WO1999009142A1 - Encapsulation of living tissue cells in a microsphere - Google Patents
Encapsulation of living tissue cells in a microsphere Download PDFInfo
- Publication number
- WO1999009142A1 WO1999009142A1 PCT/US1998/016944 US9816944W WO9909142A1 WO 1999009142 A1 WO1999009142 A1 WO 1999009142A1 US 9816944 W US9816944 W US 9816944W WO 9909142 A1 WO9909142 A1 WO 9909142A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- solution
- living tissue
- tissue cells
- mixture
- cells
- Prior art date
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Classifications
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- 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
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—Inorganic compounds
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/38—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix containing added animal cells
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- C—CHEMISTRY; METALLURGY
- C03—GLASS; MINERAL OR SLAG WOOL
- C03C—CHEMICAL COMPOSITION OF GLASSES, GLAZES OR VITREOUS ENAMELS; SURFACE TREATMENT OF GLASS; SURFACE TREATMENT OF FIBRES OR FILAMENTS MADE FROM GLASS, MINERALS OR SLAGS; JOINING GLASS TO GLASS OR OTHER MATERIALS
- C03C4/00—Compositions for glass with special properties
- C03C4/0007—Compositions for glass with special properties for biologically-compatible glass
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/02—Use of particular materials as binders, particle coatings or suspension media therefor
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/04—Luminescent, e.g. electroluminescent, chemiluminescent materials containing natural or artificial radioactive elements or unspecified radioactive elements
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
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- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/08—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials
- C09K11/59—Luminescent, e.g. electroluminescent, chemiluminescent materials containing inorganic luminescent materials containing silicon
- C09K11/592—Chalcogenides
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N11/00—Carrier-bound or immobilised enzymes; Carrier-bound or immobilised microbial cells; Preparation thereof
- C12N11/02—Enzymes or microbial cells immobilised on or in an organic carrier
- C12N11/04—Enzymes or microbial cells immobilised on or in an organic carrier entrapped within the carrier, e.g. gel or hollow fibres
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- G—PHYSICS
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- G02F—OPTICAL DEVICES OR ARRANGEMENTS FOR THE CONTROL OF LIGHT BY MODIFICATION OF THE OPTICAL PROPERTIES OF THE MEDIA OF THE ELEMENTS INVOLVED THEREIN; NON-LINEAR OPTICS; FREQUENCY-CHANGING OF LIGHT; OPTICAL LOGIC ELEMENTS; OPTICAL ANALOGUE/DIGITAL CONVERTERS
- G02F1/00—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics
- G02F1/01—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour
- G02F1/13—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour based on liquid crystals, e.g. single liquid crystal display cells
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- G02F1/1336—Illuminating devices
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J29/00—Details of cathode-ray tubes or of electron-beam tubes of the types covered by group H01J31/00
- H01J29/02—Electrodes; Screens; Mounting, supporting, spacing or insulating thereof
- H01J29/10—Screens on or from which an image or pattern is formed, picked up, converted or stored
- H01J29/18—Luminescent screens
- H01J29/30—Luminescent screens with luminescent material discontinuously arranged, e.g. in dots, in lines
- H01J29/32—Luminescent screens with luminescent material discontinuously arranged, e.g. in dots, in lines with adjacent dots or lines of different luminescent material, e.g. for colour television
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K2035/126—Immunoprotecting barriers, e.g. jackets, diffusion chambers
-
- G—PHYSICS
- G02—OPTICS
- G02F—OPTICAL DEVICES OR ARRANGEMENTS FOR THE CONTROL OF LIGHT BY MODIFICATION OF THE OPTICAL PROPERTIES OF THE MEDIA OF THE ELEMENTS INVOLVED THEREIN; NON-LINEAR OPTICS; FREQUENCY-CHANGING OF LIGHT; OPTICAL LOGIC ELEMENTS; OPTICAL ANALOGUE/DIGITAL CONVERTERS
- G02F1/00—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics
- G02F1/01—Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the intensity, phase, polarisation or colour
- G02F1/0102—Constructional details, not otherwise provided for in this subclass
Definitions
- the field of the present invention is microsphere encapsulation of living tissue.
- a process for synthesizing amorphous silica microspheres which includes the steps of placing into a container an organosilicon precursor and with a highly acidic solution and rinsing with a solvate to remove excess of the organosilicon precursor from the amorphous silica microspheres.
- the organosilicon precursor and the highly acidic solution are immiscible.
- the process for synthesizing amorphous silica microspheres also includes the steps adding a dopant from a group consisting of rhodamine-6G, rhodamine-B, europium 3+ , fluorescein, coumarin-120, coumarin-314T, thionine, uranium and uranium-sensitized europium, stirring the organosilicon precursor and the highly acidic solution to form droplets of the organosilicon precursor in the highly acidic solution whereby water in the highly acidic solution hydrolizes the droplets of the organosilicon precursor to form amorphous silica microspheres and rinsing with a solvent to remove excess of the organosilicon precursor therefrom.
- the results provide fluorescence behavior.
- tissue cells and microbial cells such as yeast cells are encapsulated in an inorganic gel prepared from an organosilicon.
- Encapsulation of tissue cells is performed by mixing an organosilicon precursor with a highly acidic aqueous solution to hydrolyze the organosilicon precursor and provide a gel forming solution, cooling the gel forming solution, forming a mixture of living tissue cells and Hank's balanced salt solution, adding a base solution to the gel forming solution, immediately thereafter adding the mixture containing tissue cells to the gel forming solution, and pouring the resultant mixture into a container where an inorganic gel forms encapsulating the tissue cells.
- the organosilicon precursor may be tetraethoxysilane, tetrabutoxysilane, tetramethoxysilane or tetrapropoxysilane .
- Microbial cells are encapsulated by a similar procedure where a gel forming solution is prepared by adding a base to a solution resulting from hydrolyzing an organosilicon with a highly acidic aqueous solution, a microbial cell dispersion is mixed with the gel forming solution and the resultant mixture is poured into a container to form an inorganic gel encapsulating the microbial cells.
- the present invention is generally directed to a process for encapsulating a living tissue cell in a microsphere .
- the process for encapsulating living tissue cells in a plurality of microspheres includes the steps of mixing an organometallic precursor and a hydrolyzing solution to form a gel forming solution, mixing living tissue cells and a salt solution to form a solution containing living tissue cells and mixing the solution containing living tissue cells with the gel forming solution to form a mixture of a specific density.
- the process also includes the steps of mixing the mixture into a container containing an oil and stirring the mixture to form a plurality of microspheres each of which encapsulates some of the living tissue cells.
- the oil is immiscible with the mixture and has a lower specific density than the specific density of the mixture.
- the process also includes the steps of forming droplets of the mixture and putting the droplets into a column of an oil.
- the oil is immiscible with the mixture and has a lower specific density than the specific density of the mixture at the top thereof to form a plurality of microspheres each of which encapsulates some of the living tissue cells.
- the organosilicon precursor is selected from a group consisting of tetraethoxysilane, tetrabutoxysilane, tetramethoxysilane and tetrapropoxysilane.
- the living tissue cells are from an animal.
- the living tissue cells are from a plant. In a sixth separate aspect of the present invention, the living tissue cells are from fungi.
- the living tissue cells are from bacteria.
- Ceramic material can be used to encapsulate live tissue cells that can secrete therapeutic compounds and are implanted in a host (patient) to mimic a natural organ's delivery of therapeutic compounds.
- the live tissue may be genetically engineered to enhance or accomplish the desired result .
- the ceramic material is porous enough to allow passage of the therapeutic molecules, but the openings are small enough to isolate the implanted cells from the host's immune system.
- the inorganic encapsulating material is biologically inert, which reduces the risk of immune or autoimmune responses.
- Fig. 1 is a side elevation of a stir bar and a container which contains an oil and into which the mixture of the solution containing living tissue cells with the gel forming solution to form a mixture according to the first embodiment of the present invention.
- Fig. 2 is a side elevation of a dropper and a column of an oil into which the mixture of the solution containing living tissue cells with the gel forming solution to form a mixture according to the second embodiment of the present invention.
- a process for synthesizing a sol-gel encapsulating living tissue cells includes the steps of placing into a first container an organometallic precursor and a hydrolyzing solution, stirring the solution until the solution becomes clear, chilling the clear solution in an ice bath, placing into a second container living tissue cells and a balanced salt solution to form a tissue solution.
- Living tissue cells are harvested.
- the living tissue cells are placed in a balanced salt solution to form a tissue solution.
- the solution for human cells can be a common medical saline solution. The need is to balance sufficiently the salinity with the cells to be encapsulated to avoid rupture.
- U.S. Patent No. 4,797,213 teaches the use of Hanks ' balanced salt solution in column 6, line 10.
- the living tissue cells may be from a plant, an animal, bacteria, fungi or yeast.
- the organometallic precursor may be an organosilicon precursor and the hydrolyzing solution may be a highly acidic solution having a molar concentration of acid in the range of 0.05 to 2.5.
- the process also includes the steps of adding a base solution having a molar concentration of base in the range of 0.05 to 2.5 to the clear solution, immediately thereafter adding the tissue solution to the clear solution and the base solution, stirring the clear solution, the base solution and the tissue solution to form a gel forming solution and treating the gel forming solution to achieve the desired physical structure of the inorganic gel encapsulating the living tissue cells.
- the base solution is added to neutralize sufficiently the solution to avoid cell damage from an extreme pH.
- the organosilicon precursor may be selected from a group consisting of tetraethoxysilane, tetrabutoxysilane, tetramethoxysilane, tetrapropoxysilane and methyl trimethoxysilane.
- the organometallic precursor may be selected from a group consisting of aluminum tri-n- propoxide, aluminum tri (sec) butoxide, aluminum acetoacetic ester chelate di (sec) butoxide, zirconium tri (sec)butoxide, boron butoxide, boron methoxide, titanium (iv) butoxide, titanium isopropoxide and zirconium isopropoxide .
- the highly acidic solution is selected from a group consisting of nitric acid (HN0 3 ) and hydrochloric acid (HC1) .
- Other highly acidic solutions may also be used including sulfuric acide (H 2 S0 4) .
- the base solution is ammonium hydroxide. Please refer to C. J. Brinker, Journal of Non-Crystaline Solutions, Volume 48, page 48 and Volume 63, page 45.
- Tissue cells of a plant may be harvested from a leaf by grinding the leaf into leaf- fragments. The leaf-fragments are are placed in a balanced salt solution to form a plant tissue solution.
- Tissue cells of an animal may be harvested from the liver, the pancreas, the thyroid, the parathyroid, the pituitary gland and the renal cortex of mammals including man.
- the sol-gel which encapsulates one of these tissue cells may be used in an artificial organ such as either an artificial liver or an artificial pancreas.
- living animal tissue cells have been harvested from beef liver (bovine hepatocytes) .
- the standard procedure for dispersing living animal tissue cells is to cut beef liver into small cubes. About 10 grams of the small cubes of beef liver are placed in 60 milliliters of Hanks' balanced salt solution for one half hour in order to remove the hemoglobin from the beef lever. The Hanks' balanced salt solution is removed. Forty milligrams of collagenase and sixty milligrams of dispase are dissolved in the Hanks ' balanced salt solution. Dispase and collagenase are enzymes. The Hanks ' balanced salt solution is shaken for one half hour and decented to form a tissue solution. The tissue solution is a supernatent solution which has individual living liver cells dispersed therein. The inventor has encapsulated liver cells in an organic gel.
- U. S. Patent No. 5,270,192 teaches a hepatocyte bioreactor, a bioartificial liver, which includes a containment vessel having a perfusion inlet and a perfusion outlet, a matrix within the containment vessel so as to entrap hepatocyte aggregates within the containment vessel while allowing perfusion of the matrix.
- U. S. Patent No. 4,391,909 teaches tissue cells such as islet of Langerhans cells or liver cells which are encapsulated within a spheroidal semipermeable membrane including a polysaccharide having acidic groups cross-linked with a polymer having a molecular weight greater than 3,000.
- the cells within the microcapsules are viable, healthy, physiologically active and capable of ongoing metabolism.
- the encapsulated cells are useful for implantation in a mammalian body to produce substances and effect chemical changes characteristic of the cells in vivo tissue.
- the inventor has encapsulated islet of Langerhans cells in an organic gel .
- the composition includes a matrix capable of delivering BMP-2A, BMP-2B or other BMP protein to the site of bone and/or cartilage damage, providing a structure for the developing bone and cartilage and optimally capable of being resorbed into the body.
- matrices may be formed of materials presently in use for other implanted medical DNA sequences encoding the osteoinductive proteins applications.
- the choice of matrix material is based on biocompatibility, biodegradability, mechanical properties, cosmetic appearance and interface properties.
- the particular application of the BMP-2 compositions will define the appropriate formulation.
- Potential matrices for the compositions may be biodegradable and chemically defined calcium sulfate, tricalciumphosphate, hydroxyapatite, polylactic acid and polyanhydrides .
- Other potential materials are biodegradable and biologically well defined, such as bone or dermal collagen.
- Further matrices consists of pure proteins or extracellular matrix components.
- Other potential matrices are nonbiodegradable and chemically defined, such as sintered hydroxyapatite, bioglass, aluminates, or other ceramics .
- Matrices may be comprised of combinations of any of the above mentioned types of material, such as polylactic acid and hydroxyapatite or collagen and tricalciumphosphate.
- the bioceramics may be altered in composition, such as in calcium-aluminate-phosphate and processing to alter pore size, particle size, particle shape, and biodegradability.
- the dosage regimen will be determined by the attending physician considering various factors which modify the action of the BMP-2 protein, e.g. amount of bone weight desired to be formed, the site of bone damage, the condition of the damaged bone, the size of a wound, type of damaged tissue, the patient's age, sex, and diet, the severity of any infection, time of administration and other clinical f ctors.
- the dosage may vary with the type of matrix used in the reconstitution and the types of BMP proteins in the composition.
- the addition of other known growth factors, such as IGF I (insulin like growth factor I) may also effect the dosage.
- the biological substance of U. S. Patent No. 5,453,368 includes PC-12 cells which were cultured in standard RPMI .
- the cells were taken up by pipette, placed in centrifuge tubes and spun down.
- the cells were brought up to a volume of 2 ml, to a cell concentration of approximately 2xl0 6 to 5xl0 6 per ml.
- the cell containing liquid was placed in sterile Hamilton syringe and placed on a Harvard apparatus injector pump.
- the pump was connected via 18 gauge polytetra-fluoroethylene tubing to a 24 gauge stainless steel tube, which served as an apparatus for dropping the liquid.
- Microcapsules containing bovine adrenal chromaffin cells in a 1.5% sodium alginate solution (W/V) were prepared.
- the PBS collection bath container contained 1.5% (W/V) calcium chloride. After six weeks in culture, the microcapsules contained viable cells.
- Red apple ground cover leaf cells (individual chlorophyl-containing cells extracted from supernatent of ground leaves) .
- Photobacterium phosphoreum bioluminescent marine bacteria
- Geospirillum arsenophiluf MIT-13
- Murine islets of Langerhans Porcine islets of Langerhans, Bovine hepatocytes.
- Porcine hepatocytes Human white blood cells, Human red blood cells,
- Rat PC-12 cells (from rat pheochromocytoma) , Lac-z transfected murine mesenchymal stem cells
- the process for encapsulating living tissue cells in a plurality of microspheres includes the steps of mixing an organometallic precursor and a hydrolyzing solution to form a gel forming solution, mixing living tissue cells and a salt solution to form a solution containing living tissue cells and mixing the solution containing living tissue cells with the gel forming solution to form a mixture of a specific density.
- the living tissue cells are from either an animal or a plant.
- the process also includes the steps of mixing the mixture into a container 11 containing an oil 12 and stirring with a stir bar 13 the mixture to form a plurality of microspheres 14. Each microsphere 14 encapsulates some of the living tissue cells.
- the oil 12 is immiscible with the mixture and has a lower specific density than the specific density of the mixture.
- the organometallic precursor may be a organosilicon precursor.
- the organosilicon precursor may be selected from a group consisting of tetraethoxysilane, tetra-butoxysilane, tetramethoxysilane and tetrapropoxysilane . Referring to Fig. 2 a process is disclosed for encapsulating a living tissue cell in a microsphere.
- the process for encapsulating living tissue cells in a plurality of microspheres includes the steps of mixing an organometallic precursor and a hydrolyzing solution to form a gel forming solution, mixing living tissue cells and a salt solution to form a solution containing living tissue cells and mixing the solution containing living tissue cells with the gel forming solution to form a mixture of a specific density.
- the living tissue cells are from either an animal or a plant .
- the process also includes the steps of forming droplets of the mixture and putting the droplets into a column 111 of an oil 112.
- the oil 112 is immiscible with the mixture and has a lower specific density than the specific density of the mixture at the top thereof to form a plurality of microspheres.
- the organometallic precursor may be a organosilicon precursor.
- the organosilicon precursor may be selected from a group consisting of tetraethoxysilane, tetra-butoxysilane, tetramethoxysilane and tetra-propoxysilane .
Abstract
Description
Claims
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000509809A JP2001514880A (en) | 1997-08-18 | 1998-08-14 | Encapsulation of living tissue cells into microspheres |
AU87843/98A AU8784398A (en) | 1997-08-18 | 1998-08-14 | Encapsulation of living tissue cells in a microsphere |
EP98939412A EP1007634A1 (en) | 1997-08-18 | 1998-08-14 | Encapsulation of living tissue cells in a microsphere |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/912,771 US5895757A (en) | 1993-06-30 | 1997-08-18 | Encapsulation of living tissue cells in inorganic microspheres prepared from an organosilicon |
US08/912,771 | 1997-08-18 |
Publications (1)
Publication Number | Publication Date |
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WO1999009142A1 true WO1999009142A1 (en) | 1999-02-25 |
Family
ID=25432417
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/US1998/016944 WO1999009142A1 (en) | 1997-08-18 | 1998-08-14 | Encapsulation of living tissue cells in a microsphere |
Country Status (6)
Country | Link |
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US (1) | US5895757A (en) |
EP (1) | EP1007634A1 (en) |
JP (1) | JP2001514880A (en) |
CN (1) | CN1292816A (en) |
AU (1) | AU8784398A (en) |
WO (1) | WO1999009142A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2785292A1 (en) * | 1998-10-30 | 2000-05-05 | Rhodia Chimie Sa | CAPSULES WITH POROUS MINERAL SHELL IN WHICH ARE IMMOBILIZED IN A LIQUID BIOLOGICAL MEDIUM, ONE OR MORE BIOLOGICAL MATERIALS, THEIR PREPARATION PROCESS AND USES |
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DE1104287T1 (en) * | 1998-08-13 | 2001-12-20 | Sol Gel Technologies Ltd | METHOD FOR PRODUCING OXIDE MICROCAPSULES LOADED WITH FUNCTIONALIZED MOLECULES AND THE PRODUCTS OBTAINED FROM THEM |
US6818594B1 (en) | 1999-11-12 | 2004-11-16 | M-I L.L.C. | Method for the triggered release of polymer-degrading agents for oil field use |
NZ531316A (en) | 1999-11-12 | 2005-08-26 | Mi Llc | Method and composition for the triggered release of polymer-degrading agents for oil field use |
US7758888B2 (en) | 2000-04-21 | 2010-07-20 | Sol-Gel Technologies Ltd. | Composition exhibiting enhanced formulation stability and delivery of topical active ingredients |
CN100453162C (en) * | 2003-07-31 | 2009-01-21 | 索尔-格尔科技有限公司 | Microcapsules loaded with active ingredients and a method for their preparation |
AU2004229070A1 (en) * | 2003-11-13 | 2005-06-02 | Dale C. Gyure | Novel bioreactor |
CN1319525C (en) * | 2004-09-16 | 2007-06-06 | 北京圣医耀科技发展有限责任公司 | Taxinol-sodium alginate micro ball vascular embolism agent and its preparation |
AU2006274541B2 (en) * | 2005-08-02 | 2012-12-13 | Sol-Gel Technologies Ltd. | Metal oxide coating of water insoluble ingredients |
CN101594854B (en) * | 2006-12-28 | 2012-02-08 | 陶氏康宁公司 | Polynuclear microcapsules |
BRPI0808160A2 (en) * | 2007-02-01 | 2014-09-23 | Sol Gel Technologies Ltd | PROCESS FOR COATING A SOLID, WATER-INSOLATED PRIVATE MATERIAL WITH A METAL OXIDE, COATED PARTICULATED MATERIALS, METHODS TO TREAT A SURFACE CONDITION ON AN INDIVIDUAL, AND TO PREVENT, REDUCE, OR ELIMINATE, OR ELIMINATE, USE OF COATED PRIVATE MATERIAL |
KR20090125243A (en) | 2007-02-01 | 2009-12-04 | 솔-겔 테크놀로지스 리미티드 | Compositions for topical application comprising a peroxide and retinoid |
JP5344417B2 (en) * | 2007-04-17 | 2013-11-20 | 国立大学法人群馬大学 | Method for producing drug-silica inclusion body using water-oil interface |
WO2011156484A2 (en) * | 2010-06-08 | 2011-12-15 | President And Fellows Of Harvard College | Low-temperature synthesis of silica |
US9273305B1 (en) * | 2012-04-25 | 2016-03-01 | Sandia Corporation | Cell-based composite materials with programmed structures and functions |
US9687465B2 (en) | 2012-11-27 | 2017-06-27 | Sol-Gel Technologies Ltd. | Compositions for the treatment of rosacea |
US11541105B2 (en) | 2018-06-01 | 2023-01-03 | The Research Foundation For The State University Of New York | Compositions and methods for disrupting biofilm formation and maintenance |
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1997
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1998
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- 1998-08-14 CN CN988102919A patent/CN1292816A/en active Pending
- 1998-08-14 AU AU87843/98A patent/AU8784398A/en not_active Abandoned
- 1998-08-14 EP EP98939412A patent/EP1007634A1/en not_active Withdrawn
- 1998-08-14 JP JP2000509809A patent/JP2001514880A/en active Pending
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FR2785292A1 (en) * | 1998-10-30 | 2000-05-05 | Rhodia Chimie Sa | CAPSULES WITH POROUS MINERAL SHELL IN WHICH ARE IMMOBILIZED IN A LIQUID BIOLOGICAL MEDIUM, ONE OR MORE BIOLOGICAL MATERIALS, THEIR PREPARATION PROCESS AND USES |
WO2000025761A1 (en) * | 1998-10-30 | 2000-05-11 | Rhodia Chimie | Capsules with porous mineral cortex |
Also Published As
Publication number | Publication date |
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AU8784398A (en) | 1999-03-08 |
EP1007634A1 (en) | 2000-06-14 |
US5895757A (en) | 1999-04-20 |
JP2001514880A (en) | 2001-09-18 |
CN1292816A (en) | 2001-04-25 |
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