WO1986002004A1 - Stabilisation de substances biologiques - Google Patents
Stabilisation de substances biologiques Download PDFInfo
- Publication number
- WO1986002004A1 WO1986002004A1 PCT/US1985/001899 US8501899W WO8602004A1 WO 1986002004 A1 WO1986002004 A1 WO 1986002004A1 US 8501899 W US8501899 W US 8501899W WO 8602004 A1 WO8602004 A1 WO 8602004A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antibody
- aqueous composition
- antigen
- preparation
- residue
- Prior art date
Links
- 239000000126 substance Substances 0.000 title abstract description 10
- 230000006641 stabilisation Effects 0.000 title description 5
- 238000011105 stabilization Methods 0.000 title description 5
- 239000000203 mixture Substances 0.000 claims abstract description 42
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000000427 antigen Substances 0.000 claims abstract description 24
- 102000036639 antigens Human genes 0.000 claims abstract description 24
- 108091007433 antigens Proteins 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 150000001720 carbohydrates Chemical class 0.000 claims abstract description 10
- 230000005714 functional activity Effects 0.000 claims abstract description 4
- 238000002360 preparation method Methods 0.000 claims description 19
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 7
- 239000004793 Polystyrene Substances 0.000 claims description 6
- 229920002223 polystyrene Polymers 0.000 claims description 6
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 5
- 229920003023 plastic Polymers 0.000 claims description 5
- 239000004033 plastic Substances 0.000 claims description 5
- 230000000087 stabilizing effect Effects 0.000 claims description 5
- 239000000463 material Substances 0.000 claims description 4
- -1 polyethylene Polymers 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 3
- 108010074605 gamma-Globulins Proteins 0.000 claims description 3
- 201000006747 infectious mononucleosis Diseases 0.000 claims description 3
- 229920000058 polyacrylate Polymers 0.000 claims description 2
- 229920000193 polymethacrylate Polymers 0.000 claims description 2
- 229920000915 polyvinyl chloride Polymers 0.000 claims description 2
- 239000004800 polyvinyl chloride Substances 0.000 claims description 2
- 239000004698 Polyethylene Substances 0.000 claims 1
- 230000002745 absorbent Effects 0.000 claims 1
- 239000002250 absorbent Substances 0.000 claims 1
- 238000002405 diagnostic procedure Methods 0.000 claims 1
- 229920000573 polyethylene Polymers 0.000 claims 1
- 239000003125 aqueous solvent Substances 0.000 abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 239000002245 particle Substances 0.000 description 4
- 229920005862 polyol Polymers 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 239000004816 latex Substances 0.000 description 3
- 229920000126 latex Polymers 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 2
- 241000209149 Zea Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 150000003077 polyols Chemical class 0.000 description 2
- 239000011118 polyvinyl acetate Substances 0.000 description 2
- 229920002689 polyvinyl acetate Polymers 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- VIESAWGOYVNHLV-UHFFFAOYSA-N 1,3-dihydropyrrol-2-one Chemical compound O=C1CC=CN1 VIESAWGOYVNHLV-UHFFFAOYSA-N 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940084986 human chorionic gonadotropin Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000010297 mechanical methods and process Methods 0.000 description 1
- 230000005226 mechanical processes and functions Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- HCTVWSOKIJULET-LQDWTQKMSA-M phenoxymethylpenicillin potassium Chemical compound [K+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)COC1=CC=CC=C1 HCTVWSOKIJULET-LQDWTQKMSA-M 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 150000003233 pyrroles Chemical class 0.000 description 1
- 238000012128 rapid plasma reagin Methods 0.000 description 1
- 239000001044 red dye Substances 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 206010040400 serum sickness Diseases 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- 238000009600 syphilis test Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
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)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Virology (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Mycology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Biophysics (AREA)
- Rehabilitation Therapy (AREA)
- Rheumatology (AREA)
- Zoology (AREA)
- Genetics & Genomics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Abstract
Le résidu de l'évaporation d'une composition comprenant un pyrrole soluble dans l'eau et au moins un saccharide dans un solvant aqueux polaire stabilise l'activité fonctionnelle de substances biologiques telles que des antigènes et des anticorps normalement labiles à des températures ambiantes normales.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US65778684A | 1984-10-04 | 1984-10-04 | |
US657,786 | 1984-10-04 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1986002004A1 true WO1986002004A1 (fr) | 1986-04-10 |
Family
ID=24638655
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1985/001899 WO1986002004A1 (fr) | 1984-10-04 | 1985-10-02 | Stabilisation de substances biologiques |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP0198882A1 (fr) |
AU (1) | AU4966785A (fr) |
WO (1) | WO1986002004A1 (fr) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1988002861A1 (fr) * | 1986-10-13 | 1988-04-21 | Anawa Laboratorien Ag | Procede pour fabriquer une preparation receptrice en vue d'une analyse de depistage de radiorecepteurs, et analyse avec un kit selon ce procede |
WO1995000174A1 (fr) * | 1993-06-25 | 1995-01-05 | Public Health Laboratory Service Board | Stockage d'anticorps |
EP1288663A1 (fr) * | 2000-11-20 | 2003-03-05 | Matsushita Electric Industrial Co., Ltd. | Diagnostics extrasomatiques |
Citations (3)
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 |
-
1985
- 1985-10-02 WO PCT/US1985/001899 patent/WO1986002004A1/fr unknown
- 1985-10-02 EP EP85905251A patent/EP0198882A1/fr not_active Withdrawn
- 1985-10-02 AU AU49667/85A patent/AU4966785A/en not_active Abandoned
Patent Citations (3)
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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 (4)
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CHEMICAL ABSTRACT, Vol. 67, issued 1967, "Stable Aqueous Suspensions of Coenzyme Q" Abstract No. 25402d * |
CHEMICAL ABSTRACT, Vol. 74, issued 1971, KALUGINA et al, "Effect of Solutions of some Synthetic Polymers on the Formed Elements of Preserved Blood", Abstract No. 29987r * |
CHEMICAL ABSTRACT, Vol. 79, issued 1973, GOEDICKE, "Stabilization of Aqueous Pepsin Solutions" Abstract No. 139647r * |
CHEMICAL ABSTRACT, Vol. 99 issued 1983, "Preparation of Stable Immobilized Solid-Phase Reagents" Abstract No. 154814z * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1988002861A1 (fr) * | 1986-10-13 | 1988-04-21 | Anawa Laboratorien Ag | Procede pour fabriquer une preparation receptrice en vue d'une analyse de depistage de radiorecepteurs, et analyse avec un kit selon ce procede |
US4992366A (en) * | 1986-10-13 | 1991-02-12 | Anawa Laboratorien Ag | Process for producing a receptor preparation for a radioreceptor assay and kit-correct radioreceptor assay according to the process |
WO1995000174A1 (fr) * | 1993-06-25 | 1995-01-05 | Public Health Laboratory Service Board | Stockage d'anticorps |
EP1288663A1 (fr) * | 2000-11-20 | 2003-03-05 | Matsushita Electric Industrial Co., Ltd. | Diagnostics extrasomatiques |
EP1288663A4 (fr) * | 2000-11-20 | 2007-11-21 | Matsushita Electric Ind Co Ltd | Diagnostics extrasomatiques |
Also Published As
Publication number | Publication date |
---|---|
AU4966785A (en) | 1986-04-17 |
EP0198882A1 (fr) | 1986-10-29 |
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