RU2585384C2 - Soluble pharmaceutical composition based on fipronil and uvemon for treating arachkoentomoses - Google Patents

Abstract

FIELD: pharmaceutics.

SUBSTANCE: invention relates to pharmaceutical industry, veterinary science and medicine and represents a multicomponent soluble pharmaceutical composition for treating arachkoentomoses characterised by that it contains fipronil, yuvemon, prednisolone, chlorhexidine or myramistine, lidocaine, dimethyl sulphoxide, 2-hydroxypropyl-β-cyclodextrin and solvent: water and alcohol component, including isopropyl or ethyl alcohol and propylene glycol, in volume ratio 1:3-1:5, ingredients of composition taken in certain proportions, wt%.

EFFECT: invention provides high level of anti-parasitic activity and therapeutic efficiency at lower concentrations fipronil, reduced toxicity and local irritant action, high stability and shelf life and higher biological availability of components.

4 cl, 3 ex, 3 tbl

Description

The present invention relates to the field of pharmaceuticals and is intended for use in veterinary medicine and in the treatment of arachnoentomoses of animals and humans. A new multicomponent soluble pharmaceutical composition is proposed that contains a combination of fipronil with juvemon (metoprene) as an insectoacaricidal agent, an anti-inflammatory component, an antimicrobial (antiseptic) component, an anesthetic, a cyclodextrin and a solvent including an aqueous component.

Arachnoentomoses cover a vast and diverse group of parasitic diseases caused by arthropods. In domestic animals, in particular in dogs and cats, the most common are diseases of this class associated with parasitization of fleas, ticks, lice and lice eaters on the body. In addition to the fact that these parasites are often carriers of dangerous infectious and invasive diseases, the invasion of these ectoparasites in itself is accompanied by such phenomena as itching, peeling of the skin, scab formation, damage to the skin, including prone to subsequent infection, edema and the development of inflammatory processes . For some types of diseases caused by ticks (demodicosis, sarcoptosis, otodectosis, etc.), the fight against which is technically complicated by the resistance of parasites to the action of many well-known acaricides, there are still cases of death among animals. In this regard, the urgency of the task associated with the development and implementation of new drugs for the treatment and prevention of arachnoentomiasis, including from the group of acaroses, is obvious.

State of the art

To date, there are a large number of drugs used to treat arachnoentomiasis, which, as the main component of the composition, which have antiparasitic effects, use insectoacaricidal compounds of various chemical nature and mechanism of action on the viability of parasites, such as synthetic pyrethroids (for example, permethrin, alfacipermetrin), amitraz, benzyl benzoate, diazinon, ivermectin, etc.

However, as practice has shown, recently, a special place among the compositions for the treatment of arachnoentomiasis is occupied by formulations based on the use of fipronil (RU 2181243, 04/20/2002; WO 2009/027506, 03/05/2009, Frontline (Merial), etc.). This is explained by the fact that fipronil is a moderately toxic compound with a wide spectrum of antiparasitic action, which demonstrates a particularly high activity against fleas, lice, hairs, ixodic and sarcoptic mites, which determines the possibility of its use in relatively low concentrations. Fipronil is stable at physiological pH and temperature and even with moderate heating. After treatment of the patient, fipronil accumulates in the sebaceous glands, hair follicles and epidermis and exhibits a prolonged contact effect without manifesting a systemic effect on the body, and also does not have an irritating effect on the skin and mucous membrane of the animal.

Until a certain time, the use of fipronil as a basic component in compositions of the indicated purpose was somewhat restrained by the fact that the effect of this compound extends mainly to adult mites and insects without causing the necessary damage to the development of eggs and / or larval forms of parasites. However, this problem was solved by using fipronil in combination with a compound that suppresses the development of imago in the body, in particular as a result of using fipronil and juvemon (metoprene) for this purpose. Yuvemon (metoprene, altoside) is a low-toxic, non-persistent agent, which is a structural analogue of the juvenile hormone necessary for the development of the larva, which inhibits the activity of the latter and causes the death of the parasite at the larval stage.

The mentioned combination has established itself as an effective solution to the problem of the quick and complete destruction of ticks, fleas, lice, and lice in animals, and has become part of a number of modern veterinary means of combating them (RU 2283590 C1, 09.20.2006; RU 2329796, 07.27.2008; US 7,820,189, 10/26/2010; US 2013 116295 A1, 05/09/2013; commercial preparations FrontlinePlus (Merial, France); BlochNet, spray (NVP Astrafarm, Russia); Leopard Forte, spray for cats (AgroVetzashchita) , Russia) and others).

The pharmaceutical composition proposed in the present study for the treatment of arachnoentomiasis also uses the combination of fipronil + juvemon as the most insecticidal agent as the most promising and preferred (see above) in comparison with many other agents traditionally used for this purpose. In this regard, the closest analogue of the claimed pharmaceutical composition is a drug for the treatment and prevention of arachnoentomiasis, disclosed in RF patent 2329796 (RU 2329796, July 27, 2008). According to the patent formula, it has the following composition (wt.%): Fipronil 0.05-4.5; kinoprene, triprene or methoprene 0.001-5.0 and an organic solvent (the rest), represented by ether, isopropyl alcohol or PEG, and is proposed for use in the treatment of arachnoentomiasis in animals, which consists in treating them with the specified drug. The description discloses specific formulations with a combination of fipronil-metoprene (No. 4 and No. 5 in Table 1), where the content of fipronil varies from 4.0 to 4.5, and the content of metoprene from 0.15 to 2.5. When checking the therapeutic effect of the preparation No. 4 according to the protocol given in Example 2, this composition was applied once to the coat or skin of an animal suffering from sarcoptosis (dogs), nothedrosis or otodectosis (cats), at a dose of 0.2 ml / kg. In this case, they evaluated mainly the effect of the destruction of parasites in scrapings, while neither the symptoms of the severity of the disease, nor the time required for the animals to recover completely, were determined. The information provided on this subject in the above example is limited to indicating that a) after a day no live parasites were found on the animals' bodies; b) the animals generally tolerated the treatment well and c) no side effects from the use of the drug were found. In a more detailed study of the preparation No. 4 (Example 4) in dogs affected by sarcoptosis, it was shown that microscopic examination of scrapings 2 days after treatment revealed not only dead ticks, but also deformed larvae and eggs. In addition, it is additionally reported that after 3-4 days the clinical signs of the disease began to gradually disappear: the number of “crusts”, the degree of hyperemia and exudation decreased. However, it should be noted that these effects were observed against the background of the additional administration to all animals of an oil solution of the drug Wittry, designed to increase the body's resistance and eliminate skin disorders.

For a specialist in this field, it seems obvious that, as such, the drug under consideration, proposed by the authors for the treatment of parasitic diseases, essentially solves the problem of only killing parasites, which, of course, is a necessary, but clearly insufficient condition for the effective cure of the disease, which, as you know, accompanied by a number of concomitant processes, expressed in violation of the integrity of the skin (with possible infection), the development of inflammatory phenomena and edema. In this regard, it should be expected that the drug described in the prototype can be effective either in animals with the initial stages of the disease, or in the case of long-term treatment of animals with good immunity in the calculation of the suppression of concomitant processes due to the body’s own forces, or subject to the appointment of additional drugs, as it really took place in the treatment of arachnoentomiasis prototype. In addition to this main disadvantage of the prototype, it should be noted that exclusively organic solvents are used to dissolve the active components of the composition, which, even if they are not highly toxic compounds, are an additional factor for irritation of damaged skin.

Disclosure of invention

In the present work, an attempt was made to create a new pharmaceutical composition for the treatment of arachnoentomoses based on fipronil and juvemon, which, while maintaining a high insectoacaricidal activity, additionally has an anti-inflammatory, antimicrobial and anesthetic effect and is characterized by a reduced general toxicity and a decrease in the irritating effect on the skin of the animal. This pharmaceutical composition can also be used to create drugs for the treatment of human arachnoentomiasis.

The task of expanding the range of therapeutic effects of the drug is achieved by the inclusion of prednisone, known as an effective anti-inflammatory agent, chlorhexidine (or miramistin) as an antimicrobial (antiseptic) component and lidocaine with a pronounced anesthetic effect. It should be noted that although the preparation of multifunctional compositions for the treatment of arachnoentomiasis, additionally (in addition to the main insectoacaridide agent) containing compounds with at least anti-inflammatory and antimicrobial effects, is known and used in the composition of such drugs as Tresaderm (Merial), Amit (Agrovetzashchita ", Russia); “Anandin +” (“Mediter”, Russia) and others, we have not found any information on multifunctional preparations of this purpose using a combination of the active components fipronil + juvemon.

It is obvious that in the preparation of any multicomponent composition, the manufacturer is faced with the need to solve the problem of "combining" compounds with different physicochemical properties, in particular compounds with different solubility characteristics. In most cases, the ingredients used in such compositions are poorly soluble in water and form true solutions only in organic and at the same time various solvents, which leads to the need to include several additional excipients, which, as a rule, are highly toxic compounds. With regard to the components of the proposed integrated composition, the following is known:

fipronil practically does not dissolve in water (at 20 ° C - 1.9-2.4 mg / l, depending on the pH of the medium), it is soluble in acetone, slightly worse in dichloromethane and toluene;

Yuvemon is essentially insoluble in water (at 1.40 mg / L at 20 ° C) and is highly soluble in most organic solvents;

prednisolone is slightly soluble in water (at 30 ° C - 50 mg / l), soluble in dioxane, chloroform, ethanol.

In the proposed combination of ingredients, chlorhexidine (bigluconate) can be replaced with water-soluble miramistin, however, it should be noted that the high cost of this substance will result in a significant increase in the price of the drug as a whole.

When developing the inventive composition, the solubility problem was solved by including cyclodextrin in the proposed multicomponent composition with appropriate adaptation to its introduction of the active concentrations of the individual ingredients. Cyclodextrins are cyclic oligosaccharides containing 6 (α-cyclodextrin), 7 (β-cyclodextrin) or 8 (γ-cyclodextrin) glucopyranose units. The structural organization of the cyclodextrin molecule is such that it distinguishes between the hydrophilic outer part, which increases water solubility, and the hydrophobic inner part, which forms the cavity. In an aqueous medium, the hydrophobic regions of many molecules are able to penetrate into the hydrophobic cavity of cyclodextrin, forming the so-called “Inclusion connections”. In addition, cyclodextrins are also capable of other types of (non-binding) interactions with molecules that are not in the hydrophobic cavity. Due to the large number of hydroxyl groups on each of the glucopyranose units, cyclodextrins form many derivatives, including hydroxypropylethers, sulfonates and sulfoalkylethers.

The use of cyclodextrins and their derivatives in many cases significantly increases the solubility of drugs. Moreover, both “inclusion compounds” and other interactions between cyclodextrins and water-insoluble or slightly soluble substances that are part of the compositions can participate in this phenomenon (see, for example, WO 2010008995, January 21, 2010).

Taking into account the results of preliminary studies on the solubility of the proposed composition, as well as taking into account the availability and relatively low cost of the substance, hydroxypropyl-β-cyclodextrin (GP-β-CC) was chosen to create a new pharmaceutical composition.

It is clear that an increase in the solubility of some of the components insoluble or poorly soluble in water in the presence of cyclodextrins in itself significantly facilitates and accelerates the process, expands the possibilities for the selection and development of dosage forms of the drug, and minimizes the use of toxic organic solvents and, as a result, increase production safety, as well as reduce the toxicity of the final product. In relation to the claimed composition, the inclusion of GP-β-CD allowed to reduce the content of organic solvents, replacing a certain part of them with water; at the same time, it was possible to successfully dissolve prednisolone necessary to achieve the optimum effective concentration, which in many cases is difficult even when using toxic solvents of an organic nature, as well as to increase the solubility of other ingredients poorly soluble in most organic solvents (in particular, chlorhexidine) not included in the clathrate complex with cyclodextrin, which is in full accordance with previously published data (WO 2010008995).

In addition, the most important result of the presence of cyclodextrins in pharmacological formulations should be considered an increase in the bioavailability of the active components, which allows the use of lower than usual concentrations in drugs, which is significant both in terms of further reducing the toxicity of the drug, and from the point of view of reducing its value. In relation to the claimed composition, this was specifically expressed in the fact that the concentration of fipronil in the composition of the new composition was reduced (in comparison with that specified in similar examples for the prototype and component according to Table 1 from 4.0 to 4.5 wt.%, As well as with usually used in most similar commercial preparations and comprising from about 5 to 10 wt.%) at least twice.

The present invention provides a soluble multicomponent pharmaceutical composition for the treatment of arachnoentomiasis, characterized by the following composition of components (wt.%):

Fipronil 0.05-15.0 Yuvemon 0.001-5.0 Prednisone 0.01-3.0 Chlorhexidine bigluconate 20% (or miramistin) 0.001-20.0 Lidocaine 0.1-10.0 Dimethyl sulfoxide (DMSO) 6.60-11.00 2-Hydroxypropyl-β-cyclodextrin (GP-β-CD) 3.30-6.60 Solvent (water and alcohol in volume ratio 1: 3-1: 5) Rest

Moreover, it is advisable to use isopropyl or ethyl alcohol and propylene glycol as the alcohol part of the solvent, preferably in a volume ratio of about 2: 1. In a particular form of implementation, trace oil may be introduced into the proposed composition as a perfume.

From the point of view of the effectiveness of the therapeutic effect, the best results were shown in formulations containing fipronil and juvemon in an amount that ensured a known therapeutic range of therapeutic doses, whereas a change (within the above range) of DMSO, the ratio of water and alcohols, and the molar ratio of GP β-CD and prednisolone and the like. was not critical for this indicator.

The therapeutic efficacy of the claimed composition of the drug was tested on animals (cats and dogs) admitted to veterinary clinics in Moscow, Ivanovo, Chelyabinsk, Ryazan and Maykop with diagnoses of sarcoptosis complicated by inflammatory processes and otodectosis complicated by microbial otitis media. When evaluating the effect of the drug, in addition to the insecticide and acaricidal action of the drug itself, the condition of the animal, the presence of known clinical manifestations of the disease (the severity of the disease: the area of the lesion, the presence of bacterial and fungal infections, local hyperemia and hyperthermia, swelling, itching, etc.) and the duration of the disease were taken into account (term for the complete disappearance of symptoms).

As a result, it was found that already a few minutes after applying the optimal variant of the composition according to the invention (see examples 2 and 3), the animals of the experimental groups did not have a painful reaction, which characterizes the analgesic effect of the agent. There was a decrease in animal anxiety, lack of itching. 12-24 hours after the start of treatment, the signs of local hyperemia and hyperthermia gradually weakened and completely disappeared on the 2nd-3rd day, the full restoration of the skin of the affected areas occurred on the 4th-6th day (depending on the area and severity of the lesion). The test drug showed 100% efficiency in the destruction of ticks at all stages of their development in relation to Sarcoptes canis - in 7 days and Otodectes cynotis - in 6 days. In the case of complications of diseases by inflammatory processes, including microbial otitis media, complete recovery occurred on 10-13 days. So, for example, the clinical signs of acute otitis media disappeared on the 7-8th day, and chronic otitis media - on the 11-12th day from the start of treatment, the complete restoration of the skin with sarcoptosis complicated by inflammatory processes was observed on the 13th day.

All animals tolerated the treatment well. In addition, experts noted the ease of use, as well as the color and smell acceptable to animals. No side effects and complications were noted. Thus, the pharmaceutical composition of the invention is 100% effective and easy to use.

Unfortunately, a direct comparison with the prototype of the timing of the onset of complete cure, as well as a decrease in the time of manifestation of the clinical signs of the disease, is not possible due to the lack of such data in the closest analogue. However, the obvious advantages in comparison with the composition of the prototype is at least comparable insectoacaricidal activity at a lower concentration (consumption) of fipronil, the fact that there is no need to introduce additional therapeutic agents designed to alleviate the condition of the animal and “heal” skin lesions, as well as eliminating the possibility of additional irritating the action of the drug due to the replacement of some organic solvents with water.

Thus, the essence of the present invention is to create a soluble multifunctional composition for the treatment of arachnoentomiasis, based on the combination of fipronil with juvemon and additionally containing hydroxypropyl-β-cyclodextrin, components with anti-inflammatory (prednisone), antimicrobial (chlorhexidine or miramistin) and anesthetizing ( and water as a solvent. The claimed composition from the closest analogues is distinguished by maintaining a high level of antiparasitic activity and increasing therapeutic efficacy at lower than commonly used concentrations of fipronil, a general decrease in toxicity and local irritating effect of the drug (technical result). As additional technical results of the invention, it should also be noted an increase in the stability of certain ingredients included in the composition, in particular prednisone, and, accordingly, an increase in the shelf life of the composition as a whole, facilitating the creation of dosage forms for which the water solubility of the composition, as well as increasing the bioavailability of the components of the drug facilities.

It is important to note that the claimed soluble composition with the specified composition can be obtained only subject to strict adherence to the protocol developed by the applicant for its production. A method of obtaining a composition according to the invention involves the implementation of the following main stages:

1. Obtaining a water-soluble complex of GP-β-CD with prednisone.

2. Adding to the resulting complex all water-soluble components of the composition.

3. Dissolution of fipronil in dimethyl sulfoxide (DMSO).

4. Mixing a solution of fipronil in DMSO with the mixture of water-soluble components obtained in the second stage.

5. Adding juvemon and (optionally) fir oil.

When changing the sequence of these operations and / or the conditions for their implementation, artifacts can be observed, expressed in complications of the process of dissolution of the components, precipitation and / or in a change in the concentrations of ingredients actually presented in the product.

The implementation of the invention

The implementation of the invention with obtaining a technical result is confirmed by the following examples (without limiting the scope of the invention by their content).

Example 1. Obtaining a pharmaceutical composition

Pour water in a vessel No. 1 in a predetermined volume necessary to obtain a composition of a specific composition (100 minus the sum of all other components), add the calculated amount of dry GP-β-CD and mix until completely dissolved. Then, the required amount of prednisolone is introduced into the resulting solution and the liquid is mixed until the latter is completely dissolved, resulting in the formation of a complex of prednisolone with GP-β-CD. Then, with constant stirring, the required quantities of lidocaine hydrochloride (mix until complete dissolution), a 20% solution of chlorhexidine bigluconate and isopropanol (or ethanol) are successively added to the vessel.

Dimethyl sulfoxide and fipronil are placed in vessel No. 2 and the suspension is mixed until fipronil is completely dissolved.

A solution of fipronil in DMSO from vessel No. 2 is added to a solution of the components in vessel No. 1 with stirring, then propylene glycol, juvemon, and Siberian fir essential oil are added.

All operations are carried out at room temperature.

According to example 1 were obtained pharmaceutical composition composition (wt.%):

Composition 1

Fipronil 2.00 Yuvemon 0.10 Prednisone 0.50 Chlorhexidine (or Miramistin) 0.15 Lidocaine 2.00 Dimethyl sulfoxide (DMSO) 11.00 2-Hydroxypropyl-β-cyclodextrin (GP-β-CD) 6.50 Solvent (water and alcohol in volume 1: 3.25 ratio) Rest

Composition 2

Fipronil 0.05 Yuvemon 0.001 Prednisone 0.01 Chlorhexidine (or Miramistin) 0.001 Lidocaine 0.1 Dimethyl sulfoxide (DMSO) 6.60 2-Hydroxypropyl-β-cyclodextrin (GP-β-CD) 6.50 Solvent (water and alcohol in volume 1: 4.7 ratio) Rest

Composition 3

Fipronil 15.00 Yuvemon 5.00 Prednisone 3.00 Chlorhexidine (or Miramistin) 20.00 Lidocaine 10.00 Dimethyl sulfoxide (DMSO) 11.00 2-Hydroxypropyl-β-cyclodextrin (GP-β-CD) 3.3 Solvent (water and alcohol in volume 1: 3.4 ratio) Rest

Example 2. In vitro study of insecticide and ovicidal efficacy of the pharmaceutical composition against sarcoptoid ticks and their eggs

The study of the acaricidal efficacy of the pharmaceutical composition in vitro was performed on isolated Sarcoptes canis and Otodectes cynotis ticks. To do this, ticks (30 for each option) were placed in Petri dishes on sheets of filter paper soaked in a composition (experiment) or water (control). Then the Petri dishes were placed in a thermostat, where they were at a temperature of 27 ° C, observation was carried out for 48 hours. A test of formulations 1-3 showed that they all have an acceptable level of acaricidal activity, however, the composition 1 was considered optimal (see Table 1), since the antiparasitic activity of composition 2 was significantly lower, and the test of composition No. 3, although it showed a higher activity, however, the observed increase was not justified from the point of view of multiple (compared with composition 1) increase in the concentration of active ingredients.

Table 1 Acaricidal activity of the pharmaceutical composition (composition 1) against adult ticks Option Ticks Structure The number of ticks in the experience Acaricidal efficacy, the number of dead individuals in 6 hours after 12 hours after 18 hours after 24 hours after 48 hours one Sarcoptes canis pharmaceutical composition 1 thirty 19 27 29th thirty thirty 2 Sarcoptes canis distilled water thirty 0 0 0 0 0 3 Otodectes cynotis pharmaceutical composition 1 thirty 21 28 thirty thirty thirty four Otodectes cynotis distilled water thirty 0 0 0 0 0

The data obtained show that the pharmaceutical composition of composition 1 after 12 hours causes the death of 90% of individuals, and after a day the acaricidal effect of the drug reaches 100%.

The ovicidal properties of the pharmaceutical composition were studied on the eggs of ticks Sarcoptes canis and Otodectes cynotis. For this, fresh masonry of tick eggs (40 eggs per option) was placed in Petri dishes on filter paper soaked with the composition (experiment) or water (control).

Option 1 Ticks Sarcoptes canis Pharmaceutical composition, composition 1 Option 2 Ticks Sarcoptes canis Distilled water Option 3 Otodectes cynotis ticks Pharmaceutical composition, composition 1 Option 4 Otodectes cynotis ticks Distilled water

Then the Petri dishes were placed in a thermostat, where they were at a temperature of 27 ° C, observation was carried out for 10 days. The normal development of eggs from larvae in the control (variants 2 and 4) and the absence of larvae that developed from eggs in the control variants served as evidence of the ovicidal action of the drug, which ensures the death of tick eggs by 100%.

Thus, the new complex acaricidal pharmaceutical composition showed high acaricidal and ovicidal activity. Based on the results of in vitro activity testing, a further study of the therapeutic effect of the composition was carried out using composition 1.

Example 3. Verification of the therapeutic effect of the composition on animals (in vivo)

The tests were carried out in veterinary clinics in Moscow, Ivanovo, Chelyabinsk, Ryazan and Maykop in accordance with the “Temporary instructions for the use of the drug.” The total number of experimental animals spontaneously infected with acaroses, including otodectosis complicated by otitis media, was 160 individuals (80 dogs and 80 cats), of which experimental and control groups were formed (table 2). The diagnosis of sarcoptosis and otodectosis complicated by acute or chronic otitis media was made based on the results of acarological studies of scraping; differentiation of inflammatory processes of the skin or outer ear was based on clinical signs and laboratory studies.

During the experiment (up to 48 days), daily monitoring of the general condition and behavior of animals, a clinical examination of the skin (with sarcoptosis) or the condition of the outer ear (with otodectosis) were performed. The lesion area was measured planimetrically.

To determine the contamination by microflora, scraping material was sown from the affected areas into Petri dishes on meat peptone agar or Hottinger agar. To determine the presence of microscopic fungi, scraping material was sown from the affected areas into Petri dishes on Saburo agar medium containing antibiotics streptomycin and penicillin to suppress bacterial microflora, pH = 6.6-6.8. Petri dishes were incubated in a thermostat for 2 days at a temperature of 37 ° C. The total number of grown colonies (CFU) was determined by the microscopic method.

table 2 Groups of animals to test the therapeutic efficacy of the pharmaceutical composition Type of animal, number of individuals Group Diagnosis, number of individuals Cats 80 No. 1 Control Sarcoptosis complicated by inflammatory processes, 20 No. 2 Experience Sarcoptosis complicated by inflammatory processes, 20 No. 3 Control Otodectosis complicated by otitis media, 20 №4 Experience Otodectosis complicated by otitis media, 20 Dogs 80 No. 5 Control Sarcoptosis complicated by inflammatory processes, 20 №6 Experience Sarcoptosis complicated by inflammatory processes, 20 No. 7 Control Otodectosis complicated by otitis media, 20 №8 Experience Otodectosis complicated by otitis media, 20

The animals of the experimental groups No. 2, 4, 6, 8 were treated with a pharmaceutical composition. The treatment was carried out daily once a day for 8 days (with a diagnosis of chronic otitis media - 10-13 days). Doses of the drug are shown in table 3.

Table 3 Doses of the drug Kind of animal Animal body weight Dose for otodectosis Dose for sarcoptosis Cat Less than 10.0 3 drops 1.0 ml Dog Less than 10.0 3 drops 1.0 ml Dog 10.1-20.0 4 drops 1,5 ml Dog More than 20.1 5 drops 2.0 ml

In case of sarcoptosis, the agent was applied cutaneously to the affected areas with 1.5–2.0 cm capture of healthy skin. With otodectosis, an appropriate amount of the drug was instilled into each auricle, followed by a light massage.

As a result of the studies, it was found that the pharmaceutical composition according to the invention showed 100% effectiveness in the destruction of ticks Sarcoptes canis and Otodectes cynotis at all stages of development within 5-7 days. Thirty minutes after the treatment, experimental animals showed a decrease in the painful reaction, the animals stopped shaking their heads and became calmer. On 2-3 days, puffiness, local hyperemia and hyperthermia disappeared, the area of soft tissue damage significantly decreased.

A microbiological study showed that in the case of otodectosis complicated by acute otitis media, complete recovery occurs on the 6-7th day from the start of treatment, and in case of chronic otitis media with the presence of microscopic fungi, the animals recover completely on the 10-11th day. Recovery of animals with sarcoptosis, complicated by the presence of bacterial and fungal microflora with significant damage to soft tissues, occurs in 10-13 days.

After recovery, the animals were under medical supervision for 40 days, while no relapses were recorded for the entire observation period.

Claims (4)

1. Soluble multicomponent pharmaceutical composition for the treatment of arachnoentomiasis, characterized by the following composition of components, wt.%:
Fipronil 0.05-15.0 Yuvemon 0.001-5.0 Prednisone 0.01-3.0 Chlorhexidine or miramistin 0.001-20.0 Lidocaine 0.1-10.0 Dimethyl sulfoxide 6.6-11.0 2-hydroxypropyl-β-cyclodextrin 3.3-6.6 Solvent: water and alcohol component, including isopropyl or ethyl alcohol and propylene glycol, in a volume ratio of 1: 3-1: 5 Rest 2. The pharmaceutical composition according to claim 1, characterized in that the volume ratio of isopropyl or ethyl alcohol and propylene glycol is 2: 1. 3. The pharmaceutical composition according to any one of paragraphs. 1, 2, characterized in that the mass fraction of fipronil is 2.0, and the mass fraction of juvemon is 0.1. 4. The pharmaceutical composition according to claim 1, additionally containing fir oil as a perfume.