| WO1996002060A1 | 1996-01-25 | |||
| WO2003066644A1 | 2003-08-14 |
| US5849369A | 1998-12-15 | |||
| JPH1083913A | 1998-03-31 | |||
| JP2007137793A | 2007-06-07 |
CLAIMS
1. A magnetically sensitive particle comprising a functional substance bonded via a thin organic layer covalently bonded to a surface thereof.
2. The magnetically sensitive particle according to claim 1 , wherein the organic layer is monomolecular.
3. The magnetically sensitive particle according to claim 2, wherein the monomolecular layer covalently bonded to the surface includes a substance comprising an epoxy group at one part and binding at another part to the magnetic microparticle surface via Si covalent bonding.
4. A magnetically responsive pharmaceutical preparation comprising a drug fixed by bonding to a thin organic layer covalently bonded to a magnetic microparticle surface.
5. The magnetically responsive pharmaceutical preparation according to claim 4, wherein the thin organic layer is monomolecular.
6. The magnetically responsive pharmaceutical preparation according to claim 5, wherein the monomolecular layer covalently bonded to the surface includes a substance comprising an epoxy group at one part and binding at another part to the magnetic microparticle surface via Si covalent bonding.
7. A method for manufacturing a magnetically sensitive particle, comprising:
(a) a step for reacting an alcoxysilane compound with a magnetic microparticle surface by dispersing a magnetic microparticle in a liquid mixture prepared by mixing, at least, an epoxy-containing alcoxysilane compound, a silanol condensation catalyst, and a non-aqueous organic solvent; (b) a step of washing the microparticle surface with an organic solvent to remove remaining surplus alcoxysilane compound for producing an epoxy-containing monomolecular layer that is covalently bonded to the microparticle surface; and (c) a step for binding a functional substance via the epoxy group.
8. The method for manufacturing the magnetically sensitive particle according to claim 7, wherein a ketimine, organic acid, aldimine, enamine, oxazolidine, or aminoalkylalcoxysilane compound is used in place of the silanol condensation catalyst.
9. The method for manufacturing the magnetically sensitive particle according to claim 7, wherein at least one cocatalyst compound selected from the group consisting of ketimines, organic acids, aldimines, enamines, oxazolidines, and aminoalkylalcoxysilane compounds is used in addition to the silanol condensation catalyst.
10. A method for manufacturing a magnetically responsive pharmaceutical preparation, comprising:
(a) a step for reacting an alcoxysilane compound with a magnetic microparticle surface by dispersing a magnetic microparticle in a liquid mixture prepared by mixing, at least, an epoxy-containing alcoxysilane compound, a silanol condensation catalyst, and a non-aqueous organic solvent; and (b) a step of washing the microparticle surface with an organic solvent to remove remaining surplus alcoxysilane compound for producing an epoxy-containing monomolecular layer that is covalently bonded to the microparticle surface.
11. The method for manufacturing the magnetically responsive pharmaceutical preparation according to claim 10, wherein an imino-containing drug is fixed to the magnetic microparticle surface after the step for producing the epoxy-containing monomolecular layer.
12. The method for manufacturing the magnetically responsive pharmaceutical preparation according to claim 10, wherein a ketimine, organic acid, aldimine, enamine, oxazolidine, or aminoalkylalcoxysilane compound is used in place of the silanol condensation catalyst.
13. The method for manufacturing the magnetically responsive pharmaceutical preparation according to claim 10, wherein at least one cocatalyst compound selected from the group consisting of ketimines, organic acids, aldimines, enamines, oxazolidines, and aminoalkylalcoxysilane compounds is used in addition to the silanol condensation catalyst.
14. The method for manufacturing the magnetically responsive pharmaceutical preparation according to claim 11 , wherein the imino-containing drug is a protein, amino acid, enzyme, antibody, antibiotic, antimicrobial, or contrast medium. |
DESCRIPTION
PHARMACEUTICAL PREPARATION AND MANUFACTURING METHOD THEREOF
BACKGROUND OF THE INVENTION
Field of the Invention
The present invention relates to a magnetically sensitive particle, manufacturing method thereof, a pharmaceutical preparation using the particle, and a manufacturing method thereof. More particularly, the present invention relates to a magnetically sensitive particle used for separation of a target substance from a mixture by means of a magnet, on which a functional substance is fixed by bonding via an organic layer that is covalently bonded to a surface of the magnetic microparticle. The present invention also relates to a magnetically responsive pharmaceutical preparation by use thereof that can be employed for a drug delivery system (DDS), a technology developed to deliver an active drug substance specifically to a target site at a given designated timing.
According to the present invention, 'magnetically responsive pharmaceutical preparations for DDS' include preparations in which an imino-containing drug, such as a protein, amino acid, enzyme, antibody, antibiotic, antimicrobial, or contrast medium, is fixed on a surface of magnetic microparticles.
Description of Related Art
To reduce or alleviate adverse drug reactions, a plurality of medication systems have currently been developed in which drugs are designed to exert the effect at a specific site at a designated timing (e.g., Japanese Unexamined Patent Application Nos. 2002-500177, 2000-503763, and 09-328438).
SUMMARY OF THE INVENTION
However, no magnetically sensitive substances that can be used for separation of a target substance by magnetic force or manufacturing methods thereof have been developed or provided. Also, no pharmaceutical preparations that can be used for a medication system that provides concentrated drug delivery to a specific
site by magnetic force or manufacturing methods thereof have been developed or provided.
It is an object of the present invention to provide magnetically sensitive particles that can be concentrated or separated from a mixture by magnetic force, whereby an efficient separation of target substances, such as catalysts, can be achieved. Another object of the present invention is to provide pharmaceutical preparations for DDS that enable concentrated delivery of a drug to a specific site of a living organism (and administration of the drug at a reduced amount), whereby adverse drug reactions can be alleviated or the dose of the drug can be reduced. A first aspect of the present invention, which is intended for solving the afore-mentioned problems, is directed to a magnetically sensitive particle comprising a functional substance fixed by bonding to an organic layer that is covalently bonded to a surface thereof.
A second aspect of the present invention is directed to the magnetically sensitive particle as defined in the first aspect, wherein the organic layer is monomolecular.
A third aspect of the present invention is directed to the magnetically sensitive particle as defined in the second aspect, wherein the monomolecular layer covalently bonded to the surface includes a substance comprising an epoxy group at one part and binding at another part to the magnetic microparticle surface via Si covalent bonding.
A fourth aspect of the present invention is directed to a magnetically responsive pharmaceutical preparation comprising a drug fixed by bonding to an organic layer that is covalently bonded to a magnetic microparticle surface. A fifth aspect of the present invention is directed to the magnetically responsive pharmaceutical preparation as defined in the fourth aspect, wherein the organic layer is monomolecular.
A sixth aspect of the present invention is directed to the magnetically responsive pharmaceutical preparation as defined in the fifth aspect, wherein the monomolecular layer covalently bonded to the surface includes a compound comprising an epoxy group at one part and binding at another part to the magnetic microparticle surface by Si covalent bonding.
A seventh aspect of the present invention is directed to a method for manufacturing a magnetically sensitive particle comprising:
(a) a step for reacting an alcoxysilane compound with a magnetic microparticle surface by dispersing a magnetic microparticle in a liquid mixture prepared by mixing, at least, an epoxy-containing alcoxysilane compound, a silanol condensation catalyst, and a non-aqueous organic solvent;
(b) a step of washing the microparticle surface with an organic solvent to remove remaining surplus alcoxysilane compound for producing an epoxy-containing monomolecular layer that is covalently bonded to the microparticle surface; and (c) a step for binding a functional substance via the epoxy group.
An eighth aspect of the present invention is directed to the method for manufacturing the magnetic microparticle as defined in the seventh aspect, wherein a ketimine, organic acid, aldimine, enamine, oxazolidine, or aminoalkylalcoxysilane compound is used in place of the silanol condensation catalyst. A ninth aspect of the present invention is directed to the method for manufacturing the magnetic microparticle as defined in the seventh aspect, wherein at least one cocatalyst compound selected from the group consisting of ketimines, organic acids, aldimines, enamines, oxazolidines, and aminoalkylalcoxysilane compounds is used in addition to the silanol condensation catalyst. A tenth aspect of the present invention is directed to a method for manufacturing a magnetically responsive pharmaceutical preparation which comprises:
(a) a step for reacting an alcoxysilane compound with a magnetic microparticle surface by dispersing a magnetic microparticle in a liquid mixture prepared by mixing, at least, an epoxy-containing alcoxysilane compound, a silanol condensation catalyst, and a non-aqueous organic solvent; and
(b) a step of washing the microparticle surface with an organic solvent to remove remaining surplus alcoxysilane compound for producing an epoxy-containing monomolecular layer that is covalently bonded to the the microparticle surface. An eleventh aspect of the present invention is directed to the method for manufacturing the magnetically responsive pharmaceutical preparation as defined in the tenth aspect, wherein an imino-containing drug is fixed onto the microparticle
surface after the step for producing the epoxy-containing monomolecular layer.
A twelfth aspect of the present invention is directed to the method for manufacturing the magnetically responsive pharmaceutical preparation as defined in the tenth aspect, wherein a ketimine, organic acid, aldimine, enamine, oxazolidine, or aminoalkylalcoxysilane compound is used in place of the silanol condensation catalyst.
A thirteenth aspect of the present invention is directed to a method for manufacturing the magnetically responsive pharmaceutical preparation as defined in the tenth aspect, wherein at least one cocatalyst compound selected from the group consisting of ketimines, organic acids, aldimines, enamines, oxazolidines, and aminoalkylalcoxysilane compounds is used in addition to the silanol condensation catalyst.
A fourteenth aspect of the present invention is directed to the method for manufacturing the magnetically responsive pharmaceutical preparation as defined in the eleventh aspect, wherein the imino-containing drug is a protein, amino acid, enzyme, antibody, antibiotic, antimicrobial, or contrast medium.
The present invention will now be illustrated in more details below. It is an object of the present invention to provide a magnetically sensitive particle having a functional substance bound onto the surface via an organic layer covalently bonded to the magnetic microparticle surface by:
(i) a step for reacting an alcoxysilane compound with a magnetic microparticle surface by dispersing a magnetic microparticle in a liquid mixture prepared by mixing, at least, an epoxy-containing alcoxysilane compound, a silanol condensation catalyst, and a non-aqueous organic solvent; (ii) a step for producing a epoxy-containing monomolecular layer that is covalently bonded to the microparticle surface by washing the microparticle surface with an organic solvent to remove remaining surplus alcoxysilane compound; and (iii) a step for binding a functional substance via the epoxy group. In one embodiment where the organic layer is monomolecular, the present invention conveniently retains the characteristics of the functional substance. Another embodiment, where the monomolecular layer covalently bound to the surface includes a substance comprising an epoxy group at one part and binding at another
part to the magnetic microparticle surface by Si covalent bonding, conveniently allows for covalent bonding of the functional substance. Yet another embodiment, where a ketimine, organic acid, aldimine, enamine, oxazolidine, or aminoalkylalcoxysilane compound is used in place of the silanol condensation catalyst, conveniently shortens manufacturing time. Still another embodiment, where at least one cocatalyst compound selected from the group consisting of ketimines, organic acids, aldimines, enamines, oxazolidines, and aminoalkylalcoxysilane compounds is used in addition to the silanol condensation catalyst, conveniently provides a further shortened manufacturing time. It is another object of the present invention to provide a magnetically responsive pharmaceutical preparation comprising a drug fixed by bonding to a magnetic microparticle surface via an organic layer covalently bonded to the microparticle surface by
(a) a step for reacting an alcoxysilane compound with the magnetic microparticle surface by dispersing the magnetic microparticle in a liquid mixture prepared by mixing, at least, an epoxy-containing alcoxysilane compound, a silanol condensation catalyst, and a non-aqueous organic solvent; and
(b) a step of washing the microparticle surface with an organic solvent to remove remaining surplus alcoxysilane compound for producing an epoxy-containing monomolecular layer that is covalently bonded to the microparticle surface.
In one embodiment where the organic layer is monomolecular, the present invention conveniently retains the characteristics of the functional substance. Another embodiment, where the monomolecular layer covalently bonded to the surface includes a substance comprising an epoxy group at one part and binding at another part to the magnetic microparticle surface by Si covalent bonding, conveniently allows for covalent binding of the functional substance. Another embodiment, where an imino-containing drug is fixed onto the microparticle surface after the step for producing the epoxy-containing monomolecular layer, conveniently provides a secure fixation of the drug. Yet another embodiment, where a ketimine, organic acid, aldimine, enamine, oxazolidine, or aminoalkylalcoxysilane compound is used in place of the silanol condensation catalyst, conveniently shortens manufacturing time. Yet another embodiment, where at least one cocatalyst compound selected from the
group consisting of ketimines, organic acids, aldimines, enamines, oxazolidines, and aminoalkylalcoxysilane compounds is used in addition to the silanol condensation catalyst, conveniently provides a further shortened manufacturing time. Still yet another embodiment, where the imino-containing drug is a protein, amino acid, enzyme, antibody, antibiotic, antimicrobial, or contrast medium, conveniently provides a secure fixation of the drug via the epoxy group.
As illustrated above, the present invention provides a magnetically sensitive particle that can be concentrated or separated from a mixture by magnetic force, whereby an efficient separation of substances, such as a catalyst, can be achieved. The present invention also provides a pharmaceutical preparation for DDS that comprises a drug fixed onto a magnetic microparticle surface without a significant reduction in the drug's action, which can be concentrated to a target site by magnetic force after administered to humans, thereby exerting a particular effect for reducing the dosing amounts or attenuating adverse drug reactions of the drug.
BRIEF DESCRIPTION OF THE DRAWINGS
The foregoing aspects and many of the attendant advantages of this invention will become more readily appreciated as the same becomes better understood by reference to the following detailed description, when taken in conjunction with the accompanying drawings, wherein like reference numerals refer to like parts throughout the various views unless otherwise specified:
FIG.1 schematically illustrates the magnetic microparticle reaction of embodiment 1 at the molecular level. Fig. 1A presents a pre-reaction condition of a magnetic microparticle surface. Fig. 1 B presents a formation of an epoxy-containing monomolecular layer. Fig. 1C presents penicillin G fixation by bonding.
DETAILED DESCRIPTION
The present invention provides a magnetically sensitive particle comprising a functional substance fixed by bonding to an organic layer that is covalently bonded to a magnetic microparticle surface by:
(a) a step for reacting an alcoxysilane compound with a magnetic microparticle surface by dispersing a magnetic microparticle in a liquid mixture prepared by mixing,
at least, an epoxy-containing alcoxysilane compound, a silanol condensation catalyst, and a non-aqueous organic solvent;
(b) a step of washing the microparticle surface with an organic solvent to remove remaining surplus alcoxysilane compound for producing an epoxy-containing monomolecular layer that is covalently bonded to the microparticle surface; and
(c) a step for binding a functional substance via the epoxy group.
The resent invention also provides a pharmaceutical preparation for DDS comprising a drug fixed by bonding to a monomolecular layer that is covalently bonded to a magnetic microparticle surface by: (i) reacting an alcoxysilane compound with the magnetic microparticle surface by dispersing a magnetic microparticle in a liquid mixture prepared by mixing, at least, an epoxy-containing alcoxysilane compound, a silanol condensation catalyst, and a non-aqueous organic solvent;
(ii) producing an epoxy-containing monomolecular layer that is covalently bound to the microparticle surface by washing the microparticle surface with an organic solvent to remove remaining surplus alcoxysilane compound; and
(iii) fixing an imino-containing drug, such as a protein, amino acid, enzyme, antibody, antibiotic, antimicrobial, or contrast medium, onto the magnetic microparticle surface. The magnetically sensitive particles of the present invention can be employed for an efficient separation of substances used as a catalyst or for other purposes.
The pharmaceutical preparations of the present invention, by being concentrated to a target site by magnetic force after administered to humans, have excellent effects for reducing the dosing amounts without reducing drug's therapeutic actions or attenuating adverse drug reactions.
The present invention will now be further illustrated with reference to specific embodiments, though the present invention should not be construed as limited to the details shown.
According to the present invention, the magnetically sensitive particles include magnetically sensitive particles on which a catalyst or a coagulant is fixed as the functional substance, and the magnetically responsive pharmaceutical preparations include pharmaceutical preparations having imino-containing drugs, such as proteins,
amino acids, enzymes, antibodies, antibiotics, antimicrobials, and contrast media, fixed onto the surface of the magnetic microparticles. Typically, the present invention is illustrated with respect to a magnetic particle comprising penicillin G fixed as the functional substance. [Embodiment 1]
Dry magnetite particles (1) having a particle size of several ten nanometers were well dried. A chemical adsorbent containing an epoxy group in one part and an alcoxysilane group in another as functional groups, such as the substance shown in formula (C1) below, and a silanol condensation catalyst, such as dibutyltin diacetylacetonate, were weighed out in a weight percent of 99% and 1 %, respectively. These compounds were then added to a silicone fluid, such as hexamethyldisiloxane, in a total weight percent of about 1 % (preferably, in a weight percent range of 0.5%-3%) to prepare an adsorbent-containing mixture. [C1]
The above-mentioned dry magnetite particles were added under stirring to the adsorbent-containing mixture to react at room temperature in ambient air (relative humidity: 45%) for about 2 hours. Under such conditions, the dry magnetite microparticles comprising a plurality of hydroxy groups on the surface thereof (Figure 1A) underwent dealcoholization reaction (in this example, demethanol reaction) with the -Si(OCH 3 ) group of the above-mentioned chemical adsorbent in the presence of silanol condensation catalyst to form a chemical bonding as shown in the below formula (C2). This reaction yielded an epoxy-containing chemical adsorbent monomolecular layer (3) bonded to the magnetic microparticle surface with a thickness of about 1 nanometer (Figure 1 B).
Washing the microparticles under stirring with a chlorine-containing solvent, such as tichloroethylene, produced magnetite microparticles (4) covered with an epoxy-containing chemical adsorbent monomolecular layer. [C2]
O O—
CH 2 -CHCH 2 O(CH 2 J 3 Si-O-
This procedure did not considerably affect the particle size, because the covering layer had a very thin thickness in an order of nanometer.
When the microparticles were exposed to air without the washing treatment, the chemical adsorbent remaining on the microparticle surface reacted with moisture in the air as the solvent evaporated, and magnetite microparticles covered with a very thin organic polymer film comprising the above-mentioned chemical adsorbent with similar functionality were produced. The films caused no operational troubles or problems to after-treatment processes, and the resulting microparticles could be handled similarly to the monomolecular layer-covered magnetite microparticles.
This manufacturing method, comprising dealcoholization reaction, is applicable to acid-reacting substances such as magnetite microparticles.
The magnetite microparticles (4) covered with an epoxy-containing chemical adsorbent monomolecular layer was then dispersed in an alcohol medium, penicillin G was added thereto, and the mixture was heated to react. Penicillin G, comprising an imino group close to the β-lactam ring, was fixed in a layered manner on the microparticle surface by addition reaction of the imino and epoxy groups, as shown in the following reaction formula (C3). Removal of unreacted penicillin G by washing produced a magnetically responsive pharmaceutical preparation (5) for DDS comprising surface-bound penicillin G (Figure 1 C). [C3]
O
/ \ — (CH 2 ) CH -C H 2 + H N= Penicillin G
→ - (C H J ) C H C H Z — I N = Penicillin G [
I
O H
This pharmaceutical preparation, comprising particles with a diameter of
several ten nanometers, is unlikely to clog blood vessels, when intravascular^ administered dispersed in purified water. In addition, this pharmaceutical preparation, being attracted by magnetic force toward a magnet placed nearby, can serve to concentrate the drug to an affected area by placing a magnet near the area as blood stream circulates within a certain period of time.
Accordingly, the present invention provides an efficient therapeutic method whereby a high penicillin G concentration is attained in the vicinity of the affected area with a small amount of dose, thereby reducing adverse drug reactions.
This technique is applicable to any imino-containing drugs, such as proteins, amino acids, enzymes, antibodies, antibiotics, antimicrobials, and contrast media as far as the effects are not invalidated. Typically, this technique was applicable to cephalexin, similarly comprising imino and amino groups.
Whereas the above embodiment employed the substance shown by the formula (C1 ) as the epoxy-containing chemical adsorbent, the following chemical substances (1 ) to (10) were also usable:
(1 ) (CH 2 OCH)CH 2 O(CH2)7Si(OCH3)3
(2) (CH 2 OCH)CH 2 O(CH 2 )H Si(OCHa) 3
(3) (CH 2 CHOCH(CH 2 ) 2 )CH(CH 2 )2Si(OCH3)3
(4) (CH 2 CHOCH(CH 2 )2)CH(CH 2 ) 4 Si(OCH3)3 (5) (CH 2 CHOCH(CH 2 ) 2 )CH(CH 2 )6Si(OCH3)3
(6) (CH 2 OCH)CH 2 O(CH 2 )7Si(OC 2 H5)3
(7) (CH 2 OCH)CH 2 O(CH 2 )I 1 Si(OC 2 Hs) 3
(8) (CH 2 CHOCH(CH 2 ) 2 )CH(CH2) 2 Si(OC 2 H 5 ) 3
(9) (CH 2 CHOCH(CH 2 ) 2 )CH(CH 2 )4Si(OC 2 H5) 3 (10) (CH 2 CHOCH(CH 2 ) 2 )CH(CH 2 ) 6 Si(OC 2 H 5 ) 3 , wherein (CH 2 OCH)- group designates a functional group shown by the following formula (C4), and (CH 2 CHOCH(CH 2 ) 2 )CH- group designates a functional group shown by the following formula (C5): [C4]
O
/ \
CH 2 -CH
[C5]
0 CH-CH 2
\ / \
CH CH
\ /
CH 2 -CH 2
In embodiment 1 , metal carboxylates, carboxylic acid ester metal salt, metal carboxylate polymers, metal carboxylate chelates, titanic esters, and titanic ester chelates could be used as the silanol condensation catalyst. More specifically, tin (II) acetate, dibutyltin dilaurate, dibutyltin dioctate, dibutyltin diacetate, dioctyltin dilaurate, dioctyltin dioctate, dioctyltin diacetate, tin (II) dioctanoate, lead naphthenate, cobalt naphthenate, iron 2-ethylhexenate, dioctyltin bisoctylthioglycolic acid ester salt, dioctyltin maleic acid ester salt, dibutyltin maleic acid salt polymer, dimethyltin mercaptopropionic acid salt polymer, dibutyltin bis(acetylacetate), dioctyltin bis-acetyl laurate, tetrabutyltitanate, tetranonyltitanate, and bis(acetylacetonyl) di-propyltitanate could be used.
For the reaction medium, non-aqueous organic solvents with a boiling point in an approximate range of 50 0 C to 250°C, such as chlorine-containing organic solvents, hydrocarbon solvents, fluorocarbon solvents, silicone solvents, dimethylformamide, or mixtures thereof, could be used. Besides these solvents, alcohol solvents, such as methanol, ethanol, or propanol, and mixtures thereof could be used for formation of the organic film resulting from evaporation of the solvent when the chemical adsorbent was an alcoxysilane compound.)
Specific examples of the reaction medium include chlorine-containing organic solvents, non-aqueous petroleum naphtha, solvent naphtha, petroleum ethers, petroleum benzine, isoparaffins, normal paraffins, decalins, industrial gasolines,
nonane, decane, kerosene, dimethyl silicone, phenyl silicone, alkyl-modified silicone, polyether silicone, dimethylformamide, and mixtures thereof.
The fluorocarbon solvents include chlorofluorocarbon solvents, Fluorinerts™
(produced by 3M Company), Afludes™ (manufactured by Asahi Glass Co., Ltd.). These solvents may be used singly or in combination if the solvents mix well.
Chlorine-containing organic solvents such as chloroform may be further added thereto.
Meanwhile, when a ketimine, organic acid, aldimine, enamine, oxazolidine, or aminoalkylalcoxysilane compound was used in place of the above-mentioned silanol condensation catalyst, the reaction time was reduced to one-half to two-thirds for similar reaction mixture concentrations.
Moreover, when a ketimine, organic acid, aldimine, enamine, oxazolidine, or aminoalkylalcoxysilane compound is used in addition to the above-mentioned silanol condensation catalyst (at a ratio to the catalyst ranging from 1 :9 to 9:1 , but preferably at a 1:1 ratio under ordinary conditions), the reaction time can be reduced several times (up to about 30 minutes), thereby shortening the total manufacturing time several times.
When, for example, dibutyltin oxide, a silanol catalyst, was replaced by H3, a ketimine compound, provided by Japan Epoxy Resins Co., Ltd. with all other conditions remaining the same, the results were similar with the exception that the reaction time was shortened to approximately one hour. Moreover, when the silanol catalyst was replaced by a mixture (1 :1 ) of H3, a ketimine compound, provided by
Japan Epoxy Resins Co., Ltd. and dibutyltin bis(acetylacetonate), a silanol catalyst, with all other conditions remaining the same, the results were similar with the exception that the reaction time was shortened to approximately 30 minutes.
Accordingly, these results indicated that ketimine, organic acid, aldimine, enamine, oxazolidine, and aminoalkylalcoxysilane compounds have higher catalytic activities than conventional silanol condensation catalysts.
It was also indicated that when a conventional silanol condensation catalyst was used together with a compound selected from the group consisting of ketimine, organic acid, aldimine, enamine, oxazolidine, and aminoalkylalcoxysilane compounds, the catalytic activity was enhanced.
Usable ketimine compounds include, but are not limited to, 2,5,8-triaza-1 ,8-nonadiene,
3, 11 -dimethyl-4,7, 10-triaza-3, 10-tridecadiene,
2,10-dimethyl-3,6,9-triaza-2,9-undecadiene, 2,4,12,14-tetramethy 1-5,8, 11 ,-triaza-4, 11 -pentadecadiene,
2,4,15,17-tetramethyl-5,8, 11 ,14-tetraaza-4, 14-octadecadiene, and
2,4,20,22-tetramethyl-5, 12,19-triaza-4, 19-trieicosadiene.
Usable organic acids include, but are not limited to, formic acid, acetic acid, propionic acid, butyric acid, and malonic acid, which provided similar results. Whereas a magnetite microparticle was employed for the purpose of illustration in the above embodiment, the present invention is applicable to magnetic microparticles or nanoparticles of any type or nature, as far as the particles comprise active hydrogen atoms such as in hydroxy groups on the surface thereof. Specifically, examples of the applicable magnetic microparticles according to the present invention include magnetic metal microparticles comprising, for example, iron, chromium, nickel, or alloys thereof and magnetic metal oxide microparticles comprising, for example, ferrite, magnetite, or chromium oxide.