separation and the like of adsorbed species by changing the pore inlet diameter. For example, it can be suitably used as a column packing material for ion exchange chromatography. In addition, by applying various characteristics of the temperature-sensitive adsorbent according to the present invention, a temperature-sensitive adsorbent holding a predetermined drug inside the pores is administered into the body, and the temperature is measured at a predetermined position in the body. It is thought that the drug can be released and released by change, and can be applied as a new drug delivery system.

10 Porous Silica 20 Functional Group 30 Thermosensitive Polymer 40 Ion Exchange Group 50 Surfactant 100 Thermosensitive Adsorbent 101 Complex 102 Functional Group Addition Complex 103 Thermosensitive Polymer Conjugate

Claims (12)

  A temperature-sensitive adsorbent comprising a temperature-sensitive polymer whose volume changes in response to a temperature change and bonded to the outer surface of porous silica via a functional group.   2. The temperature-sensitive adsorbent according to claim 1, wherein the amount of the temperature-sensitive polymer is 5% by mass or less based on the whole temperature-sensitive adsorbent (100% by mass).   The temperature-sensitive adsorbent according to claim 1 or 2, wherein the functional group is at least one selected from an amino group, a mono-substituted amino group, a di-substituted amino group, and a vinyl group.   The temperature-sensitive adsorbent according to claim 3, wherein the functional group is a dimethylamino group.   The temperature-sensitive adsorbent according to claim 1, wherein the temperature-sensitive polymer comprises a monomer unit derived from a (meth) acrylamide derivative.   The temperature-sensitive adsorbent according to claim 5, wherein the temperature-sensitive polymer is poly (N-isopropyl (meth) acrylamide).   The temperature-sensitive adsorbent according to claim 1, which has an ion exchange group inside the pores of the porous silica.   The temperature-sensitive adsorbent according to claim 7, wherein the ion exchange group is a primary to tertiary amino group, a quaternary ammonium group, a carboxyl group, or a sulfonic acid group. Adding a functional group to the outer surface of the porous silica skeleton;
A thermosensitive polymer binding step of binding a thermosensitive polymer whose volume changes in response to a temperature change to the functional group;
A method for producing a temperature-sensitive adsorbent. Using a solution containing a surfactant and a silica source, the porous silica skeleton is formed using the surfactant as a template,
Then, the manufacturing method of the thermosensitive adsorbent of Claim 9 which forms a pore by removing the said surfactant.   The method for producing a thermosensitive adsorbent according to claim 10, wherein the solution further contains an ion exchange group source in addition to the surfactant and the silica source.   In the thermosensitive polymer binding step, the functional group is polymerized with a monomer that forms the thermosensitive polymer in a liquid containing the porous silica skeleton to which the functional group has been added. The method for producing a temperature-sensitive adsorbent according to claim 9, wherein the temperature-sensitive polymer is bound.