Biotest-serum-institut Gmbh

Biotest Pharma Gmbh

Wolfgang Stephan

Ronald Kotitschke

Herbert Dichtelmuller

Wolfgang Moller

Hans Schleussner

Dieter Rudnick

Norbert Kothe

Detlef Piechaczek

Henry Hies

Axel W Stemberger

Michael Kloft

Bertram Eichentopf

Alexander Thrun

The present invention relates to a process for obtaining sterile milk, wherein the calcium ion content is reduced preferably to half of the naturally occurring amount by means, for example, of ion exchange or dialysis, and the milk is then filtered sterile, and if desired calcium ions are added again to restore the natural content. The product thus obtained has all of the biological activities as well as virtually the original composition, but it is free of bacteria, fungi and spores and will keep for a longer time.

Process for the sterile filtration of milk

A sterile-filtered colostrum solution that contains casein is made by adjusting the pH of a colostrum solution to 2.5 to 3.5 and then filtering it clear and sterile. It is preferably first defatted, and adjusted to pH 5.5 to 8 after the acid treatment but before being filtered.

Colostrum filtered sterile

A method of preparing a sterile and stable plasma-protein solution containing fibrinogen and Factor XIII from human blood plasma which has been stabilized with citrate, comprising treating the plasma with .beta.-propiolactone and irradiating it with ultraviolet light, removing the Factors II, VII, IX and X by adsorption onto anion exchangers that adsorb proteins, precipitating the companion proteins out by adding ethanol until the solution has a final concentration of about 9% by volume at -3.degree. C., centrifuging the precipitate off, dissolving the precipitate in a citrate buffer at a pH of about 6.35 and a temperature of about 37.degree. C., adjusting the protein level of the solution to about 13.3 g/l with sodium citrate solution, adding ethanol, a glycine citrate buffer, and a solution of sodium citrate to precipitate out the companion proteins, adding ethanol to the remaining solution until the solution has a final concentration of about 9% by volume at -3.degree. C., thereby precipitating fribrinogen and Factor XIII, dissolving the precipitate in a citrate buffer at a pH of about 6.35 and a temperature of about 37.degree. C., and filtering the solution.

Method of preparing a sterile plasma-protein solution containing

Process for the preparation of an immunoglobulin solution suitable for intravenous administration from a human blood protein fraction containing immunoglobulins IgG, IgA and IgM in partially concentrated from, with the process steps: addition of acetate buffer to the protein fraction, where appropriate removal of insoluble constituents by filtration, treatment with calcium phosphate and octanoic acid, centrifugation, removal of the supernatant and treatment thereof with an adsorbent, removal of the adsorbent and sterilization by filtration.

Process for the preparation of a pharmaceutical which contains IgG, IgA

A method for sterilizing blood, plasma or derivatives thereof by using vitamins or provitamins.

Sterilization of blood and its derivatives with vitamins

The present invention involves a polyvalent hyperimmunoglobulin preparation having activity against gram negative and gram positive bacteria. Such a polyvalent hyperimmunoglobulin preparation is prepared from plasma, serum or whole blood from donors. Donor selection is based upon titer against E. coli J5 antigen or against lipid A antigen.

Polyvalent hyperimmunoglobulin preparation

A method of sterilizing plasma or plasma fractions, including fractions that contain the blood-coagulating Factor VIII by treatment with .beta.-propiolactone or ultraviolet radiation. Treatment with tri-n-butyl phosphate and sodium cholate or Tween 80 is carried out either prior to or simultaneously with the .beta.-propiolactone treatment or ultraviolet radiation.

Method of sterilizing plasma or plasma fractions

A method of producing a virus-safe, storage-stable, and intravenously tolerable immunoglobulin-G preparation. The object is to make the method appropriate for industrial-scale production and economical by means of the enrichment and multistage purification of a plasma that has had the coagulation factors removed from it or of a plasma fraction or serum fraction that contains immunoglobulin G accompanied by treatment with ion exchangers and by ultrafiltration. The precipitant is eliminated, by means of diafiltration or gelfiltration, either from the plasma that has had the coagulation factors removed from it or from the plasma fraction that contains the immunoglobulin G, and the desired ion composition is established. The resulting protein solution is subjected to fractionation over an ion exchanger to separate the immunoglobulin G. The proteolytic enzymes in the resulting immunoglobulin-G solution are removed by means of affinity chromatography over a dye linked sorbent and/or are ihibited by the addition of antithrombin III. The accordingly stabilized immunoglobulin-G solution is treated, at a protein concentration of 20 to 60 g/l and a pH 6.0 to 8.0, with 0.03 to 0.07% of .beta.-propiolactone, diluted to a protein concentration of 5 to 20 g/l and subjected to ultraviolet radiation. The accordingly sterilized dilute immunoglobulin-G solution is again diafiltered or gelfiltered to remove lower molecular-weight substances. The accordingly stabilized and sterilized solution is adjusted to the desired protein content of 2 to 16% and filtered sterile.

Method of producing a virus safe, storage-stable, and intravenously

A compositon for treating diseases which comprises a therapeutically effective amount of an antibacterial, antiviral, or antimycotic agent, antitrypsin, antithrombin, interferon, or lysozyme, and an immunoenhancing amount of immunoglobulins IgG, IgM, and IgA, and a method of therapy of a mammal in need thereof are disclosed.

Combination of immunoglobulins with therapeutic agents

A method of preparing a solution of lactic or colostric immunoglobulins or both by processing milk or colostrum or both accompanied by precipitation of the caseins, characterized in that milk or colostrum or both are acidified to a pH of 4.0-5.5, subjected to cross-flow filtration in a filtration unit with a mean pore size of 0.1-1.2 .mu.m, and the low-molecular components removed by means of further cross-flow filtration in another filtration unit with a limit of separation of 5 000-80 000 daltons, as well as an agent for treating bacterial and viral infections that consists of a solution obtained by means of said method.

Method of preparing a solution of lactic or colostric immunoglobulins or

A coagulant plasma-protein solution obtained by adsorbing stabilized human plasma at least once with 20-40 mg of colloidal silicic acid per gram of plasma protein and separating the adsorbent from the adsorbate, a method of manufacturing the solution, and a pharmaceutical preparation containing the solution and intended for the intravenous treatment of complex disorders of the hemostatic system. The solution is low in fibrinogen and factors XI and XII but otherwise close in composition to the starting material.

Coagulant plasma-protein solution

A process for the cold sterilization of a preparation containing blood coagulation factor VIII, comprising

Method for the cold sterilization of preparations containing blood

A process for the preparation of an immunoglobulin solution containing IgM in concentrated form and suited for intravenous administration, comprising treating an IgM-containing protein fraction obtained by conventional fractionation from blood plasma or serum with .beta.-propiolactone in an amount such that the ratio of .beta.-propiolactone to a 5% solution of the IgM-containing proteins is from about 0.05 to 0.15 ml per 100 ml. Advantageously, prior to the treatment with .beta.-propiolactone the IgM-containing protein fraction is freed of lipids by treatment with colloidal silica gel and with crosslinked dextrans or diethylaminoethyl cellulose. The starting material used is a Cohn fraction III of human blood plasma which has been dissolved in physiological saline solution to a concentration of about 5% protein, the treatment with .beta.-propiolactone is carried out at about 20.degree. to 37.degree. C. for about 4 to 6 hours until a substantially constant pH of about 8 is obtained, and the solution is thereafter sterile filtered.

Concentrated immunoglobulin solution suited for intravenous

The present invention relates to a method for making fibrinogen, a prothrombin complex containing the coagulation factors II, VII, IX and X that can contain antithrombin III, antithrombin III and a solution of stable serum proteins from a blood plasma stabilized with citrate which is characterized in that from the plasma, by adsorption on colloidal silica of a specific surface of 50 to 400 m.sup.2 /g and a concentration of 50 to 400 mg per g plasma protein, fibrinogen is isolated; and in that thereupon (a) citrate and calcium ions are removed by ultrafiltration or dialysis and then from the protein solution, over anion exchangers or tricalcium phosphate that adsorb proteins, the coagulation factors II, VII, IX and X and antithrombin III are adsorbed, or (b) the coagulation factors II, VII, IX and X are adsorbed prior to the ultrafiltration or dialysis, antithrombin III then not being simultaneously adsorbed, and antithrombin III is adsorbed on the said adsorbents after the removal of the citrate and calcium ions by ultrafiltration or dialysis; and in that thereupon from the remaining plasma fluid further unstable proteins are removed by another adsorption on colloidal silica and a solution of stable serum proteins is obtained.

Fractionating citrate-stabilized plasma

A citrate-stabilized blood plasma is frozen and thawed, the undissolved cryoprecipitate is separated and is rich in factor VIII protein. The residual liquid is treated with cation and anion exchangers, either sequentially or in admixture, to separate calcium and citrate ions therefrom. The residual plasma is then subjected to adsorption to remove a fraction which is eluted and precipitated, enriched in factors II, VII, IX and X. The liquid left from adsorption is subjected to further adsorption with silicic acid, leaving a storage-stable serum. The silicic acid is eluted to dissolve adsorbed fibrinogen which then is re-precipitated.

Growing community of inventors

Dreieich, Germany

Wolfgang Stephan