Method of control of zooparasites

FIELD: agriculture.

SUBSTANCE: invention relates to means of control of zooparasites. The product contains N-arilpirazole of general formula , where R1 and R3 independently mean halogen, R2 means haloalkyl of 1-3 carbon atoms, R4 means a cyanogroup or -C(=S)NH2. The means additionally comprises an aliphatic cyclic carbonate, an aliphatic acyclic polyether which is a derivative of diols having up to 8 carbon atoms, and pharmaceutically acceptable auxiliary or supplementary materials. It is used for manufacture of a medicinal product.

EFFECT: invention enables to improve the effectiveness and safety of the means.

6 cl, 3 tbl, 5 ex

 

The invention relates to new means of combating parasites of animals containing arylpyrazole in the recipe, including aliphatic cyclic carbonates.

Arylpyrazole, as well as their effectiveness as insecticides and acaricides known from publications international, European and national bids US 2006014802 A1, WO 2005090313 A1, FR 2834288 A1, WO 09828277, US 06069157, WO 200031043, DE 19824487, WO 09804530, WO 09962903, EP 00933363, EP 00911329, WO 09856767, US 05814652, WO 09845274, WO 9840359, WO 09828279, WO 09828278, DE 19650197, WO 09824767, EP 00846686, EP 00839809, WO 09728126, EP 00780378, GB 02308365, US 05629335, WO 09639389, US 05556873, EP 00659745, US 05321040, EP 00511845, EP-A-234119. EP-A-295117 and WO 98/24769. Despite this abundance of applications, which shows different patterns with aripirazole, there is one predominant type of structure, which demonstrates the highest efficiency compared to other when used in the majority of readings. It is recognized that the most effective against many parasites compound in this class is 1-[2,6-sodium dichloro-4-(trifluoromethyl)phenyl]-3-cyano-4-[(trifluoromethyl)sulfinil]-5-aminopyrazole (international nonproprietary name "fipronil").

In the market of means of combating ectoparasites arylpyrazole there are more than 10 years (Hunter, J. S., Ill, D. M. Keister and P. Jeannin. 1994. Fipronil: A new compound for animal health. Proc. Amer. Assoc. Vet. Parasitol. 39th Ann. Mtg. San Francisco, CA. Pg. 48.). They are highly efficient, wide Spectro and acceptable tolerability. It is known that the existing formulations with a high proportion of DEE (transcutol) contain a strong transdermal component (FR 1996-11446 And; the security certificate: ISO/DIS 11014/29 CFR 1910.1200/ANSI Z400.1 printing date 10/23/2001: FRONTLINE® TOP SPOT™: fipronil 9.7% mass/mass). Thus, by formulations facilitate the penetration of the sebaceous gland and in the layers of the epithelium (Skin distribution of fipronil by microautoradiography following topical administration to the beagle dog. Co-chet, Pascal; Birckel, P.; Bromet-Petit, M.; Bromet, N.; Weil, A.; European Journal of Drug Metabolism and Pharmacokinetics (1997), 22(3), 211 to 216.). High concentration of sebaceous glands may contribute to long-term availability of the active substance through the excretion of sebum (if with him is the excretion of the active substance). In the case of conventional formulations, however, probably also the penetration of arylpyrazole into the blood stream, because each hair follicle is suitable blood vessel, and the follicle is separated from the blood stream is only a thin barrier (Transfollicular drug delivery - Is it a reality? ("Transfollicular drug delivery - the reality is this?") Meidan, Victor M.; Bonner, Michael S.; Michniak, Bozena Century; International Journal of Pharmaceutics (2005), 306(1-2), 1-14). Thus, the availability of the active substance on the animal also limited in time and concentration of reactant enters the blood stream and thus reduces the available concentration in the skin fat.

About the effect of this weakness is now known recipes you want to limit, why change the basic properties of the formulation, without losing, however, is in a favorable performance indicators. After carrying out these purposes intensive analytical and experimental activities on a number of additives, solvents and tools to facilitate the distribution (on the surface of the skin), unexpectedly was defined Supplement that can improve the performance arylpyrazole destruction of arthropods.

The invention relates to new means of combating parasites of animals containing arylpyrazole in the recipe, including:

- aliphatic cyclic carbonate

- aliphatic cyclic or acyclic simple polyester

Means for combating arthropods according to the invention are new and in comparison with the previously described formulations have significantly improved and longer persisting efficiency while improving safety for using their faces and for the animal receiving the tool.

Arylpyrazole as active substances for combating arthropods (arthropodicides") themselves known to the expert, for example, of the above documents are hereby given reference.

The preferred phenylpyrazoles are those of the formula (I):

where x is the N - or C-R1

R1and R3independently of one another denote halogen,

R2means halogen, halogenated with 1-3 carbon atoms, S(O)nCF3or SF5

n means 0,1 or 2

R4means hydrogen, cyano or balance with the formula:

or one of the following cyclic substituents:

R5means hydrogen, quinil with 2-4 carbon atoms, alkenyl with 2-4 carbon atoms, which optionally can be singly or multiply substituted by such substituents as halogen or alkyl with 1-3 carbon atoms, or R5means -(C=O)-alkyl with 1-4 carbon atoms, -S-alkyl with 1-4 carbon atoms, -S-halogenated with 1-4 carbon atoms, -S(=O)-alkyl with 1-4 carbon atoms or-S(=NH)-alkyl with 1-4 carbon atoms, optionally substituted with halogen phenyl, optionally substituted with halogen furyl, balance-NR14R15the rest of oxiranyl, which optionally can be singly or multiply substituted by such substituents as alkyl with 1-4 carbon atoms or halogenated with 1-4 carbon atoms, or a residue of cyclopropyl, which optionally can be singly or multiply substituted by such substituents as halogen, alkyl with 1-4 carbon atoms or halogenated with 1-4 carbon atoms,

R means hydrogen, alkylaryl with 1-4 carbon atoms or a residue-NR16R17.

R7denotes hydrogen, alkyl with 1-4 carbon atoms, -S-alkyl with 1-4 carbon atoms or-NR9R10,

Y mean =S, =O, =NH, =N-alkyl with 1-4 carbon atoms, =N-OH, or

R8means alkyl with 1-4 carbon atoms,

R9and R10independently from each other denote hydrogen, a hydroxy-group or alkyl with 1-4 carbon atoms,

R11denotes hydrogen, alkyl with 1-4 carbon atoms, -COO-alkyl with 1-4 carbon atoms or-CONR12R13,

R12and R13independently of one another denote hydrogen or alkyl with 1-4 carbon atoms,

R14and R15independently of one another denote hydrogen, alkyl with 1-4 carbon atoms, halogenated with 1-4 carbon atoms, or-SO2is alkyl with 1-4 carbon atoms,

R16and R17independently of one another denote hydrogen, alkoxygroup with 1-4 carbon atoms or alkyl with 1-4 carbon atoms, and alkyl with 1-4 carbon atoms may be optionally substituted, and the role of the substituents are phenyl, pyrazinyl or pyridyl, and phenyl, pyrazinyl or pyridyl may be substituted one or more times, and the role of the substituents are a hydroxy-group, alkyl with 1-4 carbon atoms, halogenated with 1-4 carbon atoms and/or alkoxygroup with 1-4 carbon atoms, or

R16and R17mean alkylsulphonyl with 1-4 carbon atoms, alkoxycarbonyl with 1-4 carbon atoms, alkoxycarbonyl with 1-4 carbon atoms in alkoxygroup and 1-4 carbon atoms in alkylcarboxylic or residue(C=O)NR20R21or

R16and R17together mean a group =CR18R19associated with nitrogen double bond,

R18and R19independently of one another denote phenyl, which is optionally singly or multiply substituted by such substituents as hydroxy-group, alkyl with 1-4 carbon atoms, halogenated with 1-4 carbon atoms and/or alkoxygroup with 1-4 carbon atoms, and/or R18and R19denote hydrogen, alkyl with 1-4 carbon atoms, alkenyl with 1-4 carbon atoms or alkoxygroup with 1-4 carbon atoms, and alkyl with 1-4 carbon atoms, alkenyl with 1-4 carbon atoms or alkoxygroup with 1-4 carbon atoms optionally can be substituted by phenyl, which in turn is optionally singly or multiply substituted by such substituents as hydroxy-group, alkyl with 1-4 carbon atoms, halogenated with 1-4 carbon atoms and/or alkoxygroup with 1-4 carbon atoms,

R20and R21independently of one another denote hydrogen, alkyl with 1-4 carbon atoms or phenyl, which optionally one or mnogokrat is substituted by such substituents as hydroxy-group, alkyl with 1-4 carbon atoms, halogenated with 1-4 carbon atoms and/or alkoxygroup with 1-4 carbon atoms,

R22means alkyl with 1-4 carbon atoms,

Halogen preferably denotes fluorine, chlorine, bromine or iodine, in particular fluorine, chlorine, bromine.

Alkyl with 1-4 carbon atoms means remotemachine or branched alkyl having from 1 to 4 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl.

Halogenated with 1-4 carbon atoms means remotemachine or branched alkyl having from 1 to 4 carbon atoms, which is connected with one or more identical or different halogen atoms; this includes also peralagan-alkyl compounds. Preferred foralkyl. Examples are-CF2H, -CF3, -CH2CF3, -CF2CF3.

Preferably, the substituents meant the following:

X preferably denotes C-R1.

R1and R3preferably independently of one another denote chlorine or bromine.

R2preferably means halogenated with 1-3 carbon atoms or SF5.

R4preferably means hydrogen, cyano or balance with the formula:

or one of the following cyclic substituents:

/p>

R5preferably means hydrogen, quinil with 2-3 carbon atoms, alkenyl with 2-3 carbon atoms, which optionally can be singly substituted with such substituents as halogen or alkyl with 1-3 carbon atoms, or R5preferably means -(C=O)-alkyl with 1-4 carbon atoms, -S-alkyl with 1-3 carbon atoms, -S-halogenated with 1-3 carbon atoms, -S(=O)-alkyl with 1-3 carbon atoms or-S(=NH)-alkyl with 1-3 carbon atoms, optionally substituted with halogen phenyl, optionally substituted with halogen furyl, balance-NR14R15the rest of oxiranyl, optionally substituted halogenation with 1-3 carbon atoms, or a residue of cyclopropyl, which optionally can be singly or multiply substituted by such substituents as halogen, alkyl with 1-4 carbon atoms or halogenated with 1-4 carbon atoms,

R6preferably means hydrogen, alkylaryl with 1-3 carbon atoms or the residue-NR16R17.

R7preferably means hydrogen, alkyl with 1-4 carbon atoms, -S-alkyl with 1-4 carbon atoms or-NR9R10,

Y preferably means =S, =O, =NH, =N-OH, or

R8preferably denotes alkyl with 1-3 carbon atoms,

R9and R10independently from each other preferably means is hydrogen, the hydroxy-group or alkyl with 1-3 carbon atoms,

R11preferably means hydrogen, alkyl with 1-4 carbon atoms or CONR12R13,

R12and R13independently of one another preferably denote hydrogen or alkyl with 1-3 carbon atoms,

R14and R15independently of one another preferably denote hydrogen, alkyl with 1-3 carbon atoms, halogenated with 1-3 carbon atoms or alkyl with 1-3 carbon atoms and the group-SO2;

R16and R17independently of one another preferably denote hydrogen, alkoxygroup with 1-3 carbon atoms or alkyl with 1-3 carbon atoms, and alkyl with 1-3 carbon atoms may be optionally substituted, and the role of the substituents are phenyl, pyrazinyl or pyridyl, and phenyl, pyrazinyl or pyridyl may be once or twice substituted, and the role of the substituents are a hydroxy-group, alkyl with 1-3 carbon atoms, halogenated with 1-3 carbon atoms and/or alkoxygroup with 1-3 carbon atoms,

or

R16and R17mean alkylsulphonyl with 1-4 carbon atoms, alkoxycarbonyl with 1-4 carbon atoms, alkoxy-alkylsulphonyl with 1-4 carbon atoms in alkoxygroup and 1-4 carbon atoms in alkylcarboxylic or residue =(C=O)NR20R21or

R16and R17together mean a group =CR18R19that is knitted with nitrogen double bond,

R18and R19independently of one another preferably denote phenyl, which is optionally singly or doubly substituted by such substituents as hydroxy-group, alkyl with 1-3 carbon atoms, halogenated with 1-3 carbon atoms and/or alkoxygroup with 1-3 carbon atoms, and/or R18and R19denote hydrogen, alkyl with 1 to 3 carbon atoms, alkenyl with 1-3 carbon atoms or alkoxy group with 1 to 3 carbon atoms, and alkyl with 1-3 carbon atoms, alkenyl with 1-3 carbon atoms or alkoxygroup with 1-3 carbon atoms optionally can be substituted by phenyl, which in turn, if necessary, once or twice substituted by such substituents as hydroxy-group, alkyl with 1-4 carbon atoms, halogenated with 1-4 carbon atoms and/or alkoxygroup with 1-4 carbon atoms,

R20and R21independently of one another preferably denote hydrogen, alkyl with 1-3 carbon atoms or phenyl, which is optionally once or twice substituted by such substituents as hydroxy-group, alkyl with 1-3 carbon atoms, halogenated with 1-3 carbon atoms and/or alkoxygroup with 1-3 carbon atoms,

R22preferably denotes alkyl with 1-3 carbon atoms.

Particularly preferred meanings of the substituents in the formula (I) as follows:

X is C-R1.

R1and 3in each case, the mean Cl.

R2means CF3.

R4means CN, -C(=S)NH2or-C(=O)CH3.

R5means SCHF2, -S(=O)CF3, -S(=O)CH3, -S(=O)CH2CH3or the rest

1-triptoreline.

R6means an amino group or one of the following residues:

Below are preferred examples of compounds that can be used according to the invention:

Particularly preferred examples of compounds that can be used in accordance of what bretania, following:

An example of the extremely preferred N-arylpyrazole is fipronil.

Another example of the extremely preferred N-arylpyrazole is 5-amino-4-trifloromethyl-1-(2,6-dichloro-4-trifluoromethyl-phenyl)-3-thiocarbamoylation.

Depending on the type and location of substituents active substances can be in the form of various stereoisomers, in particular enantiomers and racemates. Apply according to the invention can as pure stereoisomers, and mixtures thereof.

If necessary, you can use active substances and in the form of salts, and it is possible to apply suitable for use in pharmaceutical salt accession acid and basic salts.

As suitable for use in pharmaceutical salts can be used salts of mineral acids or organic acids (such as carboxylic or sulfonic acids). As examples should be called salt of hydrochloric acid, sulfuric acid, acetic, glycolic, lactic, succinic acid, citric, tartaric, methanesulfonic acid, 4-toluensulfonate acid, galacturonic, gluconic, monowai, CH is teminology or aspartic acid. As examples suitable for use in the pharmaceutical industry basic salts should be called alkaline salts, such as salts of sodium or potassium, salts of alkaline earth metals, for example salts of magnesium or calcium.

In addition, the active substances can also be applied in the form of a solvate, especially a hydrate. Under the solvate mean as a solvate, in particular the hydrates themselves active substances, and a solvate, in particular the hydrates of the salts of these.

Active substances as solids under certain circumstances, are able to form different crystal modifications. For use in medicines best stable modification, with appropriate indicators solubility.

Unless otherwise stated, the percentage mean percentage by weight relative to the weight of the finished formulation.

Products contain arylpyrazole usually in quantities from 1 to 27.5 wt. -%, preferably from 5 to 20 wt. -%, and particularly preferably from 7.5 to 15% of the mass.

Aliphatic cyclic carbonate preferably is an ethylene carbonate resulting or propylene carbonate, and it is also possible to use mixtures.

The amount of aliphatic cyclic carbonate in the formulation may range from 10 to 70 wt. -%, preferably from 12.5 to 50 wt. -%, and especially predpochtite the flax - from 15 to 40% of the mass.

Aliphatic cyclic and/or acyclic ethers of compounds known as such. It preferably is about ethers derived diols having up to 8 carbon atoms, examples - ethylene glycol, diethylene glycol, propylene glycol, dipropyleneglycol. In acyclic ethers, one or both hydroxyl groups are alkyl group with 1-4 carbon atoms, preferably while to etherification was only one group. It is preferable examples include: diethylene glycol-monotropy ether, diethylene glycol-monopropylene ether, dipropyleneglycol-monopropylene ether. Preferred 5 - or 6-membered cyclic ethers are in the ring one oxygen atom and 4 or 5 carbon atoms and, if necessary, are alkyl substituent with 1 to 4 carbon atoms; preferably, they carry a hydroxyl group or directly on the ring or the alkyl Deputy with 1-4 carbon atoms. A particularly preferred example is tetrahydrofurfuryl alcohol. In the media according to the invention the number of aliphatic, cyclic and/or acyclic simple ether can be widely varied in the range from 20 to 77.5 wt. -%, moreover, the number ranging from 25 to 65% of the mass. particularly preferred, and amounts ranging from 25 to 50 wt%. KRA is not preferred.

In accordance with a preferred form of execution means according to the invention can additionally include one or more esters of a diatomic or triatomic alcohol having at least three carbon atoms, with organic fatty acids with 6 to 18 carbon atoms. Used according to the invention esters contain as alcohol component diatomic or triatomic alcohol having up to three carbon atoms, such as ethylene glycol, propylene glycol or glycerin. As a rule, tarifitsirovana at least two, and preferably all of the hydroxyl groups of the alcohol. The acid components of the esters are fatty acid having 6-18 carbon atoms, which may be remotemachine, branched, and single or multiple unsaturated. You can also use mixed esters or mixtures of different types of esters. As preferred triglycerides triglycerides of Caprylic and capric acid, and Caprylic triglycerides, capric and linoleic acid. Of equal way, the preferred esters of propylene glycol with Caprylic and/or capric acid (propylene glycol-anjanettecunha). Particularly preferably, these esters of glycerol or propylene glycol with Caprylic/capric acid had visco shall be within (at 20°C) 0.08 To 1.3 PA*s, more preferably, however, 0,08-0,40 PA*C. you can Also use them modified with polyethylene oxide, polypropyleneoxide and/or propylene carbonate derivatives, whose viscosity is within the specified range. As examples, we should mention propilenglikolstearat, propylene glycol-anjanettecunha with viscosity range 0,09-0,12 PA*s, April-caprin-diglyceryl-succinate with an average viscosity of 0.23 PA*s, medium chain of capryl-caprin-triglycerides viscosity 0,27-0,30 PA*S.

Formulations according to the invention can contain one or more of the above-mentioned esters. Usually means according to the invention contain ester or mixture of esters in fractions comprising from 0 to 40 wt. -%, preferably from 1 to 35 wt. -%, and very preferably from 2.5 to 7.5 wt. -%

If necessary to stabilize these formulations can be used organic or inorganic antioxidants. As inorganic antioxidants should be mentioned, for example, sulfites and bisulfite, in particular sodium bisulfite. Preferred phenolic antioxidants, such as anisole, equivalent and hydroxyanisol, as well as their mixtures with each other. Usually they are used in quantities of from 0.01 to 1 wt. -%, preferably from 0.05% to 0.5%, particularly preferably from of 0.075 to 0.2% of the mass.

Indicated the data working substances of the formulation, in particular esters using acidifier to stabilize, predohranaa from possible hydrolytic decomposition. As an acidifier can be applied acceptable pharmaceutical acids, in particular carboxylic acids, such as succinic, tartaric, lactic or citric acid. Their preferred amounts are in the range from 0 to 0.5 wt. -%, mostly, however, from 0 to 0.2% of the mass.

Also as an aid to the formulation to improve the spreading can be applied polymeric surfactants based polyethoxysiloxane with low surface tension is less than 30 mn/m, more preferably less than 22 mn/m Such surfactants are well - known ethoxylated and/or propoxycarbonyl subsidiary prescription drugs, preferably neutral, or particularly preferably cationic. As an example of a preferred polymer AIDS should specify copolymerizate of methoxysalicylaldehyde Belisil Silvet L-77 manufactured by Voeg GE Siliconics GmbH. The number of these auxiliary prescription medications can be widely varied in the range from 0.01 to 1.0% of the mass. The preferred range is from 0.2 to 0.4% of the mass.

Optionally, the formulation may contain other acceptable pharmaceutical auxiliary or additional is sustained fashion substance.

The means according to the invention can as a partner of arylpyrazole also contain one or more active substances. As preferred examples of such active substances, the combination with which it is profitable, you must specify: growth inhibitors, such as inhibitors of chitin biosynthesis, such as benzoylferrocene (triflumuron, lufenuron), phenyloxazole (etoxazole), analogues of juvenile hormone (methoprene, hydroprene, pyriproxifen), as well as mixtures of these active substances with each other. Their number can vary widely in the range from 0.1 to 7.5 wt. -%, preferably, however, from 0.25 to 5.0 wt. -%, particularly preferably from 0.25 to 2.5 wt. -%

Formulations according to the invention may also contain synergists. In the sense of this application under the synergists mean compounds that do not have the desired effect, but when applied as a component of the mixture, lead to improving the effectiveness of existing substances. As examples here should be called piperonylbutoxide, MGK-264, verbatim, S,S,S-tributylphosphorotrithioate.

The means according to the invention does not pollute the environment and have reduced in comparison with the known means of toxicity. Therefore, they are easy to use and easy to handle. Funds are characterized by favorable the m index flash point, in excess of 70°C and therefore can make some basic equipment that does not require additional measures to protect against explosions.

The means according to the invention have a favorable indicators of toxicity to warm-blooded animals and are suitable for combating parasitic arthropods, in particular insects and arachnids, especially fleas and ticks occurring in animals, particularly warm-blooded animals, particularly mammals. It can be homemade, farm animals, animals to be kept in zoos, laboratories, experimental animals, and animals that contain as a hobby.

Described here funds are used, in particular, for combating ectoparasites on animals, which contain as a hobby, and farm animals.

The means according to the invention are effective against pests on all or individual stages of development, as well as against sensitive and resistant pest species.

To pests include:

From the order Anoplura (lice), for example Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp., Solenopotes spp.

From the order Mallophaga (hematophagous biting), for example Trimenopon spp., Menopon spp., Eomenacanthus spp., Menacanthus spp., Trichodectes spp., Felicola spp,, Damalinea spp., Bovicola spp.

From the order Diptera (Diptera), the suborder Brachycera, for example, Chrysops spp., Tabanus spp., Musca spp., Hydrotaea spp., Muscina spp., Haematobosca spp., Haematobia spp., Stomoxys sp., Fannia spp., Glossina spp., Lucilia spp., Calliphora spp., Auchmeromyia spp., Cordylobia spp.. Cochliomyia spp., Chrysomyia spp., Sarcophaga spp., Wohlfartia spp., Gasterophilus spp., Oesteromyia spp., Oedemagena spp., Hypoderma spp., Oestrus spp., Rhinoestrus spp., Melophagus spp., Hippobosca spp.

From the order Diptera (Diptera), the suborder Nematocera for example, Culex spp., Aedes spp., Anopheles spp., Culicoides spp., Phlebotomus spp., Simulium spp.

From squad Siphonapterida (fleas), for example, Ctenocephalides spp., Echidnophaga spp., Ceratophyllus spp., Pulex spp.

From the suborder Metastigmata (parasitic mites), for example, Hyalomma spp., Rhipicephalus spp., Boophilus spp., Amblyomma spp., Haemaphysalis spp., Dermacentor spp., Ixodes spp., Argas spp., Ornithodorus spp., Otobius spp.

From the suborder Mesostigmata (gamasid mites), such as Dermanyssus spp., Ornithonyssus spp., Pneumonyssus spp.

From the order Prostigmata, such as Cheyletiella spp., Psorergates spp., Myobia spp., Demodex spp., Neotrombicula spp.

From the order Astigmata, for example, Acarus spp., Myocoptes spp., Psoroptes spp., Chorioptes spp., Otodectes spp., Sarcoptes spp., Notoedres spp., Knemidocoptes spp., Neoknemidocoptes spp.Cytodites spp., Laminosioptes spp.

It should be emphasized effective against fleas (Siphonaptera, for example, Ctenocephalides spp., Echidnophaga spp., Ceratophyllus spp., Pulex spp.), ticks (Hyalomma spp., Rhipicephalus spp., Boophilus spp., Amblyomma spp., Haemaphysalis spp., Dermacentor spp., Ixodes spp., Argas spp., Ornithodorus spp., Otobius spp.) and the above two-winged flies (Chrysops spp., Tabanus spp., Musca spp., Hydrotaea spp., Muscina spp.,

Haematobosca spp,, Haematobia spp., Stomoxys spp., Fannia spp., Glossina spp., Lucilia spp., Calliphora spp., Auchmeromyia spp., Cordylobia spp., Cochliomyia spp., Chrysomyia spp., Sarcophaga spp., Wohlfartia spp., Gasterophilus spp., Oesteromyia spp., Oedemagena spp., Hypoderma spp., Oestrus spp., Rhinoestrus spp., Melophagus spp., Hippobosca spp.).

Agricultural and breeding animals from Osada mammals, as cattle, horses, sheep, pigs, goats, camels, water Buffalo, donkeys, rabbits, deer, reindeer, fur-bearing animals such as mink, chinchillas, raccoons, and birds, such as chickens, geese, turkeys, ducks.

For laboratory and experimental animals include mice, rats, Guinea pigs, rabbits, Golden hamsters, dogs and cats.

Animals, which contain as a hobby are dogs and cats.

Use on cats and dogs should be particularly emphasised.

You can use both as a preventive and therapeutic purposes.

The liquid formulations according to the invention is suitable for application by pouring or spraying (spray), and the spraying can be done, for example, spray with manual injection or aerosol spray (with the blowing agent under pressure). For special indications may also be used after dilution with water in a tub; in this case, the recipe must contain appropriate additives.

A preferred form of application is a spray, pour, and local impact. Very preferably the application by local effects (spot on).

Formulations according to the invention have excellent compatibility with conventional plastic tobikomi capacity "per dose" and stability during storage in different climatic the areas. They have low viscosity and easy to use (application).

The liquid formulations according to the invention can be produced by mixing the components with each other in an appropriate amount, for example by means of conventional mixers or other appropriate devices. If required by the properties of the components, can also work in the conditions of a protective atmosphere or using other methods of exclusion of oxygen.

Examples:

Example 1:

100 ml of a liquid formulation consisting of the following components:

10.0 g5-amino-4-trifloromethyl-1-(2,6-dichloro-4-triptoreline)-3-thiocarbamoyl
72,7 gdiethylene glycol-monoethylene ether
25,0 gof propylene carbonate
5.0 gpropylene glycol-actinotrichida
0.1 gbutylhydroxytoluene
0.2 gbutylhydroxyanisole

Example 2:

100 ml of a liquid formulation consisting of the following components:

10,5 gof fipronil
57,75 gdiethylene glycol-monoethylene ether
40,0 gof propylene carbonate
5.0 gpropylene glycol-actinotrichida
0.1 gbutylhydroxytoluene
0.2 gbutylhydroxyanisole

Example 3:

100 ml of a liquid formulation consisting of the following components:

10,5 gof fipronil
72,75 gdiethylene glycol-monoethylene ether
25,0 gof propylene carbonate
5.0 gpropylene glycol-actinotrichida
0.1 gbutylhydroxytoluene
0.2 gbutylhydroxyanisole

Example 4:

100 ml of a liquid formulation consisting of the following components:

10.0 g 5-amino-4-trifloromethyl-1-(2,6-dichloro-4-triptoreline)-3-thiocarbamoyl
57,7 gdiethylene glycol-monoethylene ether
40,0 gof propylene carbonate
5.0 gpropylene glycol-actinotrichida
0.1 gbutylhydroxytoluene 0.2 g of butylhydroxyanisole

Example 5

100 ml of a liquid formulation consisting of the following components:

11.4 gof fipronil
60,0 gdiethylene glycol-monoethylene ether
25,0 gof propylene carbonate
5.0 gpropylene glycol-actinotrichida
0.12 gbutylhydroxytoluene
0.2 gbutylhydroxyanisole
0.25 gSilvet L-77 manufactured by GE Bayer Siliconics GmbH

Control example

Presents in trade formulation of fibron the La 10% Spot on under the trademark FRONTLINE manufactured by Merial Ltd., 3239 Satellite Blvd., Duluth, GA 30096-4640, USA.

Biological examples

Subjects recipe exactly they dosaged by weight to improve the ability to compare the data. For this 20 pipettes shopping product containing fipronil (control example), poured into a glass bottle and also encrypted code.

All samples were deposited by pipette Eppendorf (amount to 0.95 ml) in a separate spot on the neck of the animal (cats and small dogs). If the amount exceeded 1 ml, was divided in half and put it on the neck in the form of two spots at a distance of about 10 cm from each other.

From laboratory tests on efficacy against fleas and ticks in accordance with examples 2 and 4, it follows that the preparations made by the above formula according to the invention, have a very strong and long-lasting effect against ticks and fleas, which according to test results significantly exceed the current technical level. In addition, preparations are made for the above formulations according to the invention, are favorable tolerability for the animal on which they are applied and for a person engaged in the application, and thus remarkably suitable for controlling fleas and ticks that affect domestic animals. For example, the formulation according to example 2 after ingestion carry twice as good, and the recipe coz the ACLs example 4 - three times better than any of the current level of technology.

A. Effectiveness in the fight against fleas (Ctenocephalides felis) on dogs

In between days -4 and -1 conducted 1-2 times infestatio (infection) dogs older hungry Ctenocephalides felis in the amount of 100 per dog. When fleas were planted on the neck of the animal. At day 0 was tested the effectiveness of investitsii dog, which was looking for fleas on the waking animal. The number of live fleas carried in the Protocol.

After counting the fleas were handling animals. Dogs in the control group the treatment was not subjected. Due to the test drug was applied to animal skin (dermal application as "Spot-on") in an amount of 0.1-0.15 ml/kg of body weight or sprayed by the spray in the amount of 1-1 .5 ml/kg of body weight. The application was carried out once at day 0. Used only clinically healthy animals. On days 1 and 2 all dogs were examined for the presence of live fleas. The results recorded in the source data.

In the days 7, 14, 21, 28, 35, and, if necessary, in the days 42 and 49 have repeated infections (reinfestation) all dogs older hungry Ctenocephalides felis in an amount of about 100 for animal. The next day after each reinfestation all dogs were examined for the presence of live fleas. The results are entered into the Protocol of the source data.

The recipe is considered highly effective if, within a period of 24 to 48 hours pic the e re-infection record efficiency of over 95%, and this effect persists for at least 3-4 weeks.

To calculate the efficiency using the modified formula for Abbott;

KG: control group; CG: treated group.

Medicines in accordance with examples of formulations 2 and 4 in the examples of the dosage of 0.1 or 0.15 ml/kg applied as Spot on, has demonstrated high efficiency in the fight against Ctenocephalides felis.

C. Efficiency in the fight against ticks (Rhipicephalus sanguineus. Dermacentor variabilis) on dogs

In between days -4 and -1 dogs were subjected to the sedative effects of the drug Rompun® (Bayer AG, active ingredient xylazine hydrochloride) at a concentration of 2% (0.1 ml/kg of body weight). Sleeping dogs (10-15 minutes were placed in boxes to carry and was placed on the neck of the animal 50 Rhipicephalus sanguineus or Dermacentor variabilis (25 females, 25 males) on a dog. After about 1.5 hours the animals were again moved from Boxing for carrying in a cage.

At day 0 was tested the effectiveness of investitsii dog, which was looking for ticks on the waking animal. When it carried out a thorough search in the area of the head and ear, including the ear crease in the neck, lower abdomen, chest, flanks, and between fingers and limbs. The number stuck living mites are entered in the Protocol. Dead mites were removed.

After counting the ticks were processed belly who's. Dogs in the control group the treatment was not subjected. Due to the test drug was applied to animal skin (dermal application as "Spot-on") in an amount of 0.1-0.15 ml/kg of body weight or sprayed by the spray in the amount of 1-1 .5 ml/kg of body weight. The application was carried out once at day 0. Used only clinically healthy animals. On days 1 and 2 all dogs were examined for the presence of the living and the dead sucking ticks. The results recorded in the source data. In day 2 of all living and dead mites on the dog removed. In the days 7, 14, 21, 28, 35, and, if necessary, in the days 42 and 49 have repeated infections (reinfestation) all dogs older hungry Rhipicephalus sanguineus or Dermacentor variabilis in the amount of 50 (25 females, 25 males) on a dog. Two days after each reinfestation all dogs were examined for the presence of the living and the dead sucking ticks. The results are entered into the Protocol of the source data. On the second day after reinfestation all living and dead mites on the dog removed.

The recipe is considered highly effective if, at day 2 and on the second day after each re-infection record efficiency of over 90%, and this effect persists for at least 3 weeks.

To calculate the efficiency using the modified formula Abbott:

KG: control group; CG: treated group.

Drug is the means in accordance with examples of formulations 2 and 4 in the examples of the dosage of 0.1 or 0.15 ml/kg, applied as Spot on, has demonstrated high efficiency in the fight against Rhipicephalus sanguineus.

C. Efficiency in the fight against fleas (Ctenocephalides felis) on cats

In day - 1 were infestatio (infection) older cats hungry Ctenocephalides felis in an amount of about 100 for cat. When fleas were planted on the neck of the animal.

At day 0 was tested the effectiveness of investitsii cats, which was looking for fleas on the waking animal. The number of live fleas carried in the Protocol.

After counting the fleas were handling animals. Cats in the control group the treatment was not subjected. Due to the test drug was applied to animal skin (dermal application as "Spot-on") in an amount of 0.1-0.15 ml/kg of body weight. The application was carried out once at day 0. Used only clinically healthy animals. On the 2nd day of cats were examined for the presence of live fleas. The results recorded in the source data.

In the days 7, 14, 21, 28, 35, and, if necessary, and on days 42 and 49 have repeated infections of all cats older hungry Ctenocephalides felis in an amount of about 100 for animal. Two after each reinfestation all cats were examined for the presence of live fleas. The results are entered into the Protocol of the source data.

The recipe is considered highly effective if, at day 2 and on the second day after each re-infection record efficiency of over 5%, and this effect persists for at least 3-4 weeks. To calculate the efficiency using the modified formula Abbott:

KG: control group; CG: treated group.

Medicines in accordance with examples of formulations 2 and 4 in the examples of the dosage of 0.1 or 0.15 ml/kg applied as Spot on, has demonstrated high efficiency in the fight against Ctenocephalides felis.

D. Effectiveness in dealing with ticks (Ixodes ricinus) on cats

In a day or 2 cats were exposed to the effect of sedative drug (acepromazine maleate). Once all the cats are asleep (after 10-15 minutes), on the neck of the animal was placed 30-50 Ixodes ricinus (15-25♀, 15-25♂) on the cat.

Day -1 examined the effectiveness of investitsii cats, which was looking for ticks on the waking animal. When it carried out a thorough search in the area of the head and ears, in the neck, lower abdomen, chest, flanks, and legs. The number stuck living mites are entered in the Protocol. Dead mites were removed. After counting the ticks collected in the group of animals. Treatment is carried out with day 0. Cats in the control group the treatment was not subjected. Due to the test drug was applied to animal skin (dermal application as "Spot-on") in an amount of 0.1-0.15 ml/kg of body weight. The application was carried out once at day 0. Use the and only clinically healthy animals.

On the 2nd day of cats were examined for the presence of the living and the dead sucking ticks. The results recorded in the source data. All living and dead mites from cats removed.

In the days 7, 14, 21, 28, 35, and, if necessary, and on days 42 and 49 held reinfection all cats Ixodes ricinus in the amount of 30-50 (15-25♀, 15-25♂) on the cat. Two days after each reinfestation all cats were examined for the presence of the living and the dead sucking ticks. The results are entered into the Protocol of the source data. On the second day after reinfestation all living and dead mites from cats removed.

The recipe is considered highly effective if, at day 2 and on the second day after each re-infection record efficiency of over 90%, and this effect persists for at least 3 weeks.

To calculate the efficiency using the modified formula Abbott:

KG: control group; CG: treated group.

Medicines in doses according to the examples of formulations 2 and 4 in 0.1 or -0,15 ml/kg applied as Spot on, has demonstrated high efficiency in the fight against Ixodes ricinus.

That is, the Efficiency in the fight against fleas and ticks for 5-7 weeks

Efficiency means according to the invention in the fight against fleas and ticks were tested for five to seven weeks. The experiments were conducted in accordance with the description of the tions, listed in items A-D. the Results are presented in tables 1A, 1b, 2a, 2b, and 3.

1. Means for combating parasites of animals containing N-arylpyrazole General formula

where R1and R2independently of one another denote halogen,
R2means halogenated with 1-3 carbon atoms,
R4means cyano or-C(=S)NH2,
in the recipe, which includes:
aliphatic cyclic carbonate, aliphatic acyclic simple polyester derived diols having up to 8 carbon atoms, and pharmaceutically acceptable auxiliary or additional substances.

2. The tool according to claim 1, further comprising esters of diatomic alcohol containing up to three carbon atoms, with organic fatty acids with 6 to 18 carbon atoms.

3. The tool according to claim 1, containing from 1 to 27.5 wt.% N-arylpyrazole.

4. The tool according to claim 1, containing from 10 to 70 wt.% aliphatic cyclic carbonate.

5. Tool according to one of claims 1 to 4, containing from 20 to 77.5 wt.% aliphatic acyclic polyether.

6. The use according to one of claims 1 to 5 for the manufacture of a medicinal product for combating parasites alive is the shaft.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine. What is described is an adhesive composition containing donepezil and a stabiliser. The stabiliser containing one or more compounds specified in a group consisting of ascorbic acid, metal salt or ester of such, isoascorbic acid or metal salt of such, ethylene-diamine-tetraacetic acid or metal salt of such, cysteine, acetylcysteine, 2-mercaptobenzimidazole, 3(2)-tert-butyl-4-hydroxyanisol, 2,6-di-tert-butyl-4-methylphenol, tetrakis[3-(3',5'-di-tert-butyl-4'-hydroxyphenyl)]propionate pentaerythrite, 3-mercapto-1,2-propanediol, tocopherol acetate, rutin, quercetin, hydroquinone, metal salt of hydroxymethansulphinic acid, metabisulphite metal salts, sulphite metal salt and thiosulphate metal salts; it is added to a layer of a pressure sensitive adhesive applied on at least one side of the substrate.

EFFECT: prepared high reliable and stable adhesive composition which inhibits formation of donepezil-related compounds in the layer of the pressure sensitive adhesive.

14 cl, 4 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, more specifically to a pharmaceutical gel of ketoprofen with analgesic and anti-inflammatory action. The presented gel contains ketoprofen (1.0-6.0 wt %) and target additives: ethanol - 10.0-20.0 wt %, propyleneglycol - 10.0-20.0 wt %, UV filter Escalol 567 - 1.0-40.0 wt %, cyclomethicone DC 345 - 5.0-20.0 wt %, organosilicone emulsifier DC 5329 - 1.0-4.0 wt %, acrylate emulsion of copolymer Salcare SC80 - 1.0-3.5 wt %, trometamol - 1.0-2.5 wt %, fragrance - 0.2-0.4 wt %, preservative SHAROMIX MCI - 0.1-0.5 wt %, purified water - to 100.0 wt %.

EFFECT: due to said composition of target additives, the invention provides stabilisation of photosensitive ketoprofen and its improved penetration in derma, ethanol reduction in the gel, improved gel protection against microorganisms.

1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, more specifically an antimicrobial pharmaceutical gel of laevomycetin. The presented gel contains laevomycetin (0.1-15.0 wt %) and excipients: propyleneglycol - 10.0-40.0 wt %, UV filter Escalol 567 - 1.0-40.0 wt %, cyclomethicone DC 345 - 5.0-20.0 wt %, organosilicone emulsifier DC 5329 - 1.0-4.0 wt %, organosilicone elastomer DC 9045 - 5.0-60.0 wt %, antioxidant Tinogard NOA - 0.02-0.1 wt %, acrylate emulsion of copolymer Salcare SC80 - 1.0-3.5 wt %, trometamol - 1.0-2.5 wt %, preservative Sharomix MCI 0.1-0.5 wt %, purified water to 100.0 wt %.

EFFECT: due to said composition of excipients the invention provides laevomycetin penetration in deep skin, skin protection against ultra-violet radiation and improved gel stability.

1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, more specifically a pharmaceutical gel exhibiting antimicrobial and antifungal action. The presented gel contains as active ingredients betamethasone dipropionate (0.01-0.3 wt %), gentamycin sulphate (0.02-0.6 wt %) and terbinafine hydrochloride (0.8-5.0 wt %), and as excipients - propylene glycol (10.0-40.0 wt %), UV filter Escalol 567 (1.0-40.0 wt %), cyclomethicone DC 345 (5.0-20.0 wt %), organosilicone emulsifier DC 5329 - (1.0-4.0 wt %), organosilicone elastomer DC 9045 (5.0-50.0 wt %), antioxidant Tinogard NOA (0.02-0.1 wt %), acrylate emulsion of copolymer Salcare SC80 (1.0-3.5 wt %), trometamol (1.0-2.5 wt %), preservative Sharomix MCI (0.1-0.5 wt %), purified water (to 100.0 wt %).

EFFECT: due to said composition of excipients the invention provides skin protection against ultra-violet radiation and improved penetration of active ingredients in derma.

3 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine. What is described is an adhesive composition which decreases a number of donepezil related compounds formed in the donepezil-containing adhesive composition containing one, two or more types of combinations of the compounds selected from the following groups of the combinations of the compounds from (a) to (j) which are mixed in a layer of a donepezil-containing pressure sensitive glue: (a) isoascorbic acid or its metal salts and 2-mercaptobenzimidazole; (b) isoascorbic acid or its metal salts and 2,6-di-tert-butyl-4-methylphenol; (c) isoascorbic acid or its metal salts and metal salts of hydroxymethane sulphinic acid; (a) isoascorbic acid or its metal salts and rutin; (e) 2-mercaptobenzimidazole and 2,6-di-tert-butyl-4-methylphenol; (f) 2-mercaptobenzimidazole and metal salts of of hydroxymethane sulphinic acid; (g) 2-mercaptobenzimidazole and rutin; (h) 2,6-di-tert-butyl-4-methylphenol and metal salts of hydroxymethane sulphinic acid; (i) 2,6-di-tert-butyl-4-methylphenol and rutin; and (j) metal salts of hydroxymethane sulphinic acid and rutin.

EFFECT: adhesive composition is highly reliable and stable.

12 cl, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a crystalline microparticle for deliverying active agents which contains diketopiperazine and polysorbate 80. The invention also refers to a method for making said microparticle. The method involves the stages for preparing a diketopiperazine solution with limited solubility and low pH value, adding polysorbate 80 to the solution and precipitating diketopiperazine microparticles at the stages of adding acid to the solution. The invention also refers to a method of coating the pre-formed said microparticle. The method involves producing a suspension containing the pre-formed crystalline microparticle, the active agent and the solvent, changing the suspension properties for controlling power interaction between the specified active agent and pre-formed crystalline microparticle and absorbing the active agent on the microparticle surface for the purpose of coating. The stage of changing the properties and the stages of absorbing proceed without removing the solvent from the suspension.

EFFECT: invention provides making stable particles whereto the active agent has higher affinity than to the solution wherein is found.

15 cl, 8 dwg, 4 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to an emulsion composition for treating cardiopathy, autoimmune disease, sepsis, septic shock, severe sepsis, organopathy, septicemia, endotoxic shock, shock, inflammatory disease, central nervous system disease or infectious disease. The composition contains (A) a compound stable in sour conditions which represents (a) a compound presented by formula:

where R represents an optionally substituted aliphatic hydrocarbon group, an optionally substituted aromatic hydrocarbon group, an optionally substituted heterocyclic group, a group presented by formula -OR1 where R1 represents hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or a group presented by formula: where R1b represents hydrogen atom or an optionally substituted aliphatic hydrocarbon group, R1c has the same value as R1b, or differs, and represents hydrogen atom or an optionally substituted aliphatic hydrocarbon group, R0 represents hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R and R0 are combined to form a bond; the ring A1 represents cycloalkene optionally substituted by 1-4 substitutes selected from a group consisting of (1) an aliphatic hydrocarbon group optionally having substitutes, (2) an aromatic hydrocarbon groups optionally having substitutes, (3) a groups presented by formula; -OR1 where R1 represents hydrogen atom or an aliphatic hydrocarbon group optionally having substitutes, and (4) halogen atom, Ar represents an optionally substituted aromatic hydrocarbon group, and a group presented by formula represents a group presented by formula or n represents an integer from 1 to 4, or (b) a compound presented by formula: where R1 represents an optionally substituted aliphatic hydrocarbon group, an optionally substituted aromatic hydrocarbon group, an optionally substituted heterocyclic group, a group presented by formula: OR1a' where R1a' represents hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or a group presented by formula: where R1b' and R1c are equal or different and represent hydrogen atom or an optionally substituted aliphatic hydrocarbon group, X represents a methylene group, nitrogen atom, sulphur atom or oxygen atom, Y represents an optionally substituted methylene group or an optionally substituted nitrogen atom, the ring A represents a 5-8-member ring which is optionally substituted additionally by 1-4 substitutes selected from a group consisting of (1) an aliphatic hydrocarbon group optionally having substitutes, (2) an aromatic hydrocarbon groups optionally having substitutes, (3) a group presented by formula: OR2' where R2' represents hydrogen atom or an aliphatic hydrocarbon group optionally having substitutes, and (4) halogen atom, Ar' represents an optionally substituted aromatic hydrocarbon group presented by formula, and a group presented by formula: presents a group presented by formula: or m represents an integer from 0 to 2, n' represents an integer from 1 to 3, and the sum m and n' is equal to 4 or less provided when X represents a methylene group, Y represents an optionally substituted methylene group, or their salt or a prodrug, (B) a buffer, (C) oil, (D) an emulsifier and (E) water. The pH value of the compositions is reduced approximately to 3.7-5.5. Also, offered are a method for preparing the emulsion compositions and a method for long-term stabilisation of the emulsion composition.

EFFECT: preparing the composition of improved stability.

28 cl, 10 ex, 24 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: composition for medical use contains a solid or semisolid matrix, at least one active ingredient uniformly dispersed therein. The matrix contains at least one pharmaceutically acceptable matrix-forming agent and compound 1,3-bis(lactamyl)butane, especially 1,3-bis(pyrrolidone-1-yl)butane. The active component has water-solubility less than 1 g/100 ml at 25°C. The active ingredient is preferentially dispersed in a matrix as a solid solution. The matrix-forming agent is chosen from a group of alcohol sugars, alcohol sugar derivatives, pharmaceutically acceptable polymers and their mixtures. The composition is used for preparing the pharmaceutical dosage forms for oral administration of the active ingredients.

EFFECT: composition provides higher bioavailability of poorly water-soluble active ingredient due to its presence in the composition in a non-crystalline state.

19 cl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to medicine and deals with composition for delivering nucleic acids into cells of mammals in presence and absence of serum in growth medium. Composition includes polycationic amphiphile and neutral phospholipid, and forms complex with nucleic acid.

EFFECT: invention ensures high efficiency and low toxicity of composition and ability to deliver to cells of mammals both short and extended nucleic acids.

1 cl, 4 ex, 2 dwg, 3 tbl

FIELD: medicine.

SUBSTANCE: invention concerns veterinary science. An endoparasiticidal drug emodepside and praziquantel or epsiprantel as active ingredients, 1,2-isopropylidenglycerine as a single solvent or combined with other pharmaceutically compatible organic solvents, and common additives, and the proportion of 1,2-isopropylidenglycerine in the mixture makes at least 60 volume %, while water ratio is no more than 1 wt %.

EFFECT: improved efficacy of the drug.

3 cl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, more specifically to a pharmaceutical gel of ketoprofen with analgesic and anti-inflammatory action. The presented gel contains ketoprofen (1.0-6.0 wt %) and target additives: ethanol - 10.0-20.0 wt %, propyleneglycol - 10.0-20.0 wt %, UV filter Escalol 567 - 1.0-40.0 wt %, cyclomethicone DC 345 - 5.0-20.0 wt %, organosilicone emulsifier DC 5329 - 1.0-4.0 wt %, acrylate emulsion of copolymer Salcare SC80 - 1.0-3.5 wt %, trometamol - 1.0-2.5 wt %, fragrance - 0.2-0.4 wt %, preservative SHAROMIX MCI - 0.1-0.5 wt %, purified water - to 100.0 wt %.

EFFECT: due to said composition of target additives, the invention provides stabilisation of photosensitive ketoprofen and its improved penetration in derma, ethanol reduction in the gel, improved gel protection against microorganisms.

1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, more specifically an antimicrobial pharmaceutical gel of laevomycetin. The presented gel contains laevomycetin (0.1-15.0 wt %) and excipients: propyleneglycol - 10.0-40.0 wt %, UV filter Escalol 567 - 1.0-40.0 wt %, cyclomethicone DC 345 - 5.0-20.0 wt %, organosilicone emulsifier DC 5329 - 1.0-4.0 wt %, organosilicone elastomer DC 9045 - 5.0-60.0 wt %, antioxidant Tinogard NOA - 0.02-0.1 wt %, acrylate emulsion of copolymer Salcare SC80 - 1.0-3.5 wt %, trometamol - 1.0-2.5 wt %, preservative Sharomix MCI 0.1-0.5 wt %, purified water to 100.0 wt %.

EFFECT: due to said composition of excipients the invention provides laevomycetin penetration in deep skin, skin protection against ultra-violet radiation and improved gel stability.

1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, more specifically a pharmaceutical gel exhibiting antimicrobial and antifungal action. The presented gel contains as active ingredients betamethasone dipropionate (0.01-0.3 wt %), gentamycin sulphate (0.02-0.6 wt %) and terbinafine hydrochloride (0.8-5.0 wt %), and as excipients - propylene glycol (10.0-40.0 wt %), UV filter Escalol 567 (1.0-40.0 wt %), cyclomethicone DC 345 (5.0-20.0 wt %), organosilicone emulsifier DC 5329 - (1.0-4.0 wt %), organosilicone elastomer DC 9045 (5.0-50.0 wt %), antioxidant Tinogard NOA (0.02-0.1 wt %), acrylate emulsion of copolymer Salcare SC80 (1.0-3.5 wt %), trometamol (1.0-2.5 wt %), preservative Sharomix MCI (0.1-0.5 wt %), purified water (to 100.0 wt %).

EFFECT: due to said composition of excipients the invention provides skin protection against ultra-violet radiation and improved penetration of active ingredients in derma.

3 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, namely to dermatology, and can be used in pathological state of nails. A method of treating wherein a first composition containing a reducing agent of potential more than +20 mV and a second composition containing an oxidising agent of potential less than -50 mV are used. The compositions are applied to coat a nail separately consistently with the first composition applied in the beginning, and then the second composition. Either the first, or second, or third compositions which is a separate option for the compositions with the restoring and oxidising agents, containing a medicinal agent. Also, there is offered a kit comprising the first and second compositions which are arranged separately, and the medicinal agent which is included either in the first composition, or in the second composition, or optionally in the third composition.

EFFECT: inventions improves clinical effectiveness in the pathological state of nails due to intensified penetration of the medicinal agent through a nail plate so that the effective concentration of active particles reaches deeper layers of the nail plate, and also the same nail bed.

45 cl, 9 tbl, 11 dwg, 10 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds forming in vivo a biologically active drug reservoir composition which contains low-viscous nonliquid crystal mixtures of diacylglycerine, tocopherol, phosphatidylcholine and an oxygen-containing organic solvent where a bioactive agent is dissolved or dispersed in said mixture and where compounds form a liquid-crystal phase structure when contacting with a body fluid. Said compounds are applicable for preparing parenteral, non-parenteral and local slow-release drug reservoir compositions. The invention also covers a method of preparing and applying the compounds under the invention and to a method of the active agent delivery.

EFFECT: compounds under the invention provide prolonged controlled release of the active agent without "explosion" or "delay" effects in initial release.

34 cl, 8 dwg, 20 tbl, 48 ex

FIELD: medicine.

SUBSTANCE: invention relates to chemical and pharmaceutical industry and a biologically active composition, containing an active ingredient, packed in vitreous or amorphous particles, which are suspended in a liquid, in which at least one component has general formula R1-X-R2 or R1-X-(CF2Y)n(CF2CF2Z)m-R2 or R1-[(X-CF-R2)n-(X-CF2)m]OR3 where X, Y and Z are defined as O (oxygen), NR3 (N is nitrogen), amine or S (sulphur); and each of R1, R2 and R3 are defined as unflourinated, partially fluorinated or completely fluorinated alkyl, cycloalkyl, aryl or arylalkyl group or organic functional group, halogen group or cyano group; and where, when the general formula is R1-X-R2, at least one of R1 or R2 are partially fluorinated or completely fluorinated alkyl, cycloalkyl, aryl or aralkyl group.

EFFECT: obtaining stable suspension of vitreous particles without need for stringent measures for selecting size of particles and their density.

12 cl, 1 ex

FIELD: medicine, surgery.

SUBSTANCE: it is necessary to obtain surgical access to femoral arteries and aorta to squeeze the latter with its branches to remove the main arteries and collaterals out of circulation. Then the interference on aorta and femoral arteries should be fulfilled followed by reconstruction of circulation along aorta and femoral arteries. Moreover, 12 h before the onset of surgical interference a patient should be intravenously injected with perfluorane at the dosage of 5 ml/kg body weight, moreover, a patient should inhale oxygen-enriched air mixture (for 40-50%) during 12 h. In the course of surgical interference it is necessary to additionally introduce oxygenated perfluorane intra-aortally - 70 ml and into common femoral arteries from both sides - per 50 ml. After operation patients should inhale the above-mentioned oxygen-enriched air mixture during 12 h. The innovation provides prophylaxis of post-ischemic syndrome in case of prolonged surgical interferences upon squeezed arteries.

EFFECT: higher efficiency of protection.

1 ex

The invention relates to a method for improved compressed products, providing the agglomerating their components

The invention relates to the preparation, for example, in the form of capsules, soft coated, containing as active ingredient cyclosporine

New compounds // 2458920

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula or to its pharmaceutically acceptable salts wherein -A-(R1)a means a group; -B-(R2)b means a group specified in the patent claim 1, R3 means hydrogen; X means CH2 or O; and Y means CH2. Also, the invention refers to a pharmaceutical composition exhibiting FGFR inhibitor activity on the basis of the declared compound.

EFFECT: there are produced new compounds and based pharmaceutical composition which can find application in medicine for preparing a cancer drug.

8 cl, 1 tbl, 180 ex

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