US3803115A - Stabilization of ahf using heparin - Google Patents

Stabilization of ahf using heparin Download PDF

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Publication number
US3803115A
US3803115A US00254148A US25414872A US3803115A US 3803115 A US3803115 A US 3803115A US 00254148 A US00254148 A US 00254148A US 25414872 A US25414872 A US 25414872A US 3803115 A US3803115 A US 3803115A
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United States
Prior art keywords
heparin
ahf
plasma
glycine
yield
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.)
Expired - Lifetime
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US00254148A
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English (en)
Inventor
L Fekete
S Holst
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Baxter International Inc
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Baxter Laboratories Inc
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Filing date
Publication date
Application filed by Baxter Laboratories Inc filed Critical Baxter Laboratories Inc
Priority to US00254148A priority Critical patent/US3803115A/en
Priority to IL42221A priority patent/IL42221A/en
Priority to ZA733138A priority patent/ZA733138B/xx
Priority to JP48054039A priority patent/JPS596845B2/ja
Priority to GB2318773A priority patent/GB1372515A/en
Priority to BE131099A priority patent/BE799525A/xx
Priority to DE2324717A priority patent/DE2324717C3/de
Priority to NL7306806A priority patent/NL7306806A/xx
Priority to CH700173A priority patent/CH630804A5/de
Priority to IT24191/73A priority patent/IT1061433B/it
Priority to FR7317649A priority patent/FR2184898B1/fr
Priority to CA171,527A priority patent/CA1007986A/en
Priority to NO2027/73A priority patent/NO142381C/no
Priority to SE7307018A priority patent/SE430020B/xx
Priority to ES414823A priority patent/ES414823A1/es
Priority to AU55849/73A priority patent/AU465351B2/en
Priority to DK274573AA priority patent/DK136016B/da
Priority to AT433573A priority patent/AT344881B/de
Application granted granted Critical
Publication of US3803115A publication Critical patent/US3803115A/en
Priority to US05/674,270 priority patent/USRE29698E/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/745—Blood coagulation or fibrinolysis factors
    • C07K14/755—Factors VIII, e.g. factor VIII C (AHF), factor VIII Ag (VWF)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
    • Y10S530/827—Proteins from mammals or birds
    • Y10S530/829—Blood
    • Y10S530/83—Plasma; serum

Definitions

  • This invention relates to a method of making a concentrate of Antihemophilic Factor (A-HF, Factor VIH). More particularly, this invention relates to a method for improving the yield of AHF obtained from blood plasma and plasma fractions.
  • A-HF Antihemophilic Factor
  • hemophilia A is a deficiency disease caused by the abaence of AHF (Factor VIII).
  • hemophilia B the blood is deficient in plasma thromboplastin component (FTC, Factor IX).
  • FTC plasma thromboplastin component
  • hemophiliacs Until recent years, treatment of hemophiliacs consisted of transfusing the patient with whole blood or blood plasma. Better medical practice dictates that, whenever possible, the patient be administered only those blood components in which he is deficient. Due to the universal shortage of blood, it is also advantageous to fractionate blood into its various components, whereby they can be used for patient treatment as required.
  • prothrombin Factor II
  • Factor VIII Factor VIII
  • the usual treatment to obviate this problem was the removal of the prothrombin complex with various agents such as aluminum hydroxide, magnesium hydroxide, barium carbonate, barium sulfate, rivanol (6,9-diamino 2-ethoxyacridine lactate), IRC-SO ion exchange resin (XE-64-Rivanol) and glycine ethyl ester.
  • the present invention resides in the addition of heparin to the aqueous media containing the blood plasma or plasma fraction, which is then fractionated to obtain a concentrate of 'AHF.
  • the amount of heparin employed in the practice of this invention during the fractionation of Al-IF can vary within reasonable limits. It has been found that a concentration of about one unit of heparin per ml. of the plasma solution or plasma fraction is about optimum. Concentrations greater than about 10 units per ml. are to be avoided as unnecessary and dangerous. Concentrations of about 0.01 unit per ml. are also effective. The preferred range is from about 0.01 to about 10 units per ml.
  • One unit of heparin is defined herein to mean one U.S.P. (United States Pharmacopoeia) unit. The U.S.P. unit of heparin is the quantity that will prevent 1.0 ml.
  • heparin also is meant to include the sodium salt of heparin, the latter substance being preferred due to its water solubility.
  • the invention defined herein has been found useful in various procedures for producing AHF concentrates and is applicable to any plasma or plasma fraction which contains AHF in admixture with any of the prothrombin complex factors.
  • it has been adapted to methods of fractionating AHF (1) from plasma by glycine precipitation, (2) from cryoprecipitate by glycine precipitation, (3) from cryoprecipitate by polyethylene glycol precipitation, (4) from cryoprecipitate by polyethylene glycol and glycine precipitation, (5) from cryoprecipitate, (6) from plasma, and (7) from cryoprecipitate by polyethylene glycol and glycine precipitation followed by Ecteola" chromatography.
  • a preferred method of producing AHF to which the present invention is adapted is the method described in U.S. Pat. 3,631,018, whereby polyethylene glycol (PEG) and glycine are used to fractionate a cryoprecipitate of AHF concentrate.
  • PEG polyethylene glycol
  • glycine glycine citrated saline
  • the redissolved precipitate is again treated to contain about one unit of heparin per ml. of the solution due to the loss of heparin during the fractionation with 10% polyethylene glycol.
  • the heparin can conveniently be added by incorporation in the citrated saline or glycine citrated saline used to dissolve the respective precipitates.
  • Reagents Citrated saline.-One part 0.1 molar sodium citrate to four parts by weight 0.9 percent saline.
  • Glycine citrated saline-Sufficient glycine is added to the above prepared citrated saline to make a 0.1 molar solution respective of glycine.
  • Buffered wash water Buffered wash water.-To distilled water is added A volume of buffered citrate which is prepared by adjusting 0.5 molar sodium citrate with 0.5 molar citric acid to pH 6.88.
  • Heparin.U.S. Pharmacopoeia grade material is used (Lipo-Hepin"-sodium heparin injection, aqueous).
  • Acetic acid Prepared in both 1.0 normal and 0.1 normal aqueous solutions.
  • Procedure Human blood plasma is received frozen (at below 4 C.) from a donor center.
  • the plasma is pooled into Pfaudler kettles and, while held at a tmperature at 20 C. to -40 C., it is centrifuged by continuous flow or bucket centrifug'ation.
  • glycine citrated saline solution containing one unit of heparin per ml. is added, the amount being one-tenth the volume of plasma the cryoprecipitate represents. Dissolution is brought about by mixing the cryoprecipitate and glycine citrated saline solution in a warm environment (normal room temperture, but not in excess of 30 C.).
  • the dissolved cryoprecipitate is adjusted to pH 6.5 with 0.1 normal acetic acid.
  • Polyethylene glycol 4000 (molecular weight average about 4000) is added to the solution to make the PEG concentration about 3.5 percent.
  • the mixture is gently agitated at room temperature for ten minutes and then centrifuged for fifteen minutes at 5000 rpm.
  • the supernate is decanted and adjusted to pH 6.88 with 0.1 normal sodium hydroxide.
  • Additional PEG 4000 is added to the solution to make the final PEG concentration about 10 percent.
  • the mixture is gently agitated at room temperature for thirty minutes and centrifuged at 5000 rpm. for one-half hour. The supernate is decanted and discarded.
  • the precipitate is washed in cold water (2 C.) and spin washing is then carried out for five minutes at 5000 rpm. at a temperature of 4 C.
  • the supernate is decanted and the precipitate is redissolved inglycine citrated saline solution containing one unit of heparin per ml. Again, the amount of the redissolving solution is about one-tenth the volume of plasma that the precipitate represents.
  • the redissolved precipitate is adjusted to pH 6.88 with 0.1 normal acetic acid and rep'recipitated with aqueous glycine having a molarity of 1.8. Sufficient glycine is added during this precipitation step to make the mixture 1.8 molal with respect to glycine.
  • the mixture is gently agitated for 45 to 60 minutes at a temperature of from 2 C. to 10 C., and then centrifuged by continuous fiow or bucket centrifugation.
  • the resulting precipitate is collected and gently washed with buffered wash water and redissolved in citrated saline.
  • the solution is clarified by filtration using a 293 mm. millipore filter (mcmbranes used: 1.2 microns, 0.45 micron, and 0.3 micron).
  • the liquid product is then frozen by shell freezing (-60 C.) and storing in a flash freezer (-20 C. to 30 C.) for at least three hours.
  • heparin was employed was 17%, whereas the yield without heparin averaged from 12.5% to 13.6%. The addition of heparin, therefore, increased the yield by 25% to 35% over the non-heparinized procedure.
  • the efficieney of the process was improved from 38% and 39% without the heparin addition to 49% and 52% with the heparin addition.
  • Example 2 The procedure of Example 1 was repeated up to the step of resuspending the initial cryoprecipitate in glycine citrated saline both with and without heparin in the solution.
  • the final AHF yield in these two cryoprecipitate concentrates of AHF was 34% when heparin was not employed and 41% when heparin was used. This is equivalent to a 21%'improvement in yield.
  • Example 3 The procedure of Example 2 was repeated except that the cryoprecipitate concentrates, both with and without heparin, were lyophilized and then reconstituted with water and allowed to stand at room temperature (ca. 25 C.) for 24 hours.
  • the heparinized sample retained 98% of the initial AHF activity prior to the standing period whereas the non-heparinized sample retained only 72% of the initial AHF activity.
  • the method of improving the yield of AHF obtained from blood plasma and plasma fractions comprising admixing from about 0.01 to about ten units of heparin to a concentrate of AHF obtained from said plasma or plasma fraction by cryoprecipitation per ml. of solution of said concentrate of AHF.
  • the plasma fraction is acryoprecipitate concentrate of AHF which is further fractionated with both polyethylene glycol and glycine.
  • cryoprecipitate concentrate is precipitated with from about 3% to about 4% polyethylene glycol
  • the resulting supernatant is precipitated with about 10% polyethylene glycol
  • the resulting supernate is then fractionated with glycine.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • General Health & Medical Sciences (AREA)
  • Toxicology (AREA)
  • Medicinal Chemistry (AREA)
  • Molecular Biology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Hematology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
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  • Developing Agents For Electrophotography (AREA)
  • Medicinal Preparation (AREA)
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US00254148A 1972-05-17 1972-05-17 Stabilization of ahf using heparin Expired - Lifetime US3803115A (en)

Priority Applications (19)

Application Number Priority Date Filing Date Title
US00254148A US3803115A (en) 1972-05-17 1972-05-17 Stabilization of ahf using heparin
IL42221A IL42221A (en) 1972-05-17 1973-05-08 Stabilization of ahf
ZA733138A ZA733138B (en) 1972-05-17 1973-05-09 Stabilization of ahf
JP48054039A JPS596845B2 (ja) 1972-05-17 1973-05-14 抗血友病因子の収率改良法
BE131099A BE799525A (fr) 1972-05-17 1973-05-15 Procede pour la stabilisation du facteur antihemophilique a.
GB2318773A GB1372515A (en) 1972-05-17 1973-05-15 Stabilization of ahf
FR7317649A FR2184898B1 (en)) 1972-05-17 1973-05-16
NL7306806A NL7306806A (en)) 1972-05-17 1973-05-16
CH700173A CH630804A5 (de) 1972-05-17 1973-05-16 Verfahren zur verhinderung des abbaus der biochemischen aktivitaet von antihaemophilie-globulin.
IT24191/73A IT1061433B (it) 1972-05-17 1973-05-16 Stabilizzazione del fattore antiemofilico
DE2324717A DE2324717C3 (de) 1972-05-17 1973-05-16 Verfahren zur Herstellung eines stabilen AHF-Konzentrates (Faktor VIII)
CA171,527A CA1007986A (en) 1972-05-17 1973-05-16 Stabilization of ahf
NO2027/73A NO142381C (no) 1972-05-17 1973-05-16 Fremgangsmaate for fremstilling av den antihemofile faktor
ES414823A ES414823A1 (es) 1972-05-17 1973-05-17 Metodo para mejorar el rendimiento de un factor anti-hemo- filico obtenido a partir de plasma sanguineo y de fraccionesde plasma.
AU55849/73A AU465351B2 (en) 1972-05-17 1973-05-17 Stabilization of ahf
DK274573AA DK136016B (da) 1972-05-17 1973-05-17 Fremgangsmåde til forøgelse af udbyttet af den antihæmophile faktor fra blodplasma eller plasmafraktioner indeholdende denne faktor.
AT433573A AT344881B (de) 1972-05-17 1973-05-17 Verfahren zur herstellung von antihaemophilfaktor (ahf)-konzentrat
SE7307018A SE430020B (sv) 1972-05-17 1973-05-17 Forfarande vid utvinning av den antihemofila faktorn (ahf)
US05/674,270 USRE29698E (en) 1972-05-17 1976-04-06 Stabilization of AHF using heparin

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Application Number Priority Date Filing Date Title
US00254148A US3803115A (en) 1972-05-17 1972-05-17 Stabilization of ahf using heparin

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US05/674,270 Reissue USRE29698E (en) 1972-05-17 1976-04-06 Stabilization of AHF using heparin

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US05/674,270 Expired - Lifetime USRE29698E (en) 1972-05-17 1976-04-06 Stabilization of AHF using heparin

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JP (1) JPS596845B2 (en))
AT (1) AT344881B (en))
AU (1) AU465351B2 (en))
BE (1) BE799525A (en))
CA (1) CA1007986A (en))
CH (1) CH630804A5 (en))
DE (1) DE2324717C3 (en))
DK (1) DK136016B (en))
ES (1) ES414823A1 (en))
FR (1) FR2184898B1 (en))
GB (1) GB1372515A (en))
IL (1) IL42221A (en))
IT (1) IT1061433B (en))
NL (1) NL7306806A (en))
NO (1) NO142381C (en))
SE (1) SE430020B (en))
ZA (1) ZA733138B (en))

Cited By (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3920625A (en) * 1973-06-19 1975-11-18 Kabi Ab Isolation of coagulation factors from biological material using cross linked sulfated, sulfonated carbohydrates
US3973002A (en) * 1974-04-12 1976-08-03 E. R. Squibb & Sons, Inc. Antihemophilic factor
US4022758A (en) * 1973-06-19 1977-05-10 Ab Kabi Isolation of coagulation factors I and VIII from biological material
US4069216A (en) * 1975-06-16 1978-01-17 Edward Shanbrom, Inc. Simplified methods for preparation of very high purity Factor VIII concentrate
US4093608A (en) * 1976-04-09 1978-06-06 The Green Cross Corporation Process for purifying coagulation factor VIII using DEAE-crosslinked dextran
US4141887A (en) * 1976-05-31 1979-02-27 Arnold Seufert Process and apparatus for the production of sterile filtered blood clotting factors
JPS5498308A (en) * 1977-12-19 1979-08-03 Rock Gail Ann Recovery of antii haemophilia factor 8 from blood and like
US4210580A (en) * 1979-06-19 1980-07-01 David Amrani Process for separation and isolation of AHF and fibronectin from blood plasma
US4278594A (en) * 1979-06-19 1981-07-14 David Amrani Process for separation and isolation of AHF, von Willebrand's ristocetin cofactor (VWF:RCF) and fibronectin from blood plasma
US4289691A (en) * 1980-01-18 1981-09-15 The Canadian Red Cross Society Method of obtaining intermediate purity factor VIII
US4305871A (en) * 1980-09-02 1981-12-15 Edward Shanbrom Method of selectively increasing yield and purity of certain cryoprecipitate proteins by heating
US4383989A (en) * 1981-10-01 1983-05-17 Rock Gail A Factor VIII concentrates prepared from heparinized plasma by the application of a cold precipitation technique
US4388232A (en) * 1979-04-19 1983-06-14 Immuno Aktiengesellschaft Fur Chemisch Medizinische Produkte Method of producing plasma fractions free of side-effects using fast-reacting antithrombin
EP0176926A3 (en) * 1984-10-04 1987-10-28 Miles Laboratories, Inc. Process for producing a high purity antihemophilic factor concentrate
US4789733A (en) * 1985-03-07 1988-12-06 The Central Blood Laboratories Authority Purification of blood coagulation factor VIII by precipitation with sulfated polysaccharides
WO1993010143A1 (en) * 1991-11-12 1993-05-27 Johnson Alan J Antihemophilic factor stabilization
USH1509H (en) * 1989-06-09 1995-12-05 Eran; Harutyun Heparin enhanced process for separating antihemophilic factor (Factor VIII) and fibronectin from cryoprecipitate
US5659017A (en) * 1995-11-07 1997-08-19 Alpha Therapeutic Corporation Anion exchange process for the purification of Factor VIII
WO2002087560A1 (en) * 2001-02-07 2002-11-07 Shanbrom Technologies, Llc Carboxylic acid such as citric acid for desinfecting or enhacing the production of blood products such as plasma, cryoprecipitate or/and platelet
US6541518B2 (en) * 2000-10-23 2003-04-01 Shanbrom Technologies, Llc Enhanced production of safe plasma preparations
US20030129167A1 (en) * 2000-10-23 2003-07-10 Shanbrom Technologies, Llc Enhanced production of blood components, blood cells and plasma without freezing
US20050196393A1 (en) * 2000-10-23 2005-09-08 Shanbrom Technologies, Llc Enhanced production of blood clotting factors and fibrin fabric
US20080281081A1 (en) * 2000-10-23 2008-11-13 Shanbrom Technologies, Llc Polyvinyl Pyrollidone Cryoprecipitate Extraction of Clotting Factors

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4089944A (en) 1975-12-22 1978-05-16 Baxter Travenol Laboratories, Inc. Rapidly solubilized AHF composition and process for preparing same
EP0033582B1 (en) * 1980-01-18 1984-04-11 The Canadian Red Cross Society Method of obtaining factor viii
US4397841A (en) 1982-06-28 1983-08-09 Monsanto Company Production of blood coagulation factor VIII:C
US5149787A (en) * 1984-05-22 1992-09-22 The Blood Center Research Foundation Method for maintaining intact, non-degraded factor VIII/von-Willebrand factor during blood processing
US4710381A (en) 1984-05-22 1987-12-01 The Blood Center Of Southeastern Wisconsin Method for maintaining intact, non-degraded factor VIII/von-Willebrand factor during blood processing
EP0238701B1 (de) * 1986-03-27 1992-03-18 Octapharma AG Verfahren zur Herstellung eines hochgereinigten Antihämophilie-Faktors
FR2651437A1 (fr) * 1989-09-05 1991-03-08 Lille Transfusion Sanguine Procede de preparation de concentre du complexe facteur viii-facteur von willebrand de la coagulation sanguine a partir de plasma total.
FR2657884B1 (fr) * 1990-02-05 1994-09-02 Tm Innovation Procede pour la preparation du facteur viii humain et d'analogues du facteur viii.
IT1248723B (it) * 1990-06-12 1995-01-26 Scalvo S P A Processo per la purificazione del fattore viii e fattore viii ottenuto con tale processo

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2867567A (en) * 1955-01-21 1959-01-06 Nat Res Dev Process of preparing anti-haemophilic globulin
DE1949314U (de) 1966-05-07 1966-11-10 Braun Fa B Bohrdraht-bereitschaftskasten.
BE713764A (en)) 1967-05-01 1968-09-16 Baxter Travenol Lab
US3652530A (en) * 1967-08-28 1972-03-28 American Nat Red Cross Antihemophilic factor prepared from blood plasma using polyethylene glycol
US3560475A (en) * 1969-06-19 1971-02-02 Baxter Laboratories Inc Prothrombin complex prepared by precipitation with polyethylene glycol
US3631018A (en) * 1970-05-01 1971-12-28 Baxter Laboratories Inc Production of stable high-potency human ahf using polyethylene glycol and glycine to fractionate a cryoprecipitate of ahf concentrate
US3682881A (en) * 1970-10-02 1972-08-08 Baxter Laboratories Inc Fractionation of plasma using glycine and polyethylene glycol

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3920625A (en) * 1973-06-19 1975-11-18 Kabi Ab Isolation of coagulation factors from biological material using cross linked sulfated, sulfonated carbohydrates
US4022758A (en) * 1973-06-19 1977-05-10 Ab Kabi Isolation of coagulation factors I and VIII from biological material
US3973002A (en) * 1974-04-12 1976-08-03 E. R. Squibb & Sons, Inc. Antihemophilic factor
US4069216A (en) * 1975-06-16 1978-01-17 Edward Shanbrom, Inc. Simplified methods for preparation of very high purity Factor VIII concentrate
US4093608A (en) * 1976-04-09 1978-06-06 The Green Cross Corporation Process for purifying coagulation factor VIII using DEAE-crosslinked dextran
US4141887A (en) * 1976-05-31 1979-02-27 Arnold Seufert Process and apparatus for the production of sterile filtered blood clotting factors
JPS5498308A (en) * 1977-12-19 1979-08-03 Rock Gail Ann Recovery of antii haemophilia factor 8 from blood and like
US4203891A (en) * 1977-12-19 1980-05-20 Rock Gail A Method of collecting anti-hemophilic factor VIII from blood and blood plasma using heparin or sodium heparin
US4388232A (en) * 1979-04-19 1983-06-14 Immuno Aktiengesellschaft Fur Chemisch Medizinische Produkte Method of producing plasma fractions free of side-effects using fast-reacting antithrombin
US4278594A (en) * 1979-06-19 1981-07-14 David Amrani Process for separation and isolation of AHF, von Willebrand's ristocetin cofactor (VWF:RCF) and fibronectin from blood plasma
EP0022052A3 (en) * 1979-06-19 1981-11-11 David Amrani Process for the separation and isolation of the ahf fraction, the fibronectin fraction and the von willebrand's ristocetin cofactor fraction from blood plasma
US4210580A (en) * 1979-06-19 1980-07-01 David Amrani Process for separation and isolation of AHF and fibronectin from blood plasma
US4289691A (en) * 1980-01-18 1981-09-15 The Canadian Red Cross Society Method of obtaining intermediate purity factor VIII
US4305871A (en) * 1980-09-02 1981-12-15 Edward Shanbrom Method of selectively increasing yield and purity of certain cryoprecipitate proteins by heating
US4383989A (en) * 1981-10-01 1983-05-17 Rock Gail A Factor VIII concentrates prepared from heparinized plasma by the application of a cold precipitation technique
EP0176926A3 (en) * 1984-10-04 1987-10-28 Miles Laboratories, Inc. Process for producing a high purity antihemophilic factor concentrate
US4789733A (en) * 1985-03-07 1988-12-06 The Central Blood Laboratories Authority Purification of blood coagulation factor VIII by precipitation with sulfated polysaccharides
USH1509H (en) * 1989-06-09 1995-12-05 Eran; Harutyun Heparin enhanced process for separating antihemophilic factor (Factor VIII) and fibronectin from cryoprecipitate
US5278289A (en) * 1991-11-12 1994-01-11 Johnson Alan J Antihemophilic factor stabilization
WO1993010143A1 (en) * 1991-11-12 1993-05-27 Johnson Alan J Antihemophilic factor stabilization
US5484890A (en) * 1991-11-12 1996-01-16 Johnson; Alan J. Antihemophilic factor stabilization
US5659017A (en) * 1995-11-07 1997-08-19 Alpha Therapeutic Corporation Anion exchange process for the purification of Factor VIII
US20030129167A1 (en) * 2000-10-23 2003-07-10 Shanbrom Technologies, Llc Enhanced production of blood components, blood cells and plasma without freezing
US6541518B2 (en) * 2000-10-23 2003-04-01 Shanbrom Technologies, Llc Enhanced production of safe plasma preparations
US20050196393A1 (en) * 2000-10-23 2005-09-08 Shanbrom Technologies, Llc Enhanced production of blood clotting factors and fibrin fabric
US7297716B2 (en) 2000-10-23 2007-11-20 Shanbrom Technologies, Llc Enhanced production of blood components, blood cells and plasma without freezing
US20080281081A1 (en) * 2000-10-23 2008-11-13 Shanbrom Technologies, Llc Polyvinyl Pyrollidone Cryoprecipitate Extraction of Clotting Factors
US20090018313A1 (en) * 2000-10-23 2009-01-15 Shanbrom Technologies, Llc Enhanced production of blood clotting factors and fibrin fabric
US8003706B2 (en) 2000-10-23 2011-08-23 Shanbrom Technologies, Llc Enhanced production of blood clotting factors and fibrin fabric
US8389687B2 (en) 2000-10-23 2013-03-05 Shanbrom Technologies, Llc Polyvinylpyrrolidone cryoprecipitate extraction of clotting factors
WO2002087560A1 (en) * 2001-02-07 2002-11-07 Shanbrom Technologies, Llc Carboxylic acid such as citric acid for desinfecting or enhacing the production of blood products such as plasma, cryoprecipitate or/and platelet

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Publication number Publication date
USRE29698E (en) 1978-07-11
DE2324717C3 (de) 1983-12-01
ATA433573A (de) 1975-04-15
ES414823A1 (es) 1976-02-01
JPS596845B2 (ja) 1984-02-15
IL42221A0 (en) 1973-07-30
AU5584973A (en) 1974-11-21
DK136016B (da) 1977-08-01
AU465351B2 (en) 1975-09-25
FR2184898A1 (en)) 1973-12-28
DE2324717B2 (de) 1980-01-03
SE430020B (sv) 1983-10-17
BE799525A (fr) 1973-08-31
AT344881B (de) 1978-08-10
JPS4956695A (en)) 1974-06-01
DE2324717A1 (de) 1973-12-13
IT1061433B (it) 1983-02-28
GB1372515A (en) 1974-10-30
NL7306806A (en)) 1973-11-20
CH630804A5 (de) 1982-07-15
IL42221A (en) 1977-04-29
ZA733138B (en) 1974-03-27
NO142381B (no) 1980-05-05
DK136016C (en)) 1978-01-02
NO142381C (no) 1980-08-13
CA1007986A (en) 1977-04-05
FR2184898B1 (en)) 1976-11-05

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