RU2157181C1 - Anti-louse agent - Google Patents

Abstract

FIELD: sanitary medicine. SUBSTANCE: agent contains permetrin, ionic and nonionic surfactant mixture, calcium alkylbenzenesulfonate, and neonol or mixture of polyethylene glycol ethers of mono- and dialkylphenols, odorant, and organic solvent in specified proportions. Agent shows high pediculocide activity and stability and also meets toxicological and hygienic safety requirements. EFFECT: increased pediculocide activity. 3 cl, 2 tbl

Description

 The present invention relates to the field of medicine, pharmacology and sanitary medicine, specifically to a new composite substance and a stable aqueous emulsion based on it.

 The tool is intended for the destruction of all types of lice: head, pubic and clothes, as well as disinfection of premises.

(1RS) - цис, транс- 3-феноксибензил- (2,2-дихлорвинил)- 2,2-диметилциклопропанкарбоксилат), который является наиболее известным синтетическим производным класса пиретроидов, разрешенным к применению по указанному назначению как за рубежом, так и в России (ТУ 6-00-5763450-78-89 или ТУ 113-04-331-91).Currently, there are quite a lot of anti-lice agents based on the active substance - permethrin, whose structural formula

(1RS) - cis, trans-3-phenoxybenzyl- (2,2-dichlorvinyl) - 2,2-dimethylcyclopropanecarboxylate), which is the most famous synthetic derivative of the pyrethroid class, approved for use for the specified purpose both abroad and in Russia (TU 6-00-5763450-78-89 or TU 113-04-331-91).

 Permethrin is a highly effective active substance of a new generation, which is a contact poison for insects, acting at all stages of the development of lice, low toxicity to humans and warm-blooded.

 Given the fame of the current beginning, specific inventions consist in the development of new composite substances based on it, which have an optimal combination of properties for various use cases.

Known stable agents (head and pubic lice) based on permethrin are true aqueous or aqueous-alcoholic solutions (due to the high content of ionic surfactant soaps in them) in the form of shampoos or liquid detergents, for example:
agent - "Stagifor" (Russian patent N 2048804, class A 61 K 7/40), containing permethrin 0.4-0.45%, water, soap, ethyl alcohol, flavoring.

 A common drawback of these agents is that the alkaline reaction of the environment through the use of soaps leads to chemical instability of permethrin, as a result of which their shelf life decreases (on average, the shelf life is not more than 1 year).

 In addition, such funds do not have sufficient ovicinity, since permethrin alone as an active principle cannot destroy the strong shell of eggs. The consequence of this is the need for re-treatments.

Closer technical solutions are pediculicides (headache, pubic lice) containing permethrin in the form of its true solutions in an organic solvent, namely in alcohols, produced in the form of water-alcohol lotions. Lotion usually contains alcohol in high concentrations (70-75%), organic acids, water and other targeted additives, for example:
Stagifor lotion (Russian patent N 2077815, class A 61 K 7/40) contains permethrin 0.32-0.42%, citric acid, ethyl alcohol, perfume, water;
Lontsid lotion (TU 64-0897438-01-9) contains permethrin (0.5%), ethyl alcohol, isopropyl alcohol, cetylpyridinium chloride, castor oil, perfume citral, water, etc.

 The high concentration of alcohol in which permethrin is highly soluble makes it possible to create true solutions without ionogenic surfactants, and the presence of acid (pH 3-4) leads to the fact that the agents are not only aggregatively stable, but also chemically stable with respect to permethrin, increasing shelf life of drugs up to 1.5-2 years.

 The combination of an acidic reaction of the medium and a high concentration of alcohol contributes to the emergence of a new property - almost 100% ovicidal activity (with low infection with lice), since this combination has a destructive effect on the egg shell.

 However, the disadvantage of these tools is their relatively high cost (use of alcohol as a solvent medium); in particular, therefore, they are not suitable for combating clothes lice, and even more so for the disinfection of premises.

 Solid stable forms of anti-pedicule agents (headache, pubic pediculosis) in the form of solid compositions are also known, such as anti-pedicular soap (Russian patent N 2134100, class A 61 K 7/40), Aviron tablets. These forms also do not have sufficient ovicinity.

 The above funds are intended for the destruction of head and pubic lice and are not applicable for the destruction of body lice and pest control.

 Body lice, despite being related to the head and pubic types of lice, have their own specific characteristics in relation to the place of distribution and nutrition.

 Along with requirements, such as great cheapness, prolonged action, high ovicinity, drugs are also required for the destruction of body lice, while more toxicity is possible than for drugs that are directly applied to the skin, and increased requirements for the preservation of the structure, color and quality of the processed fabrics, wooden surfaces, etc.

 The applicant does not know the means for treating permethrin-based body lice. To combat lice in the practice of medical pest control, sulfidophos-based preparations are used, which belongs to hazard class II according to GOST 12.1007-76. There is practically no information in the literature about a drug that is relatively safe for humans to destroy body lice with a high degree of ovicidal activity. It should be noted that the known means for the disinfection of premises based on permethrin, for example, in the form of crayons (Russian patent N 2102059, N 2111664), in the form of a powder, for example, permethrin adsorbed on perlite powder (application for Russian patent N 95/120331) , a smoke-forming composition (patent application of Russia N 94/013562), a foaming composition (Russian patent N 1311054) are not applicable for use in humans.

 In view of the unfavorable situation with regard to pediculosis congestion at present among certain population groups (shelters, prisons, mental hospitals, children's institutions, the army), when not only people are affected, but also the premises in which they are constantly located, the creation of such a tool becomes relevant It would be suitable both for combating pediculosis in all its three forms, and for disinfection of premises.

 Thus, the technical task is to create a simple, cheap, safe universal remedy against lice, which would maintain stability and pediculicidal activity for a long time, acceptable for industrial manufacture, convenient to use.

The problem is solved by the fact that a universal anti-lice product was developed containing permethrin, a mixture of inogenic and nonionic surfactants: calcium alkylbenzene sulfonate and neonol, or a mixture of polyethylene glycol esters of mono- and dialkylphenols (OP-7, OP-10), as well as perfume, an organic solvent, selected from the group: saturated hydrocarbons (C ₈ -C ₁₆ ), or mixtures thereof kerosene, nefras: SP4 30/80 (petroleum ether), oil solvent A-125/160, 110/195, in the following ratio, wt.% :
Permethrin - 15 - 30
Calcium alkylbenzosulfonate (grade A or B) - 1.3 - 2.3
Neonol (AF 9-10, AF 9-12) and / or OP-7, OP-10 - 0.6 - 1.3
Fragrance - 0.5-3
Organic Solvent - Up to 100
The composition of the components, their percentage ratio are selected empirically, as well as using previously accumulated data and experience.

 The percentage ratio of permethrin in the preparation is due to the fact that its use in a concentration below 15 (0.15% in a working aqueous emulsion) reduces the effect of exposure, and the use in a concentration of more than 30 (0.3% in a working emulsion, respectively) is not economically feasible due to the high cost the drug and the practically unchanged effect of exposure, toxicological and hygienic safety, while the limit of permethrin concentrations is lower than in similar drugs.

 Saturated hydrocarbons are used as a solvent: an individual hydrocarbon — octane, nonane, decane, undecane, etc .; hydrocarbon mixtures - technical, aviation kerosene, lighting (KO-20, KO-22, KO-25, KO-30) TU 38.401-58-10-90, the latter is used for lighting needs and in medicine for the destruction of head lice in the form of a concentrate soap-kerosene emulsion 10%, 20%; petroleum kerosene solvents - Nefras P4-30 / 80 (petroleum ether), Nefras A-110/195 or A-125/160 (GOST 10218-78), which are used in the paint and varnish, light, food industry, in veterinary sanitation.

 The use of these organic solvents in the indicated concentrations makes it possible to obtain a true solution of permethrin in an effective concentration (15-30%), in addition, the solvent acts here as a synergist, reduces the content of the main active substance, permethrin, in the working emulsion (in comparison with commonly used doses of 0, 4-0.5%) without reducing the effectiveness of the impact.

 The proposed composition of surfactants allows, when used, to obtain a highly effective self-emulsifying system with a uniformly distributed active substance - permethrin, which retains stability for a long time due to the combination of emulsifiers of the first and second kind in the emulsion. The percentage of surfactants is selected empirically.

 Calcium alkylbenzenesulfonate (TU 2421-002-00209906-93) is highly soluble in hydrocarbons and poorly in water. The content in the concentrate of 1.3-2.3 of this emulsifier promotes the formation of a stable emulsion in the preparation of a ready-to-use form.

где R₁ - алкильный радикал, содержащий 8-12 атомов углерода, R₁=R₂ или H, n= 7-9 (ОП-7), 10-12 (ОП-10). В предлагаемых концентрациях 0.6-1.3 (для концентрата) неиногенный эмульгатор при приготовлении водной эмульсии способствует смачиваемости водой перметрина и повышению устойчивости дисперсной системы.Neonol (AF 9-10 or AF 9-12), TU 38.103625-87, is a mixture of polyethylene glycol esters of isononyl phenols. OP-7 and OP-10 (GOST 8433-81) - a mixture of polyethylene glycol ethers of mono-and dialkylphenols:

where R ₁ is an alkyl radical containing 8-12 carbon atoms, R ₁ = R ₂ or H, n = 7-9 (OP-7), 10-12 (OP-10). In the proposed concentrations of 0.6-1.3 (for concentrate), a non-inogenic emulsifier in the preparation of an aqueous emulsion promotes the wettability of permethrin with water and increases the stability of the disperse system.

 Neonol is used in agriculture, in the production of herbicides, remedies, plant growth regulators.

 The combination of a hydrocarbon solvent and ethoxylated alkyl phenols at the given concentrations gives an additional effect - it destroys the shells of egg nits, while the ovicidal activity of the drug reaches 100%.

 As a flavoring, it is possible to use amyl ester of acetic acid (TU 8-09-1239-76), fragrance flower (TU 10-04-1631-87), fragrant (TU 18-16-121-77). The use of flavorings in a dose of 0.5-3 in a concentrate and, accordingly, 0.005-0.03 (in a working solution) provides a pleasant smell, which satisfies the aesthetic and hygienic needs of a person without causing an unpleasant sensation. Acetic acid amyl ester is widely used in the confectionery and food industries.

 The concentrate and its ready-to-use form have neutral properties (pH 6-7), the concentration of hydrogen ions is determined according to GOST 29188.2-91 in 0.2% aqueous emulsion. The neutral properties of the drug increase its shelf life to 60 months. The stability of the pediculicidal agent was studied in accordance with the temporary instructions for the work to determine the shelf life of drugs based on accelerated aging at elevated temperatures (I-42-2-82).

 The proposed drug and its components have the following toxicity data.

Permethrin, in accordance with toxicological and hygienic characteristics, is 1-2 orders of magnitude safer than organophosphorus insecticides, in acute toxicity when introduced into the stomach it belongs to moderately toxic compounds (class III, LD ₅₀ 2.6-3.5 g / kg, rats), conditions of inhalation exposure and when applied to the skin - to low toxic compounds (IV hazard class according to GOST 12.1.007-76).

 Calcium alkylbenzenesulfonate, according to toxicological and hygienic indicators, belongs to hazard class III according to GOST 12.1.007-76.

 According to the degree of exposure to the body, neonol (AF 9-10, AF 9-12) according to GOST 12.1.007-76 refers to moderately hazardous substances, hazard class III, skin-resorptive and sensitizing effects are absent. OP-7, OP-10 - moderately hazardous substances, hazard class III according to GOST 12.1.007-76. The amount of surfactant in the working aqueous emulsion contains not more than 0.03% and their effect on the toxicity of the drug is unlikely.

 Kerosene (lighting, technical, aviation) is a low-toxic compound, does not have a cumulative property. The average lethal dose when kerosene is introduced into the stomach, depending on the brand, ranges from 12 to 13 g / kg body weight.

 The proposed composition according to the parameters of acute toxicity when introduced into the stomach and applied to the skin according to the classification of GOST 12.1007-76 belongs to class IV low-hazard compounds. The tool in the recommended modes of use has low toxicity during inhalation, does not have a locally irritating, skin-resorptive and sensitizing effect. When inhaled in the form of aerosols and vapors in the zone of acute and subacute biocidal effect, the agent also belongs to the IV class of low toxic substances (classification of the degree of danger of disinsection agents). Long-term effects (mutagenic, carcinogenic) in the active substance have not been identified.

 The product is used in the form of an aqueous emulsion (10 ml of concentrate per 1000 ml of solution). Ready-to-use aqueous emulsion with the content of the main active substance (permethrin) 0.15-0.3 meets the requirements of toxicological and hygienic safety, belongs to the IV class of low-hazard compounds.

 In use, the proposed tool is simple. Working emulsion solutions are obtained by simple dilution of the agent with water in a ratio of 1:99 (i.e., for the preparation of 1 liter of an aqueous emulsion (0.15-0.3%), 10 ml of the agent is adjusted to 1000 ml by simple dilution with water).

 The invention is illustrated by the following examples.

 Example 1. Preparation of a composite substance and working emulsions based on it. Assessment of stability and pediculicidal activity.

To obtain the substance were prepared 5 compositions of the components, wt.% (Table 1). The preparation of emulsified concentrate was carried out according to the following technology: wt.% Permethrin, wt. % calcium alkylbenzenesulfonate brand A or B, wt.% neonol (AF 9-10 or AF 9-12) or wt. % OP-7, or OP-10, wt.% Amyl ester of acetic acid and kerosene or other solvent was adjusted to 100 wt.%. The mixture was stirred for 10 minutes at room temperature (18-22 ^° C.) until a clear solution was formed. The resulting compositions are low viscosity, slightly yellow opalescent liquid with the smell of the corresponding flavoring. Data on the study of the stability of the compositions (1-8) are shown in table 2.

 The proposed tool is used in the form of an aqueous emulsion. To do this, 10 ml of the drug is adjusted to 1000 ml with water.

 The pediculicidal activity of the drug samples in the form of an aqueous emulsion of the drug was tested on insect cultures of body lice (Pediculus humanus humanus de Gcer) by insect contact at a flow rate of 10-30 ml and exposure of 5-40 min ("Collection of methods for studying and assessing the safety and effectiveness of disinfectants ", NIIPT and D, Goskomsanepidnadzor, M .: 1995, part 3) (data are shown in table 3).

 Tests have shown that each sample retained insecticidal pediculicidal properties, ensuring the death of all stages of lice.

 Tests for the stability and pediculicidal activity of all samples showed the stability of the concentrate for 60 months and the conservation of pediculicidal activity, which significantly exceeds the similar indicators of known agents and is sufficient for the industrial preparation and implementation of the proposed drug.

 Example 2. Evaluation of the effectiveness of the drug for practical purposes.

 a) Application for the destruction of head and pubic lice.

 An aqueous emulsion (prepared from sample 2) was applied with a swab to the moistened hair of the head and other parts of the body (with pubic pediculosis), gently rubbing it into the skin. The emulsion consumption rate for head and pubic pediculosis is 30-100 ml per person, depending on the degree of infection with insects, the length and density of hair. After 15-20 minutes from the treated parts of the body, the product was washed off with running warm water, the hair was rinsed with a 5% aqueous solution of acetic acid, combed with a frequent comb to remove dead insects.

 Within 2 months, 70 volunteers with mixed pediculosis were treated with the drug. A 0.2% aqueous emulsion was used (sample 2 of the concentrate), which was rubbed into the scalp. At the same time, good tolerance by the treated persons and the absence of side effects on medical personnel were noted. The tool does not irritate the skin and mucous membranes. After 20 minutes, these persons were washed. With visual inspection, 100% death of lice and nits was observed. Observations of a group of volunteers who went through a week later showed that they were free of lice.

 b) Application for the destruction of body lice.

 For the destruction of body lice with 0.2% aqueous emulsion (sample 2 of the concentrate), 2 methods were used: soaking the curled things and irrigating them from various sprayers. Underwear, bedding and other items to be washed were soaked in an aqueous emulsion for 15-20 minutes, depending on the degree of infection with louse eggs. The consumption rate for a set of bed linen was 2.5 liters or 1 kg of dry clothes 4.5 liters. After disinfection, the clothes were thoroughly rinsed, soaked for a day in a solution of soda ash (1 tablespoon per 1 liter of water), and then washed in the usual way. During the processing of oversized linen, clothes, bedding with clothes lice, paralysis and death of lice and eggs on the treated surfaces occurs after 20 minutes. The recommended 0.2% aqueous emulsion (sample 2 of the concentrate) does not cause changes in the color and structure of various types of fabric (calico, satin, silk, wool) and does not leave greasy spots on them.

 Outerwear, bedding (with the exception of pillows) and other things were irrigated with an aqueous emulsion. The places of accumulation of insects were processed with special care: collars, belts, seams, folds. The consumption rate for a dress made of wool was 30-50 ml, for a set of bedding (mattress, blanket) 400 ml, for a set of clothes (coat, jacket, pants, hat) 350 ml.

 Processed things can only be used after they have dried and thoroughly ventilated in the open air (during the day).

 c) Use in pest control.

The floor was irrigated with 0.2% aqueous emulsion from quasar or dewdrop type apparatuses. Other surfaces were wiped with a rag moistened with an aqueous emulsion. The flow rate was 30-50 ml / m ² depending on the type of surface (non-absorbent or absorbent). After processing, the presence of insects was not detected.

Claims (2)

1. Lice control agent containing permethrin, a mixture of ionic and nonionic surfactants, calcium alkylbenzenesulfonate calcium and neonol AF 9-10 or AF 9-12, or a mixture of polyethylene glycol ethers of mono and dialkylphenols OP-7 or OP-10, flavoring and an organic solvent in the following ratio components, wt.%:
Permethrin - 15.0 - 30.0
Calcium Alkylbenzenesulfonate (A or B) - 1.3 - 2.3
Neonol AF 9-10 or AF 9-12 or
A mixture of polyethylene glycol ethers of mono- and dialkylphenols OP-7 or OP-10 - 0.6 - 1.3
Fragrance - 0.5 - 3.0
Organic Solvent - Up to 100
2. The tool according to claim 1, characterized in that the organic solvent is selected from the group of unsaturated individual hydrocarbons (C ₈ - C ₁₆ ) or mixtures thereof - kerosene, nefras, (SP 430/80, A-125/160, A-110 / 95).  3. The method according to claim 1, characterized in that as a flavoring it contains amyl ester of acetic acid, fragrance floral or aromatic.

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