Immunoglobulin Preparations For Intravenous Use Research Articles

Clinical use of a new pH 4·25 intravenous immunoglobulin preparation (gamimune-N)

A multicentre, randomised, double-blinded, cross-over study was done to evaluate the clinical use and safety of a new immunoglobulin preparation for intravenous use (IVIgG). This reagent, IVIgG pH 4.25, was compared to a standard commercially available preparation IVIgG pH 6.8. Thirty-nine patients with primary immunodeficiency disease received a total of 232 infusions at a dose of 400 mg/kg every 4 weeks. Adverse effects from such infusions were transient and minimal. Clinically significant abnormalities did not occur. There were no statistically significant differences between the results for IVIgG pH 6.8 and for the new IVIgG pH 4.25 preparation. It was possible to infuse the new IVIgG pH 4.25 reagent at rates of 0.1 ml (5.0 mg)/kg/min without inducing vasomotor adverse effects.

Opsonic and Physicochemical Characteristics of Intravenous Immunoglobulin Preparations

The composition and opsonizing activity of five commercially available immunoglobulin preparations for intravenous use (Venoglobulin I, Venilon, Gammagard, Polyglobin, and Sandoglobulin) were studied. The composition of these preparations does not differ very much as far as total protein, immunoglobulin class and IgG subclass concentrations are concerned. The only exceptions were that Veniglobulin I, Gammagard and Sandoglobulin contain IgA, which might cause side effects in patients with anti-IgA antibodies, Gammagard contains very little IgG4, and Venilon and Polyglobin contain no and almost no IgG3, respectively, which might explain their very low opsonic activity. It was found that Venilon and Gammagard activate complement in the ready-for-infusion state. The opsonic activity of Venoglobulin I, Sandoglobulin and Gammagard is about equal to that of inactivated serum: Staphylococcus aureus, Escherichia coli with K antigen, Streptococcus pyogenes and Streptococcus group B are well opsonized and E. coli without K antigen and Streptococcus pneumoniae are poorly opsonized.

Opsonic and complement-dependent bactericidal activities of various immunoglobulin preparations for intravenous use.

Some effector functions of various immunoglobulin (IgG) preparations have been compared. Tests for opsonic activity were performed in vitro with human peripheral blood leukocytes and in vivo with mice. The augmentation effects on luminol-dependent chemiluminescence were investigated with human leukocytes. The complement-dependent bactericidal activities were tested with Escherichia coli. Five IgG preparations: pH 4-treated preparation (IG-100), polyethyleneglycol-treated preparation (PEG-G), sulfonated preparation (S-G), pepsin-treated preparation (Pep-G) and a preparation for intramuscular use (GGN) were studied. The results were as follows: (1) IG-100 and PEG-G exhibited strong activities in all test systems; (2) GGN showed a strong opsonic activity; (3) S-G showed relatively weak activities in all test systems, but the revertant S-G preparation exhibited somewhat stronger activities in all systems, and (4) Pep-G showed weak or no activity in all systems. These results suggest that the IgG molecules in IG-100 and PEG-G preparations have satisfactory effector functions. On the other hand, IgG molecules in S-G and Pep-G preparation may have significant deficiencies in their biological functions.

Development of Immunoglobulin Preparations for Intravenous Use

Vox SanguinisVolume 51, Issue 2 p. 157-160 Development of Immunoglobulin Preparations for Intravenous Use S. Barandun, Corresponding Author S. Barandun Institute for Clinical and Experimental Cancer Research, University of Berne; bInstitute of Biochemistry, University of Lausanne, SwitzerlandInstitute for Clinical and Experimental Cancer Research, University of Berne, Tiefenau Hospital, CH-3004 Berne (Switzerland)Search for more papers by this authorH. Isliker, H. Isliker Institute for Clinical and Experimental Cancer Research, University of Berne; bInstitute of Biochemistry, University of Lausanne, SwitzerlandSearch for more papers by this author S. Barandun, Corresponding Author S. Barandun Institute for Clinical and Experimental Cancer Research, University of Berne; bInstitute of Biochemistry, University of Lausanne, SwitzerlandInstitute for Clinical and Experimental Cancer Research, University of Berne, Tiefenau Hospital, CH-3004 Berne (Switzerland)Search for more papers by this authorH. Isliker, H. Isliker Institute for Clinical and Experimental Cancer Research, University of Berne; bInstitute of Biochemistry, University of Lausanne, SwitzerlandSearch for more papers by this author First published: August 1986 https://doi.org/10.1111/j.1423-0410.1986.tb00235.xCitations: 47AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume51, Issue2August 1986Pages 157-160 RelatedInformation

A new intact immunoglobulin for intravenous use stabilized by chemically modified gelatin derivatives.

The stabilization of human immunoglobulin (IgG) by chemically modified gelatins (Haemaccel and Gelofusine) was investigated. The gelatins prevented IgG from aggregation induced by exposure to interfaces and lyophilization. The stabilization effects of the gelatins were significantly larger than those of amino acids or sugars. These investigations led to the large-scale production of an immunoglobulin preparation for intravenous use in the clinic. The clinical product meets the Japanese minimum requirements for immunoglobulin preparations for intravenous use, and the long-term preservation of this new freeze-dried preparation has demonstrated its stability.

Prophylactic effect of human immunoglobulin against pneumococcal post-splenectomy sepsis in the rat.

Failure to clear the blood of pneumococci after splenectomy may be corrected by active immunization, but some patients show poor antibody response to pneumococcal vaccination. Long-term antibiotic prophylaxis against post-splenectomy sepsis carries the risk of development of bacterial resistance and low patient compliance. In the present study, using a rat model for post-splenectomy sepsis, human immunoglobulin was given 24 h before challenging the animals with 10(3) Streptococcus pneumoniae. Immunoglobulin at a dosage of 300 mg/kg body weight was protective. Reducing the immunoglobulin dose to 75 mg/kg did not alter the mortality rate but significantly prolonged the survival time. The results indicate that the new immunoglobulin preparations for intravenous use might provide an effective means of reducing the risk of post-splenectomy sepsis, even in the most susceptible patients.

A New Intact Immunoglobulin for Intravenous Use Stabilized by Chemically Modified Gelatin Derivatives

The stabilization of human immunoglobulin (IgG) by chemically modified gelatins (Haemaccel and Gelofusine) was investigated. The gelatins prevented IgG from aggregation induced by exposure to interfaces and lyophilization. The stabilization effects of the gelatins were significantly larger than those of amino acids or sugars. These investigations led to the large-scale production of an immunoglobulin preparation for intravenous use in the clinic. The clinical product meets the Japanese minimum requirements for immunoglobulin preparations for intravenous use, and the long-term preservation of this new freeze-dried preparation has demonstrated its stability.

Development of Immunoglobulin Preparations for Intravenous Use

Development of Immunoglobulin Preparations for Intravenous Use

Opsonic and Complement-Dependent Bactericidal Activities of Various Immunoglobulin Preparations for Intravenous Use

Opsonic and Complement-Dependent Bactericidal Activities of Various Immunoglobulin Preparations for Intravenous Use

Comparison of antibody levels and protective efficacy against pneumococci in two immunoglobulin preparations for intravenous use.

Passive immunization with modern intravenous immunoglobulin preparations might be used prophylactically in individuals at extreme risk of contracting postsplenectomy sepsis or therapeutically in established infections. Since pneumococci are the predominant causative organisms, we determined antibodies against 14 pneumococcal serotypes in two commercially available immunoglobulin preparations (two batches of each) using enzyme-linked immunosorbent assay. The four batches were remarkably similar in antibody content. Low levels against some clinically important serotypes, i.e. types 3, 8 and 18C were recorded. The protective effect of one batch of each preparation against type 1 pneumococci was documented in splenectomized rats.

An evaluation of the safety of three intravenous immunoglobulin preparations in patients with primary hypogammaglobulinaemia

In an open study, three different immunoglobulin preparations for intravenous use (IV IgG), namely pH4 and pepsin treated immunoglobulin ('Sandoglobulin'); reduced and alkylated immunoglobulin ('Gamimune') as well as ultrafiltered, pH4 and pepsin treated immunoglobulin manufactured by the Scottish National Blood Transfusion Service ('SNBTS IV IgG'), were compared with intramuscular immunoglobulin (IM IgG) in five patients with primary hypogammaglobulinaemia, by treating each patient consecutively with each immunoglobulin preparation for 3 months. Few adverse reactions were noted with any of the intravenous immunoglobulin preparations and these mainly consisted of mild fever (less than 38 degrees C). Concentrations of serum IgG were higher with all intravenous immunoglobulin preparations compared with IM IgG. Furthermore, all the patients preferred IV to IM IgG therapy. As higher doses of immunoglobulin are associated with a reduction in infections in hypogammaglobulinaemic patients, we conclude that intravenous immunoglobulin therapy should be considered for the prophylaxis of infection in patients with primary hypogammaglobulinaemia.

Effect of Gamma Globulin Infusion on Type-Specific Pneumococcal Antibody Levels in Splenectomized Adults

Using an ELISA technique, changes in specific antibody levels against pneumococcal serotypes 1, 4, 7F, 14, 18C and 23F were studied in 8 adults healthy at the time of investigation but splenectomized previously because of hematological disease following infusion of 200 mg/kg body weight of a commercially available immunoglobulin preparation for intravenous use (Sandoglobulin). Among the 4 patients with initially low serum levels of antipneumococcal antibodies, significantly raised antibody levels were demonstrated against type 14 for 8 weeks. On the other hand, the infusion did not lead to increased antibody levels in 3 patients with high preinfusion values for antipneumococcal antibodies. In contrast, a significantly lower antibody value for type 7F was recorded 3 weeks after infusion. Efficacy of immunoglobulin prophylaxis is, therefore, probably doubtful in certain splenectomized patients, and if contemplated should be preceded by analysis of antibody levels against common pathogens.

造血器疾患に併発した重症感染症に対するGV-523と抗生剤療法の検討

The clinical efficacy and safety of GV-523, a newly developed normal human immunoglobulin preparation for intravenous use, were prospectively compared by the cross-over method with those of Venoglobulin-I in patients with severe infections complicating hematological disorders.Both test drugs were administrated at a dose of 100mg/kg/day.The results were as follows:1) 0f 76 patients studied, 46 were assessable for cross-over trials.An effective difference appeared between the drugs in 21 of 46 patients, in 12 GV-523 was most effective and in 9 Venoglobulin-I effective;this difference, however, was not statistically singnificant.Thus, the two drugs had essentially similar efficacy.2) The clinical effectiveness of both drugs was evaluable in 55 cases: the effectiveness of GV-523 was excellent in 9 cases, good in 13, fair in 5, and poor in 28;the comparable groups for Venoglobulin-I were 11, 3, 8, and 33.The efficacy rate was 40.0% in the former and 25.5% in the latter.The difference was not statistically significant.3) The efficacy of GV-523 on the first and second administration was 16.7% and 50.0%;this difference was statistically significant.The comparable efficacy of Venoglobulin-I was 9.1% and 25.0%; this difference was not statistically significant.4) No subjective or objective clinical side effects were observed in any patients treated with either drug.In conclusion, the clinical efficacy and safety of GV-523 were evaluated as similar to those of Venoglobulin-I.Thus, combination therapy with GV-523 and antibiotics was considered to be useful in patients with severe infections complicating hematological disorders.

Characterization of various immunoglobulin preparations for intravenous application. II. Complement activation and binding to staphylococcus protein A.

14 immunoglobulin preparations for intravenous use were tested to assess functions of their Fc portion. Inhibition of the hemolytic activity of complement, C1q binding and the interaction of IgG subclasses with Staphylococcus protein A were investigated. Complement studies were done on both the ready-for-infusion and the heat-aggregated preparations. Three groups of products could be distinguished: (1) Enzymatically and chemically treated products were devoid of complement-activating capacity, both when tested and ready-for-infusion and as heat-aggregated preparations. The chemically treated preparations showed atypical binding properties to Staphylococcal protein A. (2) The poly-(ethylene glycol) (PEG)-treated preparations and the untreated reference activated complement before and after heat-aggregation. (3) The albumin protected and the pH 4-treated product did not spontaneously activate complement in the ready-for-infusion state but did so after heat-aggregation. These results suggest that only the albumin-protected and the pH 4-treated products can be expected both to be well tolerated when given intravenously to high-risk agammaglobulinemic patients and to exhibit normal Fc functions in vivo.