US2097115A - Parasiticide - Google Patents

Description

Patented Oct. 26; 1937 PARASITICIDE Lewis W. Butz, Chalfont, and William A. La Lande, Jr., Philadelphia, Pa., assignors to Dr. D. Jayne & Son, Inc., Wilmington, Del., a corporation of Delaware No Drawing. Application June 13, 1935, Serial No. 26,522

2 Claims.

This invention relates to parasiticides, more particularly to new and improved compositions adapted to effect the removal of internal animal parasites from host animals, including man. Animal parasites" is here defined as all parasitic organisms exclusive of plants and bacteria.

It is known that amebas, worms and other protozoa and metazoa infest the gastro-intestinal tract as well as other sites in the body. Numerous preparations designed to kill or eliminate such parasites have been proposed, these being known as amebicides,- anthelmintics, or in general, parasiticides. A number of such preparations have met with success, but they have been highly specific in their action in the sense that only a limited group or even only one species in a group of parasites is affected. Moreover most of these have been shown to be highly toxic to the host. Probably two of the best known remedies heretofore used are oil of chenopodium (active component, ascaridole) and tetrachlorethylene.

The term vermicide is used in the claims to designate the compositions and the remedial effects contemplated by this invention and referred to in this application. The term vermicide is used in its accepted meaning and can be defined as an anthelmintic drug or medicine destructive to intestinal animal parasites. Such parasites, specifically, are those referred to above and include but are not limited to those mentioned specifically in the description of this application.

With a' view to advancing the development of the art of parasiticides, researches have been conducted resulting in the inventions and discoveries set forth in the following specification. It is an object of the invention to provide new and improved antiparasitic compounds. One improvement in view is that new remedies shall be less specific in their application than those hitherto proposed. Since the parasites envisaged in this invention exist in environments practically free of oxygen and are harmfully affected by oxygen in certain active forms,-the desired generality of the drug efiect is aimed to beaccomplished by the application of remedies supplying oxygen in suitable form and amount. The invention, then, has for its further objects the use of new and improved antiparasitic compounds containing oxygen in such suitable form, and particularly ozonized organic compounds or mixtures containing these.

The compounds found to be particularly useful according to the present invention are organic ozonides, which term is to be understood to include the products obtained by passing ozone into organic compounds or mixtures containing such compounds. This class is understood to comprise all products obtained by ozonizing or ganic compounds containing double or triple bonds between carbon atoms and in addition a product obtained by ozonizing mixtures containing such compounds such as mineral, vegetable and animal oils.

The use of oil of chenopodium has been established as an efficient antiparasitic remedy in infestations of human beings and lower animals. The remedial effect of this oil has been shown to be due to the organic peroxide, ascaridole, which it contains.

It is probable that the therapeutic effect of ascaridole is due, in part at least, to the peroxide group which it contains. This compound however contains other important groupings; namely, the olefin linkage and the para-menthene structure. Possibly because of these latter structural units this peroxide is quite toxic for human beings and lower animals. The use of chenopodium oil is unsafe in view of its high toxicity when administered in doses sufliciently large and frequent to produce its anti-parasitic effect. This invention has for one of its objects the therapeutic use of ozonized organic materials as suitable sources of oxygen in active form. We have studied a number of ozonides as anthelmintics,

These materials were tested upon Ascaris lumbricoz'des in beaker tests and upon dogs infested with Torocara cams. Ascaris Zumbrzcoides was killed by the following: ozonized olive oil, ozonized cottonseed oil,ozonized ethyl oleate,ozonized oleic acid, ozonized geranyl acetate, andozonized methylheptenone. assay with Ascaris lumb'ricoides is as follows:

Bioassa'J The efiect of the anthelmintic activity toward A typical example of a bio- 45 Ascaris lumbrz'coz'des was determined by immer- 50 sion of vigorous specimens in a solution or emulsion of the substance being tested. The apparatus was-a rectangular aquarium with glass windows which was filled with 'water and served as a constant temperature bath. The temperature was maintained between 37 C. and 38 C. The aquarium was provided with a metal cover containing holes which supported 400 cc. beakers. Five worms were placed in each beaker which contained 300 cc. of solution or emulsion. The worms were 22-24 cm. in length and weighed 2.0-2.35 gms. They were A. lumbricoides obtained from the intestines of swine. Observation was made after the immersion of the number of minutes required to produce cessation of movement, paralysis and death and were conducted at hourly intervals for a period of five hours.

To illustrate the 'results obtained in canine Ascarzasz's data are here given for ozonized cottonseed oil and ozonized olive oil.

The therapeutic experiments with dogs were conducted as follows: Dogs infested with Toxocam cam's were observed over a period of seven toten days during which time the rate of elimination of worms was determined. The ozonides were then administered in gelatin capsules and the animals observed for varying periods of time and finally sacrificed. The number of worms passed after treatment and the number found at autopsy were recorded. In this way data. shown in the following tables was secured describing (l) the percentage of worms present which were removed by treatment in a large number of dogs, and (2) the rate of elimination of worms before and after treatment. In all experiments the animals received only one dose of ozonide without any solvent and without administration of any other medicaments such as laxatives.

TABLE I Percentage of worms removed Dose 33 Worms Worms Percent Drug mm presrere- (glkg) mals ent moved moved Ozonized cottonseed oiL- 0. 2 2 29 28 96 7 In 8 out of 9 dogs 100 percent of the worms were removed.

TABLE II Rate of elimination of worms before and after treatment with ozonized cottonseed oil Rate elimi- Dose Cure natcd (worms/ of 233222 ehml' 1 Dog No.

(gJ gJ Percent Before After Before After gg Experiments have been conducted to assure that effective doses of ozonized cottonseed oil, ozonized olive oil and ozonized ethyl oleate can be tolerated by the infested animals. The lowest doses given were 0.2 and 0.5 g./kg. and these were therapeutically efiective (Table I). Dogs which received 5.0 g./kg. showed no symptoms of .intoxication whatever, even when the dose was thrice repeated. The therapeutic index of ozonized cottonseed oil is therefore at least 5.0/0.2 or 25.0. In control experiments the same index for chenopodium oil was shown to be 8.0, and the animals were visibly poisoned by even smaller I LEWIS W. BUTZ. WILLIAM A. LA LANDE, JR.