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
  • G01N33/96—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard
• • 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
  • A61K35/14—Blood; Artificial blood
  • A61K35/16—Blood plasma; Blood serum
• • C—CHEMISTRY; METALLURGY
  • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
  • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
  • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
  • C12Q1/56—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving blood clotting factors, e.g. involving thrombin, thromboplastin, fibrinogen
• • 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
  • Y10S435/00—Chemistry: molecular biology and microbiology
  • Y10S435/802—Logarithmic growth phase
• • 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
  • Y10S435/00—Chemistry: molecular biology and microbiology
  • Y10S435/8215—Microorganisms
  • Y10S435/911—Microorganisms using fungi
  • Y10S435/94—Saccharomyces
  • Y10S435/942—Saccharomyces cerevisiae
• • 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
  • Y10T436/104998—Glucose, ketone, nitrate standard or control
• • 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
  • Y10T436/106664—Blood serum or blood plasma standard or control
• • 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

• 252/408 X 3,466,249 9/1969 Anderson 252/408 3,629,142 12/1971 Marbach 252/408 3,682,835 8/1972 Louder-back 252/408 3,717,549 2/1973 Roberts 195/37 3,751,381 8/1973 Megraw 252/408 3,753,925 8/1973 Louderback et al 252/408 FOREIGN PATENTS OR APPLICATIONS 1,287,083 l/1969 Germany 195/11 4543576 5/1970 Japan 195/11 OTHER PUBLICATIONS The Chemistry and Biology of Yeasts, edited by A. H. Cook, Academic Press 1nc., N.Y., 1958, pp. 252-275.
• Blood serum is a complex biological fluid containing numerous components of substantial physiological importance. In the normal or average healthy person the concentrations of these components fall within certain reasonably well-defined limits. When one or more of these components is determined upon analysis to fall outside of these acceptable limits, various diseases or pathological conditions of the body systems are indicated.
• control standards used in actual practice are the freeze-dried serum which is reconstituted with aqueous ammonium bicarbonate prior to use as described in U.S. Pat. No. 3,466,249, and the liquid blood serum control standard which does not require reconstitution prior to use as disclosed in U.S. Pat. No. 3,682,835.
• a principal raw material used in making these and other such blood control standards is stored blood plasma obtained from blood donor centers and blood banks.
• Blood plasma is normally collected and stored in various anticoagulant materials such as, for example, sodium citrate, heparin and sodium ethylenediamine tetraacetate.
• Certain widely used anticoagulant materials contain, additionally, dextrose (D-glucose).
• ACD blood containing citric acid, sodium citrate and dextrose
• CPD blood containing citrate, phosphate and dextrose.
• the stored product Due to the extraneous additon of anticoagulant materials containing dextrose to the stored blood or blood plasma, the stored product will contain an elevated, or abnormally high, level of dextrose. Consequently, such stored blood plasma is not generally suitable for use as a raw material in the preparation of blood control standards except in the case of so-called abnormal control sera where high levels of dextrose are desired.
• the objects of the present invention are achieved by selective destruction of the dextrose in stored blood by aerobic fermentation with yeast in the negative acceleration phase or in the stationary phase of the yeast growth. It is important to use these growth phases in the practice of the present invention, otherwise the yeast feeds on the blood proteins to make more yeast cells and the protein content of the product is undesirably reduced.
• microorganisms including yeasts
• yeasts are capable of dividing at a rapid rate, e.g., at a frequency of less than once per hour, if kept under favorable growth conditions.
• a rapid rate e.g., at a frequency of less than once per hour
• a multiplication of cells which is exponential or logarithmic.
• a period of little or no growth occurs.
• the lag phase Eventually, exponential multiplication begins. After a period of time, the multiplication slows down in what is termed a period of neg ative acceleration or the late log phase.
• the death of cells balances or exceeds the formation of new cells in what is termed the stationary phase.
• the stationary phase includes the so-called real stationary phase and the phase of decline in growth.
• the cells are growing and dividing whereas in the stationary phase the cells exhibit little or no growth and division.
• yeast growth can be controlled or regulated by providing suitable conditions of nutrient, oxygen supply, pH, temperature and inoculant.
• defibrinated plasma or blood serum is incubated with the yeast for about 12 24 hours, preferably about 18 hours, at normal room temperature (ca. 2025 C).
• yeasts are widely distributed, wellknown microorganisms. Even as early as 1930, some 6,000 cultures of yeast were available from the Centraalbureau voor Schimmelculturen, Baarn, Holland.
• the commercially important yeasts which can be used in the practice of this invention are those such as Saccharomyces cerevisiae, Saccharomyses cerevisiae var. ellipsoideus, Saccharomyces carlsbergensis, Saccharomyces fragilis, and the Torula yeasts, e.g., Torulopsis spherica, Torulopsis utilis (Candida utilis) and Candida pseudotropicalis.
• yeast products are Fleischmanns Active Dry Yeast marketed by Standard Brands Inc., and Red Star Active Dry Yeast, marketed by Universal Foods Corp. These yeast products are essentially compressed distillers yeasts. Preparation of these yeast products from grain alcohol product is well known and described in many patents, e.g., the early patent of H. Fleischmann, U.S. Pat. No. 102,387 (Apr. 26, 1870), which is a modification of the Vienna Process.
• the amount of yeast used according to the present invention can vary somewhat. in general, from about 0.1 gram to about 10 grams of active dry yeast per liter of blood plasma is suitable and about one gram per liter is preferred.
• Freshly stored ACD blood plasma may contain up to 500 mg. dextrose per 100 ml. and after 21 days of storage the dextrose level may still be as high as 300 mg. per 100 ml. In accordance with the present invention, this dextrose level is reduced to about 50 mg. per 100 ml., and preferably to about 40 mg. per 100 ml. This reduction is brought about without any substantial destruction of the normal protein content of the plasma.
• the treated plasma is filtered or centrifuged to separate particulate residue and the resulting filtrate or supernatant is retained for use as the base blood control standard of this invention.
• Sufficient dextrose can then be added back to this base control standard to provide any desired predetermined dextrose level whereby various normal or abnormal blood control standards can be prepared.
• the dextrose level can be increased to a range of from about 80 to about 400 mg. per 100 ml.
• the blood control standard prepared as above can be further treated to reduce the inorganic ion level, particularly sodium, potassium and calcium, and/or to remove the lipoprotein components as described in US. Pat. No. 3,682,835.
• the above-prepared material can be admixed with a strong cation exchange resin such as Dowex-SO to substantially reduce said cation level, and the lipoprotein content can be removed by extraction with a fat-solvent such as a chlorinated hydrocarbon.
• the treated material is then conveniently reconstituted with water to about its original volume.
• the foregoing treatment can also be carried out prior to the selective destruction of the dextrose by the aerobic fermentation with yeast.
• EXAMPLE 1 Pooled human ACD stored blood plasma liters was obtained from a blood donor center. Upon assay, the plasma was determined to contain 345 mg. (mg. per 100 ml.) of glucose and had a total protein content of 6.5 gram The blood plasma was defibrinated by reaction with 30,000 units of thrombin (Thrombin Topical, Parke, Davis & Co., Detroit, Michigan) and then removal of the clotted material. Upon assay, the defibrinated plasma was determined to contain 350 mg. of glucose.
• thrombin Thrombin Topical, Parke, Davis & Co., Detroit, Michigan
• the thus prepared base blood control standard was mixed with 30 grams of Dowex-SO ion exchange resin in three increments of 10 grams each whereby the Na ion level was reduced from its original level of 163 meq./liter to 97 meq./liter and the K ion level was reduced from its original level of 11 meq./liter to 4.8 meq./liter.
• the resin was removed after treatment with each 10 gram increment by filtration through glass wool.
• the final product was determined to have a total protein content of 6.3 gram EXAMPLE 2
• the resin was removed after treatment with each 10 gram increment by filtration through glass wool.
• the resin-treated plasma was determined to contain 310 mg. of glucose.
• the method of making a blood control standard from anticoagulant stored, defibrinated blood plasma containing elevated levels of dextrose comprises selectively destroying dextrose in said blood plasma by aerobic fermentation with agitation utilizing 0.1 to 10 grams of a yeast in the negative acceleration phase or in the stationary phase of the yeast growth per liter of said plasma and separating particulate residue from the fermentation product.
• the blood plasma is incubated with said yeast for about 12 to about 24 hours at about 20 to about 25 C, and in which the dextrose in said blood plasma is reduced from an initial level of about 300 to 500 mg. per 100 ml. to a final level of about 0 to 50 mg. per 100 ml.

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Citations (10)

• 1973
  • 1973-08-10 US US387419A patent/US3897363A/en not_active Expired - Lifetime
• 1974
  • 1974-05-03 CA CA198,888A patent/CA1030448A/fr not_active Expired
  • 1974-05-17 BE BE144425A patent/BE815166A/fr unknown
  • 1974-05-20 IL IL44862A patent/IL44862A/en unknown
  • 1974-06-03 JP JP49062767A patent/JPS5040193A/ja active Pending
  • 1974-06-05 GB GB2486974A patent/GB1440289A/en not_active Expired
  • 1974-06-26 DE DE2430622A patent/DE2430622A1/de active Pending
  • 1974-06-28 FR FR7422591A patent/FR2240452A1/fr not_active Withdrawn
  • 1974-08-01 IT IT25865/74A patent/IT1017819B/it active
  • 1974-08-09 DK DK425274A patent/DK425274A/da not_active Application Discontinuation

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