HU197517B - Process for production of terapeutical composition applicable against virus infection - Google Patents

Abstract

Therapeutic preparations against certain viral and other diseases of humans. The preparations are specified as formulas containing attenuated Newcastle disease virus, Marek's disease virus, avian bronchitis virus or avian encephalitis virus, mixed in carrier substance generally used in human pharmacology, if desired along with one or more optional potentiating preparations. Another object of the invention is the use of the above viruses in the treatment of virus diseases as well as malignant and benign tumours and collagen diseases.

Description

The present invention relates to a process for the preparation of a therapeutic composition for the treatment of viral infections which comprises attenuated Newcastle virus as an active ingredient.

Vaccines are used worldwide to prevent diseases caused by a variety of viruses. A vaccine containing, inter alia, attenuated or killed form of Newcastle virus is known.

Newcastle disease (NDV) is a viral disease of the nervous, digestive and respiratory systems of birds. Mycovirus multiforme is the cause of Newcastle disease, also known as poultry plague. The vaccine is produced by methods known per se, for example, the virus can be cultured well in embryonated eggs and in several tissue cultures.

Vaccines are used to protect against diseases caused by certain viruses. However, in most cases, treatment for viral diseases is unresolved, as commonly used chemotherapeutic agents have only a modest effect and vaccines against the disease are inappropriate. Worldwide, great efforts are being made to develop antiviral compositions that are therapeutically useful.

It is therefore an object of the present invention to provide a pharmaceutical composition for the treatment of viral diseases, preferably with a broad spectrum of activity.

Surprisingly, we have found that using attenuated (attenuated) forms of Newcastle vaccines or Newcastle disease to treat a wide variety of viral infections yields surprisingly good results.

The present invention therefore relates to a process for the preparation of a therapeutic composition for treating herpes, anti-cancer, rabies and AIDS patients comprising mixing Newcastle virus with at least one pharmaceutically acceptable carrier. It is to be noted, however, that the compositions of the present invention have been found to be effective in treating other viral diseases not mentioned above.

In the case of human vaccines, they usually contain killed viruses. However, the attenuated form of the virus should preferably be used in the composition of the invention.

Viral interference is expected with the product; that is, the dosed virus tries to displace the infectious virus.

The compositions of the invention are prepared in a manner known per se by admixing the vaccine or the attenuated or killed virus with a carrier commonly used in medicine. Various potentiators, such as tranquilizers, may be added to the composition.

Vaccines, or the attenuated virus itself, are prepared by methods generally known and practiced in the art, for example, using a primary or secondary fibroblast culture of pre-incubated chicken embryos for 10 to 11 days, and vaccinated virus derived from tissue culture, with reduced virulence. Alternatively, Avian bursa or Avian bronchitis virus is introduced into pre-incubated eggs and incubated at 37 ° C. The chicken embryos are then processed and the lyophilized vaccine is prepared from the recovered virulence-reduced virus. For example, the preparation of the vaccine is described in Section VI. Pharmacologically tested sterile viral material of at least 10 ⁶ TCID50 / 0.1 ml is used. Sterile viral material is mixed with 50% sterile skimmed milk and lyophilized in 2 ml lyophilized bottles every 2 ml.

For example, the Marek virus is preferably passaged on LIBDV tissue culture and propagated on a cell culture of 7 to 10 high SPF pre-incubated egg embryos.

The above vaccines are useful as active ingredients of the composition of the invention. Of course, the attenuated viruses themselves, or any of their physiological saline solutions, can also be used.

Preferably, the composition is a lyophilisate in which both the virus and the carrier are present. The preparation may also be in the form of a solution, suppository, capsule, emulsion, suspension, ointment, etc. form.

The dosage of the compositions of the invention will always depend on the subject being treated, the composition of the composition, the stage of disease and the strain of virus.

The compositions of the present invention have been tested in a number of animal and human experiments and have shown very favorable therapeutic effects against both the above viral infections and other viral infections. The compositions of the invention did not show any toxic side effects. In addition to the symptomatic treatment, the compositions of the invention were also suitable for preventive protection.

Example 1

The effect of various heterologous virus vaccines against rabies virus in mice was investigated. The animals were divided into seven groups and treated with 0.5 ml of the following vaccines intraperitoneally:

Group 1: Newcastle virus (NDV),

Group 2 duck hepatitis virus (DHV),

Group 3: Avian encephalitis virus (AEV),

Group 4: Avian bursa virus (ABuV),

Group 5: Avian bronchitis virus (ABV),

Group 6: canine hepatitis virus (CHV),

Group 7: Canine Porcine Virus (CDV).

After three days, twenty animals from each group and twenty animals from the 8th (untreated) group were also inoculated intracellularly with Rac 2197517 by a single dose of 0.03 ml as rabies vaccine (RV). Inoculation was done with five different dilution (10 ^-5 -10 ^_l) of the virus dilutions added to each of four animals. 1-7. Five to five animals in groups 8 served as vaccine controls and five animals in group 8 served as absolute controls. Animals were observed for 25 days and mortality was determined.

In the experiment, RV killed 50% of control animals. This value was taken as the Relative Death Rate (RDF) unit (1.0). In the experiment, ABV vaccine showed no effect, whereas DHV lowered RDF to 0.9, but did not significantly affect the course of infection. The CHV vaccine accelerated the course of the infection but lowered the RDF to 0.8. NDV, ABuV and CDV vaccines reduced RDF values to 0.5, but did not influence the course of infection in unprotected animals.

In the experiment, the AEV vaccine proved to be most effective, reducing the RDF to 0.3 and slightly increasing the duration of death.

Example 2

Young adult Swiss mice were divided into 8 groups of 12 animals each. Freshly undiluted Ascytes fluid was taken from infected animals and this mouse ascytes lymphoma virus (MAV) was used as the pathogenic virus. The first group was treated with 0.5 ml of MÁV ascytes fluid and 0.5 ml of saline simultaneously. The other seven groups received 0.5 ml of MÁV ascytes fluid and 0.5 ml of the following vaccine at the same time:

Group 2 RV,

Group 3: NDV (H strain),

Group 4: AEV,

Group 5: Infectious bovine rhinotracheitis virus vaccine (IBR),

Group 6: ABV,

Group 7: Parvovirus vaccine (PV) and

Group 8: Reovirus vaccine (ReV).

Incubation was done intraperitoneally and the animals were observed for 30 days. We found that the ABV and AEV vaccines accelerated the course of MAV infection, while the RDF value remained 1, similar to the MAV-infected controls. The IBR vaccine reduced the RDF to 0.88; however, this cannot be considered a protective effect. The ReV vaccine had an RDF of 0.77 and also delayed the course of infection. RV and PV vaccines showed a significant protective effect, with an RDF of 0.33, significantly delaying the development of symptoms, even in animals that subsequently die.

The NDV vaccine completely protected mice (RDF = 0) against the development of MAV during the 30-day observation period.

Example 3 Day-old, specially pathogen-free chickens were inoculated as virulent as a pathogen

Using Rous sarcoma virus (RSV) at a single dose of 0.3 ml, diluting the virus 10 to ³⁷ , added to the humor-radial region of the right wing. The vaccines were administered in a single dose, 7 days prior to RSV infection. Group 1 consisted of 15 non-infected animals (absolute control), 15 animals of Group 2 were inoculated with RSV (virulent virus control). Twenty-four animals in Group 3 were given intramuscularly Marek virus vaccine. Twelve animals were used as vaccine controls, and 12 animals were infected with RV after 7 days. Twenty-four animals in Group 4 were inoculated intramuscularly with ABuV vaccine, and 12 animals were maintained as vaccine controls, and 12 animals were given a RSV dose after 7 days. Twenty-four animals in Group 5 were injected intradermally with NDV vaccine, 12 were used as a vaccine control, and 12 were given RSV after 7 days. The animals were observed for 5 weeks. During the experiment, we found that the ABuV vaccine showed significant protection against Rous sarcoma virus. The RDF value for RSV infection alone was 0.25 for ABuV. The NDV vaccine showed a moderate protective effect (0.6), while the Marek virus vaccine showed a weak effect.

Example 4

Thirty-three patients with a variety of cancers were treated under clinical conditions with varying amounts of Newcastle vaccine administered depending on the patient's age, physical condition, and type of disease. In our experiments, we found that a significant proportion of treated patients experienced recovery or significant prolongation of survival.

Example 5

Eight AIDS patients were treated under clinical conditions with a composition comprising the attenuated Newcastle virus of the invention. In most cases, there was a significant improvement in the degree of infection and in the transmission rate.

Example 6

Six patients with Herpes simplex I, Herpes Genitalis, and Herpes Zoster infection were treated with the composition of the invention. The milder infections were considered to be healed in a very short period of time, while in the case of chronic infections, a very significant degree of healing could be demonstrated.

Claims (1)

Patent Claim Point A process for the preparation of therapeutic pharmaceutical compositions containing the attenuated Newcastle virus (NDV) as an active ingredient, characterized in that -3197517 attenuated NDV virus is formulated with at least one pharmaceutically acceptable carrier to form a medicament for the treatment of herpes, anti-cancer, anti-loss and AlDS patients.