EP0198882A1 - Stabilisierung biologischer substanzen - Google Patents

Stabilisierung biologischer substanzen

Info

Publication number
EP0198882A1
EP0198882A1 EP85905251A EP85905251A EP0198882A1 EP 0198882 A1 EP0198882 A1 EP 0198882A1 EP 85905251 A EP85905251 A EP 85905251A EP 85905251 A EP85905251 A EP 85905251A EP 0198882 A1 EP0198882 A1 EP 0198882A1
Authority
EP
European Patent Office
Prior art keywords
antibody
aqueous composition
antigen
preparation
residue
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP85905251A
Other languages
English (en)
French (fr)
Inventor
Jack E. Dickinson
John S. Paxos
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Preco LLC
Original Assignee
Preco LLC
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
Application filed by Preco LLC filed Critical Preco LLC
Publication of EP0198882A1 publication Critical patent/EP0198882A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • 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
    • 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
    • G01N33/5306—Improving reaction conditions, e.g. reduction of non-specific binding, promotion of specific binding
    • 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
    • G01N33/54393—Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
    • 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
    • G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
    • G01N33/545—Synthetic resin
    • 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
    • G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
    • 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
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56966—Animal cells
    • 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
    • G01N33/569—Immunoassay; Biospecific binding assay; Materials therefor for microorganisms, e.g. protozoa, bacteria, viruses
    • G01N33/56983—Viruses

Definitions

  • the invention pertains to compositions which stabilize the functional activity of antibodies and antigen preparations for long periods of time at normal ambient temperatures.
  • Chemical additives as for example, protective proteins such as bovine serum albumin; saccharides such as dextrin and mannose; and ammonium salt suspensions, have been used previously to stabilize biological sub ⁇ stances.
  • Mechanical processes such as spray drying and freeze drying also have been used.
  • Test surfaces containing dried immunological components are described in, for example, U.S. Patent No. 3,666,421 and U.S. Patent No. 3,770,383. Such systems have been limited to materials of high stability or require storage at reduced temperatures to achieve stability.
  • U.S. Patent No. 4,498,321 describes a fixative and preservative composition for histology, cytology and proteinaceous preparations comprising a mixture of pyrrolide-2-one, a polyol, urea, and a zinc salt of a non-oxidizing organic or inorganic acid.
  • the activity of biological substances is stabilized for long periods of time at normal ambient temperatures, that is, from about 0° to about 40°C.
  • the inven ⁇ tion pertains to an aqueous composition which uses as stabilizing components a water soluble pyrrole and at least one saccharide polyol.
  • the preferred water sol- uble pyrroles are 2-pyrrolidone and pyrrole, especially 2-pyrrolidone.
  • the polyol is a saccharide such as sucrose, glucose, sorbitol, fructose, dextrin, corn syrup, and the like, the selection depending upon the characteristics of the biological substances to be sta ⁇ bilized and the matrix in which the substance appears.
  • the pyrrole and saccharide are mixed in a polar aqueous solvent, preferrably water, to which may be optionally added an alcohol, such as methanol and ethanol.
  • the preferred formulation of the aqueous com ⁇ position of the invention contains a water soluble pyrrole, such as but not limited to, 2-pyrrolidone, in a concentration range of about 0.01% to about 5% by weight, and one or more saccharide polyols in a usual concentration range of about 0.01% to about 10% by weight in a polar aqueous solvent.
  • a water soluble pyrrole such as but not limited to, 2-pyrrolidone
  • the preferred water soluble pyrrole, 2-pyrrolidone is used in a preferred concentration range of 0.1% to 2% by weight.
  • the ratio of saccharide to water soluble pyrrole thus is from about 200:1 to about 02:1.
  • the evaporative residue obtained upon evapora ⁇ tion of this aqueous composition of the water soluble pyrrole and the saccharide, alone or in combination with other compounds, so as to remove unbound water has the ability to stabilize the functional activity of a wide variety of biological substances at normal ambient tem ⁇ peratures.
  • a particularly important application is the stabilizing effect upon protein molecules, including lipoproteins, glycoproteins and polypeptides, most not ⁇ ably normally labile antibodies and antigens utilized in diagnostic compositions. It appears the evaporative residue of the composition exerts its stabilizing effect by protecting the internal hydrogen bonding of the protein structure from disruption.
  • the composition can be mixed with rheumatoid antigen which is coated on small latex particles, the evaporative residue of which forms the basis for a diagnostic medical device for the detec- tion of rheumatoid factor associated with rheumatoid arthritis and other similar diseases.
  • RPR antigen absorbed to particles of the water insol ⁇ uble dye toluidene red.
  • the mixture of this antigen and the composition of the invention is stable at ordinary room temperature (from about 2°C to about 35°C) for long periods of time.
  • the mixture of the composition of the invention and the TRUST antigen is dried by evaporation to form a convenient stable dry reagent which, when reconstituted with the test sample, allows the detection of syphilis. A positive is easily visualized with the unaided eye by observing obvious clumping of the red dye particles.
  • Another application is stabilization of anti ⁇ bodies.
  • the stabilization cellular stroma is the stabilization cellular stroma.
  • the composition when mixed with dyed horse erythrocyte stroma, becomes the basis of a diagnostic medical device for the detection of infectious mononucleosis, serum sickness and Forssman antibodies which is stable at room temperature. It is sometimes desirable to add other sub ⁇ stances to the basic aqueous composition. For example, it is often advantageous to add substances which, upon evaporative drying, are capable of forming a protective skin such as polyalkene acrylamides or hydroxymethyl- cellulose.
  • Particularly useful in some applications is the addition to the aqueous composition of sufficient polyvinyl alcohol, or a mixture of polyvinyl alcohol and polyvinyl acetate, to increase the viscosity and elas ⁇ ticity of the final evaporative residue. This not only improves the physical properties but also can be used to control the reaction of the antibody or antigen to improve sensitivity.
  • a buffer mixture into the basic composition to achieve pH stability.
  • surfactants to the basic compound, particularly when the biologically active sub ⁇ stance is colloidal or has been rendered colloidal by absorption on or binding to an insoluble substance such as polystyrene beads.
  • Inorganic salts also may be added.
  • the antigen or antibody and composition of the invention may be dried on an inert, solid, water insol ⁇ uble strip surface, such as glass, plastics, plastic- coated cards and the like.
  • the surface is a plastic such as polystyrene, polyacrylate, polymeth- acrylate or polyvinylchloride.
  • the preferred surface to accept the evaporative residue is a white coextruded polystyrene card containing concave depressions or wells having a diameter at the flat surface of the card of 19 mm. Into such depressions is placed a measured drop of the composition which is then allowed to dry by evapora ⁇ tion.
  • the concave depression becomes a convenient reaction vessel when the evaporative residue is recon ⁇ stituted with a sample, the preferred sample for such testing being blood serum.
  • the above solution is added to a suspension of gamma globulin attached to latex particles in a ratio of from about 1:9 to about 1:3 stabilizer:latex suspension, the preferred ratio being 1:9.
  • the resulting suspen ⁇ sion may be used in the preparation of a diagnostic medical device for the detection of rheumatoid factor.
  • a small volume of the above mixture is placed in the depression or well of a polystyrene card pre ⁇ viously described.
  • the spot is allowed to dry by evaporation at room temperature, as for example, at about 25°C and a relative humidity of about 22%.
  • the evaporation may be unaided or a gentle stream of air may be used.
  • the device When unbound water has been removed, the device is covered with aluminum foil fixed to the poly ⁇ styrene strip.
  • the evaporative residue contains the diagnostic reagent is stable at normal ambient tempera ⁇ tures of from just over the freezing point of water to about 40°C with no loss of biological activity for periods exceeding one year.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Cell Biology (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • General Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Food Science & Technology (AREA)
  • Biotechnology (AREA)
  • Pathology (AREA)
  • Virology (AREA)
  • Organic Chemistry (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Rheumatology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biophysics (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Mycology (AREA)
  • Rehabilitation Therapy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Medicinal Preparation (AREA)
EP85905251A 1984-10-04 1985-10-02 Stabilisierung biologischer substanzen Withdrawn EP0198882A1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US65778684A 1984-10-04 1984-10-04
US657786 1984-10-04

Publications (1)

Publication Number Publication Date
EP0198882A1 true EP0198882A1 (de) 1986-10-29

Family

ID=24638655

Family Applications (1)

Application Number Title Priority Date Filing Date
EP85905251A Withdrawn EP0198882A1 (de) 1984-10-04 1985-10-02 Stabilisierung biologischer substanzen

Country Status (3)

Country Link
EP (1) EP0198882A1 (de)
AU (1) AU4966785A (de)
WO (1) WO1986002004A1 (de)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH676508A5 (de) * 1986-10-13 1991-01-31 Anawa Lab Ag
GB9313163D0 (en) * 1993-06-25 1993-08-11 Health Lab Service Board Storage of antibodies
JPWO2002040999A1 (ja) * 2000-11-20 2004-03-25 松下電器産業株式会社 体外診断薬

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SU609524A1 (ru) * 1976-12-20 1978-06-05 Центральный Ордена Ленина И Ордена Трудового Красного Знамени Научно-Исследовательский Институт Гематолигии И Переливания Крови Раствор дл замораживани костного мозга
US4162242A (en) * 1977-03-28 1979-07-24 Chevron Research Company Polyol stabilization additive for polypyrrolidone
US4493821A (en) * 1982-02-04 1985-01-15 Harrison James S Preservative and fixative preparations for biological systems

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO8602004A1 *

Also Published As

Publication number Publication date
AU4966785A (en) 1986-04-17
WO1986002004A1 (en) 1986-04-10

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Inventor name: DICKINSON, JACK, E.

Inventor name: PAXOS, JOHN, S.