Tri(n-Butyl) Phosphate/Detergent Treatment of
Licensed Therapeutic and Experimental Blood Derivatives

Edwards, Carol A.; Piet, Marcel P.J.; Chin, S.W.; Horowitz, Bernard

doi:10.1159/000461609

Cited by 17 publications

(18 citation statements)

References 11 publications

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“…To eliminate the possibility that an immunoglobulin made from HIV-infected plasma could transmit HIV infection, we made use of our experience in developing virus-sterilized coagulation factors by application of solvents and detergents (7)(8)(9). Pooled plasma was first exposed to tri(n-butyl) phosphate at 2% for 4 hr at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV.

Prince

Horowitz

Baker

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

152

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To assess the possible efficacy of passive immunization against human immunodeficiency virus (HIV) an immune globulin was prepared from plasma of HIV-seropositive donors selected to be among those having the top 12.5% of virus-neutralizing antibody titers. The immune globulin was treated with pepsin to render it intravenously tolerable. The preparation, which we termed HIVIG, neutralized 100 tissue culture 50% infective doses (TCID50) of HIV at an average dilution of 1:1000 in neutralization tests in vitro. During preparation HIVIG was subjected to virus inactivation and removal procedures that in theory resulted in a reduction in HIV infectivity by a factor of 10(25). At a dose of 9-10 ml/kg of body weight both the virus-inactivated source plasma and the final immunoglobulin preparation were noninfective and without adverse effect in two chimpanzees. Two chimpanzees inoculated intravenously with HIVIG at 1 ml/kg and two inoculated with 10 ml/kg were challenged intravenously 1 day later with 400 TCID50 of the same strain of HIV (HTLV-IIIb) used in neutralization assays in vitro. All animals became infected. Incubation periods to virus isolation (by cocultivation with human mononuclear cells) in HIVIG recipients did not differ significantly from the incubation period seen in a control animal that received a normal anti-HIV-free immunoglobulin. These findings may have implications for understanding the failure of experimental vaccines to protect against HIV challenge in chimpanzee experiments.

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Section: Methodsmentioning

confidence: 99%

Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV.

Prince

Horowitz

Baker

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

152

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“…This new product contains a 75% pure factor IX, with a specific activ ity of 119±10IU factor IX:c/mg, free of all other vitamin K-dependent proteins, and contaminated by only low amounts of ITI and C4. To reduce or eliminate the risks of plasma-borne viral diseases caused by lipid-enveloped vi ruses, the product was treated with solvent detergent (SD), as developed by Horowitz and co-workers [11].…”

Section: Marker Virus Studymentioning

confidence: 99%

Properties of a Highly Purified Human Plasma Factor IX:c Therapeutic Concentrate Prepared by Conventional Chromatography

Burnouf¹,

Michalski²,

Goudemand³

et al. 1989

Vox Sanguinis

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We have characterized a highly purified (HP) factor IX concentrate intended for therapy of hemophilia B. The product has been prepared from pooled human plasma using a large-scale procedure combining three conventional chromatographic steps based on DEAE ion exchange and affinity on immobilized heparin. The specific activity of the product was 119±10 IU factor IX:c/mg protein (n = 15), corresponding to a purification factor of about 9,000. The concentrate was free of the vitamin K-dependent clotting factors II, VII and X and of proteins C and S. Most of the contaminants found in factor IX complex concentrate (PCC) were absent in this new product. High-molecular-weight kininogen, factors VIII, XI, XII or prekallikrein were not detected. There were no activated factors, such as factors IXa, and Xa, no thrombin and no phospholipids. Only two contaminants could be detected: C4 and inter-alpha-trypsin inhibitor (about 0.8 and 1.2mg/1,000IU factor IX:c, respectively). The purity of the product, as compared to PCC, was confirmed by sodium dodecylsulfate polyacrylamide gel electrophoresis, cellulose acetate electrophoresis, Grabar- Williams immunoelectrophoresis, and bidimensional immunoelectrophoresis. Thrombogenicity tests in rabbits revealed that the HP factor IX tested had a lower thrombogenic power than the PCC tested. The concentrate has been subjected to a 0.3% tri(n-butyl) phosphate-1% Tween 80 treatment for 6h at 25°C during its production to reduce or eliminate the risk of transmission of plasma-borne lipid-enveloped viruses. These conditions inactivated more than 3.8 log(10) of vesicular stomatitis virus and more than 4.3 log(10) of sindbis virus within 1 and 2 h of treatment, respectively. These data demonstrate that a highly purified therapeutic clotting factor IX concentrate can be prepared from human plasma by conventional chromatographic methods.

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“…We have given the Virus Inactivation treatment after purification of FVIII, so that the FVIII deficient plasma can be used for other plasma proteins separation like albumin, IgG. The recovery of FVlll after virucidal treatment is reported to be 80-88% (19,20). Present study shows 51.57% recovery which is less by 28.43 -36.43% as compared to the available data.…”

Section: -86mentioning

confidence: 99%

Separation of antihemophilic factor VII from human plasma by column chromatography

Baikar¹,

Kamath²,

Vishwanathan³

et al. 2003

Indian J Clin Biochem

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TMAE-Fractogel 650 (M) (Trimethylaminoethyl) is an ion exchange medium can be used to capture factor Vlll (F VIII) directly from plasma. Previous reports have focused on the use of DEAE-Fractoge1650 (M) (Dimethylaminoethyl) ion exchange medium to capture F Vlll from cryoprecipitate and plasma. Our main objectives were (I) to standardise the purification of FVIII from human plasma by column chromatographic technique. (11) to study the recovery of FVIII activity in purified fraction at 18 -20~ process condition. (Ill) to study the effect of virucidal step on recovery of FVIII activity and (IV) to study the effect of lyophilisation on FVIII activity. In this report, Citrate Phosphate Dextrose (CPD) plasma was batch stirred with dry DEAE-Sephadex A50, filtered, diluted, loaded on to a column packed with TMAE-Fractogel and chromatographed. Most of the unwanted proteins flowed through the gel unadsorbed. Bound F VIII was eluted by increasing the ionic strength of the buffer. This purification step gave an overall 80% recovery from the plasma with a specific activity of 0.97 IU FVlll/mg protein. The purified F VIII fraction was made virus safe by employing the virucidal technique developed by New York Blood Centre (NYBC). There was 48.43% loss of FVIII activity in Virus inactivation treatment and the loss of FVIII activity in lyophilisation was 8.45% which is acceptable. This method of purification gave a higher yield of FVIII than cryoprecipitation, and is a promising alternative method to cryoprecipitation of F VIII.

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Tri(n-Butyl) Phosphate/Detergent Treatment of Licensed Therapeutic and Experimental Blood Derivatives

Cited by 17 publications

References 11 publications

Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV.

Failure of a human immunodeficiency virus (HIV) immune globulin to protect chimpanzees against experimental challenge with HIV.

Properties of a Highly Purified Human Plasma Factor IX:c Therapeutic Concentrate Prepared by Conventional Chromatography

Separation of antihemophilic factor VII from human plasma by column chromatography

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