GB2052972A

GB2052972A - Injectable anthelmintic compositions

Info

Publication number: GB2052972A
Application number: GB7924266A
Authority: GB
Original assignee: Syntex USA LLC
Current assignee: Syntex USA LLC
Priority date: 1979-07-12
Filing date: 1979-07-12
Publication date: 1981-02-04

Abstract

An injectable anthelmintic composition comprises in combination with a major amount of a physiologically acceptable, lower alkylene glycol e.g. propylene glycol or a suitable oxygenated cyclic hydrocarbon derivative thereof and a minor amount of a physiologically acceptable amount of an alkali metal hydroxide, a compound of the formula: <IMAGE> wherein R is a lower alkyl group having 1 to 4 carbon atoms; R<1> is YR<2>, -SCN, R<3>R<4>NC(O)-, M'(CH2)nMR<5>, or R<6>C(O)-; R<2> is a lower alkyl having from 1 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, lower alkenyl of 3 to 6 carbon atoms, lower alkynyl having 3 to 6 carbon atoms, aralkyl, aryl, or heterocycle of 5-7 members and having 1-3 nitrogens, said alkyl, alkenyl and alkynyl being optionally substituted with alkoxy, aryl, aroyl, hydroxy, cycloalkyl, halo, cyano or nitro; Y is O, S, S(O) or S(O)2; R<3> is lower alkyl having 1 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, lower alkenyl or lower alkenyl having 3 to 6 carbon atoms, or phenyl; R<4> is hydrogen or R<3>; M and M' are independently O, S, S(O), S(O)2; R<5> is lower alkyl having 1 to 6 carbon atoms or aryl which is optionally substituted with one or more lower alkyl, alkoxy, halo, nitro, cyano, thiocyanato, isothiocyanato, trifluoromethyl, alkylthio, alkylsulfinyl, alkylsulfonyl, acyl or acylamino where the acyl portion has 1 to 6 carbon atoms, -SO2NR<8>R<7> or -N(R<8>)SO2R<7> radicals; R<6> is aryl; R<8> and R<7> are independently hydrogen or lower alkyl having 1 to 6 carbon atoms; and n is an integer of 1 to 4.y

Description

SPECIFICATION Injectablg anthelmintic solution FIELD OF THE INVENTION This invention relates to a novel injectable anthelmintic composition, a method for controlling helminths in mammals by administering the composition, and a process for preparing the composition. More particularly, this invention relates to the combination of an anthelmintically active, physiologically acceptable, 5(6)-substituted benzimidazole-2-carbamate derivative, a carrier which is a major amount of a physiologically acceptable, non-toxic lower alkylene glycol or a suitable oxygenated cyclic hydrocarbon derivative thereof, and an alkali metal hydroxide.

PRIOR ART Orally administered, anthelmintically active benzimidazole-2-carbamate derivatives substituted at the 5(6)-positions of the benzene ring are known. For example see U.S. 3,929,821; U.S.

4,002,640; U.S. 3,929,824; U.S. 3,954,791; U.S. 3,574,845; U.S. 3,915,986; and U.S.

4,086,235. It is also known that certain of anthelmintically active compounds can be parenterally administered. See for example British Patent 1,428,933; German OLS 24 38 120; U.S. 3,928,375; U.S. 3,954,791; U.S. 4,076,825; U.S. 4,076,827; and U.S. 4,076,828.

Acid addition salts, such as the hydrochlorides, are usually prepared because in most instances they are more water soluble than the parent compound. However, in the instant case, preparation of the acid addition salts, for example the hydrochloride salt of 5(6)-phenylsulfinyl-2carbomethoxyaminobenzimidazole, does not always increase its water solubility sufficiently to permit its ready use as an injectable solution. Surprisingly, however, it has been found that the combination of certain benzene ring-substituted benzimidazole carbamates, such as 5(6) phenylsulfinyl-2-carbomethoxyaminobenzimic'iazole, with a major amount physiologically acceptable lower alkylene glycol or a suitable derivtive thereof, e.g. propylene glycol, and an alkali metal hydroxide results in a solution which is eminently suitable as an injectable anthelmintic.

SUMMARY OF THE INVENTION One aspect of this invention is an injectable, anthelmintically active composition which comprises an effective amount of an anthelmintically active, benzene ring-substituted benzimidazole-2-carbamate derivative, as defined more fully hereafter, in combination with a carrier which is a major amount of a physiologically acceptable, lower alkylene glycol or a suitable oxygenated cyclic hydrocarbon derivative thereof, and an alkali metal hydroxide. Other suitable pharmaceutical excipients may optionally be present.

Another aspect of this invention is a method of controlling helminths in mammals which comprises parenterally administenng an anthlemintically effective amount of the above composition into a mammal.

Still another aspect of this invention is a process for preparing an injectable, anthelmintically active composition, which process comprises dissolving a suitable, benzene ring-substituted benzimidazole-2-carbamate derivative, defined more fully hereafter, and an alkali metal hydroxide in a physiologically acceptable, lower alkylene glycol or a suitable oxygenated cyclic hydrocarbon derivative.

FURTHER DESCRIPTION AND PREFERRED EMBODIMENTS The benzene ring substituted benzimidazole-2-carbamates useful in the injectable solution of this invention are represented by the following formula (I):

wherein R is a lower alkyl group having 1 to 4 carbon atoms; R' is YR2, -SCN, R3R4NC(0)-, M'(CH2)MR5, or R6C(O)-; R2 is a lower alkyl having from 1 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms.

lower alkenyl of 3 to 6 carbon atoms, or lower alkynyl having 3 to 6 carbon atoms, aralkyl, aryl.

or heterocycle of 5-7 members and having 0-3 nitrogens; said aryl, aralkyl, alkyl, alkenyl and alkynyl being optionally substituted with alkoxy, aryl, aroyl, hydroxy, cycloalkyl, halo, cyano or nitro; Y is 0, S, S(O) or R3 is lower alkyl having 1 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, lower alkenyl or lower allnyI having 3 to 6 carbon atoms, or phenyl; R4 is hydrogen or R3; M and M' are independently 0, S, S(O), S(O);; R5 is lower alkyl having 1 to 6 carbon atoms optionally substituted with alkoxy, aryl, aroyl, hydroxy, cycloalkyl, halo, cyano, or nitro or is aryl which is optionally substituted with one or more lower alkyl, alkoxy, halo, nitro, cyano, thiocyanato, isothiocyanato, trifluoromethyl, alkylthio, alkylsulfinyl, alkylsulonyl, acyl or acylamino where the acyi portion has 1 to 6 carbon atoms, -SO2NR8R7 or -N(R8)SO2R7 radicals; R6 is aryl; R8 and R7 are independently hydrogen or lower alkyl having 1 to 6 carbon atoms; and n is 1-4.

Representative compounds include the hollowing: 5(6)-p-fluorophenylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-naphth-2'-ylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-methylthiomethylthio-2-carbomethoxyaminobenzimidazole; 5(6)-methoxymethylthio-2-carbomethoxyaminobenzimidazole; 5(6)-methoxymethoxy-2-carbomethoxyaminobenzimidazole; 5(6)-(prop-2-en-1-ylthio)-2-carbomethoxyaminobenzimidazole; 5(6)-(prop-2-en-1-ylsulfinyl)-2-carbomethoxyaminobenzimidazole; 5(6)-(prop-2-yn-1-ylthio)-2-carbomethoxyaminobenzimidazole; 5(6)-(prop-2-yn-1-ylsulfinyl)-2-carbomethoxyaminobenzimidazole; 5(6)-n-hexylsulfonyl-2-carbomethoxyaminobenzimidazole; 5(6)-phenylsulfonyl-2-carbomethox$arninobenzirniclazole; 5(6)-p-chlorophenylsulfinyl-2-carbornethoxyaminobenzimidazole; 5(6)-m-chlorophenylsulfinyl-2-carbomethoxyaminobenzimidazole;; 5(6)-p-methylphenylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-p-methyoxyphenylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-n,n-dimethylaminocarbonyl-2-carbomethoxyaminobenzimidazole; 5(6)-phenethylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-trifluoromethylthiomethoxy-2-carbomethoxyaminobenzimidazole; 5(6)-ethoxymethylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-phenoxyethoxy-2-carbomethoxyaminobenzimidazole; 5(6)-cyclopentyisulfinyl-2-carbornetho::cyarninobenzimidazoie; 5(6)-cyclohexylsulfinyl-2-carbomethoxyaMinobenzimidazole; 5(6)-benzylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-p-nitrophenylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-p-cyanophenylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-(2-cyanoethylsulfinyl)-2-carbomethoxyaminobenzimidazole; 5(6)-p-acetamidophenylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-p-sulfamoylphenylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-p-sulfonylaminophenylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-thiocyanato-2-carEDomethoxyaminobenzi idazole; 5(6)-phenoxy-2-carbomethoxyaminobenzimidazole; and 5(6)-p-chlorophenoxy-2-carlbomethoxyaminobenzimlidazole.

A subgroup of these compounds includes those compounds represented by Formula (I) wherein R is methyl; R' is benzoyl, SR2, -S(O)R2 or R2 is phenyl or lower alkyl optionally substituted with at least one halo or cycloalkyl of 3-6 carbons; M' is O or S(O); M is 0; n is an integer of 11-4; and R5 is lower alkyl of 1-4 carbons optionally substituted with chloro or cycloalkyl or is phenyl optionally substituted with halo. Of this subgroup the preferred compounds are those where R is phenylthio, n-propylthio, benzoyl, phenylsulfinyl, phenoxyethoxy, n-propylsulfinyl, methoxyethylsulfinyl, chlorophenoxyethoxy, cyclopropylmathylsulfinyl, 3-chlornprnpylsulfinyl, and isobutylsulfinyl. Of these preferred compounds, particularly preferred are 5(6)-phenylth io-2-carbomethoxya minobenzi m idazoie; 5(6)-n-propylthio-2-carbomethoxyaminobenzimidazole; 5(6)-benzoyl-2-carbomethoxyaminobenzimidazole; 5(6)-phenylsulfinyl-2-carbornethoxyaminobenzirnidazole; 5(6)-phenoxyethoxy-2-carbomethoxseaminobenzim idazole; 5(6)-4'-chlorophenoxyethoxy-2-carbomethoxyaminobenzimidazole; 5(6)-2'-chlorophenoxyethoxy-2-carbomethoxyaminobenzimidazole; 5(6)-31-chlorophenoxyethoxy-2-carbomethoxyaminobenzimidazole; 5(6)-n-propylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-methoxyethylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-cyclopropylmethylsu lfinyl-2-carbomethoxyaminobenzimidazole;; and 5(6)-3'-chloropropylsulfinyl-2-carbomethoxyaminobenzimidazole.

As used in this specification and claims, the term "lower alkyl" refers to both straight and branched chain alkyl groups having a total of carbon atoms as indicated, e.g. 1-6, and thus includes primary, secondary and tertiary alkyl groups. Typical lower alkyls include, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, t-butyl, n-amyl, n-hexyl and the like.

The term "cycloalkyl" refers to cyclic hydrocarbon groups having from 3 to 7 carbon atoms such as, for example, cyclopropyl, cyclopentyl, cyclohexyl, and the like. The term "lower alkenyl" refers to an unsaturated hydrocarbon group having from 3 to 6 carbon atoms and a single carbon-carbon double bond, provided that the double bond cannot be on the carbon atoms. Typical alkenyl groups include, for example, 2-propenyl, 2-butenyl, 3-butenyl, and the like. The term "lower alkynyl" refers to an unsaturated hydrocarbon group having from 3 to 6 carbon atoms, and a single carbon-carbon triple bond, provided also that the triple bond cannot be on the a-carbon atom. Typical alkynyl groups include, for example, 2-propynyl, 2-butynyl, 3butynyl, and the like.

An alkyl, alkenyl or alkynyl group and the R' moiety can be optionally substituted with one or more radicals, for example, alkoxy, such as methoxy; aryl such as phenyl; aroyl, such as benzoyl; hydroxy; cycloalkyl such as cyclopropyl; halo; cyano; or nitro radicals. The term "alkoxy" refers to the group having the formula R100- wherein R'O is a lower alkyl as defined above. Typical alkoxy groups include, for example, methoxy, ethoxy, t-butoxy and the like. The term "halo" refers to iodo, bromo, chloro and fluoro groups.

The term "aryl" refers to an aromatic hydrocarbon group, such as phenyl. The term "aralkyl" refers to an aryl substituted alkyl group, such as, for example, benzyl or phenethyl. The term "aroyl" refers to the group having the formula R'C(O)- where R' is an aryl group.

The aryl or aralkyl groups can be optionally substituted with one or more lower alkyl, alkoxy, halo, nitro, cyano, thiocyanato, isothiocyanato, trifluoromethyl, alkylthio, alkylsulfinyl, alkylsulfonyl, acyl or acylamino where the acyl portion has 1 to 6 carbon atoms, -SO2NR8R7 or -N(R8)S02R7 radicals; where R8 and R7 are independently hydrogen or lower alkyl having 1 to 6 carbon atoms.

The composition of the present invention possesses broad spectrum activity against parasites of mammals (human or animal), including both mature and immature parasitic forms, as represented for example, by the genera Trichostronglylus, Haemonchus, Ostertagia, Cooperia, Nematodirus, and Stronglyoids, and specifically, for example against Namatospiroides dubius, Hymenolepis Nana, Syphacia obvelata, and/or Aspiculuris tetraptera. In particular, these compositions are found to exhibit high activity against various helminthic infections of the intestinal tract of economically important animals, coupled with low systemic toxicity to the host animal.

An effective amount of the compound to be administered will depend upon the actual compound utilized, and upon the weight of the animal being treated. In general, however, the daily dosage level will usually be between about 1.0 mg/kg and 100 mg/kg of body weight of the animal being treated, preferably about 2.5-25.0 mg/kg.

The carrier useful in the injectable composition of this invention is a physiologically acceptable, lower alkylene glycol or a suitable oxygenated cyclic derivative thereof. The term "physiologically acceptable" means that the carrier does not have a toxic effect on the animal to which it administered and further does not adversely affect the anthelmintic properties of the compound with which it is combined. A lower alkylene glycol is a glycol of 3-5 carbon atoms such as glycerol, 1,2-butanediol, 1,3-butanediol, 1,2-pentanedial and 1,2-propanediol (propylene glycol). Suitable oxygenated cyclic hydrocarbon derivatives thereof include compounds having up to 9 carbon atoms and up to 4 oxygen atoms present, i.e. with 1 or 2 free hydroxy components and 2 or 3 ether linkages.Representative compounds include acetone glycerol (Solketal), glycofurol (tetrahydrofurfurylalcohol with an average of 2 ethylene glycol groups), and the like. The lower alkylene glycols are particularly useful, and propylene glycol is preferred.

The composition of the invention also contains a minor amount of an alkali metal hydroxide dissolved in the carrier. Suitable hydroxides include for example sodium or potassium hydroxide, the former being preferred. The hydroxide is present in a physiologically acceptable amount, i.e.

an amount which is not harmful to the overall health of the animal to which the composition is administered. Generally this amount will be enough to bring the pH of the composition (when water is present) to more than about 9.0 but less than a pH which is too irritating, i.e. less than about 3.0, preferably less than 12. In 100 grams of total composition, no more than about one gram of the hydroxide is needed, preferably from about 10-100 mg will be present.

The composition of the invention utilizes the lower alkylene glycol or the derivative as the major carrier, that is at least 50% and preferably 75% of the carrier is the glycol or its derivative. Although the mixture may be partially aqueous, preferably the composition contains as little water as is consistent with good manufacturing procedures, i.e. it is substantially anhydrous. Generally this will be no more than about 5% w/v water, and preferably less than about 1 % water.

The method of administration of the invention comprises parenterally administering the composition of the invention to a mammal in need of the composition to prevent or treat helminthiasis. Parenteral administration is introducing the composition to the mammal's system by a route other than the gut. This includes, for example, intravenous, subcutaneous, intramuscular, or intraperitoneal injection into the mammal being treated, the latter three being preferred.

The process of preparing the composition of this invention is carried out by dissolving a suitable compound discussed hereinbefore and the alkali metal hydroxide in a physioiogically acceptable lower alkylene glycol or suitable oxygenated cyclic hydrocarbon derivative thereof.

The hydroxide may first be dissolved in water if an aqueous system is desired. The process is carried out at about 1 0'-50'C, preferred at ambient temperature (20 -25 C) while agitating the mixture.

Other suitable pharmaceutical excipients can also be included such as antioxidants (e.g.

vitamin E, citric acid, etc.), preservatives (e.g. benzyl alcohol), cosolvents (e.g. polyethylene glycol 400), viscosity enhancers (e.g. carboxymethylcellulose) and the like according to methods known in the art.

The free base benzimidazole-2-carbamate derivatives which are useful in this invention are readily prepared by methods known in the art such as those set forth in U.S. 3,929,821; U.S.

4,002,640; 3,929,824; 3,954,791, 3,574,845; 3,915,986; and 4,076,825 which are incorporated herein by reference.

The following Examples set forth representative compositions of this invention but are not to be read in a limiting sense.

EXAMPLES 1-8 The compositions set forth below in Table I were prepared by placing a suitable solvent in a reaction flask and adding 5(6)-phenylsulfinyl-2-carbomethoxyaminobenzimidazole there while stirring oxfendazole at room temperature to dissolve the oxfendazole. Aqueous, sodium hydroxide (0.1 ml) was added to give the pH, shown in the table. The pH was measured using a standard pH meter. The oxfendazole was completely dissolved in all cases.

In Table I, each ingredient is given in grams and the pH of the composition for each example is the last number in the column.

TABLE I Example No. 1 2 3 4 5 6 7 8 Ingredients Oxfendazole 0.5 1.0 0.5 1.0 0.2 1.2 0.5 1.0 Solketal 10.0 1 - - - 2 1.5 Butylene Glycol - 20.0 - - - - - - Propylene Glycol 14 14 - 14 - 20 Water B - 6 6 - 2 1.5 Glucofural - - - - 10.0 - - PEG 400 - - - - - - 11 - pH 10.2 10.5 11.4 11.4 11 11.2 11.2 11.2

Claims

1. An injectable anthelmintically active composition which comprises a carrier which is a major amount of a physiologically acceptable lower alkylene glycol or a suitable oxygenated cyclic derivative thereof, a minor acount an alkali metal hydroxide and compound represented by the formula

wherein R is a lower alkyl group having 1 to 4 carbon atoms; R1 is YR2, -SCN, R3R4NC(O)-, M'(CH2)nMR5, or R6C(O)-; R2 is a lower alkyl having from 1 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, lower alkenyl of 3 to 6 carbon atoms, lower alkynyl having 3 to 6 carbon atoms, aralkyl, aryl, or heterocycle of 5-7 members and having 1-3 nitrogens, said alkyl, alkenyl and alkynyl being optionally substituted with alkoxy, aryl, aroyl, hydroxy, cycloalkyl, halo, cyano or nitro;; Y is 0, S, S(O) or S(0)2; R3 is lower alkyl having 1 to 6 carbon atoms, cycloalkyl having 3 to 7 carbon atoms, lower alkenyl or lower alkenyl having 3 to 6 carbon atoms, or phenyl; R4 is hydrogen or R3; M and M' are independently 0, S, S(O), S(O); R6 is lower alkyl having 1 to 6 carbon atoms or aryl which is optionally substituted with one or more lower alkyl, alkoxy, halo, nitro, cyano, thiocyanato, isothiocyanato, trifluoromethyl, alkylthio, alkylsulfinyl, alkylsulfonyl, acyl or acylamino where the acyl portion has 1 to 6 carbon atoms, -SO2NR8R7 or -N(R8)SO2R7 radicals; R6 is aryl; R8 and R7 are independently hydrogen or lower alkyl having 1 to 6 carbon atoms; and n is an integer of 1 to 4.

2. The composition of Claim 1 wherein said compound is represented by Formula (I) wherein R is methyl; R1 is benzoyl, -SR2, S(O)R2 or M1(CH2)MR5; R2 is phenyl optionally substituted with at least one halo or is lower alkyl of 1 to 4 carbon atoms optionally substituted with chloro or cycloalkyl of 3 to 6 carbon atoms; M' is 0, S or S(O); M is O; n is an integer from 1 to 4; and R5 is lower alkyl of 1 to 4 carbons or phenyl optionally substituted with one or two chloro substituents.

3. The composition of Claim 2 wherein R' is chosen from the group consisting of phenylthio, n-propylthio, benzoyl, phenylsulfinyl, phenoxyethoxy, n-propylsulfinyl, methoxyethylsulfinyl, chlorophenoxyethoxy, cyclopropylmethylsu Ifinyl, 3-chloropropylsulfinyl, and isobutylsu Ifinyl.

4. The composition of Claim 3 wherein said compound is chosen from the physiologically acceptable acid addition salts of 5(6)-phenylthio-2-carbomethoxyarninobenzimidazole; 5(6)-n-propylthio-2-carbomethoxyaminobenzimidazole; 5(6)-benzoyl-2-carbomethoxyaminobenzimidazole; 5(6)-phenylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-phenoxyethoxy-2-carbomethoxyaminobenzimidazole; 5(6)-4'-chlorophenoxyethoxy-2-carbomethoxyaminobenzimidazole; 5(6)-2'-chlorophenoxyethoxy-2-carbomethoxyaminobenzimidazole; 5(6)-3'-chlorophenoxyethoxy-2-carbomethoxyaminobenzimidazole; 5(6)-n-propylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-methoxyethylsulfinyl-2-carbomethoxyaminobenzimidazole; 5(6)-cyclopropylmethylsulfinyl-2-carbomethoxyaminobenzimidazole;; and 5(6)-3'-chloropropylsulfinyl-2-carbomethoxyaminobenzimidazole.

5. The composition of Claims 1, 2, 3 or 4 wherein said carrier is propylene glycol and said hydroxide is sodium hydroxide.

6. The composition of Claim 1 wherein the compounds are represented by Formula (I) wherein said carrier is propylene glycol; said hydroxide is sodium hydroxide; R' is phenylsulfinyl, phenoxyethoxy, no-propylsulfinyl, methoxyethylsulfinyl, cyclopropylmethylsulfinyl, or isobutylsulfinyl; and R is methyl.

7. The composition of Claim 6 wherein the compound represented by Formula I is 5(6)phenylsulfinyl-2-carbomethoxyaminobenzimidazole.

8. The composition of Claim 6 wherein the compound represented by Formula I is 5(6)phenoxyethoxy-2-carbomethoxyaminobenzimidazole.

9. The composition of Claim 6 wherein the compound represented by Formula i is 5(6) methoxyethylsulfinyl-2-carbomethoxyaminobenzimidazole.

1 0. The composition of Claim 6 wherein the compound represented by Formula I is 5(6)-npropylsulfinyl-2-carbomethoxyaminobenzimidazole.

11. A method of controlling helminths in mammals which comprises parenterally administering an anthelmintically effective amount of a composition of Claim 1.

1 2. A method of controlling helminths in mammals which comprises injecting an anthelmintically effective amount of a composition of Claim 2.

1 3. A method of controlling helminths in mammals which comprises injecting an anthelmin tically effective amount of a composition of Claim 3.

1 4. A method of controlling helminths in mammals which comprises injecting an anthelmintically effective amount of a composition of Claim 4.

1 5. A method of controlling helminths in mammals which comprises injecting an anthelmintically effective amount of a composition of Claims 11, 12, 1 3 or 14 wherein said carrier is propylene glycol and said hydroxide is sodium hydroxide.

1 6. A process of preparing the injectable anthelmintic composition of Claim 1, which process comprises dissolving an alkali metal hydroxide and compound of Formula (i) wherein R, R1, R2, R3, R4, R5, RB, R7, RB, Y, M, M', and n are defined in Claim 1 in a physiologically acceptable lower alkylene glycol or a suitable oxygenated cyclic hydrocarbon derivative thereof and optionally adding additional suitable pharmaceutical excipients.

1 7. The process of Claim 1 6 wherein said alkylene glycol is propylene glycol and said hydroxide is sodium hydroxide.