RU2342951C1 - Preparation containing antibody antivariolic from whey of blood of horses, solution for intramuscular introduction - Google Patents

Abstract

FIELD: medicine; pharmacology.

SUBSTANCE: essence of the invention includes a preparation representing a 9.0-11.0% solution of an antibody of hyperimmune whey of blood of horses, containing scale-globulene fraction in number of not less than 90.0% from quantity of the general protein, as nonspecific impurity - an alpha-and beta-globulene fractions not more than 10.0% and residual ethyl spirit in amount of no more than 4.0%, having pH from 7.0 to 7.5 and characterised by titre of virus-neutralising antibodies to the virus of a vaccine not less 1:4000.

EFFECT: creation of a preparation for prevention and treatment of smallpox and Orthopoxvirus diseases at people.

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 the prevention and treatment of smallpox and orthopoxvirus diseases in humans, as well as the treatment of patients with complications after vaccination with smallpox vaccine (except for children with complications after vaccination).

The cessation of smallpox vaccination in 1980 led to the practical disappearance of population immunity to the causative agent of this infection.

With the cessation of vaccination, work was also curtailed to create new therapeutic drugs, vaccines and other means of specific prophylaxis of smallpox. Discontinued production of methisazone and other chemotherapeutic anti-arterial drugs.

Currently, the problem of resuming smallpox vaccination is recognized as extremely urgent by specialists from WHO, Russia, France, Germany, the USA and other countries.

However, the resumption of vaccination is associated with a high risk of developing a large number of post-vaccination complications [1, 2].

According to Russian researchers, normal donor immunoglobulin with a high content of anti-arsenic antibodies can be used for the treatment of post-vaccination complications [3, 4]. Donor immunoglobulin with a titer of neutralizing antibodies of at least 1: 4000 is also recommended for use in primary vaccination against smallpox [5]. Foreign researchers also recommend the use of immunoglobulin for the prevention and treatment of post-vaccination complications [6, 7].

However, at present, donor immunoglobulin cannot be obtained due to the lack of human donors who have a high titer of anti-inflammatory antiviral antibodies in the blood due to cessation of vaccination.

Since obtaining donor immunoglobulin is not possible, it is justified and advisable to obtain heterologous anti-arterial anti-arthritis immunoglobulin from horse serum as the only treatment and prevention of smallpox and orthopoxvirus infections, as well as post-vaccination complications in adults.

This drug can actually be obtained in modern conditions of the absence of population immunity to smallpox.

The developed drug has no analogues in the Russian Federation.

The aim of the present invention is to develop a preparation containing anti-venous immunoglobulin from the blood serum of horses, intended for the prevention and treatment of smallpox and orthopoxvirus diseases in humans, as well as the treatment of patients with complications after vaccination with smallpox vaccine (except for children with complications after vaccination).

The essence of the invention lies in the ability of the vaccine virus to induce the production of specific protective antibodies in horses and the use of the native hyperimmune blood serum of horses containing antibodies to the vaccine virus as a raw material for the production of a specific preparation. The drug containing anti-inflammatory immunoglobulin, is a 9.0-11.0% solution of immunoglobulins of hyperimmune blood serum of horses containing antibodies to the vaccine virus, has virus-neutralizing activity against the vaccine virus and is suitable for use as a means of prevention and treatment of smallpox and orthopoxvirus diseases, as well as the treatment of patients with complications after vaccination with smallpox vaccine (with the exception of children with complications after vaccination).

The technical result of the invention lies in the fact that this drug, which has a virus-neutralizing activity against a vaccine virus, characterized by a titer of virus-neutralizing antibodies of at least 1: 4000, can be used to prevent and treat smallpox and orthopoxvirus diseases in humans, as well as treat patients with complications after vaccination smallpox vaccine (except for children with complications after vaccination).

The developed preparation containing anti-venous immunoglobulin from horse serum, the solution for intramuscular administration is new and has no analogues in the Russian Federation.

Execution example

The raw material for the preparation of an immunoglobulin preparation is hyperimmune blood serum of horses, containing antibodies to the vaccine virus. Isolation of immunoglobulin from horse serum containing antibodies to the vaccine virus is carried out by the method of alcohol fractionation in the cold according to the Kohn method [8].

A preparation containing anti-venous immunoglobulin from horse serum, a solution for intramuscular administration, is a clear or slightly opalescent liquid, colorless or with a yellowish tinge, sometimes with a slight precipitate that breaks easily when shaken, with a pH value of 7.0 to 7, 5 and is a 9.0-11.0% solution of horse serum immunoglobulins containing antibodies to the vaccine virus. The content of the gamma globulin fraction in it is at least 90.0% of the total protein. Albumin, α- and β-globulins in the amount of not more than 10.0% and residual ethyl alcohol, the content of which is not more than 4.0%, are present as non-specific impurities in the preparation. The drug has a virus-neutralizing activity against the vaccine virus, characterized by a titer of virus-neutralizing antibodies of at least 1: 4000. The drug is sterile, pyrogen-free and non-toxic.

Eight series of anti-arterial immunoglobulin preparation were obtained from horse serum.

According to physicochemical and immunobiological parameters, the anti-inflammatory drug immunoglobulin corresponds to the quality indicators of anti-rabies immunoglobulin preparations isolated from the blood serum of horses [9, 10].

The characteristics of the drugs are presented in the table.

An example of the best use of a drug containing anti-venous immunoglobulin from horse blood serum, a solution for intramuscular administration can be its use for the prevention and treatment of smallpox and orthopoxvirus diseases in humans, as well as the treatment of patients with complications after vaccination with smallpox vaccine (except for children with complications after vaccination).

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-inflammatory (data on 8 series) anti-rabies [9, 10] Description Transparent or slightly opalescent liquid, colorless or with a yellowish tinge. A slight precipitate is allowed, easily breaking when shaken. Transparent or slightly opalescent liquid, colorless or slightly yellow in color. The concentration of total protein, percent 9.0 to 11.0 9.0 to 11.0 The content of gamma globulin fraction, percentage 90.5 to 93.7 No less than 80.0 The content of residual ethyl alcohol, percent 3.5 to 4.0 No more than 4,5 The concentration of hydrogen ions, units pH 7.0 to 7.5 6.6 to 7.4 Pyrogenicity Pyrogen-free Pyrogen-free Toxicity Non toxic Non toxic Sterility Sterile Sterile

Information sources

1. Non-parenteral methods of immunization against smallpox / A.A. Vorobyov, V.N. Podkuyko, V.V. Mikhailov, A.A. microbiol. - 1996. - No. 5. - S.117-121.

2. Meltzer M.I. Risks and benefits of preexposure and postexposure smallpox vaccination // Emerg. Infect. Dis. - 2003. - Vol.9, No. 11 - P.1363-1370.

3. Marennikova S. S., Manevich G. R., Light-Moldavian I. A. On the effectiveness of γ-globulin with a high content of anti-arsenic antibodies in the treatment of post-vaccine encephalitis // Vopr. virusol. - 1968. - No. 1. - S.9-13.

4. Bondarev V.N., Voitinsky E.Ya. Prevention and treatment of post-vaccination complications in children. - L .: Medicine, 1972.

5. The vaccination of smallpox: Guidelines MU 3.3.1.2044-06. - M .: Federal Center for Hygiene and Epidemiology of Rospotrebnadzor, 2006. - Introduction. 03/01/2006.

6. USAMRIID'S medical management of biological casualities. Handbook / Ed. M. Kortepeter, G. Christopher, Ted Cieslak et al. // US Army Medical Research Institute of Infections Diseases (USAMRIID'S) - Fort Detrick, Frederick, Maryland, 2001 .-- Fourth edition.

7. Casadevall A. Passive antidody administration (immediate immunity) as a specific defense against biological weapons // Emerg. Infect. Dis. - 2002. - Vol.8, No. 8 - P. 833-840.

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

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

10. 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 anti-venous immunoglobulin from horse blood serum, a solution for intramuscular administration, which has virus-neutralizing activity against the vaccine virus and is suitable for use as a means of preventing and treating smallpox and orthopoxvirus diseases in humans, as well as treating patients with complications after vaccination with smallpox vaccine (for excluding children with complications after vaccination), which is a 9.0-11.0% solution of immunoglobulins of hyperimmune blood serum of horses containing a titers to the vaccine virus, containing gamma-globulin fraction in an amount of not less than 90.0% of the total protein, as non-specific impurities containing albumin, α- and β-globulin fractions in an amount of not more than 10.0% and residual ethyl alcohol in the amount of not more than 4.0%, having a pH value of from 7.0 to 7.5 and characterized by a titer of neutralizing antibodies of not less than 1: 4000.