RU2342952C1 - Preparation containing antibody against bolivian haemorragic fever from whey of blood of horses, solution for intramuscular introduction - Google Patents

Abstract

FIELD: medicine; pharmacology.

SUBSTANCE: essence of the invention includes a 9.0-11.0% solution of an antibody for the intramuscular introduction, possessing virus neutralising activity to Machupo virus, obtained from hyperimmune whey of the horses, containing scale-globulin fraction in amount not less than 85.0%, and as nonspecific impurity - albumine, the alpha and beta-globulin fractions in amount not more than 15.0% residual ethyl spirit in amount not more than 4.5%, having pH from 7.0 to 7.5 and a titre of the virus-neutralising antibodies not less 1:1024 of fever; the preparation contains albumine, α- and β-globulin fractions in amount not more than 15.0% and residual ethyl spirit in amount not more than 4.5%.

EFFECT: working out of a preparation for emergency prevention of Bolivian haemorragic fever.

1 ex, 1 tbl

Description

The invention relates to medicine, specifically to medicines and medicines (to immunoglobulins) for therapeutic purposes, and can be used for emergency prevention of Bolivian hemorrhagic fever (BHF) in humans.

BGL is a zoonotic natural focal infection, the causative agent of which, Machupo virus, belongs to the Arenaviridae family and causes acute febrile illness in people with severe hemorrhagic syndrome and high mortality rate (up to 70%) [1, 2].

Specific means of prevention and treatment of BGL are currently not available in our country. Treatment of patients is symptomatic.

From data from foreign sources it is known that when monkeys are injected with serum immune serum convalescents after transferred BGL with a BHA titer of 1: 2048 in an amount equal to 10 and 3 equivalent units of plasma for humans (200-250 ml), 2 hours after subcutaneous infection of macaques with Machupo virus at a dose of 10 ⁵ PFU, the disease does not develop. With the therapeutic purpose of the drug, a very mild disease develops lasting up to 2 days [3].

The introduction of donor immunoglobulin at 7-9 days from the onset of the disease was ineffective [3].

Significant disadvantages of the immune plasma (serum) of convalescents, which is the raw material for the isolation of donor immunoglobulin, are the possible presence of viral contaminants (hepatitis B and C, HIV, etc.) in it, which are dangerous for humans and low levels of neutralizing antibodies.

In addition, the Russian Federation (RF) does not have serum convalescents, since BGL is not endemic for our country, therefore, donor immunoglobulin cannot be obtained in the Russian Federation.

The way out of this situation may be to obtain highly purified heterologous immunoglobulins. The developed drug has no analogues in the Russian Federation. In the practice of serum production, the horse is a traditionally used producer for obtaining immune serums against many pathogens [4].

The aim of this invention is to develop a drug containing immunoglobulin against Bolivian hemorrhagic fever from horse serum, a solution for intramuscular injection, intended for emergency prevention of BHL in humans.

The essence of the invention lies in the ability of the Machupo virus to induce the production of specific protective antibodies in horses and the use of native hyperimmune blood serum of horses containing antibodies to the Machupo virus as a raw material for the production of a specific preparation. The developed preparation containing an anti-BGL immunoglobulin is a 9.0-11.0% solution of immunoglobulins of hyperimmune blood serum of horses containing antibodies to the Machupo virus, has a neutralizing activity to the Machupo virus and has a pronounced prophylactic effect in the case of BGL.

The technical result of the invention lies in the fact that the developed drug with a titer of neutralizing antibodies of at least 1: 1024 provides specific emergency prophylaxis of BGL in experimental animals and is recommended for emergency prophylaxis of BGL in humans.

The developed drug containing immunoglobulin against Bolivian hemorrhagic fever from horse serum, the solution for intramuscular injection is new, since there is no similar heterologous drug in world practice.

Execution example

The raw material for the preparation of an immunoglobulin preparation is hyperimmune horse serum containing antibodies to the Machupo virus. Isolation of immunoglobulin from serum of horses containing antibodies to Machupo virus is carried out by the method of alcohol fractionation in the cold according to Cohn [5].

A preparation containing anti-BGL immunoglobulin from horse serum is a clear or slightly opalescent liquid, colorless or yellowish, sometimes with a slight sediment that breaks easily when shaken, with a pH value of 7.0 to 7.5 and is 9 , 0-11.0% solution of immunoglobulins in serum of horses containing antibodies to Machupo virus. The content of the gamma globulin fraction in it is at least 85.0% of the total protein. As nonspecific impurities, the preparation contains albumin, α- and β-globulins in an amount of not more than 15.0% and residual ethyl alcohol, the content of which is not more than 4.5%. The drug has a neutralizing activity against Machupo virus, characterized by a titer of neutralizing antibodies of at least 1: 1024.

The drug is sterile, pyrogen-free and non-toxic. When administered intramuscularly, it has a pronounced prophylactic effect in case of BGL.

10 series of an anti-BGL immunoglobulin preparation were obtained from horse serum.

According to physicochemical and immunobiological indicators, the preparation of equine immunoglobulin against BGL corresponds to the quality indicators of commercial heterologous immunoglobulins isolated from horse serum [6, 7].

The characteristics of the drugs are presented in the table.

An example of the best use of a drug containing immunoglobulin against Bolivian hemorrhagic fever from horse serum, a solution for intramuscular administration can be its use as an emergency means of preventing BGL in humans.

Table
Characterization of heterologous immunoglobulin preparations obtained from horse serum Name of quality indicator, unit of measure The value of the indicator for immunoglobulin preparations anti-rabies [6, 7] against BGL (data on 10 series) Description Transparent or slightly opalescent liquid, colorless or slightly yellow in color. Transparent or slightly opalescent liquid, colorless or with a yellowish tinge. A slight precipitate is allowed, easily breaking when shaken. The concentration of hydrogen ions, units pH 6.6 to 7.4 7.0 to 7.5 The amount of total protein, percentage 9.0 to 11.0 9.1 to 10.7 The content of gamma globulin fraction, percentage No less than 80.0 85.0 to 90.3 The content of residual ethyl alcohol, percent No more than 4,5 4.0 to 4.5 Pyrogenicity Pyrogen-free Pyrogen-free Toxicity Non toxic Non toxic Sterility Sterile Sterile

BIBLIOGRAPHIC DATA

1. Peters C.J., Buchmeier M., Rollin P.E., Ksiazek T.G. Arenaviruses. In: Fields. B.N. // Fields Virology. - 1996a. - P.1521-1551.

2. de Manzione N., Salas R.A., Paredes H., Godoy O., et al. Venezuelan hemorrhagic fever: clinical and epidemiological studies of 165 cases. // Clin. Infect. Dis. - 1998 .-- Vol.26. - P.308-313.

3. Eddy J.A. Prophylaxis and treatment of Bolivian hemorrhagic fever with immune serum or purified γ-globulin. // 1973. Usamriied planning sessions 18-19 October 1973. USA Medical Research Institute of Infection Disease, Fort Detrick, Frederick, Maryland. - P. 19-24.

4. Burgasov P.N. Vaccine and Serum Guide. - M., 1978.

5. Cohn E.J., Strong L., Hughes W.L. et al. Preparation and properties of serum and plasma proteins // J. Amer. Chem. Soc. - 1946. - Vol. 68, No. 3. - P.459-475.

6. Liquid rabies immunoglobulin from horse serum: FSP 42-0020-4413-03 / Ministry of Health of the Russian Federation.

7. Anti-rabies immunoglobulin from horse serum, liquid, injection for injection 150 IU / ml: ND 42-13071-04 / Ministry of Health of Ukraine.

Claims (1)

A preparation containing immunoglobulin against Bolivian hemorrhagic fever (BHF) from horse serum, an intramuscular solution with virus-neutralizing activity against Machupo virus and used for emergency prevention of BHL in humans, which is a 9.0-11.0% immunoglobulin solution hyperimmune blood serum of horses containing antibodies to Machupo virus containing γ-globulin fraction in an amount of not less than 85.0% of the total protein, containing nonspecific impurities containing al bumin, α- and β-globulin fractions in an amount of not more than 15.0% and residual ethyl alcohol in an amount of not more than 4.5%, having a pH from 7.0 to 7.5 and characterized by a titer of neutralizing antibodies of at least 1: 1024.