A tick repellent for monitoring and sampling vectors, and its preparation method and application

Abstract

The present invention provides a tick repellent for monitoring and sampling of vectors, and a preparation method and application thereof, belonging to the technical field of pesticides. The tick repellent pharmaceutical composition is composed of the following components by weight percentage: 90-99% of pepper extract and 10-1% of isolongol by weight. The present invention also provides a tick repellent for monitoring and sampling of vectors, comprising the tick repellent pharmaceutical composition, zeolite microspheres, menthol, borneol, solvent, propylene glycol, a moisturizer, a thickener, a pH regulator and water. The tick repellent provided by the present invention has the following beneficial effects: (1) it can give full play to the characteristics of plant-derived components that have little irritation to the human body and low side effects after long-term use; (2) the preparation process is simple, the binary compound tick repellent composition has a synergistic effect, and can effectively improve the protection against ticks; (3) it makes full use of the porous structure of the zeolite microspheres, can slowly release the absorbed tick repellent composition, and can still maintain a high insect repellent effect after long-term use.

Description

Technical Field

[0001] The present invention relates to the technical field of pesticides, and in particular to a tick repellent for monitoring and sampling vector organisms, and a preparation method and application thereof. Background Art

[0002] Vectors are organisms that can transmit disease, generally those that can transmit human diseases. These primarily include rodents, mosquitoes, flies, cockroaches, fleas, ticks, and mites. Vectors not only directly impact or endanger human life through bites and food contamination, but can also spread a range of important infectious diseases through various channels. Among the notifiable infectious diseases in my country, many are vector-borne, such as plague, hemorrhagic fever, leptospirosis, malaria, dengue fever, endemic typhus, and filariasis. Some gastrointestinal infections, such as dysentery and typhoid fever, spread through the human body through mechanical transmission by vectors. Effective control of vectors can reduce their impact on the human population and the resulting economic losses, while also preventing and controlling the occurrence and spread of vector-borne infectious diseases. Systematic vector monitoring not only provides a basis for developing vector control programs but also provides predictive and early warning information for epidemic trends of vector-borne infectious diseases.

[0003] With global warming, accelerated urbanization, rapid development of tourism and trade, and ongoing ecological changes, the species, density, and distribution of vector-borne diseases have undergone new changes. Not only have existing vector-borne infectious diseases expanded in scope, frequency, and intensity, but new vector-borne infectious diseases are also emerging. As a major vector-borne organism, rodents transmit dozens of diseases, including bacterial and viral diseases, as well as rickettsial and parasitic infections. Most rodent-borne infectious diseases are infectious, including bacterial infections such as plague, cholera, typhus, relapsing fever, typhoid fever, leptospirosis, and salmonella. Common viral diseases include hemorrhagic fever and forest encephalitis. Other common diseases include filariasis and trichinosis.

[0004] According to the national standard GB / T23798-2009, "Methods for Monitoring Vector Density - Rodents," rodent density monitoring methods are specified, including the sticky trap method, the night trap method, the powder trace method, the feeding method, the rat trace method, the burrow plugging and theft detection method, and visual inspection. The sticky trap and powder trace method are suitable for monitoring indoor rat density; the burrow plugging and theft detection method is suitable for outdoor rat density monitoring; the night trap method and the rat trace method are suitable for monitoring rat density in both indoor and outdoor environments; the feeding method is suitable for monitoring rat density in sewers; and the visual inspection method is suitable for monitoring marmot density. Outdoor rat density monitoring requires staff to work in the field for extended periods of time. For example, the burrow plugging and theft detection method involves the following steps: determining a survey plot, measuring the area (in hectares), plugging all rat holes within the plot, and checking the number of burrows opened 24 hours later. Rat density is expressed as the number of rat holes per unit area or the rate of burglary. The steps of the night trap method are as follows: use raw peanuts as bait, place mousetraps along a certain terrain outdoors, with a distance of 5m to 10m between traps and a row distance of 20m to 50m. Place mousetraps along the wall indoors, with the traps perpendicular to the wall and the pedals against the wall. 2 Place 1 clip in the room, 15m 2 Place 2 clamps in the room, larger than 15m 2 Rooms are calculated per 15m 2 The number of traps placed is calculated based on the number of standard rooms. Place traps in the evening and check the following morning to record the species and number of captured rats. The capture rate represents rat density. If a captured rat is a newly discovered species, sample it and prepare a specimen for storage in the laboratory.

[0005] When conducting rodent disease vector density monitoring, workers often face the challenge of being vulnerable to ticks due to the long hours of field work. Ticks, commonly known as dog ticks, cattle lice, and grass crawlers, often hide in forests, grass, and the fur of cattle and sheep in low hilly areas. They rely on blood for survival at every stage of their life. When not feeding, their abdomen and back are flat, about the size of a sesame seed. After feeding, they become the size of a soybean or even as large as a fingernail. Ticks typically bite areas with relatively vulnerable skin, such as the neck, behind the ears, armpits, and inner thighs of humans and animals. Ticks belong to the phylum Arthropoda, class Arachida, subclass Acari, order Parastiformes, and order Ixodida, and include the families Ixodidae, Argasinae, and Nuttalliellidae. Ticks are obligate, non-permanent external parasites of terrestrial vertebrates. There are 899 species worldwide, 119 of which have been described and named in China. While sucking blood, they also transmit various pathogens, causing a variety of diseases (such as forest encephalitis, hemorrhagic fever, tick-borne spotted fever, Lyme disease and tick paralysis, etc.). At the same time, because most ticks can change hosts, and some pathogens can be stored in the tick's body for a long time and even be passed on, they expand the spread of diseases and bring great harm to human health and animal husbandry.

[0006] Currently, tick control methods primarily include chemical, genetic, immunological, and biological control. Chemical control is the traditional method for controlling tick infestations. In production, drug control plays a major role. Commonly used chemical agents include pyrethroid compounds (pyrethroids) and antibiotics (ivermectin). Pyrethroids are the active ingredients of the pyrethrum plant, a member of the Asteraceae family. They have a strong knockdown effect on various insects, are highly effective and rapidly kill ticks, and are non-toxic to humans and livestock. However, natural pyrethroids are chemically unstable and have a short residual life, allowing some insects to recover after being knocked down. A series of synthetic pyrethroids, based on the chemical structure of natural pyrethroids, have been synthesized. These pyrethroids are stable and have a long residual life. However, a tick species in the UK has reportedly developed resistance to a current synthetic pyrethroid drug, significantly reducing the effectiveness of insecticides. Ivermectin is also very effective in controlling ticks. While it does not immediately kill or dismember ticks, it can affect feeding, molting, and egg laying, thereby reducing reproductive capacity. Currently, chemical control methods face numerous obstacles, including environmental concerns caused by pesticide residues left during tick control; hungry ticks often hide in burrows or crevices, making them difficult for insecticides to reach; ticks generally parasitize animals' entire bodies, making systemic deworming more complex; the increasing cost of deworming; and the increasing resistance of ticks to pesticides. Furthermore, current chemical tick control agents primarily target ticks, while field work primarily focuses on protecting workers from bites and deterring ticks from approaching. Research on such repellents is relatively rare. Therefore, there is an urgent need to develop a green, safe, highly specific, and effective tick repellent for use in vector monitoring and sampling, thereby protecting the health of workers. Summary of the Invention

[0007] In view of the shortcomings of the above-mentioned prior art, such as the lack of research on tick repellents and the difficulties in chemically controlling ticks, the purpose of the present invention is to provide a tick repellent pharmaceutical composition for monitoring and sampling vector organisms, a tick repellent containing the pharmaceutical composition, as well as a preparation method and use, to solve the problem of lack of effective tick repellents in biological monitoring and sampling in the prior art.

[0008] To achieve the above-mentioned purpose and other related purposes, the applicant has carried out a large number of drug activity screening tests to seek a safe and effective tick repellent drug. Now, a tick repellent drug for vector monitoring sampling is provided, which comprises one or both of a mountain pepper extract and isolongifolia alkaloids.

[0009] A tick repellent pharmaceutical composition for sampling and monitoring vectors, comprising a Piper melongena leaf extract and isolongifolia alkaloids.

[0010] A tick repellent pharmaceutical composition for sampling and monitoring vectors, the tick repellent pharmaceutical composition comprising the following components by weight percentage: 90-99% of a Piper nigrum leaf extract and 10-1% of isolongifolia alkaloids by weight ratio;

[0011] Furthermore, the Zanthoxylum bungeanum extract is prepared by the following method:

[0012] Fresh Zanthoxylum bungeanum leaves were rinsed with distilled water, dried, and then chopped. The leaves were then extracted by ethanol percolation to obtain the Zanthoxylum bungeanum total extract. After being suspended in water, the extracts were sequentially extracted with petroleum ether, ethyl acetate, and n-butanol. The n-butanol-extracted portion was concentrated to obtain the Zanthoxylum bungeanum extract.

[0013] The concentration of the ethanol is 50% to 95%.

[0014] Furthermore, the mountain pepper is selected from: Lindera angustifolia Cheng, Lindera erythrocarpa Makino, Lindera kariensis WWSm, Linderareflexa Hemsl, Lindera setchuenensis Gamble, Linderanacusua (D.Don) Merr. and Lindera prattii Gamble, etc.

[0015] Furthermore, the tick repellent is composed of the following raw materials: a tick repellent pharmaceutical composition, zeolite microspheres, menthol, borneol, a solvent, propylene glycol, a moisturizer, a thickener, a pH regulator, and water;

[0016] The mass fraction of the zeolite microspheres is 0.5% to 5%;

[0017] The mass ratio of the tick repellent pharmaceutical composition to the zeolite microspheres is (2.0-7.8): (0.8-5).

[0018] The solvent is ethanol;

[0019] The moisturizing agent is selected from β-glucan, ceramide, hyaluronic acid, sorbitol, and betaine;

[0020] The thickener is carbomer, algin, gum arabic, xanthan gum or tara gum;

[0021] The pH regulator is triethanolamine.

[0022] Furthermore, a tick repellent for monitoring and sampling vectors includes the following raw materials by mass fraction:

[0023] Tick repellent composition: 2.0% to 7.8%;

[0024] Zeolite microspheres: 0.8% to 5%;

[0025] Menthol: 0.1% to 2.5%;

[0026] Borneol: 0.1% to 2.5%;

[0027] Solvent: 45% to 60%;

[0028] Propylene glycol: 5% to 8%;

[0029] Moisturizer: 0.1% to 1.5%;

[0030] Thickener: 0.1% to 1.0%;

[0031] pH regulator: 0.1% to 1%;

[0032] Water: Make up 100%.

[0033] Furthermore, the tick repellent for vector monitoring sampling includes the following raw materials by mass fraction:

[0034] Tick repellent composition: 6.5%;

[0035] Zeolite microspheres: 1.2%.

[0036] The tick repellent composition comprises the following components by weight: 92% of the pepper extract and 8% of the isolongifolia alkaloids.

[0037] Furthermore, the preparation method of the tick repellent is as follows: dissolving a thickener in water and swelling it to obtain an aqueous phase; dissolving a tick repellent pharmaceutical composition, propylene glycol, and zeolite microspheres in a solvent to obtain an oil phase; after mixing the aqueous phase and the oil phase, adjusting the pH value to 5-7 with triethanolamine, and then adding menthol, borneol, and a moisturizer to obtain the tick repellent.

[0038] The present invention also provides use of the pharmaceutical composition or tick repellent in preventing and treating tick bites.

[0039] As described above, the tick repellent pharmaceutical composition for monitoring and sampling vectors of the present invention, and the tick repellent containing the pharmaceutical composition, have the following beneficial effects: (1) a simple preparation process, a binary compound tick repellent composition, and a synergistic effect between the two, which can effectively improve protection against ticks; (2) the porous structure of the zeolite microspheres is fully utilized, and the absorbed tick repellent composition can be slowly released, and long-term use can still maintain a high insect repellent effect. The present invention can be applied to the surface of exposed skin or sprayed using a spray bottle, which is convenient to carry and use. The tick repellent lasts for a long time, and a single spray can last for 4 hours, with a good tick repellent effect. DETAILED DESCRIPTION

[0040] The following describes the implementation of the present invention through specific embodiments. People skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification.

[0041] Example 1 Preparation of Piper nigrum Extract

[0042] (1) Sample source, identification and storage

[0043] Sample source: collected from Honghe River, Yunnan.

[0044] Sample identification: The sample was identified by the Pharmacognosy Teaching and Research Section of the School of Pharmacy of Shandong University as the leaf of Linderanacusua (D.Don) Merr., a plant of the genus Linderana of the Lauraceae family.

[0045] (2) Crude extraction and extraction of Piper velutipes leaves

[0046] 10 kg of leaves of Piper nigrum were air-dried and chopped, extracted with 95% ethanol percolation method, and the extract was concentrated under reduced pressure on a rotary evaporator to obtain 0.82 kg of total extract. After suspending in 5 L of water, the extract was extracted three times with 5 L of petroleum ether to obtain 101 g of petroleum ether extract; extracted three times with 5 L of ethyl acetate to obtain 172 g of ethyl acetate extract; and extracted three times with 5 L of n-butanol to obtain 150 g of n-butanol extract.

[0047] Example 2 Preparation of Piper nigrum Extract

[0048] (1) Sample source, identification and storage

[0049] Sample source: collected from Yishan, Linqu, Shandong.

[0050] Sample identification: The sample was identified by the Pharmacognosy Teaching and Research Section of the School of Pharmacy of Shandong University as the leaf of Lindera angustifolia Cheng, a plant of the genus Piper in the Lauraceae family.

[0051] (2) Crude extraction and extraction of Piper velutipes leaves

[0052] 10 kg of fresh Zanthoxylum bungeanum leaves were rinsed with distilled water, dried and chopped, extracted with 75% ethanol percolation method, and the extract was concentrated under reduced pressure on a rotary evaporator to obtain 0.79 kg of total extract. After suspending with 5 L of water, the extract was extracted with 5 L of petroleum ether three times to obtain 104 g of petroleum ether extract; extracted with 5 L of ethyl acetate three times to obtain 172 g of ethyl acetate extract; and extracted with 5 L of n-butanol three times to obtain 134 g of n-butanol extract.

[0053] Example 3 Tick repellent activity assay

[0054] (1) Solution preparation

[0055] Isocarbanone was purchased from Shanghai MacLean Biochemical Technology Co., Ltd., CAS No.: 23787-90-8, specification: mix.80%.

[0056] a. The positive control drug: two chemical repellents, 99.5% DEET original drug and 98% DEET original drug, were prepared into 5% solutions in ethanol and set aside;

[0057] b. The two laboratory-made extracts of pepper and isolongol were prepared in ethanol to a concentration of 5% solution, set aside;

[0058] c. The isolongol ketone was prepared into a 5% solution in ethanol and set aside;

[0059] d. After mixing the pepper extract and isolongol in a mass ratio of 9:1, 5:1, and 1:2, ethanol was added to prepare a 5% solution for later use;

[0060] (2) Preparation of drug-coated filter paper and determination of repellent activity

[0061] 101 filter paper was cut into two semicircles of 50 mm diameter. The two semicircular filter paper pieces were soaked in the corresponding concentrations of a, b, c, and d solutions and distilled water for 10 min, then taken out and air-dried at room temperature (23±2)°C for 5 min. The two semicircular filter paper pieces soaked in a, b, c, d, and distilled water were reassembled into a full circle and placed in the larval tick repellency test apparatus. Distilled water was added to the water tank to prevent larval ticks from escaping the test area. In each experiment, 25 ticks were placed on the iron block at the center of the circle to allow them to move freely in the field. The apparatus was covered with a light-absorbing cloth to isolate it from external light interference. After 3 min, the light-absorbing cloth was removed and the distribution of ticks on the filter paper pieces was observed (each experiment was repeated 3 times, using different larval ticks each time. After 3 min, the ticks would crawl to the control area, the treatment area, or remain in the original place). The number of ticks repelled was equal to the number of ticks in the control area minus the number of ticks in the treatment area. The average repellency rate of the three experiments was calculated according to the following formula:

[0062]

[0063] The experimental results are as follows:

[0064] Table 1 Repellent test results

[0065]

[0066] Example 4 Repellency Measurement

[0067] Including the following raw materials by mass fraction:

[0068] Tick repellent composition: 6.5%;

[0069] Zeolite microspheres: 1.2%;

[0070] Menthol: 2.5%;

[0071] Borneol: 2.5%;

[0072] Solvent: 45%;

[0073] Propylene glycol: 8%;

[0074] Moisturizer: 1.5%;

[0075] Thickener: 1.0%;

[0076] pH regulator: 0.1% to 1%;

[0077] Water: Make up 100%.

[0078] The preparation method is as follows: a thickener is dissolved in water and swelled to prepare an aqueous phase; a tick repellent drug composition, propylene glycol, and zeolite microspheres are dissolved in a solvent to prepare an oil phase; the aqueous phase and the oil phase are mixed, the pH value is adjusted to 5-7 with a pH regulator, and then menthol, borneol, and a moisturizer are added to prepare the tick repellent.

[0079] The ratio of Piper angustifolia to isolongifolia in the tick repellent composition is 9:1.

[0080] The solvent is ethanol; the moisturizing agent is selected from beta-glucan; the thickener is carbomer; and the pH regulator is triethanolamine.

[0081] Select 4 testers (half male and half female, and should not drink alcohol, tea or coffee before and during the test, and should not use products containing fragrances). Draw a 50mm×50mm skin area on the back of each hand, and press 1.5uL / cm on one hand. 2 Apply the repellent to be tested evenly with a dose of (the repellent prepared above), exposing 40mm×40mm of the skin, and tightly covering the rest. The other hand serves as a blank control. Apply the repellent for 2 hours, then put your hand into a tick cage with qualified attack power for 2 minutes to observe whether there are any ticks coming to suck blood. Thereafter, test once every 1 hour. As long as one tick comes to suck blood, the repellent is judged to be ineffective. Record the effective protection time (h) of the repellent. The test results are shown in Table 2. As can be seen from the data in Table 2, the repellent can achieve an effective protection time of 4 hours.

[0082] Table 2 Repellency determination

[0083]

[0084] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the present invention. Anyone skilled in the art may modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by one of ordinary skill in the art without departing from the spirit and technical principles disclosed herein are intended to be covered by the claims of the present invention.

Claims

1. A tick repellent pharmaceutical composition for monitoring and sampling vectors, characterized in that: The tick repellent composition comprises a Piper nigrum extract and isolongifolia alkaloids, and is composed of the following components by weight percentage: 90-99% of Piper nigrum extract and 10-1% of isolongifolia alkaloids by weight percentage; The Zanthoxylum bungeanum extract is prepared by the following method: fresh Zanthoxylum bungeanum leaves are rinsed with distilled water, dried, and then chopped, and extracted by ethanol percolation to obtain a Zanthoxylum bungeanum total extract. The extract is suspended in water and extracted with petroleum ether, ethyl acetate, and n-butanol in sequence, wherein the n-butanol extraction portion is concentrated to obtain the Zanthoxylum bungeanum extract; the concentration of the ethanol is 50% to 95%; and the Zanthoxylum bungeanum is selected from Lindera angustifolia Cheng and Lindera nacusua (D. Don) Merr.

2. A tick repellent for monitoring and sampling vectors, characterized in that The invention is composed of the following raw materials: the tick repellent composition according to claim 1, zeolite microspheres, menthol, borneol, solvent, propylene glycol, humectant, thickener, pH regulator and water; wherein: Tick repellent composition: 2.0% to 7.8%; Zeolite microspheres: 0.8% to 5%; Menthol: 0.1% to 2.5%; Borneol: 0.1% to 2.5%; Solvent: 45% to 60%; Propylene glycol: 5% to 8%; Moisturizer: 0.1% to 1.5%; Thickener: 0.1% to 1.0%; pH regulator: 0.1% to 1%; Water: replenish 100%; The mass ratio of the tick repellent composition to the zeolite microspheres is (2.0-7.8): (0.8-5); The solvent is ethanol; The moisturizing agent is selected from β-glucan, ceramide, hyaluronic acid, sorbitol, and betaine; The thickener is carbomer, algin, gum arabic, xanthan gum or tara gum; The pH regulator is triethanolamine; The preparation method of the tick repellent for vector monitoring sampling is as follows: dissolving a thickener in water and swelling the mixture to obtain an aqueous phase; dissolving a tick repellent pharmaceutical composition, propylene glycol, and zeolite microspheres in a solvent to obtain an oil phase; mixing the aqueous phase and the oil phase, adjusting the pH value to 5-7 with triethanolamine, and then adding menthol, borneol, and a moisturizer to obtain the tick repellent.

3. The tick repellent for monitoring and sampling vectors according to claim 2, characterized in that: Including the following raw materials by mass fraction: Tick repellent composition: 6.5%; Zeolite microspheres: 1.2%; The tick repellent composition comprises the following components by weight: 92% of the pepper extract and 8% of the isolongifolia alkaloids.

4. Use of the tick repellent according to claim 2 in preventing and treating tick bites.

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