CH630228A5 - Ectoparasiticides based on polyols - Google Patents

Description

The present invention relates to new insecticides based on poylols, and in particular on diols whose hydroxy groups are not neighboring; it includes the application of these products to the destruction of ectoparasites, such as lice and mites.

Currently, there are only a relatively small number of ectoparasiticides on the market. The most widely used pediculicides are Lindane (y-hexachlorobenzene), Malathion [0,0-dimethyl dithiophosphate and S-bis (ethoxycarbonyl) -l, 2 ethyl], pyrethrins in synergy and Cupres (a combination of tetrahydronaphthalene, copper oleate and acetone, which it is not known if acetone is active). The best known agents for treating scabies are sulfur, Lindane, benzyl benzoate and Crotamiton, i.e., N-ethyl N- (o-methylphenyl) butene-2 amide. Due to the growing interest in the safety of certain known ectoparasitici-known, research has recently focused on new active and safe products.

The present invention is based on the observation that certain polyols exhibit ovicidal, acaricidal and, in certain cases, pediculicidal activity. Although these products are already known, their insecticidal and / or ovicidal activity was not. However, 2-ethylhexane-1,3-diol is well known as an insect repellant (US Patent Nos. 2407205 and 3836672) and widely used as such.

The new compositions according to the invention contain, as constituents, certain diols, the hydroxyl groups of which are not neighboring. Particularly suitable are 1,3-diols, for example: 2,4-methyl-2,4-pentanediol; 2-ethylhexanediol-1,3; butanediol-1,3; heptanediol-1,3, and nonanediol-1,3.

One or more polyols according to the invention can be incorporated into an insecticidal composition, which can be in the form of a liquid, powder, lotion, cream, gel, aerosol spray or foam, depending on the inert support. pharmaceutically acceptable, and be obtained by procedures well known to those skilled in the art. Any pharmaceutically acceptable support, aqueous or nonaqueous, inert with respect to the active ingredient, may be suitable. By inert is meant that this support does not exert a marked harmful action on the insecticide, acaricide or ovicide activity of the active constituent.

The active polyol is incorporated in an effective amount into the toxic composition, intended for the substratum (man, animal or object) in need, or which it is believed to require such treatment, or which it is desired to protect prophylactically. By effective amount is meant an amount which causes the death of at least 50% of ectoparasites or their eggs. For lice and their eggs, the classic 2-minute immersion tests are described below. The minimum concentration of polyol required in the composition, for it to be effectively toxic, varies considerably depending on the polyol chosen, the inert pharmaceutically acceptable carrier used and the other constituents present. Thus, in one case, a concentration of 10% may be sufficient, while in other cases, concentrations up to 30 to 40% are required.

The 2 min immersion test, discussed above, is as follows.

Pediculicidal activity: A 50 ml beaker is filled with tap water and the ambient temperature is allowed to settle there, generally around 24 ° C. 10 young male lice, adults, and 10 young female lice, adults ( Pediculus humanis corporis) of the same age group and from the same colony, are placed on a piece of coarse mesh fabric of 2 x 2 cm. The test sample, kept at room temperature, is shaken until homogeneous and placed in a 50 ml beaker. The piece of cloth is immediately placed there, it is left to sink into it and, 2 minutes later, it is removed and immediately immersed in the beaker containing tap water; it is vigorously stirred there every 10 s and, after 1 min, it is taken out and placed on blotting paper. The pomes are then transferred to a piece of black corduroy of 4 x 4 cm, and we consider this moment as the zero moment. Then put the piece of velvet in a Petri dish which is covered and stored in a place at 30 ° C.

Ovicidal activity: 15 adult, female lice, aged 5 to 10 d (Pediculus humanis corporis), are placed on a piece of nylon mesh of 2 x 2 cm which is placed in a covered petri dish and kept for 24 h in an incubator at 30 ° C. The adult lice are then removed, and the number of well-formed, viable eggs and wrinkled, infertile eggs are recorded on the piece of tissue. The sample to be tested, kept at room temperature, is shaken until homogeneous and poured into a 50 ml beaker. Immediately afterwards, the piece is placed there and left to immerse; after 2 min, it is removed and immediately immersed in a beaker containing tap water at room temperature (24 ° C). The piece of mesh is vigorously agitated every 10 s and, after 1 min, it is removed and placed on blotting paper for 1 min. It is then placed in a petri dish which is covered and stored in an incubator at 30 ° C. 14 after this treatment, note the number of eggs hatched and the number of wrinkled or unhatched eggs.

In these two 2 min immersion tests, controls are carried out in an identical manner with replacement of the sample to be tested with tap water at room temperature (24 ° C). The results of these two reported trials are overall results.

The polyols, used according to the invention, can be incorporated as additives in a preparation which by itself exhibits insecticidal and / or ovicidal activity. In these preparations, the term effective dose is understood to mean the quantity which increases the mortality rate by at least 20% in the 2 min immersion tests concerning the same composition without polyol.

In Table 1 are reported the pediculicidal activity and the ovicidal activity of several polyols, tested in the undiluted form, in the 2 min immersion test.

5

10

15

20

25

30

35

40

45

50

55

60

65

Table 1

Polyol

Mortality (%)

Ovicide

Pediculicide

2,4-methyl-2,4-pentanediol

100

0

Ethyl-2 hexanediol-1,3

100

100

Sorbitol (70% solution)

10

-

Ethanediol-1,2

35

0

Propanediol-1,2

14

0

Butanediol-1,3

100

10

Heptanediol-1,3

100

82

Nonanediol-1,3

100

47

It should be noted that, according to this table, the polyols are excellent ovicides. 2-ethyl hexanediol is also an excellent pediculicide. It is further noted, with surprise, that methyl pentanediol, although not pediculicidal in pure form, communicates pediculicidal activity to compositions which do not themselves exhibit such activity, for example aqueous solutions of aliphatic alcohols or aliphatic esters. This fact emerges from the data presented below. In addition, it was observed that the polyols according to the invention were active on the rabbit ear mite, an in vitro substitute for the sarcoptic mite for testing toxic products. Therefore, these diols can be used to prepare compositions which are both ovicidal and acaricidal and, in the case of ethylhexanediol, also pediculicidal.

Table 2 shows the results of the tests concerning three polyols at a concentration of 15%, in combination with 25% isopropanol and 60% water. By way of comparison, it should be noted that the combination of 25% isopropanol and 75% water gives, in the same test, 0% pediculicidal activity.

Table 2

Polyol

Mortality (%)

Ovicide

Pediculicide

2,4-methyl-2,4-pentanediol

59

15

Ethyl-2 hexanediol-1,3

17

70

Butanediol-1,3

44

5

In Table 3 are collected the results of the 2 min immersion test for the ovicidal and pediculicidal activities of the three compounds at a concentration of 25%, in combination with 15% isopropyl myristate and 60% water . By way of comparison, it is noted that 15% of isopropyl myristate, emulsified in 85% of water, have 0% of pediculicidal activity.

Table 3

Polyol

Mortality (%)

Ovicide •

Pediculicide

2,4-methyl-2,4-pentanediol

34

95

Ethyl-2 hexanediol-1,3

44

100

Butanediol-1,3

100

0

The ovicidal activity (2 min immersion test) of 2-ethylhexanediol-1,3 as a function of its concentration is determined in a composition which also contains 25% (w / w) of isopropanol and water in addition to 100%. The results are shown in Table 4.

630228

Table 4

Concentration (% w / w)

Mortality (% of eggs)

5

9.4

10

9.7

15

17

20

66

30

100

40

100

Table 5 shows the results of the immersion test with regard to the ovicidal activity of five polyols as a function of their concentration in water (weight / weight).

Table 5

2,4-methyl-2,4-pentanediol (%)

Mortality (% of eggs)

100

100

90

68

80

74

70

52

60

39

50

71

40

66

30

53

20

52

10

36

Ethyl-2 hexanediol-1,3 (%)

Mortality (% of eggs)

60

100

50

100

40

42

30

43

20

46

10

63

Butanediol-1,3 (%)

Mortality (% of eggs)

100

100

90

94

80

85

70

90

60

100

50

94

40

86

30

76

20

59

10

21

Butanediol-1,3 (%) Mortality (% of eggs)

10 21

Heptanediol-1,3,% in

25% isopropanol and water Mortality (% of eggs)

in addition to 100%

50

100

40

100

30

100

20

9.4

10

12.2

3

5

10

15

20

25

30

35

40

45

50

55

60

65

630228

4

Nonadiol-1,3,% in 25% isopropanol and water in addition to 100%

Mortality (% of eggs)

50

100

40

100

30

100

20

100

10

97

The acaricidal activity of the polyols used in accordance with the invention is determined as follows. In a room of about 28 dm3, maintained at room temperature, a hollow microscope slide, covered, containing 10 adult mites of mixed sexes, Psoroptes equi var. cuniculi. The coverslip is placed, uncovered, at a distance of 25.4 cm horizontally and approximately 10 cm below the nozzle of a mechanical spraying device. The spraying device, with pump, delivers 50 (jg of sample per stroke of the nozzle. The sample to be tested, maintained at room temperature, is shaken until homogenized, then placed in the above-mentioned device. The nozzle primed is depressed twice, releasing 100 fig. of spray mist into the closed chamber. This mist is allowed to settle, and the coverslip containing the mites is removed and covered. This moment is considered as zero hour. The covered coverslip is then kept at room temperature for 24 h. Microscopic examinations are carried out 0.1, 3 and 24 h after treatment. The procedure is carried out identically for the controls, using water or dilution, and the overall mortality results are reported.

Table 6 shows the acaricidal activity of poylols at a concentration of 50% (w / w) in water (W) or isopropanol (I).

Table 6

20

30

Polyol

Mortality (%) (mites)

Butanediol-1,3

100 (W)

2,4-methyl-2,4-pentanediol

90 (W)

Ethyl-2 hexanediol-1,3

100 (1)

Heptanediol-1,3

100 (1)

Nonanediol-1,3

100 (I)

Some examples of characteristic compositions, for various uses, containing the polyols according to the invention are given below.

Clear solution, pediculicide, ovicide and acaricide for application by mechanical spray or anointing

Ethyl-2 hexanediol-1,3 75

Isopropanol 25

Clear, ovicidal liquid shampoo

Butanediol-1,3 50

Lauryl sulfate and triethanolamine 20

Water 30

Quick-release ovicidal aerosol foam

Mono and diglycerides of edible fats 8

Isopropanol 25

Nonanediol-1,3 20 Propanetriol-1,3 5

Water 34 Isobutane 8

Ovicidal aerosol spray

2-methyl-2,4-pentanediol 50

Isopropanol 25

Water 10

Isobutane 15

Ovicidal cream

Cetyl alcohol 3

2-Ethyl-1,3-hexanediol 30 Glyceryl monostearate 8 Sorbitan monostearate 8 Xanthan gum 0.3

Water 50.7

35

It is understood that the detailed description and the specific examples indicating preferred embodiments of the invention are given only by way of illustration; various changes and 40 possible modifications will appear to those skilled in the art from this detailed description, without departing from the scope of the invention.

R

Claims (9)

630228 1. Ectoparasiticide composition based on diols, applicable to humans and animals, characterized in that it contains, to combat mites, as active ingredient or as active constituent additional to another active principle, at least one diol of which the two hydroxyls are not in neighboring positions and which is chosen from 2-methyl-2,4-pentanediol, 1,3-butanediol, 1,3-heptanediol and 1,3-nonanediol. 2. Composition according to claim 1, characterized in that it contains, for combating lice and their eggs, heptanediol-1,3 or nonanediol-1,3. 2 3. Composition according to one of claims 1 or 2, characterized in that it also contains a pharmaceutically acceptable carrier. 4. Composition according to claim 3, characterized in that the support is an aqueous support. 5. Composition according to Claims 1 and 3, characterized in that the diol is 2-methyl-2,4-pentanediol, and that the support contains isopropyl myristate. 6. Composition according to claim 5, characterized in that the isopropyl myristate is present at a concentration of 15% by weight. j 7. Method for combating ectoparasites in humans and animals, characterized in that an acaricidal composition according to claim 1 is applied thereto. 8. Method according to claim 7, characterized in that there is applied a pediculicidal and ovicidal composition according to claim 2. 9. Method according to one of claims 7 or 8, characterized in that a composition is applied in the form of shampoo.