DE2005409A1 - Antihelmintic preparation and method for combating worm parasites - Google Patents

Description

PATENTANWÄLTE 2 OO 5 A 09 j

dr. W. Schalk di pl.-i ng. P. Wi rth »di pu-i ng. G, Dan ν en berg

DR. V. SCHMIED-KOWARZIK -DR, P. WEINHOLD · DR. D. GUDEL

6 FRANKFURT AM MAIN

OR. ESCHENHEIMER STRAStE 39

WD / BP

PISONS LIMITED.

Harvest House

Felixstowe, Suffolk, / England '

Antihelmintic preparation and method for combating worm parasites

The invention relates to the use of certain bismuth compounds for combating worm diseases in mammals.

According to the invention, a method for combating worm parasites is provided Created in mammals, this is characterized is that the eggs contain an effective amount of a bismuth compound the formula '

is administered, wherein η is 0 or 1, each radical R, which can be the same or different, is an aryl radical, the optionally by one or more substituents from the Group: alkyl with 1 to 6 carbon atoms, phenyl, Mtx? O,

00983571858

■ Halogen, alkoxy with "1 to 6 carbon atoms, alkoxycarbonyl may be substituted by 2 to 7 carbon atoms and carboxy; both radicals X are the same and represent fluorine, chlorine, bromine, Nitrate, hydroxy, acyloxy, cyano or cyanate or one radical X is hydroxy and the other is chlorine, bromine or acyloxy or both radicals X together represent a sulfur or oxygen atom. ι

Of course, η must mean the same number in a molecule. The invention thus includes trivalent and pentavalent bismuth compounds.

The aryl radical is expediently phenyl or naphthyl, preferably phenyl. The rest can be done in the manner indicated above be substituted. Usually there are no more than one nitro substituent and no more than one halogen substituent is present. The preferred halogen substituents are fluorine, chlorine and Bromine, especially chlorine and bromine. In order to ensure easy production, each aryl radical is expediently unsubstituted or monosubstituted. J

The two are also used to make the connection easier X radicals are usually the same and denote fluorine, chlorine, bromine, nitrate, hydroxy, acyloxy, cyano or cyanate. From these leftovers fluorine, chlorine, bromine, nitrate, hydroxy and acyloxy are preferred. Examples of acyloxy radicals, which can stand for both radicals X, or which represents an X, in the cases defined above, can be acetoxy and benzoyloxy. ,

Examples of bismuth compounds are triphenyl bismuth dichloride and triphenyl bismuth difluoride. Examples of compounds having particularly valuable activity are tris (p-biphenyl) bismuth and tris (p-tolyl) bismuth. Examples of compounds that are even more effective are triphenylwiamutdibromide! Triphenyl bismuth dinitrate and triphenylwiemut.

09836Π86 orkj.nal

The bismuth compounds are found in treating many Forms of worm parasites used in a wide variety of host animals. They can be used to prevent infection or an existing infection, for example j in Domestic and farm animals such as sheep, cows, horses, dogs and cats and eggs used in the laboratory, e.g. mice, rats, Hamsters and guinea pigs, treat. i

To intestinal worms, against which the v / ismut compounds are effective include hookworms, tapeworms, pinworms, roundworms, Roundworms and flukes. The compounds are particularly effective against liver fluke (Fäsciola hepatica), Hymenölepis nana and Haemonchus contortus, especially the first two mentioned, in particular. special the liver fluke, effective «The bismuth compounds are Appropriately used in preparations containing at least one material from the group consisting of wetting agents and pharmaceutically acceptable diluents and feed included. '

The compounds are generally administered orally to the animals. However, if necessary, parenteral administration can also be used. take place. For oral administration, the compounds are usually used in a manner customary for parasiticidal preparations is physiological in a composition mixed with others suitable components processed. They can be added to the drinking water or feed of the animals or administered separately will. >

Preparations for adding to drinking water usually contain Reaction agent to make a satisfactory solution or dispersion to ensure. ;

Preparations for adding to the feed can be made from the bismuth compound consist alone or a mixture with physiologically appropriate ones Carriers such as talc, chalk or earth, optionally with wetting agents represent.

0 09835/1353

The wetting agents used can be anionic compounds, such as soaps, fatty sulfate esters, such as dodecyl sodium sulfate, Fatty aromatic sulfonates, such as alkylbenzenesulfonates or butylnaphthalene sulfonates, more complex fatty sulfonates> like the amide condensation product of oleic acid and N-methyltaurine or the sodium sulfonate of dioctyl succinate.

The wetting agents can also include non-ionic wetting agents, such as condensates of fatty acids, fatty alcohols or fat-substituted phenols with ethylene oxide or fatty esters of sugars, polyhydric alcohols, or the products obtained from the latter by condensation with ethylene oxide or the products known as block copolymers of ethylene oxide and propylene oxide. The wetting agents can continue cationic agents include such as, for example, methyltrimethylammonium bromide and the like

The parasicidal composition may contain other effective components besides the bismuth compound, such as other parasicidal Agents and / or components that promote growth or health of animals. ;

The posture when administering the bismuth compounds depends from the respective animal to be treated, as well as the parasite that is to be fought. In general, however, about 25-1,000 Milligrams used per kilogram of body weight.

For example, good results have been obtained when sheep infected with liver fluke are generally given about 20-100 milligrams per body weight.

The compounds can be used for therapeutic treatment and as prophylactic measures . The expression "combat ¹¹ these two types of treatment should be understood.

should

009835/185 original insp ^ ted

The registration is explained by the following examples:

Examples 1-3

Rats that were three weeks old (Wistar strain) were orally infected with 3o metacercaria of the liver fluke Fasciola hepatica. After forty days / most of the leeches had settled in the biliary duct, the rats were orally administered a suspension of bismuth compounds listed in the table below in tragacantha, which corresponded to 75o, 375, 188, 94 , 46 and 23 milligrams per kilogram of body weight. The dosages were chosen taking into account the acute oral LD, - ₀ value, which was determined by previous toxicological tests Wordeiji. Five rats were used for each dose level.

Six days later the rats were sacrificed and the biliary duct dissected to determine the number of adult liver fluke that survived. The percentage of leeches in the treated "rats, compared to untreated control animals as follows:

example link

Tt iphenyl bismuth

Dose «mg / kg percentage

infection

Triphenyl bismuth dibromide

75o 375 188

94 46 23

75o 375 188

94 46

ο ο 2

25 2o 22

2o

3o

09835/188 «

ORIGINAL INSPECTED

• - 6 - link f Triphenyl bismuth
dinitrate 2005409 - infection example i
O Dose, mg / kg percentage ρ 3 O 75o ί
2 375 4th . 188 1c 94 46 23

Five week old mice (CFW strain) were given orally with 2oo ^; onchospheres of the mouse tapeworm, Hymenolepis nana, infected. Fourteen days after infection, after the worms in the distal parts of the mouse's small intestine had fully matured, the organosmuth compounds listed below were administered orally as suspensions in tragacanth gum in amounts equal to 375, 187 and 93 milligrams of active substance per kilogram of body weight. Five mice were used per dose.

The mice were sacrificed five days after treatment and the small intestine removed to examine the presence of worms, The percentage of worms that remained in the treated animals compared to untreated control animals, is listed below.

example

link

Triphenyl bismuth

Dose, mg /] Zg ₁ percentage Worm infection 375 2 187 5 93 2o

QQ983S / 185I

example Connection ^. Dose, mg / kg Percentage
infection VJl Triphenylwi bridal
dinitrate 375 3 6th Tpiö- (p-trOlyl) -
bismuth 375 18th 7th Iris (p-biphenyIyI) -
bismuth 375 2o

Claims (6)

Expectations v \ J Antihelmintic preparation for combating worm parasites, preferably protozoa, in mammals, characterized in that it contains an effective amount of a bismuth compound of the formula -Bi (X) (S) ₁ where η stands for 0 or 1, each radical R, which can be identical or different, is an aryl radical which is optionally substituted by one or more substituents from the group t alkyl with 1 to 6 carbon atoms, phenyl, nitro, haloalkoxy substituted with 1 to 6 carbon atoms, alkoxycarbonyl with 2 to 7 carbon atoms and orbocy; both radicals X are the same and represent fluorine, chlorine, bromine, nitrate, hydroxy, acyloxy, oyan or cyanate or one radical X is hydroxy and the other radical is chlorine, bromine or acyloxy or both radicals X together represent a sulfur or oxygen atom and optionally contains a pharmaceutically acceptable carrier. 0 0983 5 / 18SS 2. Preparation according to claim 1, characterized in that it contains a bismuth compound in which each aryl radical sub-j is substituted, but not more than one nitro-j ducks and has no more than one halogen substituent. 3. Preparation according to claim 1 or 2, characterized in that that it contains a bismuth compound in which each aryl radical is unsubstituted or monosubstituted. 4. A preparation according to claim 1, characterized in that it contains triphenyl bismuth dichloride or triphenyl bismuth difluoride . 5 * preparation according to claim 1, characterized in that it contains tris (p-biphenylyl) bismuth or tris (p-tolyl) bismuth. 6. A preparation according to claim 1, characterized in that it is triphenyl bismuth, triphenyl bismuth dibromide or triphenyl bismuth dinitrate contains. Methods of combating worm parasites in mammals, using an anthelmintic preparation according to claims 1-6, characterized in that the bismuth compound administered to the animal in an amount of about 25-1,000 milligrams per kilogram of its body weight will. 0 0 9835/1858 ORIGINAL INSPECTED