Russian Anti-Plague Research Institute

Russian Anti-Plague Research Institute

Bacteriophage preparations basing on the localization of their application

wound:
for superficial treatment (against conditionally pathogenic microorganisms inducing suppurations and similar pathologies – staphylococcus phage, pseudomonas phage,streptococcus phage)

intestinal:
  (dysenteriae phage, typhoid phage, salmonellosis phage, coliphage, proteus phage, coli-proteus phage, intestiphage).

Separately stands the group of phage preparations intended for subcutaneous, intramuscular, intracavernous or intravenous injections for preventing the generalization of infections invoked typically by staphylococcus, streptococcus, and pseudomonas.
In view of that, wide spread gained pyophage – a complex preparation composed of 5 components: staphylococcus phage, coli-phage, proteus phage, streptococcus phage, and pseudomonas phage.

Bacteriophages were produced in different medicinal forms

In liquid and dried form
In tablets with acid-resistant coating from acetyl phthalate cellulose or pectin.
In rectal suppository.


In due time, industry of USSR produced the following most important bacteriophage preparations for treating bacterial infections of humans:

Staphylococcus bacteriophage (pathogens – almost exclusively Staphylococcus aureus, rather rarely – Staphylococcus epidermidis)

The preparation is a filtrate of lysed staphylococcus culture. The preps of staphylococcus phage existed:

i) in liquid form, obtained on protein-enriched and protein-free medium  respectively, for local/enteric applications and parenteral injections;

ii) as rectal suppositories with dried phage preparation and filling agent (polyethylene oxide) – for treating professional disbacteriosis; as paste – for personnel prophylactics in maternity hospitals,etc.

way of preparation application

Depends on the localization of disease focus:
 
Local superficial application is achievable via spraying of liquid bacteriophage preparation over the wounds and use of wetted bandages.

-Subcutaneously the phage is applied in small doses in one or several sites.

-There were also practiced intracavernous applications (in pleural cavity, cavity of urinary bladder).

-Intramuscular and intravenous injections.


 Streptococcus bacteriophage:

Usually was produced in liquid form for superficial applications.

Pseudomonas bacteriophage:
-Liquid preparation for treating suppurative infections, osteomyelities, abscesses and similar pathologies of pseudomonas etiology.
Means of application are similar to those of staphylococcus phage.

Coli-bacteriophage:
-Preparation was produced in liquid form and used for controlling infections invoked by, or complicated by, Escherichia.
-Peroral and rectal applications were practiced.

Proteus bacteriophage:
-Preparation was produced in liquid form and used for controlling infections invoked by, or complicated by, Proteus.Means of application are identical to those for coli-phage.

Coli- proteus bacteriophage:
-Combined preparation – mixture of filtrates of lysed cultures of Escherichia coli and Proteus vulgaris, Proteus mirabilis.

Salmonella bacteriophage: 

-Produced in liquid form. Peroral and rectal applications.

Dysenteriae bacteriophage:
-Preparations produced in liquid form and in tablets (dried prep) coated with acetyl phthalate cellulose (APC) or pectin and in suppositories.
-Peroral and rectal applications.



Ubiquitous complex bacterial etiology of various pathologies (presence of different serotypes, strains of bacteria, and often different bacterial species) conditions necessity for developing polyvalent phage preparations (composed of a mixture of varied types/races of bacteriophages active towards one bacterial species), and even sometimes combined, or complex, phage preps (containing phages active toward diverge bacteria invoking pathology of a complex etiology – for instance, against acute intestinal infections or suppurative inflammatory processes).

Bacteriophages for Treatment of Diseases caused by Antibiotic-Resistant Pathogens

Pyo-Phage (5 components: Staphylococcus, E.coli, Streptococcus, Pseudomonas, Proteus). 
Intestiphage (17 components: Shigellaspp., Salmonella spp., Cholera suis, Staphylococcus, Proteus spp., E.coli –different serotypes, P.aeruginosa). 
Mono-phage preparations (Staphylococcal, E.coli, Streptococcal, Pseudomonas aeruginosa, Proteus).


Technological process of production of bacteriophage preparation


The process included the following steps:

- growing
- filtration
- conservation (sterilization);
- precipitation (usually with ammonium sulphate)
- stabilization
- drying (for dried preps, tablet forms, pastes and suppositories – lyophilization or drying over calcium chloride)
- tabletting and applying of acid-resistant coating (for tablet forms of preparations).

Acid-resistant coatings pursued the aim to escape the destruction of phage preparation in acidic gastric juices, and could have been from acetyl phthalate cellulose (APC) or pectin. APC makes an unbroken superficial coating over the whole tablet, and this does not allow divide the tablet for dosage (in children therapy, for instance).
Pectin forms sort of ‘individual’ coating over each virus particle in the tablet, enabling use of pectin-coated tablets for therapy of intestinal infections of youngest children.


Staphage Lysate (SPL) for veterinary use.