AP15A - Process for combatting the protozoa responsible for illness of vertebrates and compositions intended for putting the process to work. - Google Patents

Process for combatting the protozoa responsible for illness of vertebrates and compositions intended for putting the process to work. Download PDF

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Publication number
AP15A
AP15A APAP/P/1986/000031A AP8600031A AP15A AP 15 A AP15 A AP 15A AP 8600031 A AP8600031 A AP 8600031A AP 15 A AP15 A AP 15A
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Prior art keywords
combatting
protozoa
pyrethrinoid
compositions
vertebrates
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APAP/P/1986/000031A
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AP8600031A0 (en
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Pierre Regis Corle
Alain Richard
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Roussel Uclaf
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N53/00—Biocides, pest repellants or attractants, or plant growth regulators containing cyclopropane carboxylic acids or derivatives thereof
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pest Control & Pesticides (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Emergency Medicine (AREA)
  • Agronomy & Crop Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Plant Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A process for combatting illnesses and endemics transmitted to living beings by protozoa. The process consists in applying a sufficient quantity of a compound of the pyrethrinoid type in the place where the protozoa are foundin order to prevent the development of protozoa. The invention is also concerned with compositions intended for putting the process into operation.

Description

Process for combatting the protozoa responsible for illnesses of vertebrates and compositions intended for putting the process to work.
Company named : Roussel-Uclaf
The present invention is concerned with a process for combatting the protozoa responsible for illness of vertebrates and in particular human and animal endemics, and compositions intended for use in this process.
The subject of the invention is a process for corpbatting the 5 endemics transmitted to living-beings by protozoa, characterized in that a sufficient quantity of a compound of pyrethrinoid type is used in the place where the protozoa are found in order to prevent the development of the protozoa.
By living being, there is intended man, mammals, fish and 10 birds.
As protozoa at which the present invention aims, there can be cited spirochetes, treponema, ameba, trypanosomes, hematozoa. particularly the hematozoa of malaria or plasmodium apd the leishmania.
The invention is therefore concerned with compositions intended for combatting very diverse illnesses, such as the spirochetoses, illnesses caused by treponemes, amebiases, malaria, trypanosomiases or leishmanoses.
The pyrethrinoid compounds aimed at by the invention are compounds known in a general way; they answer to the general formula CO^B in which :
BAD ORIGINAL
- 2 Ο Ο») j either A represents a radical
in which · '
- either Z^nd Z? each represent a methyl radical, 10 - or Zj represents a hydrogen atom and ‘ either Z? represents a radical llW: in which represents a hydrogen or halogen atom and either Tj and T2 identical or different, represent a hydrogen atom, a halogen ^tom, an alkSxyl radical, an alkyl radical containing from 1 to 8 carbon atoms, a CF^ or CH radical or a phenyl nucleus possibly substituted by a halogen, or together form a cycloalkyl radical containing from 3 to 6 carbon atoms or a radical :
AP 0 0 0 0 1 5 (V in which X represents an oxygen or sulphur atom : or represents a radical :
ax__ «/I in which a, b, c and d, identical or different, each represent a 35 halogen atom, or represents a radical :
BAD ORIGINAL ί < 1 u ‘J
I ' .
•J J L in which D represents a.hydrogen or halogen atom, or an alkoxyl radical, G represents an oxygen or sulphur atom and J represents
- either a linear, branched or cyclic alkyl radical, saturated or unsaturated, containing from 1 to 8 carbon atoms , possibly sub5 stituted by one or more functional groups.identical or different,
- or an aryl group containing from 6 to 14 carbon atoms, possibly substituted by one or more functional groups, identical or different,
- or a heterocyclic radical possibly substituted by one or more 10 functional groups, identical or different,
In which U, in any position on the benzene nucleus, halogen atom, an alkyl radical containing from 1 to or an alkoxyl radical containing from 1 to 8 carbon m represents the numeral 0, 1 or 2. * II - and B represents a group:* represents a 8 carbon atoms atoms ,
in which R^ represents a hydrogen atom, a methyl ethynyl or cyano radical and R^ and R3> identical or different, represent a hydrogen, fluorine or bromine atom.
The subject of the invention is quite particularly the compositions intended to destroy the pathogenic protozoa of vertebrates and invertebrates, or to limit their multiplaction.
As vector vertebrates, there can be cited man as well as mammals, notably cattle, sheep, pigs, goats and horses, birds like fowls, batrachians, reptiles, fish and the various aquatic species.
BAD ORIGINAL
GO
As invertebrate vectors, there can be cited the terrestrial and marine arthropods, notably the acarina, the insects, the molluscs, notably the gasteropods and the worms.
As insect vectors, there can be cited mosquitoes, flies, bugs, fleas and lice.
The combat process of the invention, in the case where the proto>oa combatted are carried by arthropods and notably by insects, is particularly interesting from an economic and ecologic view-point; it is possible to use doses of pyrethrinoids lower than the lethal doses for the arthropod vectors. The treatments can be applied in the development areas of these animals, differing from those of their vertebral hosts ( e.g., water-mosquito); these treatments are easier and cost less than those aimed at suppressing the insect vectors. Furthermore, by not suppressing the arthropod totally, the equilibrium of the natural surroundings is better respected.
Quite specially, the subject of the invention is a combat process characterized in that the protozoa are destroyed which are carried by the insects.
Therefore the invention has as its subject a combat process 20 as defined above, characterized in that a compound of pyrethrinoid type is used at a dose less than the lethal dose of the insect vectors.
Quite specially, the subject of the invention is a combat process characterized in that the insect vectors are anopheles.
As.anophejes more specially aimed at by the invention, there can be cited ’
- Anopheles gambiae, Anopheles moucheti, Anopheles funestus, Anopheles hancocki, Anopheles paludis. Anopheles nili, Anopheles littoralis, Anopheles aeonitus, Anopheles flav!rostris, Anopheles r - - - . r - · - · 30 mangyanus, Anopheles stephensi, etc.....
More particularly, the subject of the invention is a process of combat characterized in that the.protozoa combatted are the Plasmodia,, such for example, as Plasmodium’falciparum, Plasmodium malariae, Plasmodium vivax, Plasmodium ovale or Plasmodium yoelii.
The fight against malaria is of very great interest; even in our days malaria is one of the great scurges of tpe modern
AP 0 0 0 0 1 5
BAD ORIGINAL ft
- 5 world, which makes ravages in very numerous countries,notably in Africa, for example in Nigeria, in Upper Volta, in the Cameroons, in the Congo, in Kenya or in Ethiopia, in Latin America, particularly in Venezuela and in Guatemala, or in
South-East Asia; there are at present reckoned to be about 1 million children killed in the world by malaria each'year.
TThe invention has more particularly as its subject a process characterized in that the pyrethrinoid utilized is deltamethrin; it also has as its subject a process Characterized in that the pyrethrinoid is chosen from the group of photostable or photolabile byrethrins constituted by tralomethrin, cypermethrin, permethrin, alphamethrin, cyfluthrin, cyhalothrin, fenfluthrin, fencythrin, and fenvalerate.
To combat protozoa in an aqueous environment, according to *15 the invention process, compositions containing the pyrethrinoid are spread in the zone where the arthropod vectors of the protozoa are found on and in marshes, lakes, pools of water, canals, rivers, in forests and savannas. To combat the protozoa in the habitation premises of human beings or animals, the compositions according to the invention are spread by treatment of surfaces, walls, roofs, mosquito nets, etc. _
The compositions according to the invention are-spread by aeroplane, by soil treatment (liquid or powdering treatment), on the vertebrates to be protected and in the premises frequented by man and the vertebrates to be protected, 'in residual or atmospheric treatment on the various'supports of habitations.
The invention has also as Its subject a combatting process characterized inthat a sufficient quantity of compound of pyrethrinoid type is administered directly to the living beings in order to prevent the development 'of the parasitic protozoa.
In this particular combatting process, the compounds of the pyrethrinoid type can advantageously be incorporated in the drinks or foodstuffs to be consumed.
When it is a matter*of combatting'the parasitic protozoa 35 of vertebrates, the compositions of the Invention can be incorporated in the*-Jrinking water or In the food compositiqns combined
- 6 mixture can vary according to the animal species, it can contain cereals, sugars and seeds, soya, ground-nut and sunflower cakes, meals of animal origin, for example fish-meals, synthetic amino acids, mineral salts, vitamins and anti-oxidants.
Quite naturally, the subject of the invention is compositions intended for putting the above process into operation; these compositions are characterized in that they contain a sufficient quantity of pyrethrinoid to prevent the development of the protozoa.
. Because the protozoa are notably carried by insects, the invention has particularly as its subject compositions characterized in that they contain a compound of pyrethrinoid type at a dose less than the lethal dose of the vector insects.
Quite specially, the subject of the invention is compositions characterized in that the pyrethrinoid utilized is deltamethrin; it also has as its subject compositions characterized in that the pyrethrinoid utilized is chosen from the following group of compounds : tralomethrin, cypermethrin, permethrin, alphamethrin, cyfluthrin, cyhalothrin, fen’fluthrin, fencythrin and fenvalerate.
The invention compositions intended for the treatment of premises preferably contain from 0.05 mg/1. to 1 g/ml. of pyrethrinoid; among the preferred compositions, there can quite specially be cited compositions containing from 0.25 to 5 mg/litre of deltamethrin.
These compositions are prepared according to the usual processes of the agrochemical or agro-alimentary industry. They can ’also have added to them one or more other pesticidal agents. These compositions can be presented in the form of powders, granules, suspensions, emulsions, solutions, solutions for aerosols, combustible strips, and baits.
In addition to the active principle, these compositions in general contain a vehicle and/or a non-ionic surface-active agent which furthermore ensures a uniform dispersion of the substances of which the mixture is made up. The vehicle utilized can be a liquid such as water, alcohol, a hydrocarbon or other organic solvent, a mineral, animal or vegetable oil, a powder such as
AP 0 0 0 0 1 5
- 7 The following examples illustrate the invention, without nevertheless limiting it.
Example 1 : Composition intended for treatment of marshes.
- Deltamethrio.............................
- Piperonyl butoxide.......................
- Tween 80 ................................
- Topanol A.......·.'.......................
- Xylene ..................................
0.1 g g
0.25 g
0.1 g
q.s. for 1 litre.
Example 2 : Composition intended for treatment of premises.
- Oeltamethrin ............................ 5 mg
- Vercoryl S .............................. 899 g
- Topanol A ............................... 16 g
- Emcol .................................. 35 g ί-
Example 3 ; Experimentation in vitro on cultures of Plasmodium falciparium.
The culture is carried out in polystyrene cupules for tissue culture placed in an oven at 37° with CO2 (6%), utilizing a modified RPMI 1640 medium.
Each cupule contains 0.7 ml. of parasited human blood
I ' suspension (starting level of parasitemia : 0.3 %). The * incubation is continued for 48 hours without renewing the medium.
The anti-plasmodium products to be tested are added before incubation in the survival medium.
The reading of the results is carried out on smears after specific'colouring with MGG and counting the number of parasited red blood corpuscles. The counts are referred to about 3,000 red blood corpuscles per cupule. The products to be tested are introduced into 3 cupules per concentration studied. ;'
The results obtained are summarized in table 1|
The parasited red blood corpuscles contain either trophozoites (juvenile form), or schizontes juvenile or old, or merozoites (in rosettes), all forms of the plasmodium. ...
The conclusion that can be drawn is that a marked activity on the development of the plasmodium is produced with a dose of 0.75 ug/ml. ———
BAD ORIGINAL ft .< 1
- 8 TABLE 1
Product I Concentra- tion (in pg/ml) * No. of corpuscles counted No. of j . Level of Level of paracorpuscles » corpuscles . sitemia in parasited j parasited · comparison 1 (in %) with the ; control (%)
Idelmethrin in aqueous formulation - 0.750 ! t 9,400 : 118 ! 126 42
at 25 g/1.
Example 4 : Effect of the pyrethrinoids on the sporogonic cycle in anopheles.
The model chosen was the couple A. stephensi- P.y.yoelii of ί ·»-- - -- Γ nhich the cycle can be easily maintained on white mice.
Plasmodium yoelii yoeiii.
Plasmodium of rodents, P.y.yoelii originates from centra Africa.
- Maintenance of the cycle of P.y.yoelii.
The maintenance of the strain on white mice OF 1 was carried out by intravenous inoculation of sporozoites obtained according to the following record :
- After verification on a sample that 75 - 80 % of the anopheles females in a cage were carriers of sporozoites in their salivary glands, 120 to 150 females were killed, then coarsely dissected .so as to keep only the head and the thorax. .. /.,..,
- These latter were put in a Thomas pot containing 4 ml. of RMP1 1640 maintained at 4°.C, then finely ground.
- The result obtained was centrifuged first at 1500 rpm, (800 a) for 5 minutes.
- 2 ml. of the supernatant was recovered with syringes, the remainder was centrifuged again for 5 minutes at 1500 rpm, and 1 ml. was recovered from the supernatant.
- After verification of the presence of sporozoites, 0.5 ml. of the supernatant was inoculated intravenously per mouse, i.e., a total of 4 to 6 mice according to the results of the second centrifuging. ----—
APOOOO 1 5
BAD ORIGINAL ft
- 9 υύΰ 3 i
From one donor mouse, on which it had previously been verified that the parasitemia extended to at least 40% of the red blood corpuscles, .1 ml. of blood was removed by puncture of the retro-orbital sinus by means of a heparinated Pasteur pipette. This blood was mixed In a watch glass with 1 ml. of RPMI 640 to which a drop of heparin was added. Then, by intraperi toneal route, 0.2 to 0.5 ml of this mixture was inoculated per mouse.
This method of infecting mice has the disadvantage of increasing the virulence of the plasmodial strain on each new passage, and above all, of making it progressively lose its capacity to produce infectious gametocytes. The donor mice are uniquely the mice infected from the start with sporozoites.
The infectivity of the mice wes verified on blood smears from the 3rd day after the inoculation. The criteria considered are : presence of immature gametocytes and of microgametes of stage 0 and 1, absence of degenerate gametocytes of which the cytoplasm is sprinkled with little round vacuoles.
The mice recognized as infectious were imprisoned in a flexible netting and put into a cage containing about 150 female anopheles aged at least one week. I
Evaluation of the action-of deltamethrin put into the breeding water of mosquito larvae on the development of the Plasmodium sporozoites in adult mosquitoes. '
The impregnation with deltamethrin at DL50 or at lower doses was carriecUout on mosquito larvae not yet infectious while being reared in water. ' The surviving adults were then put on to mice infected with plasmodium to feed on blood. ' ‘
Because the complete evolution of the sporogonic cycle of the plasmodium cannot be judged on the presence of oocysts in the stomach of the adult, the experimentation is continued by evaluating the effect of deltamethrin on the percentage of mosquitoes carrying sporozoites in the salivary glands. The dissections were carried out 14 days after feeding on blood.
All of the results are shown in the following table :
Series a
2.10'4mg/l. (DL50 of the
Deltamethrin dose used mosquito larvae).
The control group was infected first.
BAD ORIGINAL
None of the 19 mosquitoes dissected in the treated group was a carrier.of sporozoites, while in the control group, 14 out of 20 were carriers. On the evidence, the'difference is very significant.
Series b : *Deltamethrin dose used ; 2.10^mg/I. (DL5O of the mosquito larvae).
The control group was infected first.
Here also, no mosquito was found to be a carrier of sporozoites in the treated group (0/42), while more than 50% of the mosquitoes were carriers in the control group (16/31).
On the evidence, the difference is very significant.
CONCLUSION :
The complete sporogonic cycle cannot take place in insects which have been in contact kith deltamethrin.
AP 0 0 0 0 1 5 \
ϋΰ'υ j *>
TABLE : Distribution the mosquitoes carrying sporozoites in the salivary glands, according to the control groups and the groups treated with deltamethrin.
Series 1 _ Dose r-—————— , Group i Negative : 1 Positive Effective
i 1 ‘ Control 6 1 1 14 20
a 2.10~^mg/l. treated I 19 ΐ 1 0 19
1 1 Control 15 ΐ 16 31
b 2. lO'^mg/l. treated t 42 : 0 42
Example 5 :
An experiment similar to that of example 4 was carried out on Anopheles in a larval state, using a deltamethrin dose less than
2,510 mg/1. J
It was again determined that the complete sporogonic cycle could not be realized in adult insects which had been put into larval contact with deltamethrin.
Example 6 :
The experiment as in example 4 was carried out on Anopheles in the adult state, put into contact with a glass support treated with a sub-lethal dose of deltamethrin of 2,510 mg/1. It was again determined that the complete sporogonic cycle could not be realized in insects which had been put into contact with delta30 methrin.

Claims (2)

1. Process for combatting endemics transmitted to living beings by protozoa, characterized in that from 0,05 mg/€ to 1 g/€ of a compound of pyrethrinoid type is applied where the protozoa are found.
2. Process for combatting according to claim 1, characterized in that the pathogenic protozoa of vertebrates and invertebrates are destroyed or their multiplication is limited.
3. Process for combatting according to cla im 2, charac terized in that the protozoa are carried by inse cts. 4 . Process according to claim 3 c'r aracter ' i s ad. in tha t the vector insec ts are anopheles. 5. Process for combatting according to any one of the claims 1 to 4 characterized in that t .he protozoa comtatt ed ar e plas- modia. , 6. Process for combatting according to any one of the claims 1 to 5, characterized in tha t the pyre' ihrinoid utilized is deltamethrin. 7. Process for combatting according to any one o f the claims
. ·
AP 0 0 0 0 1 5
1 to 5, characterized in that the pyrethrinoid is chosen from the following group of compounds : tralomethrin, cypermethrin, permethrin, alphamethrin, cyfluthrin, cyhalothrin, fenfluthrin, fencythrin and fenvalerate.
8. Process for combatting according to any one of the claims 1 to 7, characterized in that the compound of the pyrethrinoid type is administered directly, to the living beings.
BAD ORIGiNAL Λ
13 9. Compositions for combatting endemics transmitted to living beings by protozoa, characterized in that they contain from 0,05 mg/2 to 1 g/I of a compound of pyrethrinoid type.
10. Compositions according to claim 9, characterized in that the pyrethrinoid utilized 'is del tame thrin. 11. Compositions according to claim 9 or 10, characte rized in that ·. the pyrethrinoid utilized is chosen from the fo 1lowing group of compounds tralome thrin, cypermethrin, pe r Γΰ e ~ c r I n»
alphamethrin, cyfluthrin, cyhalothrin, fenfluthrin, fencythrin and fenvalerate.
APAP/P/1986/000031A 1985-04-03 1986-03-26 Process for combatting the protozoa responsible for illness of vertebrates and compositions intended for putting the process to work. AP15A (en)

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FR8505053A FR2579867B1 (en) 1985-04-03 1985-04-03

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AP15A true AP15A (en) 1988-03-11

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AP (1) AP15A (en)
BR (1) BR8601509A (en)
FR (1) FR2579867B1 (en)
GB (1) GB2175502B (en)
OA (1) OA08274A (en)
PH (1) PH24218A (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9105694D0 (en) * 1991-03-18 1991-05-01 Hand Peter Animal Health Control of sea lice in salmon
JP3506511B2 (en) 1993-12-27 2004-03-15 三井化学株式会社 Anthelmintic
DE102004044428A1 (en) * 2004-09-14 2006-03-30 Toximed Gmbh Process and pharmaceutical agent for the control of plasmodia
MX2010002656A (en) * 2007-09-07 2010-05-20 Mevlabs Inc Formulations and devices for delivering compounds to arthropods and microorganisms within arthopods.

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0121363A2 (en) * 1983-03-31 1984-10-10 T And R Chemicals, Inc. Pyrethroid-containing pharmaceutical compositions

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2341307A1 (en) * 1976-02-19 1977-09-16 Roussel Uclaf PYRETHRINOIDS FOR MEDICINAL PRODUCTS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
US4078080A (en) * 1976-12-13 1978-03-07 American Cyanamid Company Oral administration of pyrethroids to warm-blooded animals to prevent fly development in their droppings
GB2088212B (en) * 1980-11-21 1985-12-04 Wellcome Found Pest control
GB2106390A (en) * 1981-08-27 1983-04-13 Ici Plc Combating soil-dwelling insect pests
DE3364135D1 (en) * 1982-04-05 1986-07-24 Ici Plc Method for combating insect pests, and novel cyclopropane carboxylates useful as active ingredients therein

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0121363A2 (en) * 1983-03-31 1984-10-10 T And R Chemicals, Inc. Pyrethroid-containing pharmaceutical compositions

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GB2175502A (en) 1986-12-03
PH24218A (en) 1990-04-10
AP8600031A0 (en) 1986-02-01
FR2579867B1 (en) 1989-02-24
FR2579867A1 (en) 1986-10-10
OA08274A (en) 1987-10-30
GB2175502B (en) 1989-07-05
BR8601509A (en) 1986-12-09

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