Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Mixing of two or more solid polymers; mixing of solid...
Reexamination Certificate
2003-03-21
2004-09-28
Sastri, Satya B. (Department: 1713)
Synthetic resins or natural rubbers -- part of the class 520 ser
Synthetic resins
Mixing of two or more solid polymers; mixing of solid...
C525S245000, C525S246000, C525S095000, C525S091000, C525S319000, C524S431000, C427S475000
Reexamination Certificate
active
06797782
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to a process for producing a carrier for diagnostic reagent in biochemical and medicinal fields.
DESCRIPTION OF THE RELATED ART
A method in which a magnetic substance is dispersed in a monomer, the dispersion is subjected to suspension polymerization or miniemulsion polymerization to incorporate the magnetic substance into particles, and the particles are further classified is known as a method for producing particles having a comparatively uniform particle size distribution and capable of compositing a magnetic substance. However, according to this method, the particle size distribution of the particles obtained after completion of the polymerization is very broad, so that the desired uniform particle size cannot be obtained unless a plural number of classification operations are repeated. Further, repeating the classification results in reduction of the yield, leading to failure in balance between the working efficiency and the yield. Moreover, a method in which an iron salt is neutralized, and the resulting iron hydroxide is deposited on porous particles having NH
2
and NO
2
groups and oxidized is proposed as a method of depositing a metallic compound on particles in water (JP-B-5-10808). However, this method is extremely complicated in terms of the production step, and hence, was not suitable for the mass production. In addition, there is proposed a method of utilizing hetero-coagulation (U.S. Pat. No. 5,648,124). However, according to this method, it is difficult to control the coagulation during the addition of a substance having an opposite charge. Further, since compositing is preferentially performed, in many cases, a coagulation reaction excessively takes place. Accordingly, the resulting particles form a coagulated body to an extent such that re-dispersion is difficult and fail in uniformity of the particle size. In addition, there is proposed a method in which a monomer and a magnetically responsible metal oxide are simultaneously polymerized on the surfaces of polymer core particles, to introduce a magnetic substance into the polymer particles (Japanese Patent No. 2,736,467). However, according to this method, the particles after the introduction of a magnetic substance take a structure where they are not completely polymer-coated, and the magnetic substance is present on the particle surfaces. Accordingly, this method involved problems such as falling off of the magnetic substance and elution of substances derived from magnetic components such as an iron ion. It is known that such problems bring adverse influences especially when the particles are used for a carrier for diagnostic reagent. It is reported that in the enzyme immunoassay (EIA) as an analytical method in the biochemical field, in the case where a certain chromogenic substrate such as o-phenylenediamine (OPD) is used for the assay, Fe functions as an interferent and pushes up a background of the assay, thereby causing an error in the assayed values (
Rev. Esp. Fisiol
., 45(1), 41-46, 1989). Thus, magnetic particles, on the surfaces of which is not present a magnetic substance, and which are free from problems such as falling off of a magnetic substance and elution of an iron ion and can be utilized as a carrier for diagnostic reagent in the EIA, etc., have been demanded.
SUMMARY OF THE INVENTION
An object of the invention is to simply and effectively prepare particles for diagnostic reagent, which are free from falling off of a magnetic substance and elution of substances derived from a magnetic component such as an iron ion and which have a uniform particle size.
Specifically, the invention provides a process for producing particles for diagnostic reagent, which comprises a step of polymerizing a polymerizable monomer in the presence of a matrix particle having a magnetic substance layer containing at least one of Fe
2
O
3
and Fe
3
O
4
on the surface thereof and having a mean particle size of 0.4-200 &mgr;m to form a polymer layer on the magnetic substance layer.
DETAILED DESCRIPTION OF THE INVENTION
The matrix particle used in the invention is a particle having a magnetic substance layer containing at least one of Fe
2
O
3
and Fe
3
O
4
on the surface of a nuclear particle.
The nuclear particle that is used in the invention is basically a non-magnetic substance, and any of organic substances and inorganic substances can be used and can be appropriately selected depending on the purpose of use of particles for diagnostic reagent and so on.
Representative examples of the organic substance include polymers. Vinyl-based polymers are particularly preferable as such polymers. Examples of vinyl-based monomers that are used for the production of vinyl-based polymers include aromatic vinyl monomers such as styrene, &agr;-methylstyrene, halogenated styrenes, and divinylbenzene; vinyl esters such as vinyl acetate and vinyl propionate; unsaturated nitriles such as acrylonitrile; and ethylenically unsaturated carboxylic acid alkyl esters such as methyl acrylate, ethyl acrylate, ethyl methacrylate, butyl acrylate, butyl methacrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, lauryl acrylate, lauryl methacrylate, ethylene glycol diacrylate, ethylene glycol dimethacrylate, cyclohexyl acrylate, and cyclohexyl methacrylate. This vinyl-based polymer may be a homopolymer or a copolymer of two or more monomers selected from the above vinyl-based monomers. Copolymers of the vinyl-based monomer with a conjugated diolefin (such as butadiene or isoprene) or a copolymerizable monomer (such as acrylic acid, methacrylic acid, acrylamide, methacrylamide, diglycidyl acrylate, glycidyl methacrylate, N-methylolacrylamide, N-methylolmethacrylamide, 2-hydroxyethyl acrylate, 2-hydroxyethyl methacrylate, diallyl phthalate, allyl acrylate, allyl methacrylate, trimethylolpropane triacrylate, and trimethylolpropane trimethacrylate) can also be used.
The polymer particles as the matrix particle, having a mean particle size of the above-specified range, can be obtained by, for example, suspension polymerization of the above-described vinyl-based monomer or pulverization of the polymer bulk. With respect to the preparation of the matrix particle having a uniform particle size, the matrix particle can easily be produced by a swelling polymerization method as described in JP-B-57-24369, a polymerization method as described in
J. Polym. Sci., Polymer Letter Ed
., or polymerization methods as previously proposed by the present inventors (JP-A-61-215602, JP-A-61-215603, and JP-A-61-215604).
The nuclear particle has a mean particle size of 0.4-200 &mgr;m, preferably 0.8-100 &mgr;m, and more preferably 1.0-50 &mgr;m, and a CV value of 20% or less.
In the invention, it is preferred from the standpoints of processability and lightweight properties during the compositing that the nuclear particle is made of an organic substance such as polymers. Incidentally, in the invention, the mean particle size and the particle size distribution are those as determined by randomly measuring 100 particles for the particle size on an electron microscopic photograph.
Representative magnetic substance that is used in the invention is iron oxide-based substances. Examples of the substance include ferrite represented by MnFe
2
O
4
(Mn: Co, Ni, Mg, Cu, Li
0.5
, Fe
0.5
, etc.), magnetite represented by Fe
3
O
4
, and Fe
2
O
3
. It is necessary for the magnetic substance to contain either one of Fe
2
O
3
and Fe
3
O
4
having strong saturation magnetization and small residual magnetization.
The magnetic substance that is used in the invention has a mean particle size of preferably ⅕ or less, more preferably {fraction (1/10)} or less, and most preferably {fraction (1/20)} or less the mean particle size of the nuclear particle. When the mean particle size of the magnetic substance exceeds ⅕ of the mean particle size of the nuclear particle, it is difficult to form a coating layer having a uniform and sufficient thickness on the surface of the nuclear particle.
A ratio of the nuclear particle
Fan Kejun
Hikata Mikio
Katayose Satoshi
Murata Mitsuhiro
Ozaki Ichiro
JSR Corporation
Sastri Satya B.
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