WO1984002031A1 - Particules polymeres magnetiques et leur procede de preparation - Google Patents

Particules polymeres magnetiques et leur procede de preparation Download PDF

Info

Publication number
WO1984002031A1
WO1984002031A1 PCT/NO1983/000016 NO8300016W WO8402031A1 WO 1984002031 A1 WO1984002031 A1 WO 1984002031A1 NO 8300016 W NO8300016 W NO 8300016W WO 8402031 A1 WO8402031 A1 WO 8402031A1
Authority
WO
WIPO (PCT)
Prior art keywords
particles
groups
water
added
mixture
Prior art date
Application number
PCT/NO1983/000016
Other languages
English (en)
Inventor
John Ugelstad
Turid Ellingsen
Arvid Berge
Bertil Helgee
Original Assignee
Sintef
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from NO823748A external-priority patent/NO155316C/no
Application filed by Sintef filed Critical Sintef
Priority to BR8307583A priority Critical patent/BR8307583A/pt
Priority to NO841739A priority patent/NO160036C/no
Publication of WO1984002031A1 publication Critical patent/WO1984002031A1/fr
Priority to FI842747A priority patent/FI79762C/fi
Priority to DK339484A priority patent/DK172356B1/da

Links

Classifications

    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
    • H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
    • H01F1/42—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of organic or organo-metallic materials, e.g. graphene
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B03—SEPARATION OF SOLID MATERIALS USING LIQUIDS OR USING PNEUMATIC TABLES OR JIGS; MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C—MAGNETIC OR ELECTROSTATIC SEPARATION OF SOLID MATERIALS FROM SOLID MATERIALS OR FLUIDS; SEPARATION BY HIGH-VOLTAGE ELECTRIC FIELDS
    • B03C1/00—Magnetic separation
    • B03C1/005—Pretreatment specially adapted for magnetic separation
    • B03C1/01—Pretreatment specially adapted for magnetic separation by addition of magnetic adjuvants
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G01N33/54326—Magnetic particles
    • G01N33/5434—Magnetic particles using magnetic particle immunoreagent carriers which constitute new materials per se
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01F—MAGNETS; INDUCTANCES; TRANSFORMERS; SELECTION OF MATERIALS FOR THEIR MAGNETIC PROPERTIES
    • H01F1/00—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties
    • H01F1/01—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials
    • H01F1/03—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials characterised by their coercivity
    • H01F1/032—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials characterised by their coercivity of hard-magnetic materials
    • H01F1/10—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials characterised by their coercivity of hard-magnetic materials non-metallic substances, e.g. ferrites, e.g. [(Ba,Sr)O(Fe2O3)6] ferrites with hexagonal structure
    • H01F1/11—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials characterised by their coercivity of hard-magnetic materials non-metallic substances, e.g. ferrites, e.g. [(Ba,Sr)O(Fe2O3)6] ferrites with hexagonal structure in the form of particles
    • H01F1/111—Magnets or magnetic bodies characterised by the magnetic materials therefor; Selection of materials for their magnetic properties of inorganic materials characterised by their coercivity of hard-magnetic materials non-metallic substances, e.g. ferrites, e.g. [(Ba,Sr)O(Fe2O3)6] ferrites with hexagonal structure in the form of particles with a non-magnetic core
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2446/00—Magnetic particle immunoreagent carriers
    • G01N2446/10—Magnetic particle immunoreagent carriers the magnetic material being used to coat a pre-existing polymer particle but not being present in the particle core

Definitions

  • the present invention relates to magnetic polymer particles and a process for the preparation thereof. It has been tried to use magnetic polymer particles within several fields of biochemistry and medicine. They have been tried as carriers for pharmaceutical preparations since they due to their magnetic properties are capable of transporting the preparations to the desired location in the body. Magnetic particles also have other practical applications and have been used within diagnostics since it is possible to replace separation of particles by means of centrifugation by the much simpler method of magnetic extraction. Further, magnetic particles have been used for cell separation and as carriers for enzymes. Of more technical applications may be mentioned toners for copying purposes.
  • a commonly used method employs magnetite powder which is mixed mechanically with molten polymer. After this treatment the polymeric material containing magnetite is finely divided. This provides particles having an uneven shape and being of different size. Particles prepared in this manner are often used as toner, but the uneven shape is undesired since it will result in uneven and unsharp edges on the characters.
  • Another method employs finely divided magnetite to which vinyl monomer and initiator are added in water to form polymer around the magnetite grains. This will also provide magnetic particles having an undefined and highly variable size and shape. Further, only some of the particles will be magnetic, and the content of magnetite in the particles is usually very unequal. Other methods describe admixture of albumin and other proteins with magnetite and vigorous stirring in water with emulsifyer to form drops which contain magnetite and protein.
  • Another method comprises treatment of swelling polymer particles with finely divided magnetite to obtain magnetite on and possibly some inside the particles.
  • magnetite is used will, even if it is employed in very finely divided form, represent great limitations with respect to the type and the size of the particles. A real diffusion of molecular material into the particles or into pores of the particles will not take place. With solid, porous particles very large pores would be necessary, and accordingly large particles, so that magnetite grains are deposited not only on the surface of the particles. With highly swelling particles it is possible to get some magnetite into the particles mechanically, but the magnetite will essentially be deposited on the surface and result in a very uneven surface.
  • iron is introduced into the particles in the form of salts and is then converted to magnetic iron oxide which to a great extent will be magnetite (Fe.,0.) or oxides having corresponding magnetism.
  • the particles prepared according to the invention will be advantageous since they are spherical and have an even concentration of magnetic material which may be varied as desired within wide limits.
  • the process provides the possibility for preparing monodisperse particles of desired size, compact as well as porous.
  • the process according to the present invention is suitable for compact as well as porous polymer particles and may be used for the preparation of magnetic polymer particles of all sizes.
  • the process is suitable for the preparation of particles in the range 0.5-20 ⁇ ra, but it may also be used for the preparation of particles smaller than 0.5 ⁇ m and larger than 20 ⁇ m in diameter.
  • a great advantage of the process is that it allows all the particles to have the same concentration of magnetic iron oxide.
  • the process will in particula provide monodisperse magnetic polymer particles which all contain the same amount of magnetic iron oxide.
  • a process for preparing magnetic polymer particles is characterized in that solutions of iron salts and optionally salts of other metals which may form magnetic ferrites, in water or in a mixture of water and water-soluble organic solvents or in organic solvents, are mixed with polymer particles in dry form or dispersed in water or in a mixture of water and water-soluble organic liquids or in organic liquids, and the metals are precipitated in the form ' of hydroxides, for instance by raising the pH value, and, if desired, the particles are heated.
  • compact or porous particles which contain groups which may have the effect that the iron salt is drawn into the particle and is possibly bound therein. These groups may be
  • ⁇ * incorporated in the particles by preparing the polymer from a monomer containing these groups.
  • monomers which have been found to be particularly suitable, are dimethylamino-ethylmethacrylate, N-(dimethylamino- propyD-methacrylic amide and vinyl pyridine which will bind the iron salts with coordinate bonding.
  • the iron By having acid groups on and inside the particles, the iron may be transported from the outer phase of dissolved iron salt to be bound to these groups.
  • monomers which will provide such acid groups are methacrylic acid, p-vinyl benzoic acid and maleic anhydride.
  • the iron salt-binding groups may also be attached to the premade polymers.
  • a copolymer from a monomer mixture which essentially consists of vinyl monomer with epoxy grou (s) such as glycidyl methacrylate:
  • Another method for the introduction of iron-binding groups comprises the introduction of - H 2 groups or -CH--NH- groups on the benzene nucleus in polymer particles prepared by polymerization of a monomer which to a considerable extent contains benzene rings such as styrene and divinylbenzene.
  • the ethylene oxide chain may also be introduced into the final polymer by reacting such a polymer which contains
  • acid groups may be introduced into the final polymer particles. This may for instance be obtained by hydrolysing a polymer which contains ester groups. S imilarly, by known methods it is possible to introduce sulphonic acid groups and carboxylic acid groups into the polymer which has been prepared from styrene and/or styrene-derivatives and admixture of these with divinyl benzene.
  • the polymer particles may also be prepared as porous particles having a macroreticular structure, i.e. a firm pore structure
  • the iron salts may be bound in a single layer to the surface inside the pores, but since this surface is very large, a relatively high content of iron inside the particles will nevertheless be obtained. In other cases the iron compound may to a greater or smaller extent fill the pores.
  • Porous particles having a macroreticular structure may be prepared by groups which bind iron salts directly, or the particles may be posttreated for the introduction of said groups as described above.
  • porous particles having a large surface it is also possible to introduce iron salt into the particles by coating the interior surface with substances which contain iron-binding groups and which are bound strongly to the surface, before the addition of iron salts, or said substance is added together with the iron salt.
  • substances are for instance polyamine amide with limited chain length or substances which contain one or preferably ' more acid groups or acid groups combined with other groups which provide a strong bonding of iron salts.
  • iron salts in which the anionic group is so large and is so hydrophobic that it is bound directly to the interior surface by physical adsorption. After the particles and the iron salts have been mixed, the pH is raised and iron hydroxide is formed.
  • the particles which are swollen by the liquid in the outer phase or the porous particles filled with the liquid from the outer phase do not contain groups which bind iron salts, only some of the iron salt will be found inside the particles, and by raising the pH an essential part of the added trivalent iron salt will then be precipitated in the outer phase, which would have the effect that less magnetic iron oxide would be formed inside the
  • particles prepared with some polyvinyl monomer i.e. a monomer containing several vinyl groups, such as divinyl benzene
  • the particles contain groups which will bind the iron salts so that upon the subsequent transfer of the particles to water the iron salts will remain bound inside the particles.
  • iron salts containing hydrophobic anions such as iron laurate, the iron compounds will remain in the particles when these are transferred to water, and specific iron- binding groups are not of the same importance. This will also be the case when solid, porous particles having hydrophobic structure are used.
  • the iron-binding groups are hydrazine groups -NH-NH 2
  • a trivalent iron salt is preferably used. Even in this case it is therefore important that the trivalent iron salt is bound on and inside the particles before the pH is raised to form Fe(OH),.
  • porous particles containing NO- groups bound to the benzene nuclei are prepared. These particles may for instance be prepared by the preparation of porous particles from nitrostyrene and divinyl benzene in an ordinary manner, i.e. in the presence of inert solvents which are removed after the polymerization, or porous particles may be prepared from styrene or styrene derivatives and divinyl benzene, and then nitro groups are introduced onto the benzene groups according to ordinary methods.
  • oxidizing nitro component ⁇ 0 2 groups or 0N0 groups.
  • These groups may for instance advantageously be attached to porous particles which contain a large number of hydroxy groups on the surface by allowing these to react with HNO., or H 0 2 .
  • Examples of such polymers are macroreticular porous particles prepared with a substantial part of hydroxyethyl- methacrylate in the monomer mixture.
  • Other examples are porous particles having an essential content of glycidyl methacrylate in the monomer mixture. In this case the
  • epoxy groups CH 2 — CH- may be reacted directly with HNO-, or HN0 2 , or hydroxy groups may be introduced by reacting epoxy groups with for instance aminoethanol.
  • the particles have become magnetic directly.
  • a more complete magneti ⁇ zation with formation of e 3 0 4 is obtained by heating.
  • the particles may be isolated by centrifugation or filtration or may be extracted with a magnet and dried, and may possibly also be heated in dry condition.
  • hydrazine groups are used, it is possible to use pure trivalent salt, and Fe(OH) 3 is then formed and is by means of the hydrazine groups reduced to a mixture of divalent and trivalent iron corresponding to the same oxidation stage as in magnetite. This is preferably carried out at temperatures above 100 C.
  • di- or trivalent iron hydroxide in or on the particles has been formed in any of the above processes, it is also possible to convert the hydroxide to the desired mixture of di- and trivalent iron hydroxide.
  • Divalent iron hydroxide may for instance be oxidized by the addition of a suitable oxidizing agent, such as nitrate ion or an organic nitro compound, .or the oxidation may for instance be carried out by blowing oxygen through.
  • Tri ⁇ valent iron hydroxide may be reduced with a suitable reducing agent, such as hydrazine.
  • the ratio between di- and tri ⁇ valent iron is 1:2. It is therefore suitable to use a mixture of iron salts with approximately this ratio between di- and trivalent salts when no normally reducing/oxidizing groups are present. If the ratio Fe /Fe after the raise of the pH is essentially above 1:2, the formed hydroxides are oxidized, and if it is essentially below 1:2 they are reduced to form magnetic iron oxide.
  • manganoferrite, MnFe 2 0 4 cobalt ferrite, CoFe 2 0 4 or nickel ferrite NiFe 2 0 4 -
  • the divalent iron in the form av iron hydroxide inside the particles is oxidized to trivalent iron under conditions which provide the desired metal ferrite.
  • the oxidation may take place by means of oxidizing groups such as "N0 2 , -0N0 or -0N0 2 which has been introduced Onto the polymers, or it may take place by the addition of suitable oxidizing agents.
  • MeFe_0 4 a mixture of ferroferrite with other ferrites, MeFe_0 4 , in which Me represents Co, Ni or Mn.
  • An advantage by using a mixture of iron salt with other metal salts is that in this case there is no risk of overoxidation of the iron, since in that case there will only be formed MeFe 2 0 4 at the expense of FeFe 2 0 4 -
  • the polymer particles used as starting material for the preparation of magnetic particles may in the principle be prepared according to all the methods which are known for the preparation of dispersions of polymeric particles.
  • the method will result in particles in the range up to about 0.6 ⁇ m in diameter.
  • the size and the monodispersity increase with decreasing amount of emulsifier.
  • the particles may also be prepared by initiation in drops, which may be obtained in different ways. It is for instance possible to homogenize a mixture of monomer with a small amount of a water-insoluble material having a water-solubility less than 10 g/1 H 9 0 with
  • OMPI water and emulsifier which will provide stable monomer emulsions, and then polymerize with addition of initiator and heating.
  • the water-insoluble substance used may be a water-insoluble monomer. If desired, it is possible to use an oil-soluble initiator which is added together with the monomer before the homogenization. Possibly this initiator may in itself serve as the water-insoluble substance which provides stable monomer emulsions. By this method initiation may take place exclusively inside the drops.
  • a water-insoluble substance having a water-solubility less than 10 g/1 H 2 0 with water and emulsifier.
  • monomer is added which will diffuse into the drops of water- insoluble substance and polymerize by means of water- soluble initiator or oil-soluble initiator added together with or after the monomer and which has such a high water- solubility that it just like the monomers may diffuse through the water and into the drops of the water-insoluble substance.
  • the water-insoluble substance used during the homogenization may be an initiator.
  • the polymer particles may also be prepared by seed processes.
  • a seed of polymer particles disper ⁇ sed in water is used, possibly a mixture of water and an organic solvent which is soluble in water, and the desired monomers are introduced into the polymer particles before polymerization either with a water-soluble initiator or with an oil-soluble initiator added together with or after the monomers.
  • a seed technique which comprises the preparation in a first step of particles which in addition to the polymer molecules also contain a water-insoluble substance having a relatively low molecular weight. Such a method has been described in Norwegian patent No. 142.082. When the water-insoluble substance having a water-solubility of less than 10 g/1
  • IjUREAt OMPI .
  • WIPO H ⁇ 0 and having a relatively low molecular weight is present in the particles, these are as described in said patent capable of absorbing much more monomer than ordinary polymer particles.
  • a specific embodiment of this method which has also been found to be favourable for the preparation of polymer particles which are later converted to magnetic particles, comprises that the water-insoluble substance used for swelling the polymer particles in the first step, is an oil-soluble initiator which is used for polymerizatio after the monomer has diffused into the particles.
  • the preparation of polymer particles by seed technique is particularly favourable when it is desired to prepare spherical magnetic particles which are monodisperse and which will therefore also contain the same amount of magnetic ferrite in each particle.
  • a monodisperse seed i.e. a polymer dispersion where all the particles have approximately the same size, for instance a standard deviation of less than 5%.
  • the ' standard deviation for the content of magnetic ferrite will then normally be less than 10%.
  • the polymeric particles may also be prepared by ordinary suspension polymerization. In this case large particles are obtained directly, but with a broad size-distribution.
  • the particles prepared according to the above methods by polymerization in drops or swelled particles may be obtained as porous particles by using ordinary methods which, involve the use of a mixture of monomers at least one of which is a polyvinyl compound, and in addition inert solvents for the monomers are present, which are removed after the polymerization.
  • ordinary methods involve the use of a mixture of monomers at least one of which is a polyvinyl compound, and in addition inert solvents for the monomers are present, which are removed after the polymerization.
  • ordinary vinyl monomers and polyvinyl monomers and mixtures thereof for the preparation of the polymer particles it is possible to use ordinary vinyl monomers and polyvinyl monomers and mixtures thereof.
  • vinyl monomers which are used are styrene and styrene derivatives, maleic anhydride, acrylates and methacrylates such as methylacrylate, methylmethacrylate, ethylacrylate, ethylmethacrylate, butylacrylate and butyl- methacryla e, and vinyl esters such as vinyl acetate.
  • polyvinyl monomers which may be used comprise divinyl benzene, ethylene glycol dimethacrylate, trimethylolpropane trimethacrylate and adipic acid divinyl ester.
  • emulsifier ordinary ionic or non-ionic emulsifiers may be used.
  • initiator water-soluble initiators such as potassium persulphate and H_0 2 or oil- soluble initiators such as azobisisobutyric nitrile and benzoyl peroxide may be used.
  • inert materials which are used to stabilize emulsions of monomer or to increase the swelling capacity of the polymer particles, one may use substances which are disclosed in Norwegian patents 139.410 and 142.082. Examples are alkanes having a chain length above 10 C-atoms, halogenated alkanes, esters and diesters such as dioctyl adipate. Examples of water-insoluble initiators used as additive for increasing the swelling of particles with monomer as well as for polymerization, are dioctanoyl peroxide and didecanoyl peroxide.
  • the preparation of dispersions of polymers in water may also be carried out by dissolving the polymer in a solvent which is slightly soluble in water and then mixing the solution of the polymer with water and emulsifier and subjecting the mixture to strong shear forces, for instance by means of ultraturrax stirrer or pressure homogenizer, to obtain a fine emulsion of the polymer solution in water with varying drop size.
  • a solvent which is slightly soluble in water
  • By removing the solvent for instance by evaporation, there will be formed a finely divided dispersion of polymer particles in water.
  • the incorporation of metal salts in the particles may take place before or after the removal of the organic solvent.
  • the polymer dispersion is prepared from a final polymer it is irrelevant how the polymer has been prepared. It may have been prepared by radical polymerization of vinyl monomers as described above, but it may also have been prepared by any process which results in polymers, such as cationic and anionic polymerization, stepwise addition polymerization and * condensation
  • the temperature was raised to 65 C, and polymerization was carried out for 6 hours. After polymerization a latex containing 10% of polymer, particle size 0.2-0.3 ⁇ m, was obtained. 5 100 ml of the latex were- treated with 100 ml of ethylene diamine at 80°C for 3 hours. After the reaction excess of ethylene diamine was removed by dialysis for 10 days, with change of water every day.
  • . ⁇ -- W1PO particles contain magnetic iron oxide.
  • the iron content in the particles was found to be 4.9%.
  • the final particles contain magnetic iron oxide.
  • the iron content in the particles was found to be 5.2%.
  • the mixture was transferred to a reactor. 800 ml of water and 1.0 g of Na-laurylsulphate were added. Under stirring at 25°C a mixture of 110 ml of methylmethacrylate, 90 ml of glycidylmethacrylate and 10 ml of ethylene glycol- dimethacrylate was added slowly. After 2 hours the temperature was raised to 65 C. When the polymerization was terminated, a latex having a particle size of 0.5-2 ⁇ m
  • the final particles contain magnetic iron oxide.
  • the iron content in the particles was found to be 7.5%.
  • OMPI example 1 In this case 1954 mg (3.9 mmole) of in 20 ml of water, 457 mg (2.3 mmole) of FeCl 2 .4H 2 0 in 20 ml of water and 15 ml of ammonia solution (25%) were added. The further treatment and the recovery of the particles were carried out as described in example 1.
  • the final particles contain magnetic iron oxide.
  • the iron content in the particles was found to be 10.0%.
  • Example 6 5 ml of dioctanoyl peroxide, 50 ml of water and
  • 0.15 g of Na-laurylsulphate were homogenized to an emulsion with drops size 0.15-0.25 ⁇ m.
  • This emulsion was mixed with a latex consisting of polystyrene particles having a diameter of 0.5-1.0 ⁇ m.
  • the amount of latex that was added (40 ml) contained 5 ml of polystyrene particles and 35 ml of H-0. After careful stirring for .24 hours, the mixture was transferred to a reactor containing 800 ml of water and 2.4 g of Na-laurylsulphate.
  • the particles were recovered by filtration and washing with water and finally with methanol before drying. 5 After the treatment the particles contained magnetic iron oxide. The iron content was found to be 7.1%.
  • Example 8 5 ml of dioctyl adipate, 42.5 ml of water, 7.4 ml of acetone and 0.15 g of Na-laurylsulphate were homogenized to an emulsion with a drop size of 0.2-0.3 ⁇ m.
  • This emulsion was mixed with a latex consisting of monodisperse polystyrene particles having a diameter of 1.04 ⁇ m (determined by electron microscopy) .
  • the amount of latex added (25 ml) contained 2.5 ml of polystyrene particles and 22.5 ml of H 2 0.
  • Example 9 10 ml of dioctanoyl peroxide, 85 ml of water, 15 ml of acetone and 0.30 g of Na-laurylsulphate were homogenized to an emulsion with a drop size of 0.2-0.3 ⁇ m.
  • This emulsion was mixed with 37 ml of a latex consisting of monodisperse polymer/oligomer particles (in which each particle contained 70% oligomer styrene with molecular weight 2500 and
  • the amount of latex added contained 4 ml of polymer/oligomer particles and 33 ml of H 2 0. After careful stirring for 20 hours acetone was removed by evaporation in vacuo. The amount of latex after the removal of acetone, was 132 ml.
  • a mixture -of 81.5 ml of glycidyl methacrylate, 122 ml of ethyleneglycol dimethacryl te, 314.5 ml of cyclohexanol, 1450 ml of H 2 0 and 20 g of polyvinylpyrrolidone (molecular weight 360.000) was emulsified in an ultraturrax mixer for 1 1/2 minute. The emulsion was transferred to a reactor, and the above latex residue of 132 ml was added. This mixture was stirred with a moderate stirring rate for 2 hours. Then 1450 ml of water were added, and the temperature was raised to 60 C.
  • This residue was transferred to a reactor containing 800 ml of H-,0 and 3.25 g of Na- laurylsulphate.
  • a mixture of 40 ml of di ethylaminoethyl- ⁇ methacrylate, 90 ml of ethylene glycoldimethacrylate and 200 ml of cyclohexanol was added slowly under efficient stirring. After 2 hours800 ml of water were added, and the temperature was raised to 60 C. After 6 hours of polymerization, the reactor was cooled and cyclohexanol was removed from the. particles by several washings with
  • the particles were filtered from the solution and washed with water and finally with methanol. The particles were then dried.
  • the particles After the treatment the particles contain magnetic iron oxide.
  • the iron content was found to be 6.1%.
  • f OMPI particles having a diameter of 2.0 ⁇ m and a specific surface of 472 m 2/g polymer (BET) were obtained.
  • Monodisperse porous particles were prepared as described in example 12. 5 g of porous particles, 1 g of polyamine amide
  • the particles contained magnetic iron oxide.
  • the iron content was found to be 17.3%.
  • the particles were separated from ' the aqueous phase by centrifugation.
  • the particles were washed with acetone and tried. 2 g of the dry particles were then transferred to 50 ml of a sodium hydroxide solution (2%) in a glass flask fitted with a stirrer. After stirring for 20 minutes the particles were separated from the solution by centrifugation. Alternate washing with water and centrifugation were then carried out until the washings had an approximately neutral pH.
  • the particles were then transferred to 50 ml of water and treated with iron chloride and ammonia solution as described in example 1. In this case 334 mg (1.3 mmole) of FeCl 3 .6H 2 0 in 20 ml of water, 145 mg (0.7 mmole) of FeCl 2 .4H 2 0 in 20 ml of water and 10 ml of ammonia solution (25%) were added. The recovery of the particles was carried out as in example 6. After the treatment the particles contain magnetic iron oxide. The iron content was found to be 5.2%.
  • Porous, monodisperse particles having a diameter of 2.0 ⁇ m prepared as described in example 12 were treated with chloromethyl ether, C1CH_0CH 3 , in a known manner for the introduction of -CH 2 C1 on the benzene nucleus. By this treatment porous particles with 1.2 mmole -CH-C1 groups per g particles were obtained.
  • Example 19 The particles were separated from the solution by filtration, washed with water and finally with methanol. The particles were then dried. After the treatment the particles contain ferromagnetic ironoxide. The iron content was found to be 10%.
  • the suspension of the particles in acetone was stirred for 30 minutes under an atmosphere of nitrogen.
  • the partic were then filtered off on a suction funnel while all the time a blanket of nitrogen was kept covering the filter cake.
  • the particles were treated with a flow of moist NH- ' vapour.
  • the particl were then washed with water and finally with methanol.
  • the particles then were dried. After the treatment the particl contain magnetic iron oxide. The iron content was found to be 9.5%.
  • a linear polya ide was prepared by known methods from equimolar amounts of 1,ll-diamino-3,6,9-trioxaundecane NH 2 -CH 2 -CH 2 - (0CH 2 CH 2 ) 3 NH 2 and sebacic acid dichloride
  • the particles were separated from the solution by filtration, washed with water and finally with methanol. The particles were then dried. After the treatment the particles contain magnetic iron oxide. The iron content was found to be 11.5%.
  • the mixture was cooled and filtered.
  • the particles were washed several times with water and methanol. After this treatment the particles contain magnetic iron oxide.
  • the iron content in the particles was found to be 18.4%.
  • Monodisperse porous particles prepared as described in example 21 were used.
  • the particles had a diameter
  • Monodisperse porous particles prepared as described in example.9 were used.
  • the particles had a dimeter of 4.8 ⁇ m and a specific surface of 151 m /g, and after treat- ment with ethylene diamine the particles contained 4.9% N.
  • 1 g of dry particles was mixed with 834 mg of FeS0 4 .7H 2 0 ( 3 mmole) dissolved in 40 ml of water.
  • the mixture was rotated for 30 minutes under an atmosphere of N_. 10 ml of concentrated ammonia solution (25%) were then added by suction.
  • the temperature was then raised to 80°C with a light suction of air through the apparatus. After 15 minutes at 80°C the mixture was cooled and the particles were washed several times with water and finally dried. After this treatment the particles contain magnetic iron oxide. The iron content in the particles was found to be 10.5%.
  • Monodisperse, porous polymer particles with amino groups were used, prepared as described in example 9.
  • the particles had a diameter of 4.8 ⁇ m, and after treatment with ethylene diamine the particles contained 4.9%-N.
  • the particles were then cleaned by several washings with water and finally dried. After this treatment the particles contain a magnetic material.
  • Example 25 Monodisperse porous particles with nitro groups were used, prepared as described in example 12. The particles had a diameter of 2.0 ⁇ m and after nitration they contained 8.8% N.
  • Monodisperse polymer particles with amino groups were used, prepared as described in example 7.
  • the particles had a diameter of 2.0 ⁇ m and after treatment with ethylene diamine they contained 9.5% N.
  • the particles After this treatment the particles contain a magnetic material. Analyses of the particles showed a content of 4.3% Fe and 2.2% Mn.
  • emulsion 7.5 ml of acetone and 0.15 g of Na-laurylsulphate were homogenized to an emulsion with a drop size of 0.2-0.4 ⁇ m.
  • This emulsion was combined with 28 ml of a latex consisting of monodisperse polystyrene particles having a diameter of 2.0 ⁇ m.
  • the amount of latex added contained 2.27 ml of polystyrene particles and 25.73 ml of H 2 0.

Landscapes

  • Health & Medical Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Power Engineering (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • Medicinal Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Microbiology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Soft Magnetic Materials (AREA)
  • Developing Agents For Electrophotography (AREA)
  • Compositions Of Macromolecular Compounds (AREA)
  • Compounds Of Iron (AREA)

Abstract

Le procédé de préparation de particules polymères magnétiques consiste à traiter des particules polymères compactes ou poreuses avec une solution de sels de fer et, si on le désire, des sels d'autres métaux capables de former des ferrites magnétiques, la solution gonflant ou pénétrant dans les particules. Des hydroxydes de fer et éventuellement des hydroxydes d'autres métaux sont précipités, par exemple en augmentant la valeur du pH, puis les particules sont éventuellement chauffées. Dans les sels de fer utilisés, le rapport entre le fer divalent et le fer trivalent est choisi de manière appropriée pour que l'oxyde de fer magnétique se forme directement. Il est également possible d'utiliser des groupes ou des additifs d'oxydation ou de réduction pour obtenir un tel rapport. Lorsque l'on utilise des sels d'autres métaux en plus des sels de fer, le procédé s'effectue de la même manière. Par exemple, lorsque des sels de Mn++, Co++ ou Ni++ sont utilisés outre les sels Fe++, le fer bivalent est oxydé en fer trivalent pour obtenir de la ferrite magnétique. Les particules polymères qui sont traitées avec des sels métalliques contiennent de préférence des groupes de liaison de métaux. De tels groupes sont incorporés en utilisant par exemple des monomères qui contiennent lesdits groupes pour la préparation des particules polymères, ou bien les groupes sont incorporés dans les particules polymères préparées. Les particules polymères magnétiques sont sphériques et ont une concentration uniforme de matériau magnétique. Elles peuvent être utilisées à des fins médicales, diagnostiques ou autres.
PCT/NO1983/000016 1982-11-10 1983-04-27 Particules polymeres magnetiques et leur procede de preparation WO1984002031A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
BR8307583A BR8307583A (pt) 1982-11-10 1983-04-27 Particulas polimeras magneticas e processo para sua preparacao
NO841739A NO160036C (no) 1982-11-10 1984-05-02 Magnetiske polymerte for fremstill ing derav.
FI842747A FI79762C (fi) 1982-11-10 1984-07-09 Magnetiska polymerpartiklar och foerfarande foer framstaellning daerav.
DK339484A DK172356B1 (da) 1982-11-10 1984-07-10 Fremgangsmåde til fremstilling af magnetiske polymerpartikler

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
NO823748A NO155316C (no) 1982-04-23 1982-11-10 Fremgangsmaate for fremstilling av magnetiske polymerpartikler.

Publications (1)

Publication Number Publication Date
WO1984002031A1 true WO1984002031A1 (fr) 1984-05-24

Family

ID=19886792

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/NO1983/000016 WO1984002031A1 (fr) 1982-11-10 1983-04-27 Particules polymeres magnetiques et leur procede de preparation

Country Status (3)

Country Link
DK (1) DK172356B1 (fr)
FI (1) FI79762C (fr)
WO (1) WO1984002031A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4325071A1 (de) * 1993-07-19 1995-01-26 Lancaster Group Ag Präparat zur Durchblutungsförderung
GB2355012A (en) * 1999-10-05 2001-04-11 Solid Phase Sciences Corp Paramagnetic polymer particles
WO2018189286A1 (fr) * 2017-04-13 2018-10-18 Roche Diagnostics Gmbh Particules de polymère superparamagnétiques et hautement poreuses pour des applications diagnostiques

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3278441A (en) * 1963-12-20 1966-10-11 Exxon Research Engineering Co Process for making magnetic metalcontaining polymer compositions
US3764539A (en) * 1970-10-14 1973-10-09 Community Building Ass Of Wash Flexible ferrite permanent magnet and methods for its manufacture
US3892673A (en) * 1971-03-24 1975-07-01 Graham Magnetics Inc Composition of metal salt crystals having a polymeric coating
US3904540A (en) * 1972-02-11 1975-09-09 Pfizer Magnetic impulse record member
US4018691A (en) * 1975-08-28 1977-04-19 Georgia-Pacific Corporation Aryl sulfonate-aldehyde composition and process for its preparation
US4335094A (en) * 1979-01-26 1982-06-15 Mosbach Klaus H Magnetic polymer particles
US4339337A (en) * 1979-08-24 1982-07-13 Rhone-Poulenc Industries Process for the preparation of magnetic beads of vinylaromatic polymers

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3278441A (en) * 1963-12-20 1966-10-11 Exxon Research Engineering Co Process for making magnetic metalcontaining polymer compositions
US3764539A (en) * 1970-10-14 1973-10-09 Community Building Ass Of Wash Flexible ferrite permanent magnet and methods for its manufacture
US3892673A (en) * 1971-03-24 1975-07-01 Graham Magnetics Inc Composition of metal salt crystals having a polymeric coating
US3904540A (en) * 1972-02-11 1975-09-09 Pfizer Magnetic impulse record member
US4018691A (en) * 1975-08-28 1977-04-19 Georgia-Pacific Corporation Aryl sulfonate-aldehyde composition and process for its preparation
US4335094A (en) * 1979-01-26 1982-06-15 Mosbach Klaus H Magnetic polymer particles
US4339337A (en) * 1979-08-24 1982-07-13 Rhone-Poulenc Industries Process for the preparation of magnetic beads of vinylaromatic polymers

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4325071A1 (de) * 1993-07-19 1995-01-26 Lancaster Group Ag Präparat zur Durchblutungsförderung
GB2355012A (en) * 1999-10-05 2001-04-11 Solid Phase Sciences Corp Paramagnetic polymer particles
GB2355012B (en) * 1999-10-05 2004-01-14 Solid Phase Sciences Corp Paramagnetic polymer practice
WO2018189286A1 (fr) * 2017-04-13 2018-10-18 Roche Diagnostics Gmbh Particules de polymère superparamagnétiques et hautement poreuses pour des applications diagnostiques
CN110741258A (zh) * 2017-04-13 2020-01-31 豪夫迈·罗氏有限公司 用于诊断应用的超顺磁和高度多孔聚合物颗粒

Also Published As

Publication number Publication date
FI842747A (fi) 1984-07-09
DK172356B1 (da) 1998-04-06
FI79762C (fi) 1990-02-12
FI842747A0 (fi) 1984-07-09
FI79762B (fi) 1989-10-31
DK339484A (da) 1984-07-10
DK339484D0 (da) 1984-07-10

Similar Documents

Publication Publication Date Title
US4654267A (en) Magnetic polymer particles and process for the preparation thereof
US4873102A (en) Magnetic particles
US5356713A (en) Magnetizable composite microspheres of hydrophobic crosslinked polymer, process for preparing them and their application in biology
Butterworth et al. Synthesis and characterization of polypyrrole–magnetite–silica particles
JP3738847B2 (ja) 診断薬用粒子の製造方法
US3560378A (en) Ion-exchange process
CN109776743B (zh) 一种吸附功能磁性Fe3O4@PS-TMT纳米粒子及其制备方法
JP4947288B2 (ja) 磁性粒子およびその製造方法、ならびに生化学用担体
JP2003513093A (ja) 複合ナノスフェアおよびそれらの生体分子との複合体
EP2221327A1 (fr) Particule inorganique fine à revêtement polymère et son procédé de production
EP1707963B1 (fr) Particules magnétiques à surface poreuse, procédé de production de celles-ci, support pour utilisation biochimique et particules de liaison biotine
Li et al. Mechanistic investigation of surfactant-free emulsion polymerization using magnetite nanoparticles modified by citric acid as stabilizers
Rahman et al. Organic–inorganic hybrid magnetic latex
US4707523A (en) Magnetic particles
JP4548598B2 (ja) 磁性粒子およびその製造方法、ならびに生化学用担体
US4170685A (en) Polyvinyl pyridine microspheres
Huang et al. Preparation of narrow or mono-disperse crosslinked poly ((meth) acrylic acid)/iron oxide magnetic microspheres
WO1984002031A1 (fr) Particules polymeres magnetiques et leur procede de preparation
CN113278194A (zh) 一种单分散磁性聚苯乙烯微球的制备方法及微球及其应用
Macková et al. Magnetic poly (N‐isopropylacrylamide) microspheres by dispersion and inverse emulsion polymerization
US4259223A (en) Cross-linked polyvinyl pyridine coated glass particle catalyst support and aqueous composition or polyvinyl pyridine adducted microspheres
TW200302233A (en) Complexing resins and method for preparation thereof
US20120220048A1 (en) Magnetic marker particle and method for producing the same
CN109650602B (zh) 一种磁性吸附材料去除水体中锑离子的方法
CN115710373B (zh) 一种水凝胶磁性微球的制备方法

Legal Events

Date Code Title Description
AK Designated states

Designated state(s): BR DK FI NO

WWE Wipo information: entry into national phase

Ref document number: 842747

Country of ref document: FI

WWG Wipo information: grant in national office

Ref document number: 842747

Country of ref document: FI