HU228751B1 - Flea and tick control collar containing n-phenylpyrazole for use on cats and dogs - Google Patents

Description

A-FENH.-HRAZOL CONTAINING ANTI-COLLAR FOR DOGS AND CATS

Alahn's refers to the exogenous antiparasitic structure, the collar of your examples, to the animal snouting animal, especially dog and cat, and to such an ectoparasitic structure, especially in fleas and kullati.

The invention also relates to the use of certain active ingredients in the manufacture of such collars or externally worn devices and to a related treatment method.

The invention relates mainly to the genus Ctenoeephaïldes. fleas, such as C fetish and C. eanis, and ticks, especially those of the genus E Innlcephelus, such as the "mgutneus" and the frontbicnia aotoumabs, which are mainly mites that attack hunting dogs.

Collars for removing common ectoparasites from dogs and cats have long been made. These collars consist of a matrix, usually a plastic matrix, containing 5-40% of the active ingredient. which the matrix can release over time. So these collars are: in theory, they serve the purpose of providing lasting protection.

However, although the collars are claimed to be efficacious, in practice they do not provide the desired efficacy, nor do they ensure the effective removal of said parasites. This may be because the active ingredient incorporated in the matrix is not sufficiently effective. Another reason is that the active ingredients are rapidly degraded to environmental influences such as light, heat, and rain. Finally, the controllability of release of the active ingredient from the matrix is often overestimated. The formulation of the active ingredient is generally difficult and variable, and the manufacturing conditions may vary greatly depending on the Samsung, the conditions of use, particularly climatic changes, especially humidity, temperature and the like. These stones actually release only a relatively small amount of the active ingredient, and it is very difficult to control and optimize the release.

Λ collars that occur in practice come from another disadvantage of using a structure that can, of course, be worn off, worn on the system, but also torn as it is. chin; moving in the scrub, for example. The problem is particularly significant for hunting dogs, from which the collar is removed. hunting Before departure, when the animals are exposed to fleas and ticks, which are heavily contaminated.

WO-A S7-1378I. and EF-A-h.295, ß 17, suggesting N-Phenylpyrazolyl family of inoculum fuels,

These materials have been reported to be effective against a large number of parasites in a wide variety of areas, such as agriculture. in public health, human and veterinary medicine. In the latter field, the substances may be effective against, for example, fleas and ticks of companion animals such as cats and dogs. The substances may be administered by various routes, for example orally, parenterally. perkotáo or locally. The latter mode of administration also provides a number of options, such as spray (spray), powder. bath, shower, water jet, grease. shampoo, cream, wax, lotion for skin) and external devices such as earrings or collars for local or

80733: · 2709 BE7Pk

systematic start, for the purpose. LvP-A-0.295.117. and EF-A-0.5Ö0.299. U.S. Patent No. 4,123,121 to Las Vegas proposes a lasias release composition which can be used in the form of a collar or earring against harmful insects. Such a composition contains 0.5-25% of active ingredient, 75-99.5% of polyvinyl chloride and a cudilic topical softener. nuts may contain il-phthalates.

ER-A-2,713,8S9. French Patent Application No. 5,123,128, which contains an insect growth regulator. and an N-anl-dtazole derivative. which can be my 4-i2-fi- i. ·, 2,2-tetrafluoroethyl!) -! - (3-chloro-5-trifluoro-1 H -methyl-piperidin-2-yl) -2-methyl-imidazole, 5-amino-3-cyano-1,6-d6-dichloride ('4-Fluorophenyl) -phenyl) -4-trifluoromethylsulfonylsulfonyl or 5-aratno-3-cyano-1- (2,6-dichloro-d-) Iridyl tert-methyl-phenyl-4-tri.Ou.o? -methyl-: t''ep'irazole As in the foregoing documents, the ready-to-use product can also be applied to a large number of insects in different areas and in different formulations. Among the proposed formulations, the document mentions resin formulations that can be prepared in the form of an insecticide collar for animals.

One of the documents described. However, neither the application of crtditi pesztieid collars that are S-amino-S-cianir-l - (2, ^{6-dlkf.ór-4-trirtu;} or-met.il-phenyl) -4-trifluoromethyl-sulfonic MET3 'l.fmil-p: irazole ((dproprol), which can be used against fleas and ticks in human companion animals, such as dogs and cats)) very effectively and for revenge.

As with the known Pesticide compounds, one of ordinary skill in the art would expect that the usual problems with collar release, i.e., concomitant activity, would be in the foot.

After all, FR-A-2,713,3-89. French Patent Application No. 5,123,125 also proposes the use of iVetted tuberculosis with insect growth control compounds.

C. Gertchi et al., Proicssionale Vetennaria L Supplément 1995, 19-22; 3. M. Postai, Profössione Veterinam Supplément 1995, 17-18, and A. Seaerle, et al., Australiian Vetermary Eractn ionor, 25, 3, 1995, 157-158, also suggest that a compound of this type containing Use a spray solution to effectively control fleas and bites.

Surprisingly, it has been found that although thipronyl can be used with the same release problems, rtriro is a known compound. yet perfectly effective .collars have been made to remove canine and feline ecoparasites for a very long period of time, for example 6-18 months, and in addition, the efficacy after removal of the collar rs is maintained, namely 2 months or more Iciesg, so that perfectly: we can produce an effective collar, whatever the road {.use. conditions. And since the protection is retained even after the collar is removed, it is obvious that o irregular application, which may be intentional or may result from the loss of the collar, does not temporarily afford the protection it is. develops in an animal.

It has further been found that long-term efficacy is achieved by co-concentration of active ingredient in the collar matrix that is significantly lower than conventional products. It has been found that performance is achieved within a very short time after application of the collar, and more specifically 24 watches> 95% - <:> ι; efficacy against <d fleas, and after an hour> 90% inactivity against tick.

very surprisingly it is; We have found that fiproni 1, which is very lipophilic and high in vapor: · its horse (low volatility) has a very high affinity for animal hair (which includes bot and hair ss), and is usually a dandruff Iran, that when you compound the compound, it gets into the dandruff and that is the consequence. to form a transococcal phenomenon that distributes the active ingredient throughout the animal's body. In addition, and remarkably, the active ingredient accumulates in the sebaceous gland, thereby making the glands a reservoir that provides longitudinal effectiveness and temporarily compensates for the lack of collar in the bed to release its active ingredient by passive diffusion.

This phenomenon is due to changes in the release of the active ingredient from the collar. which are caused, for example, by changes in weather conditions, are compensated for by the possibility that the active ingredient may be released from sebum envy.

It has also been found that after a bath, which may lead to the removal of bran that is distributed on the body of the animal, the animal very quickly becomes protected again, with or without a collar, by choosing a new bran. release of the active ingredient from sebum envy,

The present invention therefore relates to a flea collar and an external collar or other external structure for the human companion animal, especially dog and cat, comprising a matrix in which 1 to 15% by weight of an anti-flea or tick active agent is applied. structure with respect to the total 'weight' of the compound of formula (I), i.e., l-iso-Cb-d-CHrtenyl-d-CN-A-10SO-CE _? J-5-'NH> -piríízol,

CFs that have a collar or other external structure effective for at least 6 months against fleas and at least 3 months effective for ticks.

The compound of formula (IIi) used in the present invention of srinine is I- [2, 8-Cl 1 -C 4 -biphenyl-3-CNto- [SOCl] -O-Ni-b-pyrazole, hereinafter also referred to as fiprenins.

The compound of formula (I) is known in the art (see, for example, WO-A-87 / 378i, EP-A-29 / 5.117, EP-A-29 / 5.117). ) or by any other method known to one of ordinary skill in the art of chemical chemistry. It is contemplated by the skilled artisan that the entire contents of the Chemical Ahstraet and the documents therein are readily available to one of ordinary skill in the art. .

♦ · **

According to the invention the concentration of drug M5 Λ ^w: between eg%, preferably between 1 .25 and breaking Ö between gk.

Optimally, the compound of formula (II) is present in the collar in a weight ratio of from 2 to 6%, more preferably from 2.5 to 5% by weight.

Of course, any other insecticidal agent which is considered useful may also be used for tiproril breasts.

These sectectics may be in the same matrix as the lower-alpha compound. But you can also use a compound collar. - which at the very bottom is made up of two parts, each of which contains two different active ingredients

In accordance with the present invention, bellii matrices commonly used to make collars are crushed. Preferred examples include basic matrices of PVC (polyvinylchloride), see, for example, 15S-A -3.3 i 8.769, 3,852,416. or 4,150,109 or 5,437,869. U.S. Pat. But we can use other debates! polymer.

The plasticizers are preferably selected from the group consisting of adipates, grates, phosphates and germs.

Preferably one or more plasticizers are added to the PVC, of which

- dietary drink 1,

- dioctyl sebacate,

- di-cyclic S-adipate,

- Ozodecd phthalate,

- the tea i 1 -1 r i b u t i 1 - e l tea,

- dlietsl-hexi;

- dithecate-fish,

benzyl bmyl phthalate.

- acetyltribylcyls,

- triclosyl · phosphate,

- 2'Ctti-hexyldiphenyl fatty acid.

More preferably, a PVC matrix is used in the formulation of a residual primary plasticizer and a secondary plasticizer (see, in particular, bP-A-li, 539,295 and kP-A-Q, § 537.99).

Secondary soft writing materials include, but are not limited to, the following:

acetyltriethyl citruses

-fietd address

- Tiaceskesk

- dlet11é n g 1 ik ο 1 - m onoe 111 - é t e r,

triphenylphosphines

We can also add a stabilizer,

In the context of the present invention, the appearance of a sleeve is a structure that can be attached to the animal externally, i.e. for the same purpose as a collar.

- 5 Changing the concentration and composition of the matrix. then collars and other externally usable structures of the present invention can be used to provide effective and supportive protection against fleas. Collars or other externally applied devices can be produced which have an efficacy of more than 6 months. for example, 12 or IS months or more. ts if the collar or other outer structure is removed for a longer or shorter period of time. When the collar or structure is removed, the effective protection duration can reach 2-3 • days.

By varying the concentration and / or composition of the matrix, collars or other externally usable structures of the invention can be provided that provide effective and durable protection of ticks against ticks. Can we knife collars or other externally usable structures that have an efficacy of more than 3 months, for example? 12 or 15 months or more. even if the collar or outer structure is removed for a longer period. When the collar or outer structure is removed, effective protection may last for up to 1-2 months.

Of note, this complete and sustained efficacy can only be achieved with the fip.ro.nii compound, without the addition of other insecticides.

It is a further object of the present invention to provide a method of removing ectoparasites, in particular fleas and ticks, from a companion animal such as a dog or cat by attaching at least one inventive collar or other externally applicable structure to an animal to provide effective and durable protection. animal against said parasites and if the collar or. other externally usable structures are removed. See the reference to time teaching above. Preferably, in the method of the invention, the collar or outer structure is tin-plated on the first half-loading titanium for at least 24 hours in order to provide sufficient amount of active ingredient to the animal and thereby allow the sebaceous glands to do so. active ingredient.

The purpose of the process is not to purify the hair and skin of animals, in particular to remove the parasites present, as well as their residues and excreta. The hair of the treated animals thus provides a more pleasant sight and a pleasant touch.

The invention also relates to a method of treatment for the treatment and prevention of diseases caused by parasites with pathogenic consequences.

The present invention also relates to the use of a film topping compound for the preparation of a collar or other externally applicable device. which can be attached to your accompanying arias, needles for dogs and cats, which are very effective and against fleas for more than 6 months, ticks are filling. for more than 3 months, the efficacy of which is preferably maintained for several weeks also in the event that the collar or outer structure is removed or the animal is lost, or the collar or outer structure of the image (1) exhibits a life-like malformation,

The compound of formula (fi) is included in an amount of from 1 to 15% by weight in the matrix for forming the collar or other outer structures.

More preferably, the compound is used in a concentration of 1.25 to 10% by weight, for example 2 to 2, preferably 2.5 to 5% by weight.

»X * · ♦ ί * ~ ί'ΐ The purpose of the padding application is to provide collars or exterior structures that provide '95%, even> 98 or> 99% anti-flea performance

Λ in the case of kylans, the desired efficacy is greater than SO or about 90%; it is an object of the present invention to provide a durable effect on fleas for a duration of more than 12 months and even 18 days.

for teallots this is the time range, an ·> 12 months, even> 15 months.

More preferably, the present invention is directed to the production of collars or outer structures that can be effective for 2 to 2 months or longer in the absence of a collar or outer structure, and for a period of b-2 months or longer. until the end of ticks.

The invention will now be described in more detail by way of examples, which are not intended to limit the scope of the invention and are not mentioned in detail and advantages; jllusztrálják,

In the examples,% by weight is%.

Ljyykte% A compound is a collar that has a belt

The following two types of collars are made by mixing and then extruding the components.

Preparation I: PVC

2, incited; PVC

59.0% Stabilizer 0.5% Epoxylated Soybean Oil S., O% Diisoctyl Addition 24.5% Compound (I) O%

59.0% Stabilizer Ö, 5% Epoxy Soybean Oil 5.0% Z-Ethyl Hexd Diphosphate 34.5%

Formula III 10.0%

Nine adult dogs were selected for the study, with no mectectile or whatever for at least 40 days. The dogs were washed with insecticidal shampoo and combed to remove existing parasites.

The dogs were divided into three groups:

The group.

net treated comparator group lo% A collar containing Compound A, No. 1. Preparation 5% of the calf containing Compound 2 according to Preparation 2, zk dogs approx. T h e t h e 10 Crenooephalhies telis feline cathawk is pronounced Urtféd tat judeasj, and 50.

Rhtpleephüius sangolneus (Terovm dog tick tick)

χ. , ¢, • 7 Carry out the treatment according to the following diagram:

NAP flea and tick infestation collar flea and tick comb count tick infestation flea comb comb intentional vision tick flea comb comb count infection with flea infection comb count

The same with fleas and tick! infections continue every month until we have a satisfactory level of efficacy.

Hair sampling was performed on all dogs at days 295 and 261.

The collar is removed on day 149 from field dogs 363 and 291, on day 177 from dogs 87 and 300 and on day 203 from dogs 256 and 3 35.

The active ingredient concentrate according to the invention is present on the stalk on days 265 and 261 in the fever / g spray unit of fever I and foot 2 respectively.

Uáhlázat

The present invention provides an agent; Corrosion control of active ingredient I on the diffuser s 265. on the sun

Father's number Concentration fg.g 3] Under the collar Better wine shit Left flap If Central Bedding 18 groups 565 ! 0.63 3:11 2:33 ! , 7 3 6.99 137 9.08 2.28 3:08 5.8 i 4:54 256 r, 4.66 3:04 3.01 2.48 10.99 C tube dust 289 27,47 1.75 15.19 8..99 30.9 300 482.4 34.6 5.69 17.97 36.7 335 257.4 23.86 28.86 22.8 4i, 2

·· 8 TjxHouseM

Cot concentration of the active ingredient according to the tuft on the hair on day 261

Father K's pity CoacestóAciö (pg.g 7 1 Under the collar .lob'b horpas-z Bei hump If Central Basin 1 B esopoti 263 0.94 0.65 > 0.29 > 0.39 1.47 87 0.61 0.94 > 0.32 > 9.40 NA j 226 > 0.97 SO 9.8 5 0.78 0.69 1 C esepert 289 5.56 > 0.75 • 0:59 > 0.60 2.03 500 5.79 > 02'0 2.04 1.55 5.52 555 1.84 1.67 2.99 4.61 4, i 9

SO. no data available

The distribution of the active substance is observed a. the concentrations obtained on the hair are higher with the <2 group formulation and relatively homogeneous between the individual areas.

Removing the collar «even after 16 weeks: detectable · concealer ,. and it is still effective. The base of Tables 3, 4 and S; become visible between kouesotection and active dispute? context.

5, · loose:

Concentration / Activity Percentage Fall at day 149

Dog . \ / AI: va concentration tpg, g i Activity ⁵ dog collar under llsit and flab • Flea Tick 1 Average Mi: n. Other Group B 563 559.5 15.6 10.7 247 0 1 € group 289 871.3 48.9 94.4 0 0

: 1: í The dog: jethora · fleas ·.: · $ Up to the word ♦ *. *.> · · * «. , Ϊ.

• Í i;> bl; 5z; sÍ

íLjáfetásaí

K.on <: entrá <:: ó /; 3kfj controversial k a pt? So í a · a a 26 i. day)

Dog in the words of Activity' dog collar under Well and hotps Flea Tick Average M! you \ 0; s. Group B • 63 0.64 > 0.70 > 0.20 1.4 ' 0 21 8o (064 <0.55 <i..OQ 0.94 0 12. 256 > 0.97 <0.76 <LOQ 0.8! 1 24 L <$ ΟΡΟΠ 260 3,: 6 > 0.09 > 0.59 2.63 0 23 500 3.79 > 2.40 > 6.70 5.52 0 19 555 1.84 5.5 1.6? 4.6; 0 3

Mii) ~ Ot ifit 0: 0 Oh

Msx · == maximum

The LOQ limit of quantification is 0.25 pg / g.

Λ 26t. flea activity against fleas (00%) is present in all dogs except one dog.

The fleas and ticks are still effective toothpicks (defined on the following values:

- 20 μζΊ for dispersive ticks

- ΐ ijgb g fur fleas exchange ♦ *

- 10 With these formulations, we can observe at least 5 heat washings in ticks and at least 9 months in fleas.

ŐjTkih

Six. each group of h dogs was examined.

- Comparative group: the collar contains no active ingredient;

- B: Reference product :: commercial flea and gnocchial collar, containing 8% chlorophosphorus: [O, δ-diethyl] -O-3,5,5,6'-trichloro-2-pyridyl-ε-fissionorthothioate; wooden table marked with ref);

- C: a collar containing 2.5% by weight of a compound of the formula (t);

A collar containing 5 to 5 weight (µ) of pictureicin compound;

- E 10 by weight of formula (1). collar containing chemical ether,

The collars are made from the same components as the compound of Example 1, Example 2, a pigment (thane dioxide) is also added.

Experiments should be performed as follows:

NAP-z flea and tick infection is a collar assumption of a comb count tick; resuscitation. § price resuscitation with boihava comb counting tick re-infection

3? comb counting

Every month, according to the principle, I continue to experiment.

The infection; and re-infecting the following:

: 1O9 - 1 9 flea;

-v 5 ticks,, Tables 6 and 7 show the mean efficiency results.

fhJákhizat

Efficiency% for fleas calculated as geometric mean

Days Hands in groups Ref S% ________________ 2.55 c 5% 19% -S He Ö% 9.3% 0.9% 9.0% > 63.9% 9: S% 199.0% 100.0% 0 96.3% 190,95¾ 1 99.9% 199.0% 57 96.1% 99.9% 100 9% 199.0%. 65 99.1: 5¾ 1 99:, 99¾ 190.0% 199.9% 93 99.6% 109.05a 1 («3.0% 109.9-¾ 721 99. the salt Ϊ 99.0% 109.9% 109.9%

♦ * »* Λ« »* ♦ ♦« Λ »XX

149 98.3% 100.376 ! 00.052 5,00,0% 1 7? 97.97¾ 100.972 ! 06 to 0% • 00.052 205 98.5% 190.072 ; 09.083 100 353 * —I A - » L.? .: · 96,65¾ 130.083 5,00,083 5 90,053: 262 89.6% 100.07¾ 5,005,552 100.07-¾ 2x9 68.453 500.0% 5,005,552 5 00.07¾ 277 76.0 5,00,0% 500 032 5 00.04¾ 245 79.5 509.083 5, 30,052 5,005,552 273rd · 5,00,050 130.052 5,00,0% 204 - 99.2% 590.053 99.8% 727 99.2% 99.852 99.352 25? - 96.952 98.852 90.2 '% 285 - 96.772. 98.252 98.782 513 ·· 90.3% 99.053 99.383 5-25 ·· 08.852 5 00,052 ·

.,% 95% 2

Efficiency% -han for knila-rics, calculated as geometric -circle

Days j Hands in groups Re 6,853 2.552 5% 1052 • '5 4783 19th i% 5, 9,183 32.053 > 34.3 67 052 5 00,082: 98.5% 0 86.952 96.285 5,00,0% 5, 30,082 57 0085 95.285 95.453 65 3 5.7% 85.05: 2 500 052 95.883 93 3 5,853 86.7% 100 082 95.783 521 65.283 91.35-2 88.883 92.183 5 29 59 083 93.7% 92,07¾ 92.583 177 67.252 88.9% 95 353 95.283 305 62.092 86 283 50: 9.085 98.483 2 5353 62.652 80.885 98.3%: 97.9%: 568 57.552 77.262 98.2% 99.582: 389 44.682 92.45 :! · 97.2% 98.5 83 3 57 74.5% 85 682 92.47: 2 56.5 88.183 98.8% 98.073 ·% ' - 72.452; 83.962 95.7% 201 63.4% 98.565 93.682 239 2 2,722 83.253 93.383

♦ ♦

- ί 2. ··

457 THE 84.1A, 86.7% 48? - - - 51 3 - - 541 - ··

Claims (14)

SZ A Β A Ο LM ΓΙΓ »Ν ΥΡΟΝ ϊ Ό Κ ί. Anti-flea and anti-tick collar or other exterior structure for an accompanying animal, a mallard dog and a cat consisting of a matrix in which 5-15% by weight of flea or cataracts are incorporated, the collar or exterior structure based on the total weight of the compound of formula (I). l- {i.e. 2.ó Cl _~: .- 4-CH; phenyl] -3-CN-4- SO CF.-4-S-NH ski _s p e-1!. which has a collar or other external structure effective for more than h months on flea starvation and more than 3 months effective for ticks. Collar according to claim 1, characterized in that it contains from 5 to 5% by weight of the active ingredient. Collar according to claim I or 2, characterized in that the tip contains from 2 to 6, preferably from 2.5 to 5 pt ·· foam. Aces 1-3. A collar or other exterior structure as claimed in any one of claims 1 to 4, wherein the efficacy of removing or losing the remaining collar or exterior structure is maintained for 2-3 'months against fleas and 1-2 months for diarrhea. A collar according to claim 4, characterized in that it contains a concentration of active ingredient. which provides effective protection against fleas for 12 or 18 months or more Oi.ZtOSit. »* 9 X 9 9 * * 9 * 6. Λ 4 demand points screen collar. characterized in that it contains an active compound that provides effective protection against ticks for 12-15 months or more. For example, the use of a compound of the formula: 1- [2,6-Cl: - 4-CH2-phenyl] -3-CN-4- (SO-CF3j-5'N'H) -pyrazole as a collar or other topical application , for use in the manufacture of a device for attaching an animal to a companion animal, such as a dog or cat, and which is highly effective in preventing and treating fleas for more than 6 months, ticks for more than 3 months, preferably for several weeks even in the event of removal of the collar or outer structure or change in the release of the compound of formula (I) from the collar or outer structure, wherein the compound of formula Iii is incorporated in 1-15 weight to produce a collar or other exterior matrix, Use according to Claim 7, characterized in that the compound of formula (I) is incorporated in an amount of 1.25% by weight, preferably 2-6% by weight, more preferably 2.5-5% by weight, of a collar or other matrix for externally applicable structure. SHE. Use according to claim 7 or 8, characterized in that it is effective against fleas 9'8 or 99%. Use according to claim 7 or 8, characterized in that the efficacy against ticks is 80% or 5%. Use according to claim 7 or 8, characterized in that the long-term efficacy against fleas is> 12 months, Use according to claim 7 or 8, characterized in that the efficacy against vomiting of fleas is> 18 months. Use according to claim 7 or 8, characterized in that the efficacy against ticks is 212 months. Use according to claim 7 or 8, characterized in that the ticks have a sustained efficacy of> 5 months. Use according to claim 15, 7 or 8, characterized in that the efficacy is maintained even when the collar or outer structure is removed or lost. fleas for 2-2 months, and ticks for 1-2 months. - 1416. Procedure for the removal of fleas and ticks from sentinel animals, such as dogs and cats, by means of «| characterized in that the animal has an animal according to claims 1 to 55; A collar or other externally applied device according to any one of claims 1 to 6.