WO1996011054A2 - Process for the preparation of microspheres and microspheres made thereby - Google Patents
Process for the preparation of microspheres and microspheres made thereby Download PDFInfo
- Publication number
- WO1996011054A2 WO1996011054A2 PCT/US1995/012988 US9512988W WO9611054A2 WO 1996011054 A2 WO1996011054 A2 WO 1996011054A2 US 9512988 W US9512988 W US 9512988W WO 9611054 A2 WO9611054 A2 WO 9611054A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- microspheres
- microsphere
- process according
- silica
- ligands
- Prior art date
Links
Classifications
-
- 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
- G01N33/54346—Nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6923—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6921—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
- A61K47/6927—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores
- A61K47/6929—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
-
- 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
-
- 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
- G01N33/551—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being inorganic
- G01N33/552—Glass or silica
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2446/00—Magnetic particle immunoreagent carriers
- G01N2446/80—Magnetic particle immunoreagent carriers characterised by the agent used to coat the magnetic particles, e.g. lipids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2446/00—Magnetic particle immunoreagent carriers
- G01N2446/80—Magnetic particle immunoreagent carriers characterised by the agent used to coat the magnetic particles, e.g. lipids
- G01N2446/86—Magnetic particle immunoreagent carriers characterised by the agent used to coat the magnetic particles, e.g. lipids the coating being pre-functionalised for attaching immunoreagents, e.g. aminodextran
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2446/00—Magnetic particle immunoreagent carriers
- G01N2446/80—Magnetic particle immunoreagent carriers characterised by the agent used to coat the magnetic particles, e.g. lipids
- G01N2446/90—Magnetic particle immunoreagent carriers characterised by the agent used to coat the magnetic particles, e.g. lipids characterised by small molecule linker used to couple immunoreagents to magnetic particles
Definitions
- the present invention relates to a process for the preparation of microspheres, which may be optionally hollow, and which are consisting of one or more layers of silica shells and may also involve other coatings of different materials, characterized by variety of desirable properties.
- Another important type of coating is one exhibiting magnetic properties.
- a method for the preparation of ferrite plating of various chemical compositions is known in the art [Abe et al., J. of Applied Physics 57, pp. 3795-3797, (1985)], yet this method is characterized by several disadvantages and limitations.
- an essential condition for the formation of the ferrite film is the presence of hydroxyl groups on the substrate to be coated, because these groups enhance the adhesion of the film to the surface.
- the microsphere diameter is smaller than 0.5 ⁇ m, a continued magnetic coating can not be obtained .
- Abe et al. failed to disclose means for the protection of the ferrite coating, in order to avoid a partial leakage of the ferrite into the solution.
- the invention is directed to the preparation and use of microspheres, the diameter of which is in the range of about 0.2 ⁇ m up to a few microns, which are made of polymeric materials and contain surfactants of hydrophilic nature on their surfaces.
- This microspheres are then subjected to further coating stages.
- the final coated microspheres can then serve in a variety of biological apphcations.
- the microspheres can be rendered hollow by removing therefrom the inner polymeric core.
- the microspheres are obtained by polymerization of monomeric units, such as styrene, chloromethylstyerene, divinylbenzene and methylmethacrylate, in the presence of surfactants of hydrophilic nature and an initiator.
- monomeric units such as styrene, chloromethylstyerene, divinylbenzene and methylmethacrylate
- surfactants of hydrophilic nature such as styrene, chloromethylstyerene, divinylbenzene and methylmethacrylate.
- the choice of the surfactant composition and concentration, as well as other parameters of the reaction, such as initiator type, monomer concentration, governs the distribution of the microspheres diameters.
- the inventors have found that the quality of the coatings to be crated on the microspheres is also affected by two of these factors, namely, by the surfactant composition and by the initiator. As said, proper surfactants for coating purposes are of hydrophilic nature.
- the inventors have found that the magnetic properties of the coated microsphere are determined by the nature of the surfactant adsorbed initially on the particle surface. If hydrophobic surfactants are used, in combination with a hydrophihc one, a significant retardness is observed in the magnetic intensity of these coated microspheres, compared with those obtained with hydrophihc surfactant alone.
- a further object of the present invention is to provide a process for the preparation of sohd or hollow microspheres optionally comprising magnetic coatings, and further enveloped by sihca layers. These coated microspheres are then subjected to further modification which have extremely important uses.
- the sihca functionalizes in two different levels: it provides a defensive shell to the ferrite coating, and it serves as a source of optional covalent bonds, through which desired hgand may be attached to the system, in order to form the final, desired particle.
- sihca coating of said microspheres (which are optionally magnetic) is performed as hereinbefore described.
- hgands are added, comprising a functional group at their ⁇ -position.
- these hgands can form covalent bonds with the sihca coating.
- the hgands may be chosen from among alkylsilane and/or alkylhydrox l compounds, in particular SiCl3(CH2)nX > Si(OR)3(CH2)nX> OH(CH2)nX.
- R is an alkyl substituent
- n is between 2 to 20 and X is -NH 2, -CH 3 , -CO 2 R, -CN, etc.
- the amine group, or other functional groups which can be converted to an amine group because covalent binding of polyaldehyde hgands onto these groups may be further apphed.
- the polyaldehyde derivatized microsphere surface obtained may be now coupled to biomaterials such as proteins.
- the residual ⁇ -amine groups can be blocked by a proper reagent, for instance, acetic acid N- hydroxysuccin-imide ester.
- acetic acid N- hydroxysuccin-imide ester the inventors have found that acidic pH conditions improve the content of said aldehyde in the derivatized microsphere.
- Fig. 1 is a SEM photograph of polystyrene microspheres
- Figs. 2B and 2C are TEM and SEM pictures, respectively of hollow microspheres obtained by burning off the organic content of these coated microspheres at 800°C for 12 h;
- Figs. 3 are cross-section pictures obtained by TEM of hollow sihca microspheres prepared from polystyrene microspheres of ca. 1.8 ⁇ m average diameter coated with three layers of sihca nanoparticles of ca.. 30 nm average diameter;
- Fig. 4 shows SEM pictures of hollow sihca microspheres obtained by burning off the organic core of polystyrene microspheres of ca. 2.3 ⁇ m coated with a single layer of sihca nanoparticles of ca. 30 nm diameter (Fig. 4A), and three layers of similar sihca nanoparticles (Fig. 4B);
- Fig. 6 summarizes various preferred embodiments of the present invention, wherein P is the polymeric microsphere and S is the surfactant adsorbed on its surface.
- Polystyrene microspheres were prepared according to the literature/ C.K. Ober, K.P. Lok and M.L. Hair, J. of Polymer Sci., Polymer Letters Edition 23, 103 (1985)/. Briefly, These microspheres were prepared in a three-neck round- bottom flask equipped with a condenser. The flask was immersed in a constant temperature silicone oil bath at a preset temperature. In a typical reaction, A solution containing PVP (M.W. 360,000, 3.75 g) dissolved in ethanol (156 ml) and methyl cellosove (2-methoxyethanol, 62.5 ml) at room temperature was placed into the reaction flask and mechanically stirred (ca. 200 rpm).
- the diameter of the formed microspheres were controlled by changing conditions, such as surfactant type, surfactant concentration, initiator type, monomer concentration, reaction time, etc. Thereby, monodispersed and polydispersed microsphere systems in sizes ranging from approximately 0.2 ⁇ m up to several microns were formed.
- similar polymerization procedure as described above substituting the initiator benzoyl peroxide with azobisisobutironitrile, resulted in the formation of polydispersed microspheres with 4.2 ⁇ m average diameter instead of monodispersed microspheres of 2.3 ⁇ m average diameter obtained when benzoyl peroxide was used.
- Crosshnked polystyrene microspheres of ca. 0.3 ⁇ m diameter were synthesized by a procedure similar to the procedure described above, substituting styrene with divinylbenzene or substituting styrene with a monomer mixture composed of 45% styrene and 55% divinylbenzene.
- Microns sized polydispersed crosslinked polystyrene microspheres were prepared by a suspension polymerization process, through a procedure similar to that described in the Q.C. Wang, F. Svec and M.J. Frechet, Polymer Bulletin 28, 569 (1992).
- Monodispersed polychloromethylstyrene microspheres were prepared by a procedure similar to that described for polystyrene microspheres, substituting the solvent mixture (ethanol + methyl cellosove) with ethanol.
- 5.0 ml chloromethylstyrene were polymerized in 100 ml ethanol solution containing 1.15 g PVP (M.W. 360,000) and 100 mg azobisisobutironitrile.
- monodispersed polychloromethylstyrene microspheres of ca. 1.2 ⁇ m diameter (standard deviation of ca. 5%) were formed.
- Microspheres with a variety of diameters were formed by changing conditions, such as monomer concentration, surfactant concentration, etc.
- PMMA microspheres Monodispersed polymethylmethacrylate (PMMA) microspheres were prepared by a procedure similar to that described for polystyrene microspheres, substituting the solvent mixture (ethanol + methyl cellosove) with ethanol. In a typical reaction, 23 ml methylmathacrylate were polymerized in 212 ml ethanol solution containing 3.75 g PVP (M.W. 360,000) and 1.5 g bezoylperoxide. Thereby, PMMA microspheres of ca. 2.0 ⁇ m diameter were formed. Microspheres with a variety of diameters were formed by changing conditions, such as monomer concentration, surfactant concentration, etc.
- Sihca nanoparticles were prepared by the sol-gel technique by polymerization of Si(OEt)4 according to the Stober Method W. Stober, A. Fink and E. Bohn, J. Colloid Interface Sci. 26, 62 (1968)/. Briefly, particles of 30 nm average diameter were prepared by adding into a flask according to the hsted order the following reagents: ethanol (93.6 ml), distilled water (1.9 ml), ammonium hydroxide (1.3 ml) and Si(OEt)4 (3.2 ml). The resulting solution was then shaken at room temperature for ca. 12 h. The formed nanoparticles were washed by evaporation of the unreacted monomer, ethanol and ammonia.
- Example 1 The reaction was then continued for additional ca. 5h.
- the formed sihca coated polystyrene microspheres were then washed according to the description in Example 1.
- the percent sihca obtained for the first and second coatings of the polystyrene was similar to that obtained in Example 1.
- a third continuous sihca coating on polystyrene microspheres was difficult to prepare because of the difficulties existed in separation of grafted sihca nanoparticles from ungrafted sihca nanoparticles.
- Examples 1-7 were repeated, substituting the polystyrene microspheres with polychloromethylstyrene microspheres and/or polymethylmethacrylate microspheres prepared according to the description in the experimental part.
- Cross section photomicrographs indicated similar results.
- Hollow sihca microspheres were also prepared by dissolving with appropriate solvents (e.g. toluene, dime thy Iformamide, etc.) the organic core of polystyrene microspheres coated with sihca nanoparticles, prepared according to Examples 1-5.
- solvents e.g. toluene, dime thy Iformamide, etc.
- the hollow microspheres obtained in this way usually contained, except sihca, also traces of organic polymers which could not be removed by this process.
- Fig . 5A illustrates SEM photomicrograph of polystyrene microspheres of ca. 2.3 ⁇ m.
- Fig. 5C illustrates the first sihca nanoparticles coating on magnetic polystyrene microspheres of ca. 2.3 ⁇ m, prepared according to example 13.
- Example 8 was repeated substituting the polychloromethylstyrene microspheres and/or polymethylmethacrylate microspheres with similar microspheres thin coated with Fe3 ⁇ 4 prepared according to the description in experiment 18. Similar results were obtained. Examnle 21 Preparation of magnetic hollow silica microspheres.
- the derivatized microspheres were washed by two centrifugation cycles with bicyclohexyl (or toluene) and another two centrifugation cycles with acetone.
- the derivatized microsphere surfaces were then dried by lyophihzation.
- the reduction of the ⁇ -nitrile microsphere surfaces to ⁇ -amine derivatized surfaces was accomphshed by suspending the derivatized microspheres at 50°C for ca. 18 h in a THF solution containing 1 M diborane.
- the reduced surfaces were then washed by centrifugation in THF and then in acetone.
- the primary amino derivatized microsphere surfaces were then dried by lyophihzation. If necessary, albumin blocking of the derivatized microspheres was then performed as described previously.
- Example 25 Covalent binding of acrolein onto the ⁇ -amine derivatized microsphere surfaces.
- microspheres composed of polyaldehyde derivatized sihca coated polystyrene microspheres of ca. 1.8 ⁇ m diameter were shaken at room temperature for 4 h with 1 mg trypsin in 5 ml PBS. Unbound trypsin was then separated by 3 centrifugation cycles in PBS. Residual aldehyde groups on the microspheres were then blocked by shaking the conjugated microspheres at room temperature for 4 h with BSA (1%) in PBS. Unbound BSA was then removed by 2 centrifugation cycles in PBS and then 2 centrifugation cycles in distilled water. The trypsin conjugated microspheres were then dried by lyophihzation.
- ⁇ j-antitrypsin in human serum was based on the inhibitory effect of antitrypsin of serum on the hydrolysis of BAPNA by the conjugated trypsin in Tris buffer. The reaction is stopped by adding acetic acid, and the absorbance is then read at 400 nm. At this wavelength the hberated p- nitroaniline has a molar absorptivity of 10,500. Briefly, before the assay, each examined serum was diluted 1000 fold with Tris buffer. 2 ml of the diluted serum were then incubated at 37°C for 30 min with 1 ml suspension containing
- RIgG magnetic conjugated microspheres (5 mg) prepared as described in example 26.
- the labeled cells were then separated from excess microspheres by 3 centrifugations with PBS.
- the control cells on the other hand, were not labeled at all.
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU41934/96A AU4193496A (en) | 1994-10-06 | 1995-10-05 | Process for the preparation of microspheres and microspheres made thereby |
DE19581787T DE19581787T1 (en) | 1994-10-06 | 1995-10-05 | Process for the production of microspheres and microspheres produced thereby |
US08/809,957 US6103379A (en) | 1994-10-06 | 1995-10-05 | Process for the preparation of microspheres and microspheres made thereby |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL111186 | 1994-10-06 | ||
IL11118694A IL111186A (en) | 1994-10-06 | 1994-10-06 | Process for the preparation of microspheres and microspheres made thereby |
Publications (3)
Publication Number | Publication Date |
---|---|
WO1996011054A2 true WO1996011054A2 (en) | 1996-04-18 |
WO1996011054A3 WO1996011054A3 (en) | 1996-05-23 |
WO1996011054A9 WO1996011054A9 (en) | 1996-08-15 |
Family
ID=11066612
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1995/012988 WO1996011054A2 (en) | 1994-10-06 | 1995-10-05 | Process for the preparation of microspheres and microspheres made thereby |
Country Status (4)
Country | Link |
---|---|
AU (1) | AU4193496A (en) |
DE (1) | DE19581787T1 (en) |
IL (1) | IL111186A (en) |
WO (1) | WO1996011054A2 (en) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2747669A1 (en) * | 1996-04-22 | 1997-10-24 | Rhone Poulenc Chimie | PROCESS FOR THE PREPARATION OF HOLLOW SILICA PARTICLES |
US6296937B2 (en) | 1997-01-21 | 2001-10-02 | W. R. Grace & Co.-Conn. | Silica adsorbent on magnetic substrate |
JP2002159848A (en) * | 2000-11-27 | 2002-06-04 | Japan Science & Technology Corp | Method for producing organic-inorganic composite and metal oxide using saccharide derivertive |
GB2376524A (en) * | 2001-03-27 | 2002-12-18 | Amersham Biosciences Uk Ltd | Scintillation proximity assays for NO synthase |
US6890703B2 (en) | 2002-03-06 | 2005-05-10 | International Business Machines Corporation | Preparation of crosslinked particles from polymers having activatible crosslinking groups |
US7919333B2 (en) | 2003-11-25 | 2011-04-05 | Magnamedics Gmbh | Spherical and magnetical silicagel carriers having an increase surface for purifying nucleic acids |
WO2011131644A1 (en) * | 2010-04-20 | 2011-10-27 | Basf Se | Capsule comprising active ingredient |
US20140228252A1 (en) * | 2012-11-16 | 2014-08-14 | Snu R&Db Foundation | Encoded polymeric microparticles |
EP1608973B1 (en) * | 2003-04-03 | 2015-05-06 | Kimberly-Clark Worldwide, Inc. | Assay devices that utilize hollow particles |
US9278866B2 (en) | 2005-08-10 | 2016-03-08 | The Procter & Gamble Company | Hollow silica particles, compositions comprising them, and methods for making same |
CN110508222A (en) * | 2019-08-02 | 2019-11-29 | 复旦大学 | Monodisperse core-shell particles and preparation method thereof with mesoporous silicon oxide shell |
CN113578214A (en) * | 2021-08-11 | 2021-11-02 | 天津博蕴纯化装备材料科技有限公司 | Micron-sized porous magnetic microsphere and preparation method and application thereof |
CN115893980A (en) * | 2022-09-30 | 2023-04-04 | 安徽华仕新材有限公司 | Process for preparing porous support body ceramic by using nodulizer micro powder |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102016105122B4 (en) * | 2016-03-18 | 2019-07-11 | Bundesrepublik Deutschland, Vertreten Durch Den Bundesminister Für Wirtschaft Und Energie, Dieser Vertreten Durch Den Präsidenten Der Bundesanstalt Für Materialforschung Und -Prüfung (Bam) | A method of synthesizing hybrid core-shell microparticles comprising a polymer core and a controlled-surface silica shell |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2564336A1 (en) * | 1984-05-16 | 1985-11-22 | Ohayon Hanania | Device for separating blood and producing serum |
EP0321322A1 (en) * | 1987-12-18 | 1989-06-21 | Rhone-Poulenc Chimie | Magnetic composite particles from crosslinked organopolysiloxane, process for their preparation and use of them in biology |
WO1992016838A1 (en) * | 1991-03-20 | 1992-10-01 | Gec-Marconi Limited | Separation method |
EP0573150A2 (en) * | 1992-06-04 | 1993-12-08 | Tioxide Group Services Limited | Composite pigmentary material |
-
1994
- 1994-10-06 IL IL11118694A patent/IL111186A/en not_active IP Right Cessation
-
1995
- 1995-10-05 AU AU41934/96A patent/AU4193496A/en not_active Abandoned
- 1995-10-05 WO PCT/US1995/012988 patent/WO1996011054A2/en active Application Filing
- 1995-10-05 DE DE19581787T patent/DE19581787T1/en not_active Ceased
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2564336A1 (en) * | 1984-05-16 | 1985-11-22 | Ohayon Hanania | Device for separating blood and producing serum |
EP0321322A1 (en) * | 1987-12-18 | 1989-06-21 | Rhone-Poulenc Chimie | Magnetic composite particles from crosslinked organopolysiloxane, process for their preparation and use of them in biology |
WO1992016838A1 (en) * | 1991-03-20 | 1992-10-01 | Gec-Marconi Limited | Separation method |
EP0573150A2 (en) * | 1992-06-04 | 1993-12-08 | Tioxide Group Services Limited | Composite pigmentary material |
Non-Patent Citations (3)
Title |
---|
J. OF COLLOID AND INTERFACE SCIENCE, vol. 138, no. 2, September 1990 pages 53434-542, XP 000561465 KAWAHASHI ET AL. 'Preparation and Properties of Uniform Coated Colloidal Particles' cited in the application * |
J. OF COLLOID AND INTERFACE SCIENCE, vol. 143, no. 1, April 1991 pages 103-110, XP 000561464 KAWAHASHI ET AL. 'Preparation of Hollow Spherical Particles of Yttrium Compounds' cited in the application * |
MATIJEVIC: 'Uniform Inorganic Colloid Dispersions. Achievements and Challenges' LANGMUIR vol. 10, no. 1, pages 8 - 16, XP000561075 * |
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1997040105A1 (en) * | 1996-04-22 | 1997-10-30 | Rhodia Chimie | Method for preparing hollow silica particles |
FR2747669A1 (en) * | 1996-04-22 | 1997-10-24 | Rhone Poulenc Chimie | PROCESS FOR THE PREPARATION OF HOLLOW SILICA PARTICLES |
US6296937B2 (en) | 1997-01-21 | 2001-10-02 | W. R. Grace & Co.-Conn. | Silica adsorbent on magnetic substrate |
US6447911B1 (en) | 1997-01-21 | 2002-09-10 | W. R. Grace & Co.-Conn. | Silica adsorbent on magnetic substrate |
JP2002159848A (en) * | 2000-11-27 | 2002-06-04 | Japan Science & Technology Corp | Method for producing organic-inorganic composite and metal oxide using saccharide derivertive |
GB2376524A (en) * | 2001-03-27 | 2002-12-18 | Amersham Biosciences Uk Ltd | Scintillation proximity assays for NO synthase |
GB2376524B (en) * | 2001-03-27 | 2003-12-10 | Amersham Biosciences Uk Ltd | NO synthase assay particles and method |
US7264921B2 (en) | 2001-03-27 | 2007-09-04 | Ge Healthcare Uk Limited | No synthase assay particles and method |
US6890703B2 (en) | 2002-03-06 | 2005-05-10 | International Business Machines Corporation | Preparation of crosslinked particles from polymers having activatible crosslinking groups |
US6992115B2 (en) | 2002-03-06 | 2006-01-31 | International Business Machines Corporation | Preparation of crosslinked particles from polymers having activatible crosslinking groups |
EP1608973B1 (en) * | 2003-04-03 | 2015-05-06 | Kimberly-Clark Worldwide, Inc. | Assay devices that utilize hollow particles |
US7919333B2 (en) | 2003-11-25 | 2011-04-05 | Magnamedics Gmbh | Spherical and magnetical silicagel carriers having an increase surface for purifying nucleic acids |
US9278866B2 (en) | 2005-08-10 | 2016-03-08 | The Procter & Gamble Company | Hollow silica particles, compositions comprising them, and methods for making same |
KR101457287B1 (en) * | 2010-04-20 | 2014-11-04 | 바스프 에스이 | Capsule comprising active ingredient |
WO2011131644A1 (en) * | 2010-04-20 | 2011-10-27 | Basf Se | Capsule comprising active ingredient |
US20140228252A1 (en) * | 2012-11-16 | 2014-08-14 | Snu R&Db Foundation | Encoded polymeric microparticles |
US10557846B2 (en) * | 2012-11-16 | 2020-02-11 | Quantamatrix Inc. | Encoded polymeric microparticles |
CN110508222A (en) * | 2019-08-02 | 2019-11-29 | 复旦大学 | Monodisperse core-shell particles and preparation method thereof with mesoporous silicon oxide shell |
CN113578214A (en) * | 2021-08-11 | 2021-11-02 | 天津博蕴纯化装备材料科技有限公司 | Micron-sized porous magnetic microsphere and preparation method and application thereof |
CN113578214B (en) * | 2021-08-11 | 2023-08-11 | 天津博蕴纯化装备材料科技有限公司 | Micron-sized porous magnetic microsphere and preparation method and application thereof |
CN115893980A (en) * | 2022-09-30 | 2023-04-04 | 安徽华仕新材有限公司 | Process for preparing porous support body ceramic by using nodulizer micro powder |
CN115893980B (en) * | 2022-09-30 | 2023-08-11 | 安徽华仕新材有限公司 | Process for preparing porous support ceramic by using nodulizer micropowder |
Also Published As
Publication number | Publication date |
---|---|
IL111186A (en) | 1999-09-22 |
DE19581787T1 (en) | 1997-11-27 |
WO1996011054A3 (en) | 1996-05-23 |
IL111186A0 (en) | 1994-12-29 |
AU4193496A (en) | 1996-05-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6103379A (en) | Process for the preparation of microspheres and microspheres made thereby | |
WO1996011054A2 (en) | Process for the preparation of microspheres and microspheres made thereby | |
WO1996011054A9 (en) | Process for the preparation of microspheres and microspheres made thereby | |
EP1088315B1 (en) | Nucleation and growth of magnetic metal oxide nanoparticles and its use | |
CA2410023C (en) | Coated nanoparticles | |
US5814687A (en) | Magnetic polymer particle and process for manufacturing the same | |
US8092836B2 (en) | Production of nanocapsules and microcapsules by layer-wise polyelectrolyte self-assembly | |
Oyama et al. | Coating of uniform inorganic particles with polymers, I | |
JP5531232B2 (en) | Polymer-coated inorganic fine particles and method for producing the same | |
JP2003513093A (en) | Composite nanospheres and their complexes with biomolecules | |
AU2001261841A1 (en) | Coated nanoparticles | |
US20060134420A1 (en) | Nanometric or mesoscopic dissymetric particles, and method for preparing same | |
JPH10270233A (en) | Magnetic polymer particles and manufacture therefor | |
EP0105079A1 (en) | A method of producing a magnetic coating composition | |
JP4426819B2 (en) | Method for producing magnetic inclusion particles | |
JPS59221302A (en) | Preparation of magnetic polymer particle | |
JPH11191510A (en) | Magnetic polymer article, its manufacturing and diagnostic medicine | |
US20080038176A1 (en) | Unsymmetrical Inorganic Particles, and Method for Producing the Same | |
CN114192079B (en) | Magnetic hollow polymer microsphere and preparation method and application thereof | |
JP4080798B2 (en) | Magnetic carrier for binding nucleic acid and method for producing the same | |
EP0544450B1 (en) | Supported Microspheres | |
JP4485823B2 (en) | Magnetic inclusion particles and immunoassay particles | |
Elmas et al. | DNA-responsive uniform latex particles based on p-chloromethylstyrene | |
Margel et al. | Synthesis and characterization of nano‐and micron‐sized iron oxide and iron particles for biomedical applications | |
JP4148301B2 (en) | Dry polymer bead preparation |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AL AM AT AU BB BG BR BY CA CH CN CZ DE DK EE ES FI GB GE HU IS JP KE KG KP KR KZ LK LR LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK TJ TT UA UG US UZ VN |
|
AL | Designated countries for regional patents |
Kind code of ref document: A2 Designated state(s): KE MW SD SZ UG AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE BF BJ CF CG CI CM GA GN ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
COP | Corrected version of pamphlet |
Free format text: PAGES 1/6-6/6,DRAWINGS,REPLACED BY NEW PAGES BEARING THE SAME NUMBER;DUE TO LATE TRANSMITTAL BY THE RECEIVING OFFICE |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 08809957 Country of ref document: US |
|
RET | De translation (de og part 6b) |
Ref document number: 19581787 Country of ref document: DE Date of ref document: 19971127 |
|
WWE | Wipo information: entry into national phase |
Ref document number: 19581787 Country of ref document: DE |
|
122 | Ep: pct application non-entry in european phase | ||
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8607 |