RU2568869C1 - Method of treatment of demodicosis of dogs - Google Patents

Abstract

FIELD: veterinary medicine.

SUBSTANCE: clozantin is administered subcutaneously to dogs at a dose of 10.0 mg/kg on active substance once per week for 8-12 weeks, in combination with an immunomodulator polyoxydony-vet which is administered subcutaneously two times per week during the first 3 weeks of treatment.

EFFECT: method enables to increase the efficacy of treatment of demodicosis of dogs and to avoid possible complications.

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Description

The invention relates to the field of veterinary medicine, in particular, can be used to treat dog demodicosis.

Demodecosis is a widespread disease in animals and humans caused by iron mites of the genus Demodex. Demodex mites are strictly species-specific parasites: each species of animals and humans have their own species that do not develop in other hosts. The causative agent of dog demodicosis, the tick Demodex canis, is localized in the hair follicles and sebaceous glands of the skin. The transmission of ticks from mother to puppies occurs mainly in the suction period, when there is close direct contact between the mother and the offspring. Possible infection of dogs in a later period in contact with a sick animal. The risk group often includes weakened animals or having skin lesions. The development of demodicosis is often facilitated by unbalanced feeding (deficiency of protein, sulfur-containing amino acids and vitamins, excess lipids), transmitted infectious and invasive diseases, stress, immunosuppressive (chemo- and glucocorticoid) therapy or long-term antibiotic treatment. Usually, invasion develops against the background of immunodeficiency, often congenital. Among the primary immunodeficiencies against which demodecosis occurs, IgA deficiency is distinguished, as well as a hereditary deficiency of T-lymphocyte-mediated immunity. Dogs of all ages suffer from demodicosis, but the maximum incidence rate is observed in animals from 6 months to 1 year (2).

The diagnosis of demodicosis is usually made on the basis of clinical manifestations and is confirmed by the presence of ticks at different stages of development in skin scrapings. Treatment is based on drug control of ticks and supportive care. Currently available therapeutic agents (amitraz, macrocyclic lactones, saifles, etc.) allow treatment to be carried out daily, 2 times a week, weekly for 3 months or more. The use of existing drugs is time-consuming, expensive, can cause toxicosis and is not always effective (2, 6).

The drug amitraz has a number of commercial names ("Mitaban", "Ectodex", "Tactic") and contains a different concentration of the active substance. Therefore, in relation to the dilution of the drug in each case, you should focus on the attached instructions for use. Recommended frequency of use: once every 7 or 14 days until complete recovery. Before applying the drug, dogs are sheared and washed with a treatment shampoo such as Doctor or Peroxiderm. The amitrase solution is applied with a sponge to the entire body, both on healthy and affected areas of the skin. Although the amitraz solution does not have an irritating effect, the person applying the amitraz should wear protective gloves and work in a well-ventilated area, as in some people, contact with amitraz can cause skin dermatitis, migraine-like headaches or asthmatic attacks. In dogs, amitraz causes a short-term sedative effect for 12-24 hours, especially after the first application. In some dogs, at the initial stage, against the background of the treatments, itching and other allergic reactions (redness or urticaria), skin irritation and various systemic signs of allergies are observed. Sometimes, as a reaction to amitraz, dogs may experience severe weakness, ataxia, and drowsiness. Severe reactions in the form of intoxication are treated with yohimbine or atipametsolom (6).

In the early 90s, scientists conducted studies on the use of macrocyclic lactones (Milbemycin, Moxidectin, Doramectin, Ivermectin) as an alternative for dogs that do not tolerate or do not respond to amitraz. Milbemycins are prescribed in a dose of 0.5-2.0 mg / kg daily. The duration of the course depends on the specific situation and can be from 60 to 300 days. Ivermectin is used in a dose of 0.45-0.6 mg / kg and its effectiveness is high. Temporary side effects with ivermectin may include lethargy, anorexia, ataxia, and stupor. Ivermectin is highly toxic for dogs of the following breeds: collie, sheltie, bobtail (2, 6).

Of organophosphorus preparations, Sifli (cytioate), a systemic action drug, is most often used at the rate of 1 tablet per 10 kg of body weight 2 times a week for 6-12 weeks. The disadvantage of the representatives of the FOS group is their high toxicity to mammals, which entails the need to observe strict precautions when prescribed (2, 3).

The objective of our research was to develop an effective method of treating dog demodicosis with an affordable remedy, given the absence of negative effects on animals, reducing stress and time-consuming procedures.

The solution of this problem is achieved by the fact that closanthin was used as a therapeutic drug for dog demodicosis, the active substance of which is closantel - a drug from the class of salicylanilides, in combination with an immunomodulator polyoxidonium-vet.

Known highly effective drug is closanthin injectable, which contains closantel as an active substance used in cattle and sheep against fascioliasis, hemonchiasis, esophagostomiasis, bunostomosis, trichostrongiasis, nemadodirosis, ostertagiosis, hypodermatosis and estrosis. The drug is not dangerous for humans and warm-blooded. It does not have a systemic and cumulative effect, does not cause resistance in parasites. Applied by subcutaneous or intramuscular injection in doses of 5.0-10.0 mg / kg in terms of DV. The mechanism of action of closantel is to change the processes of phosphorylation and electron transfer, which leads to a violation of metabolic processes and death of the parasite. In addition, closantel also acts as a systemic anticholinesterase agent (1).

It is known that a predisposing factor for the development of demodicosis is hereditary T-cell deficiency, which alone or in combination with other immunosuppressive factors leads to the disease (4). From this, given the versatility of the forms of treatment and the complex nature of the development of demodicosis, it follows that its treatment should be comprehensive, including both specific acaricidal therapy and systemic therapy, including modern immunomodulators in its composition. As immunomodulators, we used ribotan, roncoleukin and polyoxidonium-vet. Ribotan refers to drugs of natural origin, consists of a mixture of low molecular weight thymus polypeptides (0.5-1 kD) and RNA fragments, products of yeast hydrolysis. Ribotan has an immunostimulating effect on the T- and B-system of animal immunity. It stimulates immunoreactivity to specific antigens, the functional activity of macrophages, subpopulations of T and B lymphocytes, as well as the synthesis of interferon and lymphocaines. Roncoleukin and polyoxidonium-vet are synthetic drugs. Roncoleukin is a dosage form of recombinant human interleukin-2 (rIL-2), isolated and purified from Saccharomyces cerevisiae yeast cells. Roncoleukin acts on T-lymphocytes, enhancing their proliferation and subsequent synthesis of IL-2. The main active substance that is part of the polyoxidonium vet is azoximer bromide, which has an activating effect on the nonspecific resistance of the body, phagocytosis, humoral and cellular immunity, in addition, it has the properties of a hepatoprotector.

From the sources of information available to the applicant, the specified set of existing features is unknown, which allows to obtain the specified technical result, therefore, the claimed invention meets the patentability condition “novelty”.

The applicant does not know means of a similar purpose, in which the distinguishing features of the claimed invention would be disclosed with the use of it in any combination of signs of the specified technical result. Therefore, the claimed invention meets the condition of patentability "inventive step".

Evidence of industrial applicability is claimed in the following examples.

Example 1. The study of the effectiveness of treatment depending on the dose of the active substance.

The work was carried out on the basis of a private veterinary clinic in Moscow on 18 domestic dogs of different breeds from the age of 5 months. up to 2 years, spontaneously infested with demodexes. For the formation of experimental groups of animals, preliminary infection of dogs was determined by the study of the skin. For this, the following were determined: a) tick count index; b) clinical signs in each animal.

a) Tick count index. To determine the level of mite infestation with Demodex, deep skin scrapings were taken from at least five parts of the body of each animal. Days of taking scrapings: 0, 28, 56, 84. The skin areas from which the first scrapings were taken were recorded schematically. Each subsequent scraping was taken from the same areas and / or newly appeared affected areas. Skin scrapings were performed with a single scalpel until blood oozing from the capillaries appeared. Each skin scraping was placed on an individual glass slide with mineral oil. Glass had registration codes - animal, group, body area. Each sample was examined under a microscope for the presence of adult living and dead ticks, larvae, nymphs and eggs.

b) Clinical signs. Assessment of clinical signs and the degree of damage of each animal was carried out on the days of taking scrapings from the skin. For each dog, the following parameters were evaluated and schematically plotted on the silhouettes of the right and left: body parts covered with gum; body parts covered with scales and crusts; body parts that have lost hair; reddened and pigmented areas of the body. Groups of animals were selected according to the principle of analogues (5 dogs in each group).

The titration of a therapeutic dose of closanthin was carried out in three groups of dogs. The dose calculation for each animal was carried out taking into account body weight before treatment. Closanthin was administered subcutaneously on the 0th, 7th, 14th, 21st, 28th, 35th, 42nd and 49th days at doses of 5.0; 7.5 and 10 mg / kg in each group, respectively. The effectiveness of the drug against ectoparasites was taken into account according to the results of clinical and laboratory studies of skin scrapings 4 and 8 weeks after application (on the 28th and 56th days from the start of treatment).

The use of closanthin at a dose of 5 mg / kg showed that on the 28th day after treatment the number of ticks decreased by 59.4%, and on the 56th day - by 80.2%, but the EE of the drug was zero, since all 5 dogs in the 1st group remained infected (Table 1). The dose efficiency of 7.5 mg was higher (reduction in the number of ticks by 78.4% and 90.8%, respectively). In group 2, 1 dog was completely freed from ticks (EE = 20.0%), the remaining 4 animals remained infected.

The dose efficiency of 10.0 mg / kg was significantly higher compared to the first two (reduction in the number of ticks by 89.0% and 98.9%, respectively). Three dogs were completely freed from ticks (EE = 60%), and in two dogs single parasites were found (0-1 specimens of ticks in the field of view). Three dogs with local scaly form of juvenile demodicosis were treated as untreated. The number of ticks in the control group increased on the 28th day by 144.7%, and on the 56th day - by 182.4%.

Example 2. The development of schemes for the use of closanthin with different immunomodulators.

After determining the therapeutic dose (10.0 mg / kg) in 27 dogs (5 groups), 4 schemes of drug use with different immunomodulators and without them worked out. Sifli tablets (manufactured by Forte Dogde USA) at a dose of 3.0 mg / kg by cytioate with a ratio of 2 times a week for 12 consecutive weeks were used as the basic preparation.

Since with 8-fold use of closanthin at a dose of 10.0 mg / kg, 100% efficiency was not obtained, we increased the frequency of use of the drug up to 12 times in combination with different immunomodulators: ribotan, roncoleukin and polyoxidonium-vet, which were used subcutaneously in doses according to the instructions 2 times a week for 3 weeks from the start of treatment. The results of the experiment are shown in Table 2.

The use of closanthin with immunomodulators for 3 months at weekly intervals led to a rapid reduction in the number of ticks and a noticeable positive dynamics in the clinical manifestations of the disease in all experimental animals. However, we obtained 100% effectiveness only in the group where closanthin was used in combination with polyoxidonium-vet. In the group with the basic drug, Sifli received an extensivity of 80%.

In the pustular form of demodicosis, a 0.05% chlorhexidine solution was applied externally daily as an antiseptic. Along with the treatment, diet therapy was carried out. Animal owners were advised to exclude from the diet bakery products and other products containing starch. Of the cereals, buckwheat and rice, as well as poultry, were recommended.

Thus, closanthin at a dose of 10.0 mg / kg with 12-fold subcutaneous administration with a frequency of 1 time per week in combination with a polyoxidonium-vet immunomodulator used subcutaneously 2 times a week at a dose of 0.15-0.3 mg / kg (depending on the weight of the dogs) within 3 weeks from the start of treatment, showed 100% effectiveness in demodicosis of dogs.

Information sources

1. Arkhipov I.A. Anthelmintics: pharmacology and use. - M., 2009 .-- 509 p.

2. Vasilevich F.I., Kirillov A.K. Demodecosis of dogs: Textbook for higher education. - M., 1997 .-- 49 p.

3. Kirillovsky V.A. Insect acaricidal drugs used in veterinary medicine and animal husbandry. / Ed. B.A. Timofeeva. - M., 1998 .-- 372 p.

4. Shipstone M. Generalized demodicosis in dogs, clinical prospects // Russian Veterinary Journal. Small domestic and wild animals. - 2008, No. 1. - S. 33-35.

5. Mueller R. S., Bensignort E., Ferrer L. et al. Treatments of demodecosis in dogs: 2011 clinical practice guidelines // Veterinary Dermatology. - 2012. - V. 23, N 2. - P. 86-96, E 20-21.

6. Scott D.W., Miller W.H., Griffin C.E. Canine demodecosis. In: Muller & Kirk′s Small Animal Dermatology, Philadelphia, W.B. Saunders. - 2001 .-- P. 457-474.

Claims (1)

A method for the treatment of dog demodicosis, including subcutaneous administration of closanthin at a dose of 10.0 mg / kg DV once a week for 8-12 weeks and additional subcutaneous administration of the immunomodulator polyoxidonium-vet 2 times a week for 3 weeks from the start of treatment.