DESC:FIELD OF THE INVENTION
[0001] The present invention relates to a mosquito and housefly repellent vaporizer compositions comprising an anthranilate ester and a mixture of essential oils. More particularly, this invention relates to mosquito and housefly repellent vaporizer compositions comprising an anthranilate ester and essential oils selected from neem oil, citronella oil, eucalyptus oil and lemon grass oil or combination thereof.

BACKGROUND OF THE INVENTION
[0002] Insect and acarid pests can cause severe damage to humans, crops and horticultural plants. Moreover insects, mosquito and housefly can carry agents that cause disease in both people and animals. For example, mosquitoes can carry viruses that cause encephalitis, and ticks can carry bacteria that cause Lyme disease. One method of controlling such mosquito and housefly involves the application of chemicals which repels such mosquito and housefly from a given environment. Thus, chemicals such as N,N-diethyl-m-toluamide (also known as DEET) is employed in repellents to protect individuals from mosquitoes, ticks and other similar pests. Other chemicals which affect insect behaviour are used to attract or repel insects from a given environment in order to enhance the effectiveness of insecticides, either by attracting insects to the area where insecticides can be more effectively employed, or by repelling them from areas where insecticides are inefficient.

[0003] There are many well-known insect repellents on the market. Historically, most include the chemical DEET (N, N diethyl-3-methylbenzamide) or DEET derivatives. The efficacy of DEET in repelling biting insects, mosquitoes has so far not been matched by any other natural or synthetic product since being introduced in 1975. However, whilst this chemical has been proven to be highly effective in repelling insects, it is highly toxic and can be absorbed through the skin. The toxicity, due to the pharmacokinetics of the chemical, has resulted in a catalogue of reported minor to serious adverse effects in use. Heavy exposure to the chemical is known to induce memory loss, weakness, headache, fatigue, muscle and joint pain tremors and shortness of breath. Yet further, DEET can act as a skin irritant and has a disagreeable odour. Accordingly, in recent years there has been a move towards the search for natural, non-toxic yet effective insect repellents, which do not cause irritation or toxicity to the user.

[0004] Plant materials and plant oils have been used for thousands of years to repel insects and for medicinal purposes. The recorded use of plant materials and plant oils can be dated back to Egyptian periods. Recent monographs on essential oil safety (Tisserand and Balacs 1995) and the chemistry, biochemistry, production and properties of essential oils clearly indicate that certain essential oils can be safely used for many applications. The classes of compounds found in essential oils include hydrocarbons, such as terpenes and oxygenated compounds, such as alcohols, aldehydes, ketones, esters, phenols, acids and furans. The volatile compounds in plant biological essential oils include mono- and sesquiterpenoids, benzenoids, and phenylpropanoids. However, the number of essential oils based commercial biopesticide remains low chiefly due to strict legislation, low persistence of effects, lack of proper quality control procedure and sufficient quantities of materials at affordable prices. Additionally, the presumed toxic effects such as allergenicity, genotoxicity, mutagenicity, and negative effects on the human endocrine system has negated the commercial availability.

[0005] Currently control of mosquito vectors use integrated approach employing many intervention methods simultaneously. These methods primarily include, synthetic insecticides, long lasting insecticidal nets (LLIN), sterile insect technique, transgenic mosquitoes, and synthetic repellents, which have produced encouraging results, however none of these strategies used singly has been proved to be fully successful.

[0006] Environmental awareness and consumers demand has promoted the search for better products for pest control and their use. Thus, there is an increasing need for improved, non-toxic, low-cost, and environmentally friendly mosquito and housefly repellent materials and technologies that are effective to repel them, or otherwise prevent or reduce damage or offensive to mosquito and housefly, without compromising the environment or the humans and/or animals.

OBJECT OF THE PRESENT INVENTION
[0007] It is an object of the present invention to provide a natural mosquito and housefly repellent liquid vaporizer.

[0008] It is a further object of the present invention to provide a mosquito and housefly repellent liquid vaporizer with slow release of actives.

[0009] It is yet another object of the present invention to provide a mosquito and house fly repellent liquid vaporizer compositions which are environmentally friendly, non-toxic and cost-effective.

SUMMARY OF THE PRESENT INVENTION
[0010] The present invention provides a slow-release mosquito and house fly repellent liquid composition comprising anthranilate present in a range from 0.5 to 5% (wt./wt.); essential oil present in a range from 0.1 to 1% (wt./wt.); stabilizer present in a range from 0.1 to 1% (wt./wt.); and solvent.

[0011] In an embodiment of the present invention the anthranilate is selected from ethyl anthranilate or butyl anthranilate and the essential oil is selected from the group comprising eucalyptus oil, lemongrass oil, citronella oil and neem oil.

[0012] In another embodiment of the present invention the stabilizer is butylated hydroxytoluene.

[0013] In yet another embodiment of the present invention the solvent is selected from the group comprising deodorized kerosene and d-limonene.
[0014] In yet another embodiment of the present invention a method of preparing slow-release liquid mosquito and house fly repellent composition comprising steps of taking solvent, essential oils and stabilizer in a mixer and stirring it for 30-60 min followed by subsequent addition of anthranilate followed by stirring for 30-60 min.

DETAILED DESCRIPTION OF THE PRESENT INVENTION
[0015] The following detailed description is presented to enable any person skilled in the art to make and use the invention. For purposes of explanation, specific nomenclature is set forth to provide a thorough understanding of the present application. However, it will be apparent to one skilled in the art that these specific details are not required to practice the invention. Descriptions of specific applications are provided only as representative examples. The present application is not intended to be limited to the embodiments shown but is to be accorded the widest possible scope consistent with the principles and features disclosed herein.

[0016] Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which the disclosed method and compositions belong. It must be noted that as used herein and in the appended claims, the singular forms “a”, “an”, and “the” include plural reference unless the context clearly dictates otherwise.

[0017] Similarly, the words "comprise", "comprises" and "comprising" are to be interpreted inclusively rather than exclusively. Likewise, the terms "include", "including" and "or" should all be construed to be inclusive, unless such a construction is clearly prohibited from the context. However, the embodiments provided by the present disclosure may lack any element that is not specifically disclosed herein. Thus, a disclosure of an embodiment defined using the term "comprising" is also a disclosure of embodiments "consisting essentially of” and "consisting of” the disclosed components. Where used herein, the term "example" particularly when followed by a listing of terms, is merely exemplary and illustrative, and should not be deemed to be exclusive or comprehensive. Any embodiment disclosed herein can be combined with any other embodiment disclosed herein unless explicitly indicated otherwise.

[0018] The present invention provides a natural mosquito and house fly repellent liquid vaporizer composition comprising a combination of anthranilate and essential oils. Preferably, the essential oils suitable for the purpose of the present invention are citronella oil, lemongrass oil, eucalyptus oil, and neem oil.

[0019] In an embodiment of the invention, the anthranilates preferred for the present invention are ethyl anthranilate and butyl anthranilate.

[0020] The liquid mosquito repellent vaporizer composition of the present invention is expected to repel different species of mosquitoes including Aedes aegypti (vector of Dengue virus), Anopheles stephensi (vector of Malaria parasite) and Culex quinquefasciatus (vector of Japanese encephalitis virus).

[0021] The composition of the present invention is also expected to repel house fly, Musca domestica (vector of Escherichia coli, responsible for causing enteric infections such as infantile diarrhoea, bacillary dysentery, shigellosis, typhoid, cholera, and parasitic worm infections).

[0022] Most importantly, the incorporation of safe active ingredients in the liquid repellent composition of the present invention would render the mosquito and housefly repellent vaporizer as an alternative to existing synthetic repellents without any potential health hazards.

[0023] Neem oil is a naturally occurring pesticide found in seeds from the neem tree. It is yellow to brown, has a bitter taste, and has a garlic/sulfur smell. It has been used for hundreds of years to control pests and diseases. Components of neem oil can be found in many products today. These include toothpaste, cosmetics, soaps, and pet shampoos. Neem oil is a mixture of many components like azadirachtin, nimbin, picrin, and sialin. Azadirachtin is the most active component for repelling and killing mosquito and housefly and can be extracted from neem oil.

[0024] Azadirachtin reduces mosquito, housefly, insect feeding and acts as a repellent. It also interferes with insect, mosquito hormone systems, making it harder for insects to grow and lay eggs. Other components of neem oil kill insects by hindering their ability to feed.

[0025] Lemongrass oil is obtained from Cymbopogon citratus belonging to family Poaceae. It contains not less than 75% of aldehydes calculated as citral. Lemongrass is indigenous to India and is found in Tinnevelli, Travancore, and Cochin. A light-coloured oil, rich in citral content, is obtained by steam distillation. Lemongrass oil is the principal source of citral (68–85%) from which ionone is derived. The oil also contains methyl heptanone, decyl aldehyde, geraniol, linalool, limonene. The oil is used in perfumery, soaps, and cosmetics and as a mosquito repellent.

[0026] Citronella oil is obtained by the steam distillation of fresh leaves of Cymbopogon nardus (L.) Rendle, belonging to family Poaceae. Citronella is native to Southeast Asia and grown commercially in Sri Lanka, India, Burma, Indonesia, and Java.

[0027] Citronella grass contains of volatile oil. The main chemical components of citronella oil are citronellic acid, geraniol, nerol, citral, borneol, camphene, citronellol, citronellal, dipentene, and limonene. It consists about 3.0% limonene, 35.3% citronellal, 12.0% citronellol, 24.9 % geraniol, 4.3% citronellyl acetate, 6.3% geranyl acetate, and 0.8% linalool. Citronella grass is the source of the commercial citronella oil, used in perfumery, as an insect repellent. Citronella oil is antiseptic, deodorant, tonic, insecticide, diaphoretic, parasitic, bactericidal, and stimulant.

[0028] Eucalyptus oil is the essential oil obtained by the distillation of fresh leaves of Eucalyptus globulus and other species like E. polybractea, E. viminalis, and E. smithii, belonging to family Myrtaceae. It is mainly found in Australia, Tasmania, United States, Spain, Portugal, Brazil, North and South Africa, India, France, and Southern Europe.

[0029] Eucalyptus oil is a colourless or straw-coloured fluid, with a characteristic odour and taste, soluble in its own weight of alcohol. According to the British Pharmacopoeia Eucalyptus oil should contain not less than 55%, by volume of Eucalyptol, have a specific gravity 0.910 to 0.930, and optical rotation –10 degrees to 10 degrees. Eucalyptus oil contains volatile oil of which 70 to 85% is 1,8-cineole also known as eucalyptol. The other constituents present are a-pinene; small quantity of sesquiterpenes like ledol, aromadendrene; aldehydes, ketones, and alcohols. The eucalyptus oil is used as stimulant, antiseptic, flavouring agent, aromatic, deodorant, expectorant, antimicrobial, febrifuge, diuretic, and antispasmodic. It is also used in the treatment of lung diseases, sore throat, and cold, as a vapour bath for asthma and various respiratory ailments and in bronchitis.

[0030] Anthranilate is a new member in the realm of entomology, has drawn significant attention in repellent research in the recent years and is being considered as an improved alternative to DEET. Ethyl anthranilate was found to interfere with both hosts seeking behaviour and oviposition of Aedes aegypti mosquitoes (Afify et al., 2014).

[0031] The anti-mosquito protection achieved using ethyl anthranilate and butyl anthranilate, could be considered as viable alternative to DEET. Unlike DEET (undesirable properties), their application as a potential insect repellent may be well accepted due to their high chemical stability under use conditions, good aesthetic reactions and affordable cost per use of the final product, which has been regarded essential criteria in preliminary product development. More significantly, considering the usability parameters of anthranilates, such as safety, smell, and vapour pressure anthranilates appear to be viable alternative to DEET. Additionally, ethyl anthranilate and butyl anthranilate does not damage synthetic fabrics, plastics and, painted and varnished surfaces which further widen the utility of anthranilates in bed nets, cloths and different surfaces in the endemic settings.

[0032] In one aspect, the present invention is directed to a composition comprising a mosquito and housefly repellent composition in form of a slow-release liquid vaporizer, comprising: (a) an anthranilate; (b) essential oils and other excipients. In this application, the terms “composition” and “formulation” are interchangeable.

[0033] In another aspect, the present invention is directed to a composition comprising a mosquito and housefly repellent composition in form of a slow release liquid vaporizer comprising: (a) a first active ingredient selected from the group consisting of, ethyl anthranilate or butyl anthranilate; (b) essential oils selected from the group comprising of eucalyptus oil, lemon grass oil, citronella oil and neem oil; (c) optionally at least one additional carrier oil/ solvent selected from the group consisting of deodorized kerosene and D-Limonene and (d) a suitable stabilizer such as Butylated hydroxytoluene or other.

[0034] In another aspect of the invention mosquito and housefly repellent composition in form of a slow-release liquid vaporizer comprises (i) anthranilates in a range from 0.5% to 5% (wt./wt.); (ii) essential oils in a range from 0.1% to 1% (wt./wt.); (iii) stabilizer in a range from 0.1% to 1% (wt./wt.); and (iv) solvent in a range from 93% to 99.3% (wt./wt.).
[0035] The embodiments of the present invention are more particularly described in the following examples that are intended as illustrations only, since numerous modifications and variations within the scope of the present invention will be apparent to those of skilled in the art. Unless otherwise noted, all parts, percentages and ratios reported in the following examples are on a weight basis and all reagents used in the examples were obtained or are available from the chemical suppliers.
EXAMPLE:
[0036] Example 1: Composition of the slow-release liquid vaporizer of the present invention
The compositions of the present invention can be formulated by taking required quantity of the solvent, essential oils and stabilizer in mixer and stirring it for 30-60 min. Finally, the active ingredient (ethyl anthranilate/ butyl anthranilate) is added to this mixture and stirred for 30-60 min to obtain the desired liquid vaporizer.
[0037] Table 1: Compositions of the present invention
S. No. Compositions Function Charge in
(% wt./wt.)
1 Ethyl anthranilate/ Butyl anthranilate Active ingredient 0.5-5
2 Eucalyptus oil/ Lemongrass oil/ Citronella oil/ Neem oil Essential oil (Active ingredient) 0.1-1
3 Butylated
hydroxytoluene Stabilizer 0.1-1
4 Deodorized
Kerosene/ D-Limonene Solvent Q.S.

[0038] Example 2: Composition of the slow-release liquid mosquito repellent vaporizer of the present invention
Sr. No. Compositions Function Charge in
(% wt./wt.)
1 Ethyl anthranilate Technical 99% pure Active Ingredient 1.00
2 Citronella oil Active ingredient 0.50
3 Butylated hydroxytoluene Stabilizer 0.10
4 Deodorized kerosene Solvent 98.40
Total 100
Table 2: Specific composition of the present invention

[0039] Example 3: Bio-efficacy of slow-release mosquito and house fly repellent liquid vaporizer

[0040] The bio-efficacy study was performed to determine the bio-efficacy of slow-release liquid repellent composition of the present invention against Aedes aegypti, Anopheles stephensi and C. quinquefasciatus under laboratory condition. The formulation as disclosed in Example 2. Table 2 is used for evaluating the bio-efficacy of the liquid compositions of the present invention. The efficacy testing as described in the present invention is in accordance with WHO/HTM/NTD/WHOPES/2009.3.

[0041] Larval stage of mosquitoes was collected in BRF insectary and reared under laboratory condition. Aedes aegypti, Anopheles stephensi and C. quinquefasciatus are maintained (individual species) insectary at 27+ 2 °C temperature and 75+10% relative humidity.

[0042] The efficacy assessment of the composition of the present invention, and placebo vaporizer, was conducted in Peet-Grady chamber using free-flying mosquitoes. Placebo vaporizer comprises of similar composition as mentioned in Table-1 and Table 2 except active ingredient like ethyl/butyl anthranilate i.e., placebo vaporizer compositions is having essential oils, stabilizer, and solvent.

[0043] Before the exposure, the liquid vaporizer was preheated for 1 hour, outside the chamber with its specific device. A liquid vaporizer was placed inside the trial chamber prior to mosquito release. Following that, 50 mosquitos were released on one side of the observation window. Once the mosquitos have been released, the window was closed. The opposite window was opened 15 cm for observing repellence. During the 60-minute observation period, the device was allowed to operate continuously. The experiment was conducted for 60 minutes. The number of mosquito’s repellency and knockdown were recorded in 10 minutes intervals up to 60 minutes. Percentage of repellency was calculated. The knocked-down mosquitoes were collected by aspirator and transferred into separate clean holding cups. Mosquitoes were provided with l0% sucrose solution on cotton wool and held for 24 hours at 27 + 2 °C temperature and 80% + 10% relative humidity. Mortality was recorded in 24 hours post-exposure.

[0044] To avoid any interference with the test studies, the heating of the device before and between two consecutive tests is done away from the test chamber. The efficacy of the liquid vaporizer was assessed using three replicates, tested on different batches of mosquitoes. For control, before testing each product, free-flying female mosquitoes were released in the chamber for 60 minutes. The percentage of repellency, knockdown and mortality were observed and are listed in Table 5. Results of the Pre-weight and Post-weight of liquid vaporizer studied are given in Tables 3 to 4.
[0045] Table-3: Pre-Weight and Post-Weight of liquid vaporizer of the present invention

Mosquito
Replication
Pre-weight
(g)
Post-weight
(g) Released
weight
(g)

A. aegypti R1 75.619 75.248 0.371
R2 75.256 74.891 0.365
R3 74.882 74.531 0.351

A. stephensi R1 74.531 74.148 0.383
R2 74.158 73.781 0.377
R3 73.783 73.431 0.352

C. quinquefasciatus R1 73.431 73.088 0.343
R2 72.092 71.731 0.361
R3 71.723 71.385 0.338

[0046] Table-4: Pre-Weight and Post-Weight of Placebo vaporizer

Mosquito
Replication
Pre-weight (g)
Post-weight (g) Released weight (g)

A. aegypti R1 78.619 75.248 3.371
R2 75.241 74.882 0.359
R3 74.879 74.525 0.354

A. stephensi R1 74.521 74.148 0.373
R2 74.143 73.782 0.361
R3 73.779 73.437 0.342

C. quinquefasciatus R1 73.437 73.058 0.379
R2 73.051 72.694 0.357
R3 72.694 72.325 0.369

[0047] Table 5: Mean Value of Repellency and Knockdown against A. aegypti, A. stephensi and C. quinquefasciatus on Liquid Vaporizer composition of present invention and placebo vaporizer
Product
Name Mosquito Species Repellency
% Knock--down
% Mortality
%
Liquid Vaporizer composition of the present invention A. aegypti 24.67 31.33 32.67
A. stephensi 22.00 29.33 31.33
C. quinquefasciatus
20.67 28.00 29.33
Placebo Product A. aegypti 20.00 25.33 26.67
A. stephensi 19.33 23.33 24.67
C. quinquefasciatus

18.67
21.33
22.00

[0048] Table 5 shows that the highest percentage of repellency 24.67% repellency was observed against A. aegypti, followed by A. stephensi and C. quinquefasciatus in the liquid vaporizer composition of the present invention. Placebo product had 20.00% repellency against A. aegypti, followed by A. stephensi and C. quinquefasciatus.

[0049] It was observed that knockdown (%) and mortality (%) of the liquid vaporizer of the present invention is better than that of placebo vaporizer against A. aegypti followed by A. stephensi and C. quinquefasciatus.

[0050] The advantage of the liquid mosquito repellent compositions of the present invention is to provide a natural composition based on anthranilate (an FDA approved food flavour) and essential oils selected from the group of eucalyptus oil/ lemongrass oil/ citronella oil/ neem oil. The incorporation of safe active ingredients, the observed knockdown (%) and mortality (%) make the mosquito repellent vaporizer liquid compositions of the present invention as an alternative to existing synthetic repellents without any potential health hazards to environment, human and animals.

[0051] From the foregoing it will be observed that numerous modifications and variations can be effectuated without departing from the scope of the novel concepts of the present invention. It is to be understood that no limitations with respect to the specific embodiments illustrated is intended or should be inferred. It should be understood that all such modifications and improvements have been deleted herein for the sake of conciseness and readability but are properly within the scope of the following claims.
,CLAIMS:WE CLAIM:
1. A slow-release mosquito and house fly repellent liquid composition comprising
Anthranilate present in a range from 0.5 to 5% (wt./wt.);
Essential oil present in a range from 0.1 to 1% (wt./wt.);
Stabilizer present in a range from 0.1 to 1% (wt./wt.); and
Solvent.
2. The slow-release repellent liquid composition as claimed in claim 1, wherein the anthranilate is selected from ethyl anthranilate or butyl anthranilate.
3. The slow-release repellent liquid composition as claimed in claim 1, wherein the essential oil is selected from the group comprising eucalyptus oil, lemongrass oil, citronella oil and neem oil.
4. The slow-release repellent liquid composition as claimed in claim 1, wherein the stabilizer is butylated hydroxytoluene.
5. The slow-release repellent liquid composition as claimed in claim 1, wherein the solvent is selected from the group comprising deodorized kerosene and d-limonene.
6. A method of preparing slow-release liquid mosquito and house fly repellent composition comprising the steps of:
- taking solvent, essential oils and stabilizer in a mixer and stirring it for 30-60 min;
- adding anthranilate followed by stirring for 30-60 min.