HU182802B - Fotostabil delousing (insecticide) composition containing synthetic piretroides - Google Patents

Abstract

The invention relates to a Laeusevernichtungsmittel with synergistic effect. The agent according to the invention contains 0.1-5.0% of photostable pyrethroids, preferably permethrin, decamethrin and / or fenvalerate. As synergistic substances the agent contains 0.2-10.0% vegetable oils and / or 0.6-60.0% cationic or nonionic detergent, as solvent 25-80% lower alkanols and optionally 13-40% distilled water. Also fragrances can be used. As vegetable oil, castor oil is preferred, as a detergent, preferably, sterogenol (cetylpyridinium bromide) is included. The agent according to the invention is used like a hair tonic and does not need to be washed off afterwards. As a result, its effect is very durable.

Description

FIELD OF THE INVENTION The present invention relates to a lichen erosion composition comprising synthetic pyrethroids. The active ingredient is 0.1-0.5% by weight of photostable synthetic pyridine, 0.2-10.0% by weight of castor oil as synergist and 0.1-0.5% by weight of cetylpyridinium bromide as solvent.

It contains from 99.6 to 80.0% by weight of an organic solvent-water mixture and, if desired, from 0.1 to 1.0% by weight of a fragrance.

The compositions of the present invention do not exhibit eye and skin irritation over conventional compositions and have an antifungal activity over known compositions.

It is known that insecticidal compounds, due to their low toxicity to mammals and their good biodegradation, are known as the herbicides produced by extraction of herbal drugs. pyrethrum extracts were the focus of interest. In addition to its safe use, this natural active ingredient mixture (pyrethrin and pyrethrin analogs, commonly known as pyrethroid generic) has a broad spectrum insecticidal and fast deactivating action, but the active components of the active ingredient mixture are degraded by light, air and heat. Therefore, there is only a limited scope for their use. (J. Science of Food and Agriculture Vol. 13, 260, 1962; J. E. Casida, "Pyretrum the Natural Insecticide", Academic Press, N. Y. London 1973).

To overcome these difficulties, many compounds structurally similar to natural pyrethroids have been prepared to produce derivatives which are less or not degraded in the air or by heat or light, while retaining the beneficial biological properties. These compounds include, e.g. permethrin ((2,2-dimethyl-3- (2,2-dichloro-vinyl) -cyclopropanecarboxylic acid - metaphenoxybenzyl alcohol ester), decamethrin (2,2-dimethyl (-3- (2,2-dibromovinyl) cyclopropanecarboxylic acid - metafenoxy-benzyl alcohol) Cyano (3-phenoxy-phenyl) -methyl ester of 3-methyl-2- (4-chloro-phenyl) -butyric acid, phenvalerate ("Synthetic pyrethroids", M. Elliot, ÁCS Sym. Elliot et al., J. Chem. Soc. Perkin 1, 24 70, 1974; Pestic. Sci. 6, 537, 1975;

In the case of synthetic pyrethroids (eg permethrin) the insecticidal activity is generally satisfactory but the articulating effect is poor.

No. 27 04 066 According to the disclosure document of the Federal Republic of Germany, permethrin-containing preparations can also be used as a lice suppressant. The lice dressing composition of the present invention comprises permethrin as active ingredient and synthetic and vegetable pyrethroids as the synergist. Synthetic pyrethroid type synergist

3.4.5.6-Tetrahydrophthalimidomethyl chrysanthemate, pyrethroid extract of natural origin is used as plant pyrethrum extract. The synergists used, due to their good articulating effect, enhance the needle action of permethrin. The solvent used is petroleum extract or alcohol, optionally an emulsifier. The use of the antifungal composition according to the invention is extremely limited because one of the components (natural pyrethroids) used as a synergist is degraded by light, heat and air, and therefore the storage and distribution of the composition according to the invention is practically impossible.

According to the disclosure documents Nos. 27 57 768 and 27 57 769, the insecticidal and acaricidal activity of synthetic pyrethroids can be enhanced by using phosphorous-containing organic compounds as synergists. There is no reference in the above descriptions to the lice-killing effect of the preparations.

The disadvantage of the lichen eradicants (ERGO, NEOCYCLOTOX, manufactured by Biogal Pharmaceuticals, Debrecen) currently on the market in Hungary, containing non-pyrethroid active ingredient, is that they have to be removed after use on the hair or body. As a result, the effect is eliminated at the same time as washing or bathing, and in the event of a re-infection, the treated person may fall back into love within a short time.

Our aim was to develop a new formulation that does not need to be removed after treatment so that its efficacy can be maintained for a long time.

Λ Due to the increasing number of cephalopods nowadays and the frequency of infestation with flatfish, we have found the best hair formula.

In view of the pharmacological requirements, we sought an active ingredient which, even at low concentrations, would rapidly produce a killing effect on the lice and mites, and, when applied to the hair or hair, would remain effective for a long time. From a toxicological point of view, we searched for a substance which is not absorbed through the skin, is non-toxic at the application concentration, does not cause skin or skin irritation. eye irritation and no allergenic effect.

The above detailed requirements were met by photostable synthetic pyrethroids (such as permethrin, decamethrin, fenvalerate), the concentration of which was found to be in the range of 0.1-5.0% by weight. The most favorable result was obtained using 0.5% by weight.

In order to avoid skin irritation and allergic effects of hair lotion, we have chosen to use water and ethanol as well as other solvents with a lower concentration, but we also used this property of castor oil to reduce the skin irritation effect.

Based on our preliminary studies, it has been found that the following solvent combination is most advantageously used to dissolve the optimal amount of 0.5% by weight of permethrin:

Spiritus concentratissimus (Ph. Hg. VI.): I-propanol: water ratio 54: 25: 13.

In our further experiments, our goal was to find an adjuvant which is incompatible with permethrin r.em and harmless to the skin.

In our work, it has been surprisingly observed that cetylpyridinium bromide, which kills the chaff by itself, only in high concentration and over a long period of time, significantly enhances the killing effect of permethrin, especially in the presence of castor oil.

The synergistic effect of cetyl pyridinium bromide and castor oil was demonstrated in the following model experiments:

The pedicles of Pediculus human vestimenti were dipped in the following solutions:

1.2. 3.4. 5th Permethrin (g) 0.5 0.5 0.5 0.5 Ol. ricini (g) 1.0 - 1.0 - 1.0 Sterogenol (ml) * 6.0 - 6.0 6.0 Spiro. conss. (Ml) 54.0 61.0 60.0 55.0 54.0

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First Second Third 4th 5th i-propanol (ml) Dist. water (ml) 25.0 13.0 25.0 13.0 25.0 13.0 25.0 13.0 25.0 13.0

* 10% Ethyl Pyridinium Bromide in Ethyl Alcohol [Pharm.].

After dipping, the pieces were dried at room temperature and incubated in a thermostat at 30 ° C. Eight days later, hatching was recorded, i.e., the popliteal lobe surviving the treatment and the number of littermates killed by the treatment were determined.

Serkemortality was expressed as the percentage of dead warts relative to all wounds.

Our test results are presented in Table 1. are summarized in Table.

No. 1 Spreadsheet

The number of samples tested indicates the composition according to the table above Total Serial Number, pcs perished nit The number, db mortality Tas % First 213 32 15.0 Second 186 96 51.6 Third 197 117 59.4 4th 225 182 80.9 5th 196 191 97.4 Decamethrin and fenvalerate solutions, and the

solutions containing these two active substances supplemented with castor oil and / or cetylpyridinium bromide.

its eradication effect was also investigated. The following formulations were prepared: 1 2 3 4 5 6 Decamethrin (g) 0.6 0.6 0.6 - - - Fenvalerate (g) - - - 0.6 0.6 0.6 Castor oil (g) Cetylpyridinium - 1.0 1.0 1.0 1.0 bromides (g) - - 0.6 - - 0.6 Ethanol (ml) 61.4 60.4 59.8 61.4 60.4 59.8 Isopropanol (ml) 23 23 23 23 23 23 Dist. water (ml) 15 15 15 15 15 15

Experiments according to the method on page 6

The results are shown in Fig. 2. The following table summarizes: No. 2 Spreadsheet Solution Number Total perished mortality serke number serke number OTING db db % First 251 124 49.4 Second 203 113 55.7 Third 237 228 96.4 4th 281 180 64.1 5th 200 140 70.0 6th 175 171 97.7

From the data in the table it can be seen that decamethrin and fenvalerate solutions (1 and 4), which do not contain synergists, kill approximately half of the ferrets under our experimental conditions. Solutions containing castor oil as a synergist show a slightly better effect; 198.0% (relative effect calculated as 100% for solutions without synergists).

In addition, during the study of the antifungals formulation, it was surprisingly discovered that the combination of permethrin cetyl pyridinium bromide in the hair alcohol results in a rapid paralysis and death of the lice, thus the knock-down effect of pernetrine to a great extent.

The knock-down effect was investigated as follows:

9.5 cm diameter ground petri dishes were charged with ² g of methyl1010 ⁴ and 333 X 10 ' ⁵ grams of permethrin in 2 ml of methyleryl ketone solution.

In addition, a series of samples were prepared which, in addition to the above amount of permethrin, were maintained at 1.0: 0.5, 1.0: 1.0, 1.0: 2.0, 1.0: 4.0 and 1.0: 8.0 permethrin: sterogenol. containing sterogenol in the form of cetylpyridinium bromide.

After drying, 20 to 20 domestic flies (Musca domestica) were placed in petri dishes and the number of dead flies was read every 5 minutes.

Each measurement was repeated 2 to 2 times.

The time of death was calculated in terms of death. probit mortality% regression line, then out of that value) 50, that time. which was needed to kill 50% of the flies for each sample.

The KD 50 values of the samples containing different permethrin and permethrin-cetylpyridinium bromide mixtures are shown in Fig. 3. are summarized in Table.

s. Spreadsheet

permethrin g 'plate permethrin cetylpyridinium bromide 1: 0 1: 0.5 1: 1 1: 2 1: 4 kd is 50 in minutes 1: 8 Ι, ΟΟΧΙΟ ' ⁴ 10.2 7.7 6.8 8.3 9.4 10.7 3.33X10 ' ⁵ 14.2 11.9 9.5 10.5 12.1 15.3

No. 2 Table 1 shows that the use of 1: 1 permethrin tetretin pyridinium bromide shows a KD 50 depreciation of more than 30%.

Similar results were obtained with the decemethrin-cetylpyridinium bromide mixture.

Taken together, cetylpyridinium bromide significantly enhanced the kneck down effect of permethrin, and the articulating effect was significantly higher than that of permethrin or decameter alone when applied at a 1: 1 ratio of the two components.

It should be noted that the combination of low-articulating pernretrin with a good-articulating synthetic pyrethroid has not been successful in our experiments because these materials are rapidly degraded in hair combination!

182 802

Based on our experiments, we have developed the hair lotion formulation in which the very favorable lice-killing properties of permethrin, its potency and the strong knock-down effect of something _{L are} best exerted by the potentiating and synergizing effect of sterogenol on these properties. Hair composition:

permethrin tech. 0.5% by weight

Oleum ricini Ph. Hg. VI. l 0súly%

Bodietta fragrance 0,5% by weight

Sterogenol * 6.0% by weight

Spiro. concentratis. pH. Hg. VI. 54.0% by weight of isopropanol 25.0% by weight of distillate. water 13.0% by weight * 10% Ethyl Pyridinium Bromide in Ethanol (Pharm. Package).

The stability of hair lotions with the above composition was further examined.

During the tests, the hair sample in a sealed dark glass is approx. They were placed in a 6 ° C refrigerator and a 50 ° C thermostat and their biological activity was determined by periodic titration.

Experience has shown that storage at 50 ° C for 1 month corresponds to 2 years (Andriska V., Bozzay, I .: Technological Basis of Pesticide Preparations. BME Note, Bp. 1978, p. 97).

Biological titration was performed as follows: Serial dilutions of hair spirit samples were made and 0.5-0.5 microliters of each dilution was applied to the pharynx.

60-60 pet flies were used per test series. After instillation after 24 hours of incubation, mortality was read and the regression line Ig conc./probit% mortality was calculated, followed by LC50 values. The LC 50 values for hair cream samples incubated in the refrigerator and thermostat for different periods of time are shown in Fig. 3. table:

No. 3 Spreadsheet

Examination time days 5 ° C 50 ° C 5th 0.49% 0.47% 15th 0.40% 0.42% 35th 0.36% 0.31% 75th 0.38% 0.36%

It can be seen from the data in the table that after more than 2 months no difference was detected between the biological activity of the samples incubated in the refrigerator and the thermostat beyond the measurement error limit. No significant decrease in activity was observed even at week 11 after storage. According to the tests performed, the hair lotion can be stored in a cool place in a dark bottle for 2 years.

With the above composition and the hairs we produced, we performed laboratory and field experiments, the results of which confirmed our expectations. A total of 66 subjects were examined in 4 groups.

The use of hair lotion provided immediate safe lice relief, and even one-off treatment, provided it was carefully done and those who did not wash their hair after treatment, provided relief for several weeks, despite being proven to be in a lice-like environment.

The invention is further illustrated by the following examples.

Example 1

0.5 weight% permethrin 1.0 weight% Castor oil 0.6 weight% cetylpyridinium bromide 10 59.4 weight% 96% ethyl alcohol 25.0 weight% isopropanol 13.0 weight% distilled water 0.5 weight% Bodietta Fragrance (Manufactured by: CAOLA HKV) 15 Example 2 0.1 weight% decamethrin 0.2 weight% Castor oil 20 0.1 weight% cetylpyridinium bromide 65.6 ml 96% ethyl alcohol 15.0 ml isopropanol 18.0 ml distilled water 1.0 ml Bodietta Fragrance (Manufactured by: CAOLA HKV) 25 Example 3 1.0 weight% fenvalerate 30 4.0 weight% Castor oil 2.0 weight% cetylpyridinium bromide 60.0 ml 96% ethyl alcohol 20.0 ml isopropanol 12.0 ml distilled water 35 1.0 ml Bodietta Fragrance (Manufactured by: CAOLA HKV) Example 4 40 0.5 weight% permethrin 10.0 weight% Castor oil 0.5 weight% cetylpyridinium bromide 50.0 ml 96% ethyl alcohol 25.0 ml isopropanol 45 13.0 ml Dist. water 1.0 ml Bodietta fragrance (Manufactured by: CAOLA

HKV, Budapest)

Claims (9)

50 Patent claims CLAIMS 1. A photostable synthetic pyrethroid lice composition comprising 0.1 to 5.0% by weight of active ingredient, 0.2 to 10.0% by weight of castor oil and 0.1 to 5.0% by weight It contains 55% by weight of cetylpyridinium bromide, 99.6-80% by weight of organic solvent-distilled water as solvent, and 0.1-1.0% by weight of perfume, if desired. 2. The composition of claim 1, wherein the active ingredient is permethrin (metaphenoxybenzyl alcohol ester of 2,260 dimethyl-3- (2,2-dichlorvinyl) cyclopropanecarboxylic acid). 3. The composition of claim 1 wherein the active ingredient is decamethrin (2,2-dimethyl-3- (2,2-dibromo-vinyl) -cyclopropanecarboxylic acid). 65 metaphenoxybenzyl alcohol ester). 182 802 4. The composition of claim 1 wherein the active ingredient is fenvalerate (3-methyl-2- (4-chlorophenyl) butyric acid, cyano (3-phenoxyphenyl) methyl ester). 5. An embodiment of the composition of claims 1 to 5, wherein the composition comprises 0.3 to 0.6% by weight of the active ingredient. 6. An embodiment of the composition according to any one of claims 1 to 3, characterized in that it contains from 0.6 to 1.2% by weight of castor oil. 10 7. An embodiment of the composition according to any one of claims 1 to 4, comprising 0.3 to 0.6% by weight cetylpyridinium bromide. 8. Figures 1-7. An embodiment of the composition according to claims 1 to 4, wherein the organic solvent is ethyl alcohol and isopropanol. 9 Figures 1-8. The composition of claims 1 to 4, wherein the solvent is a mixture of alcohol: isopropanol: water (2-3): (0.5-1.5): (0.1-0.5). (without drawing)