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Antiviral Aerosol Preparations

#2163


Search of the Ways to Increase the Efficiency of Aerosol Preparations Based on Siberian Silver Fir (Abies Sibirica) Polyprenols

Tech Area / Field

  • MED-DRG/Drug Discovery/Medicine
  • BIO-IND/Industrial Biotechnology/Biotechnology

Status
3 Approved without Funding

Registration date
05.04.2001

Leading Institute
State Research Center of Virology and Biotechnology VECTOR, Russia, Novosibirsk reg., Koltsovo

Project summary

At present the development of new antiviral preparations is one of the most urgent tasks of public health service. In this respect special attention should be paid to the construction of prophylactic preparations capable of increasing the resistance of man to infection nonspecifically to the viral strain. Respiratory infections cause the greatest damage to mankind. As respiratory tract is the infection atrium for these infections, preparations for aerosol administration are needed capable of protecting the respiratory tract efficiently due to purpose delivery. Preparations based on Abies sibirica polyprenols isolated from Siberian silver fir (Abies sibirica) are preparations of the kind. As it was shown in our experiments carried out under ISTC Project #459-98, these preparations possess protective activity against challenge of white outbred mice with aerosol of influenza virus A/Aichi/2/68 (H3N2) at the doses up to 5LD50.

The main mechanism of the preparations action has been also studied. They were found to stimulate the activity of pulmonary macrophages and neutrophils (phagocytic activity and production of active oxygen forms) but were not found to increase the production of cytokines (interferon, tumor necrosis factor) in the lungs. Naturally, a combination of polyprenols isolated from Abies sibirica with one of the known interferon inducers (for instance, ridostin) can be investigated as a possible more efficient antiviral preparation. It should be noted that the developed formulation can be used both as two independent (in time) preparations and simultaneously; they can contain initial components both independently and in a single suspension or even as a part of the same particles. Besides, as a weakened organism is often infected, it is necessary to evaluate the effect of the organism immunity status on its reaction to treatment with an antiviral preparation followed by the virus challenge.

Proceeding from the above, the objectives of the proposed study are as follows:

1. To obtain experimental samples of complex formulations for aerosol administration containing polyprenols isolated from Abies sibirica and one of the known interferon inducers and to evaluate their antiviral activity.

2. To determine by experiments the components of natural polyprenols isolated form Abies sibirica possessing the highest antiviral activity. To estimate the possibility of mass production of the required compounds from natural raw material.

3. To study the main mechanism of action on the organism (including its immunodepressed states) of the developed aerosol preparations.

4. To select optimal compositions of the preparations and the most efficient administration schemes on the basis of the performed studies and, if they show a high protective activity, to give recommendations for the development and testing of commercial forms of preparations.

The development of new highly-efficient prophylactic antiviral preparations will allow to extend the range of preparations capable of competing with specific prophylactic means against infectious diseases. The data on the main mechanisms of action of the developed preparations to be obtained within the proposed Project will provide a better understanding of the infection pathogenesis, the organism ability to resist it and will serve as a basis for construction of antiviral preparations of the next generation.

The Project activities will involve 31 specialists previously dealing with biological safety problems. They have a more than ten-year experience of theoretical and experimental studies in the field of development of antiviral preparations as well as aerosol studies. Implementation of the Project will allow to use their capabilities in fulfilling the national economic tasks, which meets ISTC requirements.

The investigation methods in general are analogous to those used in our activities under ISTC Project #459-98. It should be noted that as we have already shown [4], only laboratory animals can serve as an adequate experimental system for evaluation of the protective activity of the developed preparations against influenza infection and the mechanisms of their action. That’s why all the studies planned under the proposed Project will be performed using laboratory animals. In particular, aerosol studies on purpose delivery of the preparations to animals and their aerosol challenge will be carried out in equipment described in the work [3], determination of the numbers of macrophages, neutrophils and leukocytes in the animals’ lungs as well as their activities (phagocytizing activity and production of active oxygen forms by them) will be performed according the methods described in the work [2]. Works associated with the construction of the preparations, experimental evaluation of their protective activity and search for optimal administration schemes will be conducted with the methods of mathematical planning of experiments.

The same methods will be employed in the work on determination of the most active components of natural Abies sibirica polyprenols which later can be included into the formulations. Besides, methods of high performance liquid chromatography and magnetic spectroscopy will be used to isolate and to purify the components of the natural mixture of polyprenols.

The following participation of the Collaborator is supposed in the Project:

– in discussion of the obtained results;


– in independent verification of the obtained experimental data and conducting additional studies;
– in information exchange;
– in presentation of comments to the technical reports (quarter, annual, final, etc.);
– in organization of joint symposia and work seminars.


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