SK260090A3 - Specific hyperimmune anti-cytomegaloviral immunoglobulin preparation for intravenous application and method of producing the same - Google Patents

Abstract

The basic principle of the suggested production procedure is closed to the stabilisation of immunoglobulins with the use of oligosaccharides a dosage of which 80 up to 170 g/l of immunoglobulin solution and thermal exposition, at the temperature of + 4 up to + 30 Celsius degrees, for 2 up to 30 days. The preparation created based on the above mentioned principle contains 10,0 up to 100,0 g/l of proteins (90 percent IgG) and 75 up to 200 g/l oligosaccharides selected based on the group glucose and saccharose.

Description

The invention relates to a process for the preparation of human specific anti-cytomegalovirus immunoglobulin for intravenous administration of Tros / Rt-dioL. sa, ^ yisíTirA, χια, “prts”. KJii'kjkjiíC / Ĺcb Mpr- at - / r ^ c ^ pluh ^ fee'tec / j _} JL. A / bb cM ^u .

'JŽ'kjrg / sr š / gr -fcjttiniÍy

Gytomegálla is one of the most widespread diseases caused by the virus * Eytomegálle virus was discovered more than 100 years ago · • but expertly described later ·

His research focused on researching a characteristic histological picture that can be seen in stillborn individuals. • Infection caused by the virus causes an anatomical-pathological effect in the form of a giant cell with typical inclusions. In the vast core, central inclusions are formed surrounded by a bright court that passes to the molecular nuclei (Jesionek, A, Kiolemenoglou, B: Uber einen Befung von protozoenartigen Gebilden in der Organen eines herditär-leutischen Fotus. Mirnch · Med · Wochenschr · 51, 1905-1907 (1904)) · (fibbert, H · s The Department of Protozoenartige Lellen in the Hiere and the Syphilitischen Hevgeborenen and in the Parotis of Kindem. Allg. Pathology 15, 945-948 (1904)).

Based on the above picture, the disease was given its name cytomegaly. The cytogenicity viral genesis was not confirmed until the 1950s in the research of Weller and his collaborators (We11er, TH, Macanlay, JC, Oraig, J, M., firth, P). .: Isolation of Xntra Nuclear Inclusion Producing Agents Ir Znflants with Illnesses Resembling Cytomegallc Inclusion Disease, Soc., Esp. Biol. Med, 94, 4-12 (1957)).

The virus was isolated from the salivary gland tissue and from there was given its scientific name Salivary Gland Virus (Smith, M.G. Propagation in Tissue Cultures of a Cytomathogenic Virus from Human Salivary Gland Virus (SGV) disease. Proo. Soc. Exp. Biol. Med., 92, 424-430 (1956)) · Later, when it was laboratory isolated from kidney and liver biopsies and its cyto * pathogenic effect was found, the virus finally got the name Cytomegalovirus COT. Cytomegaloviruses belong to a group of herpes viruses, which share common structural and chemical properties, but also that they persist for a long time in an infected organism.

They show considerable heterogeneity in terms of antigenic properties. • All attempts to infect animals with human CMV virus have not been successful.

Overview of herpesviruses (Blaškovič D .:

'Basics of Medical Virologi'é Science SAS 1978 p. 520 Bratislava) t

1. Ileipeô-simplex-virus

- type I / labialis /

- type II (genitalia)

2. Varisella-Zoster-Virus (VZV)

3. Cytomegalo virus (CuV)

4. Epstein-Barr virus (EBV)

The target virus is by its huge® mostly on fibroblasts.

Human pathogenic (MV is a species-specific virus and growth is successfully cultivated exclusively on human diploion cells, but

5 Infected cells in a living host organism are primarily fibroblasts, epithelial cells and white blood cells - lymphocytes and leukocytes · CMV * attacks the lungs, liver, kidneys, brain, intestinal tract and other organs. In view of this fact, we emphasize the central discovery that the common feature of viruses of the whole herpetic group is their persistence in the host organism. The virus remains in the cell without replicating after often inapparent infectious infection. Immunity is established which can last for life. In the case of exogenous or endogenous weakening of the host's resistance, the viruses can go into a nonproductive stage and relapse. Under specific conditions associated with a weakening of the body's resistance, exogenously-infected viruses can also cause secondary infection.

Journeys Infections j

In normal CMV infections, virus detection is possible in almost all body excretions and secretions (saliva, urine, ejaculate, post secretion, breast milk). Transmission b by infected body fluids is the most common route of infection. Close human-to-human contact enhances the spread of infection. In most cases, the infection is clinically inpatient in healthy children and adults. Like rubella virus, CLVV can infect the fetus through the placenta. Infection can also be induced perlnatally through contact with the secretory or in contact with the blood of the mother. The course of primary infection in the mother's body is usually associated with more severe damage to the infant, which has greater consequences for his organistaue than for infections acquired after a trauma, when canned blood has been crippled after surgery. ¹ seronegativítu. The C-1V virus can kill throx + planar plowed organs of infection and disease.

and í. to kiss with the olives

Prophylaxis and treatment of others

Thus, numerous experiments have been conducted in which florion patients (2V infection and impaired resistance to synthetic anti-viral chemotherapeutics) have been involved in these observations * These substances show severe side reactions »which must be accounted for when deployed« Prophylaxis and treatment » manifestation of CVA diseases caused by Speicic atatylcytomegalovirus hyperlraunoglobulinEd is not only effective but also free from side effects that can be observed with antiviral chemotherapeutic agents ·

Cytomegaly in clinical medicine t

- burns

- cardio-surgery

- leukemia

- AIDS

- gynecology and paediatrics

- kidney transplantation of the liver of the bone marrow

burns

The burns leave an average to fatal consequence because the patient's immune system is damaged by plasma loss and the effects of burn toxins. The burned area is a gateway to infectious agents, which can lead to septic processes. Polytransfusion is gradually associated as a result of CMV infection if it has not been given enough CMV negative blood. • Prophylactic administration of anti-CHV immunoglobulins not only prevents CMV infection, but will also protect the recipient against others due to its other antibody content (such as IVEGA). infections (Kegon, RJ, Naraqi, S, Ma t suda, T ,, Jonasson, O.Mä Herpes Simplex Virus and Oytomegalovirus Infection in Bumed Patients · The Journal of Trauma 25 (1), 40-45 (1985) ·

Cardiac surgery mimotclcdo tej

Cardiac surgery, especially surgery, the use of circulatory circulation leads to a decrease in the patient's immune status to the extent that ChV reactivation may occur. Massive and repeated blood transfusions often lead to recurrent CvVV infection. Beneke and epol. report on 28 CKV infections in 51 operated patients with extracorporeal circulation · Prophylactic use of anti CMV immunoglobulin has its full justification (Beneke, JS · Tegtmeicr * GJS *, Leukemeyer, RB ·, Alter, HJ ·, Bayor, WL ·: Relationship of Donor Cytomogalovirus Antibody Titers and Transfusion Transfusion 22 (5) · 422, Abstract 573 (1982) ·

L e u m e a

In the treatment of leukemias ea utilizes aggressive chemotherapy, which induces effective immunosuppression · From unwanted side effects ea first infections and among them QáV in particular · Transmission of CMV by blood should be avoided using exclusively seronegative cans · Infection external or possibly reactivation in children Gerein · Collaborators report on the cost of prophylaxis in patients during the intensive phase of chemotherapy with an initial dose of anti CMV immunoglobulin of 2 ml / kg body weight * then 14 days later 1 ml / kg body weight · In case of chemotherapy. Continued longer, every 4 weeks prophylactic dose of 2 nil / kg body weight, other patients did not receive additional doses. Immunosuppreasiver Therapy · In t Patient, Infection, Immunoglobulin · Hrsg. Kornhuber, B · (1984) ·

AIDS

AIDS ea can easily be distinguished from other acquired immune system defects · □ HIV infected patients in the advanced stage of the

Gynecology and pediatrics

Infections caused by CMV are among the most common intrauterine infections · Of the total number of children born in the monitored period, 1% is already infected in the mother's body · Of these, a significant proportion remain uncomplicated · 10% of children are born with the most severe damage *

- periventriMail calcites

- optic nerve atrophy

- retinitis

- thrombocytopenia

- hepatosplenomegáliou

- prolonged stroke

In the next 10% of children born in the reporting period there are late damages as we consider *

- hearing damage

- neurological disorders

- mental retardation

- psychomotor retardation

Primary pregnancy infections are more frequent complications for a child than those caused by maternal reinfection. · Embropathy after CKV infection is more severe than rubella in their consequences. Therefore, they should be given a pregnancy suspected of having a CMV prophylactic dose of anti-CM7. of immunoglobulin until · the introduction of C18 antibody testing into comprehensive care for pregnant women ·

Another risk · when a child may become infected with CMV is a feather and early postnatal phase, as shown by lace, urine and breast milk examinations, where up to 25% of mothers are positive · We believe it is necessary to protect the unborn baby by prophylaxis. For newborns, untested blood cans pose a significant risk of infection and are particularly dangerous for children

Goronegative mothers. This is also because these children do not have the immunity they receive from raatorin antibodies. Premature birth and low birthing rolls (less than 1200 g) are another morbidity and lethal factor. In the near future, the links indicated will require the introduction of systematic investigations into previously untreated or soropositive blood cans.

Blaoklock reports on good therapeutic effect Entish CMV immunoglobulin at predčane births (Blacklook HA _f Griffiths, PB, Watkins, P · An Attempt to punishment Cytomegalovirus Pneumonitis in Premature Heonates with Hyperimmune CNV-specifiy Imrnunoglobulin. Abstract 57 »4th International Symposium on Infections in the Immununocomproinised Host (Ronneby, Sweden 1986) ·

transplants

The introduction of new immosuppressive drugs has greatly increased transplantation numbers. However, the success of transplants is still threatened by the “Graf t versu3 host” response as well as viral infections in which CKV is at the forefront. CMV virus is most commonly transmitted by contaminated därsou organs as well as by blood transfusion. Infection from virus carriers is rare. During immunosuppressive modification, seropositive subjects experience secondary infection (secondary) or reactivation of CMV. Seronegative recipients whose clinical manifestation is more frequent and more difficult to develop than seropositive individuals are particularly at risk.

Finding different data in the literature on the incidence of sorologically diagnosed CMV infections (60 to 80%) · The number and typological series of diseases induced by CHV is currently incomplete because it is difficult to distinguish

Graph t verqus host response from clinical picture of CSJV infection.

• There is clear evidence that primary infections that are transmitted by organisms or blood often lead to vshiku of CMV syndrome than secondary infections or reinfection.

Hamilton reports the percentage incidence of CTAV disease depending on donor and recipient seronegativity or seropositivity (Hamilt _t JD with Cytomegalovirus and Immunity, In: Llonographs in Virology, Vol. 12, 5. Sargar-Verlag (B) 1932).

j Därca: j C *; IV disease: | nsgat. | neg. io r, j ne ^ at. Ϊ ? _________________ ... .. pos. L -----------......... J 11 č | POZIOM. Negi. ... . - ..... .......... 56 * i pozit. pos. . . 1 I-1-I 25%

Kidney transplantation

CMV infection is the most common complication in kidney transplantation. In his study (1962-1983), ßassbinger evaluated 83 patients who had CUV disease (CmV status). · 43 patients were seroegative and 40 sheropositive before transplantation. In 18 patients, a primary infection was demonstrated after transplantation. 8 18 patients with a group of 40 seropositives reported a 4-fold increase in CLV antibody titer. · 8 patients and primary infection developed severe C.IV pnemmonitis, with 2 cases of CSLt. In these patients, i.v. anti CKV immunoglobulins (Pascbinder, et al.: Cv.V-Infectionen nach IJierentranGlc & tation. Ergobnisae einer lyperindriunoglobulin-Prophylaxis. Workshop, Arosa 1986, in prees.) ·

Pettersson et al. Report on a set of 65 transplements, among which 12 patients (14 />) had CHV disease. Patients received iv anti CL1V immunoglobulin at a dose of 2 ml / kg body weight (Pottersson, E, iiclund, B. _r Hookectedt _t Κ ». SOLMET,»> ·, Ahonen, t »t Bassive Immune Tkerapy eye Gli · Nical CHV-Bisease was held in allograft Reclpients · 13 th Congress of the Scandinavian Tranaplantaticn äociety, Stockholra (1985)). Also, Kraeiser-IIanson reports successful anti-CJ.IV immunoglobulin therapy in 27 patients who have a virologically and serologically confirmed CZV disease. · Patients received a dose of 2 to 4 ml / kg body weight daily or every other day (Kraemer-Ianson, et al. Hyperlmuna Globulin f or Cytomegalovirus Pneumonitis in Immunosuppressed Patient (Zur Publication eängex'oicht).

Heart transplantation

Jf J.

J. CÍ UC? C5 X'd CC «f Λ · '“ Ý. * ·· » 'and Γ' tv ·» * · <, r ·· »* · · ^ν, 3ΛΓ · ^'·· ι.' ··, ·· / *» * » '*> ···. <*, * - »· -: '·· i' ώ J, Λ vu l- .u '--jrv

Ir nulo C, .V ocnoronae fi tídc. n cpcmedsi them in 1 case of pnoumonl · patients also fever and gastritis. Clinical advent of the iodine r-group of patients in u

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ν.ννίϊ.— »· v

- 3 years of disease resolved after 14 days of dosing with 2 ml / kg body weight of anti CMV immunoglobulin ·

Havel and coworkers recommend the following prophylaxis: on the day of surgery and then at 7-day intervals for 30 days, administer 1 ml / kg body weight of anti-CS1V immunoglobulin (Havel M Laczkovics, Preiss, P.). , MUl & er, MM, Wolner, E .: Wertigkeit der CMV-Infection-Prophylaxis mit Hyperimmunglobulin bei Immunosupprimierten Herztransplantierten Patienten, Jahrestag der Ssterr, Ges fttr Innere Medizin, Salzburg (1986),

Liver transplantation

As with heart transplantation, liver transplantation has as its priority the maintenance of organ ooz administration of immunosuppressive medication, which, however, carries the risk of infection by oprtunistic inducers (lamas). Prophylaxis with anti-CMV immunoglobulins improves transplantation results, as Burdelslci and his co-workers investigating the problem reported in 22 children. In this study, i.v · anti-CMV immunoglobulin was administered at a dose of 1 ml / kg body weight at 20-day intervals.

Bone marrow transplantation

Currently, the only treatment concept for chronic myeloid leukemia is bone marrow transplantation. • The success of the transplant depends not only on the absence of a Graft versus host reaction and the onset of revision, but also on the absence of viral infections. It was found that at the death of approximately 20% of all recipients of the Biogenic Transplant, they were the ones who suffered from CTi pneumonitis, which generally leads up to 65% to lethal-to-end

planting centers in 40 countries of the world.

Prophylactic intravenous immune globulin on tho insidenoe of sopticcinia in March trnnsplant recipients. Bone Hlarrow Transplant

1987, 2: 141-148.

Bowox, RA, Sayers, Li. _e Plornoy, et al.: Cytoinogalovirus Immunoglobulin and Scronegative Blood Product to Primary Primary Cytomegalovirus Infection After Marrow Transplant Engl J. Med 1986, 314: 1006-1010.

Peterson et al. and Bowden et al. report good results ε by application of Q! V hyperimmune globulin in 97 allogeneic bone marrow recipients. Their preparation had a titer of 1: 128 CMV antibodies (in complement fixation test). • Application dose of 150 mg / kg body weight 7-play for 62 days. In a French study, patients receiving C8AV hyperimmune globulin (titer 1: 3200 and 1: 12800 enzyme line d immunosorbent assay) at 200 mg / kg body weight for 75 days and 100 days after transplantation showed a lower incidence of incremental pneumonia than the control group (Havel, H., Iiaozkovics, A., Preiss, P., Mftller, MM, Wolner, E .: Wertigkeit der CMV-Infectionproflaxen mit Hypsriramunglobulin bei Immunsupprimierten Herztransplatierten PatienΠ von Jahresag der Osterr · Ges. für Innere Medizin , Salzburg (1986)). IN

Winston et al report a reduction in the incidence of GfVV infections from 46% to 21% when polyvalent immunoglobulin i.v. at a dose of 1000 mg / kg body weight weekly for 120 days (Winston, DJ, Ho, W, G, Lin, CH ·, et al. with Intravenous Irnmune Globulin for prevention of cytomegalovirus infection and interstitial pneumonia after hone marrow transplantation. Ann. Intern · Med · 1987, 106: 12 ·) ·

In the prophylaxis and therapy of CVA infection, i.v. preparations of polyvalent immunoglobulins or specific anti-CMV iraunoglobulins are used.

Polyvalent preparations:

preparation: dose: App interval: Garaimune-N /fy.Cutter Biologocal V / est Hawaii Conn.7 Titer neutralic. antibodies 1 with 64 1000 mg / kg per week 120 days after transplantation Intraejlobulin / £ y. Biotest Frankfurt KS H 2 ral / kg in kidney transplantation in bone marrow transplantation J p í +73 day | -7 + + 13 33 +33, +53. +73, +93

nômmagard. (Hyland / USA) 2 ml / ml / Ethanol / Antibody content 55 µl / ml |

Specific anti-CMV preparations!

preparation: dose: Globulin (France) / titer 1: 3,200 or 1:12,800 enzyme linked immunosorbent assay 200 mg / kg Cytoteot · Biotcst Frankfurt Germany / /..titer.50 ra.j »/ ral prophylaxis therapy - 2 ml / kg

App interval! | every two days until clinical symptoms are resolved.

up to 100 days after transplantation every 21 days

So far, the most widespread large-scale cellulose ethanol fractionation method according to Colin based on ethyl alcohol concentration, pH, temperature, ionic strength and dielectric constant does not give us an immunoglotulin preparation suitable for intravenous administration (Cohn, 3 · J, Strong, LE, Hughes, WL) , DY, Ashworth, Melin, Taylor, · Preparation and Froperties of Serum and Plaama Proteins ·

Amer. Chem · Soo. 68, 1946, e (459-475) ·

A variety of techniques are used to eliminate unwanted post-application reactions in immunoglobulin preparations.

The procedures used in recent years can be summarized in three totals:

- subsequent elimination of enteric-acting aggregates from the imtuioglobulin otendard preparations for i * m administration

Primary prevention of complement activating aggregates formation during fractionation.

11 * (Barandun, S ·, Škvaril, F ·, Horeli, A ·: Prophylaxis and Trsatment of Diséaee by Means of Immunoglobulins Monographs of Allergy 9 · 1975 pp. 39-60) ·

The most commonly used methods are:

- cleavage of immunoglobulin by IgG with pepsin (Schultze H.E., Schwick, G. Uber neue MBglichkeiten intravenÔser Gammaglobulin - Applikation.

Dtaoh. med · Wochr. 87 1962, e. 1643-1690).

centrifugation (Barandun, S., Kistler, P., Yeunet, P., Isliker, H .: Intravenous admlniatration of human gamma-globulin.

Vox Sang, 7, 1962 * 8, 157-174).

- incubation of IgG immunoglobulins at pH 4 at 37 ° C

- incubation of IgG immunoglobulins at pH 4 at 37 ° C in the presence of small amounts of Pépsin (Barandun, S., Kistler, P., leunet, F., Isliker, H.): Intravenous administration of human globulin-globulin.

Vox Sang. 7, 1962, e. 157-174).

ld Kobldt, H ·, Barandun, S ·, Diggelmon, H: luxnover of Standard Gammaglobulin, pH 4 Gaemoglobulin and Pepsin Desaggregated Gamma Globulin and Clinical Implications.

Vox Sang. 13 »1967» ¢ .1 p. 93-102).

- heat incubation at 37 ° C and pH acid in the presence of pepsin in a maltose environment (Banda, I., Bulík, J. Stachý, A., Luoanský, A., Andraraina, J .:

A.O. 239838 of 15.6.1987)

- chemistry of activated carbon (Audran, H., Steinbuch, Li .: Etude des condition d'apparaxion ei; de prévention de l'acxivite anticoraplcraentaire des globulines.

Paeters H .: Editor

Protldes of the biological fluids Amsterdam, 15 ° Colloque, 1967, h. 479)

- reduction of anticomplementary activity of plasmas (Sgouris, J.T. The Preparation of Plasmin Treated Immune Serum Globulin f or In.traven.ous Use.

Vox Sang, 13 »1967» No 1 p. 71-34) ^ 7 β

- stabilization by human albumin (Stachy, A. ,, Luke, J., Bulik, J., Banda * I.t. A.O. 242313 dated November 15, 1987)

Stachy, A., Bulik, J. $ Banda, I.: A.O. 237866 of 15/03 · 1987)

reduction and alkylation of disulfide bridges between the heavy chains of an IgG molecule (Bappenh & gen, A., Lunblad, J., Schroeder, D. B. U.S. Patent Bo 3903262, 1975)

- chemical stabilization with the botulinum-propiolactone Pc-region of the IgG molecule (Stophan, tf: Undorgraded Human Immunoglobulin f or Intravenouso Ueo.

Vox Song. 28, 1975, 8 ¢ 22-437)

An advantage of the proposed method for the preparation of a specific hyperimmune anti-Ca immunoglobulin. for iv administration, no other chemo-physical procedures other than heat exposure and stabilization of olfigosaccharide are used. Prepared Preparation i .v. immunoglobulin has a native, untreated and unprocessed molecule that retains all biological activities of the immunoglobulin molecule · if maltose and sucrose are used, the texturization of the viruses is possible and thus ensures the safety of the recipient in terms of • x transmission of viral infections with human blood products · _w - ** - fr —Tr · - - -, ρ

ZH 2 PJA nl / jrui-jpp-ejia. fyfeŕt </ 2

The preparation consists of human iraunoglobulins with a high>> 0 fS content of monomeric IgG, but also IgA and Igγ1. The product is stabilized with sodium chloride and maltose. It does not contain an antiseptic. It is prepared with plasma of high titres of enticytomegalovirus-

wherein the purification of the antibody molecule is said to be complete (JU-c / y)

"Tcc-s.hJv. a preparation of a specific hyperimmune anti-CMV immunoglobulin class IgG, IgA, IgM containing at least 60,000 IU / ml. in 1 l of a 5% solution consisting of 10.0 to 10%

100.0 g / l of said proteins and 75 to 200 g / l of oligosaccharides selected from the group glucose, maltose, sucrose · pript-curkiM

A process for the preparation of co-oxides. that to a solution of specific hyperimmune anti-CMV immunoglobulins of class IgG, IgA, IgM h a protein concentration of 10,0 to

Oligosaccharides selected from glucose, maltose, saoharose in an amount of 75-170 g / l are added at 100.0 g / l, and the solution thus obtained is taken at a temperature of + 4 ° C to + 50 ° C for 2 to 10 ° C. days.

N.

/ 1 f

Mental cascade · During the cascade, opsonizing substances are formed first and secondary to phagocytosis. Another effect is achieved by opsonization, which in the second part of the cascade directs the attacker and contributes to its neutralization ·

The GOEGA package contains $ 00 mg of protein (or 2500 mg of protein). · The osmolality obtained by diluting a 5% solution is 267 mosmol / ml of a 5% solution containing at least 60 IU. anti-cytomegalovirus antibodies (determined by ELISA),

Ensuring the safety of re-patients of C M V E G A in terms of viral infections by individual technological operations

II

III plasma from. donors tested for B-hepatitis and HIV with a negative result

Cohn ethanol fractionation

- precipitation:

of ethanol for 6 hours at 6 ° C, thermodetraction at 10 ° C for 10 hours by suspending v / v ethanol at 6 ° C for 6 hours at + 3 ° C. To the invention, a solution of a supernatant of hyperglycalated ontin-C18 immunoglobulins having a protein concentration of 50.0 g / l is added S5 g of sucrose. After perfect homogenization and pH adjustment to 6 _t 4 to

7 * 0 e is sterilized by filtration of phical hyperimmune anti-Cl at a temperature. + 2 5 ° g for 13

The 2 npp solution of rcpirairaoglobulin obtained is incubated for days.

ύ / Lic. cJ λ 'ovi £ ¹ * Φ' specific solutions hypsrlnún.nyoh ant: ^l-ur., in imuHa.-Iloko: a protein concentration of 55.0 g / 1 was added 1L3 frames of maltose, thoroughly homogenizing and adjusting the pH to a value of 6 »7 ~ _e 4 ^D: sterile filtration, the solution Dakto zľCokarý čpoc.ifí.ckóhc hypeimúnnehe cuit-bq immunoglobulin en írikubujc the tcpj.o- * -t 2 of that $ C for 10 days.

, nc ·· ío, j 4 x - determinations made by Immuno Vienna xx - determinations made by Biotest Frankfurt

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1 $ Table # 2

preparation: Dimer and monomer content: Content of aggregates: CMVEGA š.010289 96.7% 1.4% x GMA-VENIN / Behring NSR / 88.0% 2.0 - 9.0% x iv GLOMAN / Vienna Sohwab / 90.0% 5.9% x VEHIMMUN / Behring West Germany / 80.0% and l ø 15, o% x | 1

x - determined by the firm. Immuno Vienna

Tabu Ilk et al. 3

preparation:

CMVEGA š. 010289 _: IVEGA

Ϊ š.840939

AKA in CH50 j / og AK A after incubation for 30 days for proteins: + 37 O in CH50 j / mg protein:

I i

í J »t

I

0.68

0.91

0.76

GELIFIKtoá i. «J

- 1 *

Table no. 4

preparation: Solubility before thermal load per minute: Solubility after incubation 30 days at + 37 ° C / min · CMVEGA ä · 010289 2 6 J IVEGA š. 840989 8 4 s GELIFICATION 1 1

Table 5

preparation: solubility per minute: CMVEGA š.010289 2 x IVEGA š · 840989 8 x ENDOBULÍN / Immuno Vienna / 20

- determined by · immuno Vienna

Table δ. 6

Results of some qualitative indicators in CMVEGA š. 010289 before and after thermostructures.

Indicator: Pre-thermodeuction values Values after thermo-destruction at + 57 ° 0 for 10 hours Anticomplementary activity at CH50 j / mg protein 0.81 0.88 solubility 7 mins · 6 mins · Content of monomers in% 88.2 95.5 Dimer Content% 10.3 3,2 í < Aggregate content in% 1.5 1.3 j

Table 7

Stability test with CMVEGA w. 010289 _o before and after heating in a tropicalization cabinet at + 7.5 ° C and + 34.5 ° C rotation at 24 hour intervals for 30 days ·

Indicator: Before test: After the test: Anti-complementary activity in CH50 3 / mg protein 0.81 0.77 solubility 10 min. 8 min. Content of monomers in% 88.2 of 5 Dimer Content% 10.5 8.1 : Aggregate content in% <1.5 1.4 j T

<2600 - <? #

Claims (2)

Patent claims 1. A specific hyperimmune anti-CMV immunoglobulin class IgG, IgA, IgM preparation contains at least 60,000 IU / ml of a 1% 5% solution, characterized in that it contains 10.0 to 100.0 g / l of said proteins and 75 to 200 g / l of oligosaccharides selected from the group of glucose, maltose, sucrose · prprc-i-bij _t mwĹhJ _t · A method according to claim 1, characterized in that oligosaccharides selected from glucose, maltose are added to a solution of spheroid hyperimmune anti-CMV immunoglobulins of class IgG, IgA, IgM for protein concentrations of 10.0 to 100.0 g / l. sucrose in an amount of 75 to 170 g / l and the solution thus obtained is aecfef at a temperature of + 4 ° 0 to + 30 ° C for 2 to 30 days ·