Classifications

• • 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
  • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
  • C12N9/0004—Oxidoreductases (1.)
  • C12N9/0006—Oxidoreductases (1.) acting on CH-OH groups as donors (1.1)
• • 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
• • 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
  • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
  • C12N1/04—Preserving or maintaining viable microorganisms
• • 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
  • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
  • C12N9/96—Stabilising an enzyme by forming an adduct or a composition; Forming enzyme conjugates
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10S516/00—Colloid systems and wetting agents; subcombinations thereof; processes of
  • Y10S516/924—Significant dispersive or manipulative operation or step in making or stabilizing colloid system
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T428/00—Stock material or miscellaneous articles
  • Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
  • Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
  • Y10T428/2984—Microcapsule with fluid core [includes liposome]
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T436/00—Chemistry: analytical and immunological testing
  • Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
  • Y10T436/107497—Preparation composition [e.g., lysing or precipitation, etc.]
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T436/00—Chemistry: analytical and immunological testing
  • Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
  • Y10T436/108331—Preservative, buffer, anticoagulant or diluent

Definitions

• the invention relates to methods for preserving sensitive biologically active solutes and suspensions, emulsions and dispersions of, for example, enzymes, proteins, viruses, serums, vaccines, liposomes and cell suspensions .
• the present invention is a method of preserving sensitive biological suspensions and solutions by forming stable foams from fluid materials to be dried, as an aid both to the drying of one or more biologically active substrates in the fluid and as an aid in preparing an easily soluble dried product suitable for further commercial use.
• the stable foams are formed by partially removing water in the biologically active sample to form a viscous liquid and by further subjecting the reduced liquid to vacuum to cause it to "boil" during further drying at temperatures substantially lower than 100 degrees C.
• the present invention is a method of preserving sensitive biological dispersions, suspensions, emulsions and solutions by forming stable foams from fluid materials to be dried, as an aid both to the drying of one or more biologically active substrates in the fluid and as an aid in preparing an easily divisible dried product suitable for further commercial use.
• the stable foams are formed by partially removing the water to form a viscous liquid and by further subjecting the reduced liquid to vacuum, to cause it to "boil" during further drying at temperatures substantially lower than 100 degrees C.
• reduced pressure is applied to viscous solutions or suspensions of biologically active materials to cause the solutions or suspensions to foam during boiling, and during the foaming process further solvent removal causes the ultimate production of a stable open-cell or closed-cell foam.
• foams are easily divisible by cutting, milling or other dividing techniques, and the foaming action itself enhances water removal by maximizing liquid surface area available for evaporation.
• the solvent fraction of the materials to be dried will be aqueous, however, it should be understood that the present method may be applied to solutions and suspensions of various types including those containing nonaqueous solvents or mixture of such solvents .
• the inventive apparatus is a novel combination of a vacuum pump with a temperature controlled desiccator device.
• Optional features of such a combination include sensors for temperature measurement and heat flow control, microprocessors for calculating other process parameters based on data collected from these and other sensors and etc.
• Such a device allows implementation of a novel two- dimensional vacuum and temperature protocol for drying.
• the foam forming process includes two steps: (a) an intensive dehydration of the solution or dispersion containing the biologically active agent by boiling under vacuum, to form a stable, non-collapsing foam and (b) subsequent secondary drying of the foams, to the extent that the foams are stable and do not collapse during storage.
• the invention provides a scalable method for preserving sensitive biologically active materials (proteins, enzymes, serums, vaccines, viruses, liposomes and cell suspensions) with a uniquely engineered drying method. Using this method, it is possible to rehydrate the samples with water or aqueous solutions to reverse the process to the initial biological activity. The method may be applied for the preservation of pharmaceutical, fluid or virtually any other biologically active products or solutes.
• foams are a kinetic process and depends on the rate of temperature and vacuum changes during formation of the foam as well as the initial concentration and composition of the solution or dispersion containing the biologically active substance. Stability of the foams may be further enhanced by the addition of surfactants or other synthetic or biological polymers as long as those additives do not interfere with the biological activity of the solute intended for conversion to dry form. Secondary drying and optional cooling of the formed and initially dry foams may be conducted to assure stability of the foam during storage. Cooling may be used to convert the foamed material to the glass state. Foams prepared according to the present invention may be stored whole or subdivided or milled, and when they are to be used need only be rehydrated in order to restore their original biologic activity.
• Aqueous 50% glycerol isocitrate dehydrogenase solution from Sigma Chemical Co. containing 59.4 units of activity per ml. was dialyzed for 5 hours in 0.1 M TRIS HC1 buffer (pH 7.4).
• the activity decrease was associated with decrease in the enzyme concentration because of dilution during the dialysis.
• the samples were rehydrated with 500 microliters water. Rehydration of the samples containing dry foams was an easy process that was completed within several seconds. Reconstituted sample was assayed for activity by assaying ability to reduce NADP, measured spectrophotometrically at 340 nm.
• the activity was 2.6 +/- 0.2 units/ml. which means there was no loss of activity during drying and subsequent storage at room temperature .

Landscapes

• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Engineering & Computer Science (AREA)
• Genetics & Genomics (AREA)
• Zoology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Wood Science & Technology (AREA)
• Biotechnology (AREA)
• Microbiology (AREA)
• Biomedical Technology (AREA)
• Biochemistry (AREA)
• General Engineering & Computer Science (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Molecular Biology (AREA)
• Dispersion Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Virology (AREA)
• Tropical Medicine & Parasitology (AREA)
• Micro-Organisms Or Cultivation Processes Thereof (AREA)
• Investigating Or Analysing Biological Materials (AREA)
• Agricultural Chemicals And Associated Chemicals (AREA)
• Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
• Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
• Medicinal Preparation (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Medicines Containing Material From Animals Or Micro-Organisms (AREA)
• Manufacture Of Porous Articles, And Recovery And Treatment Of Waste Products (AREA)
• Vaporization, Distillation, Condensation, Sublimation, And Cold Traps (AREA)
• Colloid Chemistry (AREA)
• Drying Of Solid Materials (AREA)

Priority Applications (10)

Applications Claiming Priority (4)

Publications (2)

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ID=26695104

Family Applications (1)

Country Status (18)

Cited By (9)

Families Citing this family (88)

Citations (3)

Family Cites Families (6)

• 1997
  • 1997-01-17 US US08/785,473 patent/US5766520A/en not_active Expired - Fee Related
  • 1997-07-14 EA EA199900268A patent/EA001138B1/ru not_active IP Right Cessation
  • 1997-07-14 DE DE0914202T patent/DE914202T1/de active Pending
  • 1997-07-14 CA CA002260233A patent/CA2260233A1/en not_active Abandoned
  • 1997-07-14 BR BR9711808-7A patent/BR9711808A/pt unknown
  • 1997-07-14 CZ CZ9979A patent/CZ7999A3/cs unknown
  • 1997-07-14 AU AU36606/97A patent/AU714328B2/en not_active Ceased
  • 1997-07-14 EP EP97933415A patent/EP0914202A4/en not_active Withdrawn
  • 1997-07-14 HU HU9903917A patent/HUP9903917A3/hu not_active Application Discontinuation
  • 1997-07-14 CN CN97196422A patent/CN1116104C/zh not_active Expired - Fee Related
  • 1997-07-14 PL PL97331174A patent/PL331174A1/xx unknown
  • 1997-07-14 NZ NZ333738A patent/NZ333738A/xx unknown
  • 1997-07-14 JP JP10506201A patent/JP2000515856A/ja not_active Ceased
  • 1997-07-14 WO PCT/US1997/012156 patent/WO1998002240A1/en not_active Ceased
  • 1997-07-14 IL IL12797197A patent/IL127971A/en not_active IP Right Cessation
  • 1997-07-14 KR KR10-1999-7000253A patent/KR100457748B1/ko not_active Expired - Fee Related
  • 1997-07-14 TR TR1999/00127T patent/TR199900127T2/xx unknown
• 1999
  • 1999-01-14 NO NO990158A patent/NO990158D0/no not_active Application Discontinuation

Patent Citations (3)

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