RU2576814C1 - Agent for treatment and prophylaxis of natural infectious diseases in cats - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: for treatment and prophylaxis of natural infections in a cat the composition is used, comprising a recombinant feline interferon in a therapeutically active concentration. Interferon used as the active component relates to a family of nonglycosylated interferons of omega type. The proposed composition provides a pronounced therapeutic effect with respect to natural common diseases of cats, such as panleukopenia, feline calicivirosis, herpesvirus rhinotracheitis, chlamydiosis, mycoplasmosis, presented in the form of mono- and in the form of mixed infections.

EFFECT: reduction of term of treatment of the animal.

6 cl, 5 tbl, 8 ex

Description

The invention relates to the field of pharmaceuticals and can be used in veterinary medicine for the treatment and prevention of natural diseases of cats of viral, bacterial or mixed origin. A veterinary composition for treating diseases of cats of a viral and / or bacterial nature is proposed, containing as an active principle a recombinant interferon, which is one of the subtypes of non-glycosylated omega-interferon of a cat, and pharmaceutically acceptable carriers and / or additives.

Viral infections are common in domestic animals. The most common in cats include such natural diseases as panleukopenia, viral leukemia, infectious enteritis and peritonitis, infectious rhinotracheitis, stomatitis and keratoconjunctivitis of various etiologies. Many of the above diseases are heavily tolerated by animals and often lead to death. So, for example, coronavirus peritonitis is legal in the vast majority of cases. Mortality in patients with panleukopenia in the absence of proper treatment in cats reaches 25-75% (R. Gaskell, M. Benet, 1996), in kittens reaches 90% (V.N.Syurin, N.V. Fomina, 1979; S.V. . Starchenkov, 2001). With rhinotracheitis, originally caused by the herpes virus and complicated in the subsequent calicivirus infection, the fatal outcome can be up to 80% (Sanin A.V., Veterinary Clinic, 2002, No. 3-4).

Until recently, the treatment of viral diseases in cats was very laborious and at the same time insufficiently effective, because in the arsenal of veterinarians there were no drugs (with the exception of sera) that had specific antiviral activity, and treatment actually amounted to combating the symptomatic manifestations of such infections. Today, domestic veterinary medicine is quite actively using drugs with an antiviral effect, among which the most popular are roncoleukin, immunofan, ribotan, fosprenil, anandine, salmosan, maxidine.

The most common bacterial diseases in cats are chlamydia, mycoplasmosis, bronchoseptic bordetellosis, toxoplasmosis and staphylococcosis. Bacterial infections occur as primary, as well as concomitant infections against the background of a decrease in the overall immune status of the body as a result of, for example, viral infection. This phenomenon plays an important role in the development of pathogenesis, causing a rapid progression of the infectious process and a vivid clinical manifestation of the disease in acute form. Post-infectious and post-vaccination immunity to most bacterial diseases is usually very weak and has a short-term character. Modern vaccines are not able to provide adequate protection also because of the large antigenic diversity of pathogens. In this regard, antiviral drugs that have an immunostimulating effect and are able to inhibit the development of a secondary viral or bacterial infection are of particular importance in the complex treatment of many natural infectious diseases of cats.

Recently, in the treatment of natural infections of cats, more attention has been paid to the issue of the prospects for the use of "interferon" drugs. It should be noted, however, that the use of such drugs has a number of features, among which an important place is occupied by the need to take into account their species-specificity. It is well known that beta and gamma interferons found in all mammalian species are proteins characterized by strict species specificity in terms of biological activity (Gibbs V. et al., Mol. Cell Biol., 1991, 11 (12), 5860-5866; Hemmi S. et al., Proc. Natl. Acad. Sci USA, 1992, 89, 2737-2741; Qin X. et al., Mol. Ther., 2001, 4 (4), 356-364 ; www.ienabioscience.com/images/PDF/ABD-082.pdf). Alpha, tau, and omega-interferons are usually encoded by several genes, the expression products of which form "families" consisting of subtypes - polypeptides with a high level of similarity of amino acid sequences (95-99%). When tested on cell cultures of different animal species, alpha, tau, and omega interferons often exhibit interspecific effects. However, it has been experimentally established that attempts at “interspecific” use at the organism level (even in the case of in vivo activity) do not justify themselves under long-term treatment or the use of high doses of the drug due to the formation of significant amounts of antibodies to such drugs. On this basis, most researchers make an unambiguous conclusion about the preferred use of species-specific "interferon" drugs for the treatment of animals.

Unfortunately, despite the fact that a large number of different types of interferons of animal origin have been obtained in the laboratories of the world, including cat interferons (alpha, beta, gamma, omega), their widespread use in veterinary practice is extremely limited. In fact, to date, there are only two species-specific commercial drugs used for treating cats in the world, Intercat (Taura Industrial Inc., Japan) and Virbagen (Virbac, France), which are positioned as effective means to fight some of the most common viral infections.

In connection with the foregoing, the relevance of the development of new veterinary compositions intended for the treatment of viral and / or bacterial infections in cats based on species-specific interferons is obvious. This task, first of all, provides a solution to the question of choosing the most suitable active components of the composition for this purpose.

State of the art

In 1988, the first polypeptide with the characteristic structure and properties of interferon was discovered in cats by Japanese researchers in cats and in subsequent years (Nakamura et al., Biosci. Biotech. Biochem. 56 (2), 211-214). This protein, due to the relatively low level of sequence homology (about 60%) with human alpha-interferons known at that time and the presence of several other features that distinguish it from the alpha forms known at that time, in particular the presence of a carbohydrate residue (glycosylation), was attributed by the authors to a new type of IFN, namely the omega-type (Ueda et al., 1993, J. Vet. Med. Sci., 55 (1), 1-6), which previously included only one polypeptide of human origin (Hauptmann et al., Nucl. Acids Res., 1985, 13, 4739-4749). Today, a glycosylated recombinant analogue of the first feline interferon, defined by the authors as omega-interferon and retaining its original name (rFeIFN-omega), is used in practice or as part of the drug manufactured by Toreu (Japan) INTERCAT (for example, CIIIA (US) patents 5508291; US 5714382; US 6194381); or as part of a licensed drug manufactured by Virbac (France), called Virbagen omega (Southerden P., 2007, J Small Anim Pract. 2007, 48 (2): 104-6; Gutzwiller M. et al. Vet. Dermatol. , 2007, 18 (1), 50-54; Gil S, Res. Vet. Sci., 2013, 94, 753-763, etc.).

In 2004, a group of Japanese authors published data on their receipt of 14 cat proteins that have between themselves 95-99% sequence homology and structural characteristics characteristic of alpha interferons, as well as exhibiting high antiviral and antiproliferative activities inherent to interferons of this type, which allowed us to define them as subtypes that form the "family" of alpha cat interferons. Moreover, all representatives of this group of feline interferons, in contrast to human IFN-alpha, contained carbohydrate residues bound in a site typical for glycosylation (Nagai et al., 2004, J. Vet. Med. Sci., 66 (b), 725 -728). After 2 years, another “family” of interferons was discovered in the cat, including 13 proteins (YangL.-W. Et al., 2007, J. Interf. Cytokine Res., 27, 119-127), which also had a high degree of structural homology ( 96-99%), while having common differences from the previously discovered group of feline IFN alpha subtypes, consisting of 6 additional amino acid residues at the C-terminus of the molecule, the absence of an N-glycosylation site, the number and location of conserved cysteine and proline residues. Based on a comparison of the characteristics of this group of proteins with the types of interferons of other animals known at that time, their relation to the omega type was unambiguously established. In addition, it is known that IFN-omega subtypes and IFN-alpha subtypes a) act on different parts of the receptor and, accordingly, send different signals to the cell (Cutrone E. and Langer J., 1997, FEBS Lett., 404, 197- 202; Xue Q. et al., 2010, J. Inter. Cytokine Res., 30 (2), 81-88) and b) generate the formation of various antibodies, i.e. the activity of omega-interferons is not suppressed by antibodies to alpha-interferons (Adolf G. Et al., J. Gen. ViroL, 1987, 68, 1669-1676).

It should be noted that a comparison of the cat omega-interferon family with the cat interferon-alpha family provides all grounds for concluding that the first “feline” interferon (Nakamura et al., 1992), which is part of the INTERCAT and Virbagen preparations, most likely does not apply to omega, and to alpha. In favor of this, it is evidenced that a) said protein is glycosylated (at the N-glycosylation site); b) the degree of homology of the amino acid sequences of the mature polypeptide with any interferon from the omega feline “family” is not more than 60%, while the similarity of the same sequence to any of the cat’s 14 alpha interferons is 95-98%, and c) the number and location of conservative amino acid residues in the structure of the molecule coincides with that for feline alpha interferons. Today, many authors either call the first feline interferon omega “similar” (″ FeIFN-omega-like ″), or directly consider it in the same group as feline alpha interferons (Yang et al., 2007; Taira O. Et al., 2005, J. Vet. Med. Sci., 67 (5), 543-545), and the latest versions of it in the databases are given either without specifying the type (GenBank, AAB27160), or are directly defined as referring to alpha interferon (see GenPeptP35849.1; gi 547724).

In the absence of information in the prior art on the development and use of veterinary drugs for the treatment of natural diseases that would contain “true” (non-glycosylated) omega-interferons in cats, the closest analogue of the invention should be recognized as a means for treating viral infections in cats based on the first “feline” "Interferon obtained by Japanese researchers and by indirect signs defined by them as IFN-omega (rFeIFN-omega), in particular any of the two known drugs, INTERCAT or Virbagen.

For example, US 6194381 (prototype) discloses the successful use of the INTERCAT preparation, which, in addition to cat interferon, discovered in 1992, contains gelatin, D-sorbitol and a stabilizer for the treatment of infections characterized by immunodeficiency, including anemia and chronic stomatitis, and also atopic dermatitis in cats. The type of recombinant interferon used in the well-known medicinal preparation was obtained in silkworms transformed with recombinant baculovirus, and is a glycopeptide with mol. mass of 25,000, which is characterized by the amino acid sequence corresponding to the sequence of the mature protein in the precursor with access number GenPept P 35849.1.

Among the disadvantages of the prototype, in addition to the above uncertainty regarding the classification of the interferon component, it should be noted that a) the preparation of a glycosylated recombinant product with the “correct” (native) structure and, accordingly, full biological functions requires the use of expression systems, in particular, animal cell cultures, not very suitable for scaling the process and obtaining high yields of the target product; b) as for any glycopeptide obtained by the recombinant method, problems may occur due to insufficient homogeneity of the product, which is often a mixture of glycosylated and non-glycosylated molecules; c) in the practice of treatment with alpha interferons, with which, as it has been established, the active component of the prototype is similar, cases of manifestation by the body of the initial or acquired resistance are quite often observed (US 7727519; 06/01/2010). In addition, in the prior art there is no reliable information about the results of using the prototype in relation to infectious diseases of cats of bacterial origin.

In this regard, in the implementation of the present invention the task was to propose a new tool for the treatment of natural infectious diseases of cats, based on the action of species-specific interferon and at the same time devoid of the above disadvantages of the prototype.

Disclosure of invention

The problem was solved by developing a pharmaceutical veterinary composition, including as an active ingredient one of the subtypes of non-glycosylated omega-type cat interferon (according to Yang et al., 2007) as an active ingredient, as well as additives and stabilizers that are traditionally used in this field .

The development scheme of the present invention included the following steps:

a) analysis of information presented in the prior art, with the identification of interferon candidates for use as an active principle;

b) obtaining and purification of recombinant products selected according to the results of a literature study;

c) a preliminary analysis of the general antiviral effect of purified proteins on cell cultures using various types of viruses;

g) the preparation of compositions with subsequent verification of their activity and stability and the selection of preferred options;

d) verification of the toxicity of the selected compositions;

f) study of the therapeutic effect of the obtained compositions in vivo on cats with various natural infections;

g) evaluation of the results.

a) As a result of the analysis of literature data, the following conclusions were made.

Feline interferons beta and gamma are rarely used as the active principle of antiviral prescription compositions, which seems logical in light of the available information about their relatively weak antiviral effect, in particular, due to the predominance of immunomodulating action (Tanabe T. et al., 2001; Gil et al ., 2013). In contrast, the IFN-alpha family is characterized by high levels of antiviral and antiproliferative activity. However, all representatives of this group of feline interferons in nature are glycosylated, which is a certain technical obstacle to obtaining high-quality and at the same time relatively cheap recombinant products (see the section "Prior Art").

Omega-cat interferons, which have a great structural and functional similarity to the feline alpha-interferon family and usually exhibit the same, and sometimes greater (depending on the type of virus), level of total antiviral activity (Wang H., Sheng Wu, Gong Cheng, Xue Bao, 2008; 24 (9): 1556-60), have a number of obvious advantages over alpha interferons, the main of which is that they are non-glycosylated proteins and, accordingly, can be obtained as a completely homogeneous preparation quite simple and easy to scale method, and also have their own immunogenic characteristics, due to which they do not lose their activity under the influence of antibodies not specific to them (see the section "Prior Art").

Based on this, as a candidate for the implementation of the present invention, we pre-selected the omega type of feline interferon, namely a family of 13 polypeptides with the sequences presented in GenBank under the numbers DQ 420220 - DQ 420232. In this case, it was considered expedient to use in the evidence part subtypes that, according to published data (Yang et al., 2007), have the minimum and maximum in vitro antiviral activity within this group, namely IFN-omega 1 (GenBank DQ 420220, ABD78704; NCBLNPJ 082772) and IFN-OMera 2 (GenBank DQ 420221, ABD78705; NPJ095910 )

Despite the fact that the Chinese authors used a recombinant protein expressed in E. coli cells for scientific purposes, attempts to incorporate it into the drug and to use it for treating natural diseases of cats were neither undertaken by the authors of this work, nor by other researchers. Meanwhile, specialists in this field are well aware that many effects observed in vitro are not reproduced in vivo, because at the level of the organism, additional and not yet fully understood mechanisms come into effect. So, quite often the “cross action” (interspecific activity) that occurs when testing on cell cultures disappears (Rodriguez M. et al., J Biotechnol. 1998; 60 (1-2): 3-14), in many cases with treatment natural diseases of animals, including cats, there is no positive effect of interferon, which showed antiviral activity in vitro tests (Slack J., Am J Vet Res., 2013; 74 (2): 281-289; Ritz S., J Vet Intern Med. 2007; 21 (6): 1193-7). In full accordance with the idea that the result from the use of interferons for the treatment of viral infections, for which antiviral activity is shown in in vitro test systems, is not obvious, the fact is found that for the previously proposed (RU 2482871 C2, 05.27.2013 ) as the active ingredients of the mixture of alpha and omega interferons, we were not able to confirm the synergism established in in vitro experiments on the synergism of action on sick animals, without which their use in the composition of drugs loses economic feasibility.

An essential point for choosing the non-glycosylated interferon-omega was the lack of published data on its use as the main active component of veterinary compositions used to treat diseases of bacterial origin in cats.

b) Recombinant non-glycosylated feline omega interferons in this work were obtained by expression of the corresponding genes in the E. coli strain as inclusion bodies, followed by reactivation and chromatographic purification. The purified proteins were stored as a lyophilisate (at + 4 ° C) or as a frozen solution (at minus 20 ° C). The molecular weights of the obtained products fully corresponded to those calculated from the amino acid sequences of the mature forms (for IFN-omega 1 - 19.3 kDa; for IFN-omega 2 - 19.9 kDa), which was a direct confirmation of the absence of carbohydrate residues.

c) An analysis of the antiviral effect was evaluated by inhibition of the cytopathic effect of the vesicular stomatitis virus or feline calicivirosis virus on CRFK or fCWF-4 cell lines by a known method (Armstrong, Methods in Enzymol., 1981, v. 78 (PtA), pp. 381-387) . As a result, it was found that the specific activity of IFN-omega 2 determined in this system was significantly higher for most of the preparations than IFN-omega 1. The total interval of specific activity for all preparations of both types ranged from 0.5 × 10 ⁸ to 5 , 0 × 10 ⁸ IU / mg, which corresponds to the best performance for the rFeIFN used in the prototype (see the formula in US 5508291).

d) Before starting experiments on animals, the composition of the medicinal compositions was selected to ensure the best solubility of interferon and the stability of the drug during storage. Acetate, citrate, and phosphate buffers were used as the buffer system. The tested pH range was from 3.5 to 8.0. To increase the stability of the drug and make the solution physiological, the composition additionally included EDTA-Na, NaCl and one or two neutral carriers selected from sorbitol, mannitol, polysorbate, polyvinylpyrrolidone, dextran, tween, etc., traditionally used in this field.

To check the stability of the drug during storage at specific intervals in an in vitro test on a cell culture, specific activity was determined, and the quantitative content of interferon in the sample was determined using the ELISA method. The stability of interferons in various compositions was observed under storage at 4 ° C and in accelerated storage at 25 ° C. Stability monitoring was continued for at least 1 year at 4 ° C and 3 months at 25 ° C. The data obtained showed the presence of various acceptable compositions giving a similar picture for the solubility of IFN and the stability of the preparations, however, the results obtained for the compositions based on acetate buffer with a pH of 4.5-5.0 with the addition of dextran were recognized as the best.

e) A toxicity study of the selected compositions was performed in mice and rats. For experiments, lyophilized or frozen substances of cat interferon were diluted in the selected composition to obtain a cat interferon concentration of 2 μg / ml. The drug was administered to mice and rats intragastrically or intramuscularly in an amount of 50 ml / kg of body weight and the general condition and behavior of animals, weight gain, and the results of microscopic examination of tissues (liver, lungs, kidneys, heart, muscles) were evaluated. Based on the totality of the data obtained, the recombinant products obtained (compositions with IFN-omega 1 and IFN-omega 2) were recognized as low-toxic compounds corresponding to hazard class 4 according to GOST 12.1.007-76.

f) Checking the therapeutic effect of the proposed drugs was carried out on the basis of several veterinary clinics in Moscow according to the general scheme, according to which the experiment in all cases included at least 20 cats of both sexes aged 1 to 7 years old, weighing from 3.5 to 5 , 5 kg, with a reliable diagnosis; preparations were administered to experimental animals intramuscularly once a day in a volume of 0.5 or 1.0 ml (approximately 200,000 and 400,000 IU, respectively) per animal for 5-7 days depending on the disease (herpesvirus rhinotracheitis; calicivirusosis; pancopenia; calicivirusosis + panleukopenia, mycoplasmosis, chlamydia, mycoplasmosis + chlamydia); observation of the condition of the animals was carried out during the entire period of treatment, noting the timing of the appearance of the first signs of improvement, the disappearance of the main clinical signs of the disease and clinical recovery (data in each group were averaged and rounded up to a day). Prior to the studies, the tolerance of the drug was determined, for which the drug was administered once to healthy animals at a dose 1.5-3 times higher than the therapeutic one and examined on the 3rd and 7th days. However, in no case of adverse reactions were recorded.

g) In assessing the therapeutic effect of the drug, the dynamics of improving the overall clinical condition and the duration of treatment until clinical recovery, as well as the results of clinical and, in some cases, biochemical blood tests, were taken into account.

The data obtained allowed us to conclude that the agents of the present invention, which comprise non-glycosylated feline interferon-omega veterinary compositions, exhibit a pronounced therapeutic effect in relation to common natural diseases of cats, such as panleukopenia, calicivirus, herpes virus rhinotracheitis, chlamydia, mycoplasmosis , presented both in the form of mono-and in the form of mixed infections, and, on average, reduce the time required for a full recovery by about 30% I am an animal. Moreover, in all cases, with the exception of herpes virus rhinotracheitis, the smaller (200,000 ME) of the two daily doses used was sufficient. Over the entire observation period, none of the treated animals showed any side effects and complications.

An important result is that there were no significant differences between the data obtained for preparations with IFN-omega 1 (with minimal activity in vitro) and IFN-omega 2 (with maximum activity in vitro). This allows us to conclude that any of the subtypes of feline interferon-omega with an "intermediate" level of antiviral activity in vitro can be used as an active ingredient in the proposed tool with the same success.

Thus, the use as an active principle of the composition for the treatment of infectious diseases in cats of one of the representatives of the feline non-glycosylated omega-interferon family (instead of the glycosylated feline interferon in the prototype) provides a new effective drug that differs from the prototype in terms of low cost and simple preparation of the main component in required quantities, as well as a wider spectrum of action (main technical results). In addition, the proposed veterinary composition can be used as a stand-alone medicine, or as a substitute for drugs with alpha-interferon widely used in veterinary practice, including INTERCAT (prototype), in cases of resistance to the latter (additional technical result )

Information about the treatment of specific diseases and its results are presented below in the form of examples of implementation, which should not be construed as limiting the scope of the invention.

Examples

Example 1. Obtaining compositions for testing in vivo.

Composition number 1. Prepared a solution of the following composition:

Sodium chloride - 5.86 g / l;

Sodium acetate - 2.71 g / l;

Dextran - 40-50 g / l;

EDTA-Na - 0.058 g / l;

Glacial acetic acid to a pH of 4.5-5.0;

Water for injection - up to 1 liter.

The IFN-omega 1 cat interferon substance was added to the buffer solution so that the resulting activity was 400,000 IU / ml. Then, the solution under aseptic conditions was filtered through a filter with a pore diameter of 0.22 μm and poured into sterile 3 ml 2.5 ml vials. The vials were corked with rubber stoppers and crimped with aluminum caps. Ready vials were stored at a temperature of 2 to 8 ° C. Composition No. 2 was prepared similarly to composition 1, except that IFN-omega 2 was used as the active component.

Example 2. Treatment of herpes virus rhinotracheitis.

The experiment was conducted on 27 cats with a diagnosis of herpes virus rhinotracheitis. Animals were divided into three groups: control (n = 9), the first experimental (n = 9) and the second experimental (n = 9). The animals of the first experimental group were injected 200,000 ME of interferon-omega 1 (0.5 ml of composition No. 1) once a day for 5 days, the animals of the second experimental group according to the same scheme - 400000 ME (1 ml of composition No. 1). Cats in the control group received treatment without the inclusion of etiotropic therapy in the regimen. The dynamics of the treatment of the disease and the timing of recovery were evaluated (in days after the start of the administration of interferon to experimental animals). The results are shown in table. one

From the data obtained, it is obvious that there is an improvement in the dynamics of treatment and a reduction in the time to complete recovery, which in this case is more pronounced in the second experimental group.

Example 3. The treatment of calicivirus.

The study of the therapeutic effect of the proposed composition was carried out according to the same scheme as in example 1, except that both experimental groups were injected with 0.5 ml (200,000 IU), but the first experimental group of animals received composition No. 1 (with IFN- omega 1), and the second - composition No. 2, representing the same composition, but with IFN-omega 2. Due to the fact that in most cases calicivirus infection was accompanied by anorexia, stomatitis, conjunctivitis and impaired respiratory function, the dynamics of improvement were monitored per speaker nd these symptoms (Table. 2)

It was found that the improvement in the condition of animals is accelerated in both experimental groups, while demonstrating similar dynamics. Both drugs shorten treatment time by an average of 2 days.

Example 4. The treatment of panleukopenia.

In the study of the therapeutic effect of the proposed drugs used the same scheme as in example 1, using composition No. 2 in two different single doses (200,000 IU and 400,000 ME). Each of the three groups (control and two experimental) included 8 animals in this experiment. Before and after the course of treatment, a clinical blood test was additionally performed. Table 3 shows the results of the study.

As follows from the above data, an improvement in the dynamics of the disease and a reduction in the time of clinical recovery was approximately 30% at both maximum and minimum single doses.

A clinical analysis of blood after the completion of treatment revealed small residual deviations, expressed in a slight increase in ESR and the number of leukocytes and neutrophils, slightly beyond the reference values, which returned to normal over the next 1-2 days.

Example 5. The treatment of panleukopenia, weighed by calicivirosis.

In the treatment of animals with panleukopenia complicated by a calicivirus infection, the experiment was conducted on 30 animals, which were divided into 3 groups, 10 animals each. The first experimental group received 200,000 ME compositions No. 1, the second experimental group received intramuscularly 400,000 ME compositions No. 1, once a day for 5 days. According to the results of the tests, it was found that the dynamics of the improvement and the terms of clinical recovery were almost completely consistent with the treatment results for panleukopenia, which proceeds as a monovirus infection, described in Example 3. During the use of interferon-containing preparations in experimental animals, biochemical blood tests were performed, as a result of which a temporary increase in the activity of the enzymes AST, ALAT and LDH, as well as the total protein content, which returned to normal after the clinical recovery of the animals, was revealed.

Example 6. The treatment of mycoplasmosis.

When determining the therapeutic effect of omega-interferon cats when adding them to the treatment regimen of mycoplasmosis, cats with a reliable diagnosis of mycoplasmosis (33 animals) were studied as a means of etiotropic therapy. The therapeutic effect of composition No. 1 was determined on two experimental groups of cats (n = 11), using different doses, 200,000 ME (0.5 ml of composition No. 1) and 400,000 IU (1.0 ml of composition No. 1), respectively, in the first and the second experimental groups. The results of the study showed an earlier clinical recovery in cats, compared with animals not receiving interferon, an average of 20%. The use of interferon allowed to reduce the general course of antibiotic therapy by 2-4 days, the duration of which in the control group was 12-14 days, and in the experimental group - 10.

Example 7. The treatment of chlamydia.

The effectiveness of treatment of chlamydia in cats according to the scheme using composition No. 2 was studied in two experimental groups of cats (n = 10), using different doses of interferon: 200000 ME (0.5 ml of composition No. 2) and 400000 ME (1.0 ml of composition No. 2). As a result of treatment, it was found that a lower dose of the drug (200,000 ME) is sufficient. An earlier disappearance of characteristic clinical signs was noted in comparison with animals not receiving the drug.

Example 8. The treatment of rhinotracheitis of mixed etiology (herpesvirus cat, bronchiseptic bordetellosis).

In the experiments, the effectiveness of the use of interferon in the treatment regimen of infectious (herpes virus) rhinotracheitis of cats complicated by a bacterial infection caused by Bordetella bronchiseptica was studied. Two compositions of the preparation were used in the experiment: composition No. 1 and composition No. 2, both in a single dose of 200,000 ME. The results showed that when a drug containing omega-interferon cat was added to the treatment regimen, on the second day of therapy, clinical symptoms were relieved (hyperthermia, catarrhal inflammation of the upper respiratory tract), while in animals that did not receive omega-interferon, clinical relief Symptoms occurred on average a day later. Complete clinical recovery with the use of omega-interferon was observed on days 4-5, which is 20% faster compared to control (6-7 days).

Claims (6)

1. Veterinary composition for the treatment and prevention of natural infectious diseases in cats, containing an effective amount of recombinant interferon, which is a member of the family of non-glycosylated omega-interferon cats, as an active principle and pharmaceutically acceptable excipients and / or additives. 2. The composition according to p. 1, characterized in that the natural disease is a monoviral infection. 3. The composition according to p. 1, characterized in that the natural disease is a mixed viral infection. 4. The composition according to p. 1, characterized in that the natural disease is a bacterial infection. 5. The composition according to p. 1, characterized in that the disease is a mixed viral-bacterial infection. 6. The composition according to any one of paragraphs. 1-5, characterized in that it is used in the complex treatment of the disease.