WO2019112416A1

WO2019112416A1 - Mosquito repellent composition

Info

Publication number: WO2019112416A1
Application number: PCT/MY2018/050086
Authority: WO
Inventors: Wai Sun YEE; Muney SERIT
Original assignee: Sumitomo Chemical Enviro-Agro Asia Pacific Sdn. Bhd.
Priority date: 2017-12-06
Filing date: 2018-12-03
Publication date: 2019-06-13
Also published as: TW201936053A; TWI800570B; WO2019112416A8; CN111511208A; ZA202003146B; AR113914A1; BR112020011177A2

Abstract

The current invention relates to an insect repellent composition comprising: a vapour-active pyrethroid; a flammable bulk material; and a binder; wherein the vapour-active pyrethroid is selected from one or more of the group selected from metofluthrin, transfluthrin, dimefluthrin, meperfluthrin, renofluthrin and heptafluthrin. The invention also includes a method of preparing an insect repellent composition, an article comprising the composition, a kit comprising such an article and a method of repelling insects by igniting the composition.

Description

Mosquito Repellent Composition

Field of Invention

The present invention relates to a composition and method for repelling insects, in particular flying insects such as mosquitos.

Background

The listing or discussion of an apparently prior-published document in this specification should not necessarily be taken as an acknowledgement that the document is part of the state of the art or is common general knowledge.

In a number of regions of the world, the buzz of a mosquito may be more than a distraction. It may herald a bite that may pass to an individual a disease such as malaria, dengue fever, chikungunya and zika. As such, even when an individual has sought to protect themselves from being bitten by use of an insect repellent, the repellent may not be effective until the mosquito is within a few inches of the individual. The close proximity of the mosquito may cause feelings of annoyance in the individual due to the constant buzzing of the mosquito, and even anxiety or panic if they fear being bitten.

Other pest species may also pose a bite or sting threat to an individual, which bite or sting may be irritating or, at worst, life threatening due to anaphylaxis. Such species include, but are not limited to biting midges, sand flies, black flies, house flies, bush flies, march flies, horse flies, bees, wasps, ants, cockroaches, leeches, ticks and mites. While the majority of these species (but not all) are not vectors for disease, their presence in or around humans and animals may be distressing to the individuals concerned for a variety of reasons.

Given the above, there have been many efforts to keep these pests away from humans and/or animals, with varying degrees of success. These efforts have generally focussed on physical barriers, pesticidal compositions and repellent compositions.

Physical barriers such as mosquito nets, which can be impregnated with a pesticide and/or a repellent, have proven to be effective at preventing biting of an individual provided that person stays in one place, such as if a person is in bed asleep. However, such barriers are impractical for a person on the move (due to restriction of movement) or in a recreational setting, either inside or outside, where the barrier may impede the individual’s enjoyment of the surrounding environment.

Pesticides have been used with limited success in reducing or eliminating biting threats to an individual situated within an enclosed environment (e.g. while indoors). Pesticides have been provided as aerosol sprays, combustible mosquito coils and in the form of electrical devices that release pesticide into the atmosphere over a period of time. All of these forms rely upon the release of an effective amount of the pesticide into the atmosphere, with the aim of ridding a defined space of pest species during the period of effectiveness of the pesticide.

The active agents (particularly insecticides/pesticides) used in conventional mosquito coils are released slowly to the environment as the coil smoulders. As such, mosquito coils (and similar products) require an initialising period before they can provide a sufficient concentration of the pesticide to the enclosed environment to give an acceptable level of protection. In other words, the use of a mosquito coil does not provide instant protection from mosquitos, leading to a period of time where a user perceives that they are protected when they are not, resulting in an increased risk of the user being bitten by a mosquito. In places where mosquitos are already resistant to some insecticides, it is necessary for a greater amount of the insecticide to enter the environment before a mosquito will be knocked down, thereby increasing the initialisation period and so also increasing the risk of mosquito bites. Conventional mosquito coils must also burn for an extended period of time in order to provide protection. This means that there can be a fire risk if they are used indoors, such as to protect a user while they are sleeping, or at least a possibility that the user will feel uncomfortable due to the smoke generated as the coil burns.

JP201 1012056 discloses a method for controlling pests in which a pyrethroid compound having a vapour pressure at 30°C of 2x 10⁴ to 1 x10 ² mm Hg is released when a mosquito coil is burned. The specification indicates that the pyrethroid has a particle size less than 1 pm and so is carried into the atmosphere in the smoke generated by burning the coil as small particles, as well as being volatilized by heating. These coils contain a greater amount of insecticidal component compared to conventional mosquito coils, apparently to prevent the volatilization rate of the insecticidal component from decreasing as the coil burns and insecticide particles are carried off in the smoke generated by burning.

Thus, there is a need for an alternative to mosquito coils that enables fast release of the active agent(s), while providing an extended period of protection without excessive loading of insecticide and without the need for generation of smoke for an extended period to carry particulate insecticide into the atmosphere.

Summary of Invention

In a first aspect, there is provided an insect repellent composition comprising:

a vapour-active pyrethroid;

a flammable bulk material; and

a binder;

wherein the vapour-active pyrethroid is selected from one or more of the group selected from meperfluthrin, renofluthrin, heptafluthrin and, more particularly, metofluthrin, transfluthrin, and dimefluthrin, and the vapour-active pyrethroid is present in an amount so as to provide a release rate such that:

where the pyrethroid is metofluthrin, the release rate is from 0.05 to 0.30 mg per minute;

where the pyrethroid is transfluthrin, the release rate is from 0.15 to 0.45 mg per minute;

where the pyrethroid is dimefluthrin, the release rate is from 0.05 to 0.50 mg per minute;

where the pyrethroid is meperfluthrin, the release rate is from 0.04 to 0.40 mg per minute;

where the pyrethroid is renofluthrin, the release rate is from 0.05 to 0.50 mg per minute; and

where the pyrethroid is heptafluthrin, the release rate is from 0.05 to 0.50 mg per minute.

In a second aspect, there is provided a method of preparing an insect repellent composition in accordance with the present invention comprising the steps of:

a) providing a vapour-active pyrethroid;

b) providing a flammable bulk material;

c) providing a binder; and

d) mixing the vapour-active pyrethroid, flammable bulk material and binder with the addition of water.

In a third aspect, there is provided an article comprising an insect repellent composition in accordance with the present invention. In a fourth aspect, there is provided a kit comprising an article in accordance with the present invention and a base for supporting the article

In a fifth aspect, there is provided a method of repelling insects, wherein the method involves igniting an insect repellent composition in accordance with the present invention to repel insects.

Description

The present invention relates to an insect repellent composition comprising a vapour-active pyrethroid. It relates additionally to articles comprising the insect repellent composition and methods for preparing the composition and articles made therefrom. The present invention relates further to a kit containing such articles together with a base to support the article. It relates still further to a method of repelling insects, wherein the method involves igniting an insect repellent composition to repel insects. The composition of the invention comprises a flammable bulk material and a binder, and may optionally contain a preservative and excipients or other additives. The vapour-active pyrethroid is selected from one or more of the group consisting of meperfluthrin, renofluthrin, heptafluthrin and, more particularly, metofluthrin, transfluthrin, and dimefluthrin, and is present in an amount so as to provide a release rate such that:

When used herein, the term“repel” or its equivalents,“repelling or“repellent” refer generally to deterring insects from entering or remaining in a locus or deterring them from landing on humans and/or animals if they enter the locus. This includes the situation where behavioural impacts of exposure such as confusion and disorientation lead to an inability to coordinate landings on a human and/or animal target as well as situations where they are knocked down or killed.

When used herein, the term“release rate” is the product of the amount of the pyrethroid present in a composition and its evaporation rate divided by the burning time of the bulk material. The person skilled in the art will appreciate that the release rate for each of the pyrethroids may differ, but still achieve the same effect, provided that the release rate enables a sufficient amount of pyrethroid to be released to the environment to cause insect knockdown. The present invention achieves effective knockdown without using excessive quantities of pyrethroids in the composition, there being recognition by the present inventors that a relatively low concentration of pyrethroid in a flammable bulk material can be effective in certain circumstances (e.g. indoors or in enclosed space).

When used herein, the term“evaporation rate” means the proportion of pyrethroid present in a composition that is released to the atmosphere as vapour when a composition burns. This will be less than 100% as, for example, some of the pyrethroid may be degraded as the composition burns.

When used herein, the term“burning time” means the time for which an article made from the compositions disclosed herein burns before it is consumed or reaches the point where combustion can no longer be supported.

In an embodiment, the pyrethroid may be metofluthrin and the release rate may be from 0.05 to 0.30 mg per minute.

In an embodiment, the pyrethroid may be dimefluthrin and the release rate may be from 0.05 to 0.50 mg per minute.

In an embodiment, the pyrethroid may be transfluthrin and the release rate may be from 0.15 to 0.45 mg per minute.

In an embodiment, the pyrethroid may be meperfluthrin and the release rate is from 0.04 to 0.40 mg per minute.

In an embodiment, the pyrethroid may be renofluthrin and the release rate is from 0.05 to 0.50 mg per minute. In an embodiment, the pyrethroid may be heptafluthrin and the release rate is from 0.05 to 0.50 mg per minute.

In an embodiment, metofluthrin may be provided in an amount within a composition disclosed herein such that a release rate of from 0.08 to 0.27 mg per minute is achieved. In an embodiment transfluthrin may be provided such that a release rate of from 0.16 to 0.45 mg per minute may be achieved. In an embodiment, dimefluthrin is provided such that a release rate of from 0.06 to 0.21 mg per minute may be achieved.

The person skilled in the art will be able to determine a suitable amount of the pyrethroid for inclusion in the composition within the ranges for the release rate set out above. In an embodiment, metofluthrin may be present in an amount of from 0.10 to 5.00% w/w, preferably in an amount of from 0.50 to 3.00% w/w, more preferably in an amount of from 0.35 to 0.66%w/w. In an embodiment, transfluthrin is present in an amount of from 0.1 to 5.00% w/w, preferably in an amount of from 1 .00 to 3.00 % w/w, more preferably in an amount of from 0.56 to 1 .00%w/w. In an embodiment, dimefluthrin may be present in an amount of from 0 to 5.00% w/w, preferably in an amount of from 1 .00 to 3.00 % w/w, more preferably in an amount of from 0.24 to 1.10%w/w.

The pyrethroid can be provided in any physical form. In an embodiment, the pyrethroid may be provided in the form of the compound per se. The compounds may be in solid form, semi-solid or in liquid form.

Typically when the compound per se is provided, it may be designated as“technical grade”. In an alternative embodiment, the pyrethroid may be provided in the form of an emulsifiable concentrate. In a still further embodiment, the pyrethroid may be provided in the form of a microemulsion.

Any suitable flammable bulk material may be used. In an embodiment, the flammable bulk material may be a powdered form of a substance selected from one or more of the group consisting of wood, sawdust, paper, cardboard, coconut shell, flour made from leaves or nutshells other than coconut shell, jute, sugarcane bagasse, rice husks, tea refuse, coffee refuse, charcoal, and pyrethrum marc.

In an embodiment, the flammable bulk material may be a substance selected from one or more of the group consisting of wood flour, coconut shell powder, charcoal powder, and pyrethrum marc. The person skilled in the art will be able to determine a suitable amount of the flammable bulk material for inclusion in the composition. The amount of the flammable bulk material will be influenced by the flammability of the material chosen and the desired burning time, as well as by the nature of the other components in the composition. In an embodiment, the flammable bulk material may be provided in an amount of from 60 to 95% w/w, preferably from 70 to 90% w/w, more preferably from 75 to 85% w/w.

Any suitable binder may be used. In an embodiment, the binder may be selected from one or more materials selected from Joss powder, a-starch, Makko powder, tabu powder, carboxymethyl cellulose, guar gum, tapioca starch, tamarind starch, and tamarind kernel powder.

In an embodiment, the binder may be selected from one or more materials selected from Joss powder, a-starch, Makko powder, tabu powder, carboxymethyl cellulose, and guar gum.

In an embodiment, the binder may be Joss powder and/or a-starch. In an embodiment the ratio of Joss powder to a-starch is from 4:1 to 6:1 .

The person skilled in the art will be able to determine a suitable amount of binder for inclusion in the composition. The amount of binder will be influenced by the binding strength of the binder, as well as by the nature of the other components in the composition. In an embodiment, the binder may be provided in an amount of from 5 to 40% w/w, preferably from 10 to 30% w/w, more preferably from 15 to 20% w/w.

In an embodiment, the insect repellent composition may further comprise a preservative. For example, the preservative may be selected from one or more materials selected from sodium dehydroacetate, potassium sorbate and sodium benzoate (e.g. sodium dehydroacetate and sodium benzoate, such as sodium dehydroacetate).

The person skilled in the art will be able to determine a suitable amount of preservative for inclusion in the composition. The function of the preservative is to prevent the growth of mould and microorganisms that may otherwise affect the performance or appearance of an article comprising the composition. The amount of preservative will be influenced by the desired shelf-life, as well as by the nature of the other components in the composition. The preservative may be provided in an amount of from 0 to 5% w/w, preferably from 0.05 to 3% w/w, more preferably from 0.1 to 1 % w/w. In an embodiment, the insect repellent composition further comprises other additives or excipients. Other additives include but are not limited to emulsifying agents, accelerants or oxygen suppliers for the fuel, retardants, preservatives, colouring agents, and perfumes. These may be incorporated into the composition or, in some cases, may be applied as an external coating to an article formed from the composition.

A colouring agent enables an article comprising the composition to be coloured for aesthetic reasons. In an embodiment, the colouring agent may be present in an amount of from 0 to 5% w/w, more preferably from 0.1 to 0.5% w/w. Suitable colouring agents include but are not limited to malachite green, carmoisine red and rhodamine B. The presence of a perfume in an article provides a consumer friendly scent when the article is burned. In an embodiment, the perfume may be present in the article in an amount of from 0 to 1 % w/w, more particularly from 0.1 to 0.5% w/w. Suitable perfumes include but are not limited to jasmine or other floral oils or synthetic versions thereof. Joss powder may also function as a perfume. Perfumes are generally introduced to the surface of an article by dipping after the article has been formed.

An emulsifying agent may be present in the composition. The emulsifying agent may be combined with the pyrethroid before it is added to the composition, or the emulsifying agent and the pyrethroid may be added separately. In a particularly advantageous embodiment the emulsifying agent is introduced to the composition through the use of an emulsifiable concentrate (EC) which contains the pyrethroid in solution in an organic solvent as well as at least one emulsifying agent. Typically, the emulsifying agent may be present in the EC in an amount of from 5 to 25% w/w, preferably from 10 to 20% w/w. A range of emulsifying agent may be used including but not limited to any one or a combination of anionic, cationic, zwitterionic, nonionic and polymeric surfactants. Solvents typically used in EC formulations include hydrocarbon fluids e.g. de-aromatised fluids, isoparaffinic fluids and aromatic fluids.

An oxygen supplier or accelerant, if present, acts by increasing the rate at which the substrate combusts. The oxygen supplier or accelerant may be present in an amount of from 0 to 5% w/w. Suitable accelerants or oxygen suppliers for the fuel include but are not limited to potassium nitrate and lead acetate. A retardant, if present, acts to decrease the rate at which the substrate combusts. The retardant may be present in an amount of from 0 to 5% w/w. Suitable retardants include but are not limited to potassium carbonate, boric acid and talc. In an embodiment, the composition may be made from:

a vapour-active pyrethroid selected from metofluthrin and dimefluthrin, singly or in combination, where the pyrethroid may be present in an amount of from 0.2 to 1 .0% w/w; covering both metofluthrin and dimefluthrin.

a flammable bulk material which may be one or more of the group consisting of wood flour, coconut shell powder, charcoal powder, and pyrethrum marc and may be present in an amount of from 70 to 90% w/w;

a binder which may be Joss powder and a-starch in a w/w ratio of Joss powder: a- starch of from 4:1 to 6:1

a preservative which may be sodium dehydroacetate, which may be present in an amount of from 0.1 to 043 0.5% w/w; and

excipients and/or additives which may be present in an amount of from 0.5 to 5% w/w.

In an embodiment, a 1.3 to 1 .5 g dosage form of the composition containing at least 0.25% w/w of metofluthrin and/or dimefluthrin is provided. Such a composition is capable of providing a KT₅o of from 7.0 minutes to 10 minutes in a 30 m³ room when tested using Culex quinquefasciatus in a free fly test immediately following substantially complete pyrolysis of the composition. The composition further provides a KT₅o of from 21 minutes to 60 minutes under the same conditions 8 hours thereafter. Typically, the dosage forms disclosed herein may be capable of providing a KT₅o of from 7.0 minutes to 8.5 minutes following substantially complete consumption of the composition and a KT₅o of from 22 minutes to 33 minutes 8 hours thereafter.

In an embodiment, the composition may further comprise water. Water is generally added to facilitate mixing and shaping the composition. Water will generally be removed by drying once the composition has been shaped, though some residual water may remain in the composition and article following formation.

In addition, meperfluthrin, renofluthrin, heptafluthrin and transfluthrin may also be used in similar compositions to those outlined above for metofluthrin and dimefluthrin. In these compositions, meperfluthrin, renofluthrin, heptafluthrin and transfluthrin may be present alone or in combination with one or more of the other active agents mentioned herein (including metofluthrin and dimefluthrin).

The person skilled in the art will understand that compositions of the present invention may be prepared in a variety of ways and then incorporated into an article. Typically the flammable bulk material and binder are ground to powder form, combined, and added to water containing the pyrethroid and other materials such as dye, fragrance, binder and preservatives. The insect repellent composition so produced takes the form of a dough, and may be formed into an article.

The article can be any article, including in the conventional form of a coil or a stick, but can also include other arrangements. For example, the composition may be provided in a form where it is contained within a vessel or a container and will be ignited therein. Such vessel or container would be partially open to the atmosphere. For example, it could have an opening exposing the insect repellent composition, or the insect repellent composition may be located in a chamber within the article with vents from the chamber so that vaporized pyrethroid may be introduced to the atmosphere.

It will be appreciated that an article may take the form of a coil or a stick. Coils may be formed as planar circular, hexagonal or other shaped helices in a process which involves rolling or pressing a sheet of dough formed in the process described above to a uniform thickness, followed by cutting of coils and baking to remove moisture. Coated sticks may be prepared by coating a thin wooden stick with dough formed in the process described above.

Alternatively, moulding or other shaping processes (e.g. vacuum forming) could be employed to shape dough formed in the process described above.

In an embodiment, an article is moulded from an insect repellent composition. In an embodiment a base is moulded into the article. Alternatively a base may be supplied with the article for insertion therein prior to use. For example, a small aperture can be incorporated or formed in the article, and this can be used to locate the article on an upstanding pin, which forms part of a stand for the article. This stand may also form part of a dish or tray which is used to collect the ashes of the combusted article.

A moulded article according to the present invention can be formed into any suitable shape. The article may be spiral-shaped or may be formed into a rod, a plate, a cylinder, a prism, a ball, a pyramid or a cone. A pyramid will have an n-sided polygonal base where n is 3, 4 or more, say 3 to 8, preferably from 3 to 6 and typically 3 (i.e. a triangular-based pyramid) or (i.e. a square-based pyramid). A prism will have an n-sided base polygonal base, a second base which is a translated copy of the base, and n other faces joining corresponding sides of the two bases, where n is 3, 4 or more, say 3 to 12, preferably from 4 to 8 and typically 4 (i.e. a cube or rectangular prism), 6 or 8. The article may be truncated, for example, a truncated cone or pyramid. The article can be any shape provided it is feasible to ignite the article and maintain it in a disposition so that burning continues for the desired period. The person skilled in the art will appreciate that certain shapes may be moulded easily, but also that the moulding process may dictate a deviation from the general description of the shape. For example a moulding process may dictate that an indentation is formed in an article to receive a support member during the moulding process or to facilitate removal from the mould. An indentation could also be provided to facilitate stacking of the moulded article if, for example, it is generally conical or generally pyramidal in shape. Typically an indentation may be provided in the base but there may also be a depression, dent, dimple or opening formed in the top surface or on a side, if desired.

The person skilled in the art will appreciate that certain shapes may need to be supported to ensure that burning continues while others, such as a cone-shape or a cylinder, are self- supporting so can burn without toppling provided that they are placed on a surface which will not ignite. The shape of an item may be adjusted to make it more stable, for example, by adding a flange to increase the area in contact with a supporting surface. The shape may also be adjusted for other purpose such as by incorporating tabs to facilitate handling. The article may include grooves on any surface or may be patterned in any way. The article can be formed from two or pieces that are joined together in any suitable way.

In an embodiment, the moulded article may be self-supporting.

In an embodiment, the moulded article may be generally cone-shaped. It will be appreciated that a generally cone-shaped article may be truncated and may contain an indentation in either the top surface (if truncated) or the base, or both, and may include other structural elements as set forth above.

Typically a moulded article according to the present invention weighs from 0.5 to 5.0g, preferably 0.8g to 3.0g, most preferably 1 .0 to 2.0g. The weight is influenced by a desire for a typical burning time. In an embodiment, it is desirable for the moulded article to burn for ³10 to 60 minutes, preferably ³15 to 40 minutes, most preferably ³20 to 30 minutes. In particularly advantageous embodiments the current invention provides a small and fast burning product to provide both rapid and extended protection against insects such as mosquitos. A relatively small cone will burn more quickly than a larger cone formulated in the same way. The smaller cone will give protection against insects more rapidly than the larger cone, albeit with slightly lesser duration for the protection. The burning time may also be influenced by the formulation of the cone. For example, addition of an accelerant will increase the burn time. Selection of the flammable bulk material may also influence the burn time. Accordingly these parameters are selected to achieve a burn time that will provide protection for an appropriate period. A shorter burn time is selected where immediate protection is more important and a longer burn time where the duration of protection is to be emphasised.

The weight of a moulded article can also be influenced by the form in which the pyrethroid is supplied. When the pyrethroid is supplied in the form of an emulsifiable concentrate, while not wishing to be bound by theory, it is believed that surfactants and/or organic solvents in the emulsifiable concentrate are present in amounts sufficient to give the insect repellent composition an oily texture, which makes it difficult to mould to shape. However, this may be solved by increasing the product size which, in turn, makes moulding to a self-supporting shape such as cone-shape desirable.

In an embodiment, an article comprising a composition in which an emulsifying agent is present, such as one where the pyrethroid is provided in the form of an emulsifiable concentrate or microemulsion, may be formed in a self-supporting shape, such as a cone- shape.

The amount of pyrethroid in each moulded article may be selected so as to achieve the desired release rate. To a greater or lesser extent this will be determined by the size of the moulded article. The person skilled in the art can adjust the components of the composition and the size and shape of the moulded article to achieve a predetermined burning time, and thereby achieve release of the pyrethroid at the desired rate.

The present invention also provides a kit comprising an article comprising an insect repellent composition and a base for supporting the article.

In an embodiment, the article may be friable to an extent, and the base may be adapted for insertion into the article. In particular, the base typically comprises a portion adapted for penetrating the article and a portion which serves to support the article once it is secured to the base. However, the base could equally well contain support members for supporting the article without penetration.

In one arrangement, the article may include an aperture where the base is adapted to engage the aperture. In an alternate or additional arrangement, the stand may comprise a dish or tray for collecting the ashes of the combusted article The kit may further comprise instructions for use.

The method of the present invention involves igniting an insect repellent composition to repel insects. Generally, this method involves igniting one or more articles containing a composition according to the invention.

It will be appreciated by the person skilled in the art that insects may be killed as the pyrethroids are insecticidal. The person skilled in the art will further appreciate that knocking down or killing the insects serves the purpose of repelling insects, and so protects a person within a locus protected by a burnt article or articles of the invention, from insect bites. The person skilled in the art will also appreciate that the behavioural impacts of exposure on the insect, such as confusion and disorientation lead to an inability to coordinate landings on a human and/or animal target, and that this also serves the purpose of repelling insects.

In an embodiment, the insect repellent composition can be ignited within an enclosed space. In particular, the insect repellent composition may be ignited indoors, such as in bedroom to repel insects while the occupant sleeps.

The number and spacing of moulded articles according to the present invention is determined by a number of factors. If the use is indoors, the size and shape of the room will influence the number of said articles to be placed in each room. If the use is in a partially open space the size and shape of the space will influence the number of said articles to be placed in each space. This will also be affected by, for example, the degree to which the space is enclosed and the presence or absence of a breeze. The size of the moulded article and its pyrethroid content will also influence the number of said articles to be placed in each room or space. Typically a moulded article according to the invention can provided coverage for a space in an enclosed room of <12.0 m², this being a typical room size.

The compositions of the invention are active against a range of insects, particularly flying insects. In an embodiment, the insect is selected from one or more of the group consisting of mosquitos, biting midges, sand flies, black flies, house flies, bush flies, march flies, horse flies, bees, wasps, ants, cockroaches, leeches, ticks and mites.

In an embodiment, the insect is a mosquito.

The person skilled in the art will appreciate that insects in some places have become resistant to insecticides commonly used in those areas. The person skilled in the art will appreciate that the compositions of the invention, which provide extended periods of protection, are likely to be particularly useful in epidemic situations where exposure to mosquitos has to be minimised or even eliminated.

Examples

Materials and Methods

Metofluthrin and dimefluthrin were provided as SumiOne™5% Emulsifiable Concentrate and Detrans™ 1209 5% Microemulsion respectively, both of which were obtained from Sumitomo Chemical Asia (Singapore). Transfluthrin were of technical grade or analytical standard, and were obtained from Sumitomo Chemical Company, LTD (JAPAN).

Standard mosquito coils containing Pynamin Forte 0.2% w/w (also referred herein as Malaysia Standard reference coil) were obtained from a retail shop. These coils are recommended by the Department of Standards Malaysia, as detailed under Household insecticide products - physical, chemical and biological efficacy requirements - mosquito coil (Fourth revision) MS 23: PART 1 :2006 Malaysia: Department of Standards Malaysia; 2006.

A paper-based insecticide (also referred herein as transfluthrin-impregnated paper) was obtained for comparison purposes from Godrej, Indonesia. This paper burns for around three minutes and is impregnated with around 4 mg of transfluthrin.

Female mosquitos of the Culex quinquefasciatus species were 2-5 days old. The mosquitos were of a susceptible strain that were obtained from a laboratory.

Resistant field mosquitos ( Aedes aegypti) were collected from Gombak district, Selangor, Malaysia, a dengue hotspot (February/March 2017).

Unless otherwise stated, other chemicals were obtained from standard commercial suppliers.

A large chamber (L 4.0m x W 3.0m x H 2.5m = 30 m³) was used in the below examples, unless otherwise specified. Example 1

Formulation and Dispenser

Table 1 below lists the ingredients that are present in the insecticide composition.

Table 1

Joss powder, coconut shell powder and alpha starch were weighed and mixed well to form a powder mixture. Sodium dehydroacetate was weighed into a beaker and to it was added water to form a clear solution. The sodium dehydroacetate solution and a metofluthrin composition (SumiOne™ 5%EC with 5.05% w/w metofluthrin) were then added to the powder mixture and the beaker that had contained the solution was rinsed with water, which was also added to the powder mixture. The resulting mixture was kneaded to form a dough and then the dough was moulded using a cone-shaped mould (internal dimension of cone mould provided a cone with a height of 3.00 cm and a broadest diameter of 1.5 cm), with a target weight of from 2.50 to 2.70 g per cone while the dough is wet (from 1 .30 to 1.50 when dried). The wet cones were dried in an oven under heating at 60^SC until a constant weight was achieved (approximately 3 hours).

It will be appreciated that the amount of water to add into the powder mixture will vary depending on the quality of the base material used.

The above procedure illustrates only one possible method for preparation of the insecticide composition. Other known methods for preparation of insecticides could also be used, provided it results in an insecticide having the composition that is provided by Table 1 . Example 2

Laboratory Trials

The dried cones containing ~5 mg of metofluthrin per cone (prepared by procedure of Example 1 ) was then compared to the transfluthrin-impregnated paper and the Malaysia Standard reference coil (containing 0.20 % w/w Pynamin Forte) in a large chamber having four walls and having a volume of 30 m³. The test protocol uses the free flying method and the procedure used for each of the above is described in more detail below.

Mosquito Coil (Malaysian Standard) Test Method

A smouldering coil was clipped onto a metal holder and after the initial weight had been recorded it was immediately introduced into the middle of the large chamber followed by immediate release of one hundred female mosquitoes ( Culex quinquefasciatus) into the chamber. Mosquitoes knocked down (turned upside down) were counted at appropriate intervals for up to 120 minutes. At the end of the observation period, the coil was weighed again to calculate the burning rate. No fan was used in this test and each test below was repeated between 3 to 5 times.

Cone Test Method

A dried cone was evaluated for knockdown effectiveness at 0, 4 and 8 hours after its introduction into the large chamber. Prior to testing, one cone was placed onto a metal plate in the centre of the chamber and was then ignited. The flame was quickly extinguished and was left to smoulder until the entire cone was spent.

In an initial test immediately after ignition, one hundred female mosquitoes ( Culex quinquefasciatus) were released into the chamber. Fresh batches of one hundred female mosquitoes were released into the chamber at 4 and 8 hours from the initial ignition. In each case, the mosquitos knocked down (turned upside down) were counted at appropriate intervals for up to 120 minutes from the release time and the KT₅o values estimated using Probit Analysis.

Impregnated Paper Test Method

A paper impregnated with ~4mg of transfluthrin was evaluated for knockdown effectiveness at 0, 4 and 8 hours after its introduction into the large Peet Grady chamber. Prior to testing, one piece of paper was placed onto a metal plate in the centre of the chamber and was then ignited at one side only. The flame was quickly extinguished and was left to smoulder until the entire paper was spent. In an initial test immediately after ignition, one hundred female mosquitoes ( Culex quinquefasciatus) were released into the chamber. Fresh batches of one hundred female mosquitoes were released into the chamber at 4 and 8 hours from the initial ignition. In each case, the mosquitos knocked down (turned upside down) were counted at appropriate intervals for up to 120 minutes from the release time and the KT₅o values estimated using Probit Analysis.

Results

The results obtained in the tests are summarized in Table 2.

Table 2

The test data above demonstrate that the cone provided immediate and extended protection from mosquitos as soon as it is ignited for up to 8 hours. In contrast, while the paper provides useful protection immediately upon burning, it has limited effectiveness following its ignition. As shown, the coil takes a significant amount of time before it starts to provide useful protection. The experiment of Example 2 is repeated but the comparison was done against the Malaysian standard reference coil containing 0.6 % w/w Pynamin Forte. It was found that at least 7.20 mg of metofluthrin is required in the composition to achieve the same or lower KT₅o values than the reference. Example 3

Cones containing metofluthrin were compared to cones containing other vapour-active pyrethroids and against the Malaysian Standard coil.

Cones

The recipe and method of Example 1 (60^sC-drying) was used to manufacture cones containing one of metofluthrin, dimefluthrin, transfluthrin and profluthrin. The amount of active agent in each cone (based on pure active agent) is adjusted and listed in Table 3 below.

Test Method

The test method set out in Example 2 for the cone was repeated for each of the cones containing metofluthrin, dimefluthrin, transfluthrin and profluthrin, except that data was only collected once at 8 hours after the initial ignition.

Results

The results obtained in the tests are presented in Table 3 below.

Table 3

As shown in Table 3, dimefluthrin was more active than the other pyrethroids tested, with at least metofluthrin, dimefluthrin and transfluthrin proving effective for up to 8 hours over a range of concentrations (effectiveness determined based on comparison to standard coil’s KT₅o value). Reference Example 1

Susceptibility check on lab strain and Gombak strain Aedes aegypti

The susceptible laboratory and field strain Aedes aegypti (collected from dengue endemic area Gombak district, Selangor, Malaysia) were compared for their susceptibility to the Malaysian Standard Coil. The tests were done in a Peet Grady chamber (L 1 8m x W 1 8m x H 1 8m = 5.8 m³) using Pynamin Forte coil with various concentrations.

Coil Test Method

A white paper was placed on the floor of a Peet Grady Chamber (5.8 m³). A smoldering coil was clipped onto a metal holder and after initial weight has been recorded it was immediately introduced into the Peet Grady Chamber followed by immediate release of 100 female mosquitoes into the chamber. Mosquitoes that landed (landed and rested on the floor) and knocked down (turned upside down) were counted at appropriate time intervals for up to 120 minutes. The time required to land and knockdown 50% of test population (l_T₅o and KT₅o respectively) were analysed and estimated using Probit Analysis.

Results

^#1 Bio-efficacy testing was not conducted. #² Landing or knockdown efficacy on 50% of the test population was not achieved within the testing time limit (i.e. within 120 minutes)

Table 4

The test data shows the field strain Aedes aegypti has much lower susceptibility (that is, much higher tolerance) as compared to the susceptible laboratory strain. Example 4

The efficacy of metoflut rin and dimefluthrin were evaluated in higher-dose cones against the resistant field strain Aedes aegypti. Both active agents were compared with the Malaysian Standard coil.

Cones

The recipe and method of Example 1 (60^sC-drying) was used to manufacture cones containing one of metofluthrin or dimefluthrin in an amount of 0.35 % w/w or 0.60 % w/w (based on pure active agent). This was achieved by using the same amount (for 0.35 % w/w) or reducing the amount (for 0.60 % w/w) of coconut shell powder used in the recipe of Example 1.

Coil Test Method

White paper was placed on the floor of a glass chamber (0.3 m³) and 0.5g of a mosquito coil was fixed onto a coil stand and both of its ends were ignited. Once the coil was completely burnt out, twenty female mosquitos were released into the chamber through a sliding door and then timing was started. The landing and knockdown of mosquitos were observed and recorded at appropriate time intervals for up to 30 minutes. Landing time (LT₉₀) and knockdown (KT₅o) values were estimated using Probit analysis.

Cone Test Method

White paper was placed on the floor of a glass chamber (0.3 m³) and a cone (0.35 % w/w or 0.60 % w/w of metofluthrin or dimefluthrin) was placed on a metal plate and ignited at it tip. The flame was quickly extinguished and the cone left to smoulder until it was completely burnt out. Twenty female mosquitos were released into the chamber through a sliding door and then timing was started. The landing and knockdown of mosquitos were observed and recorded at appropriate time intervals for up to 30 minutes. Landing time (LT₉₀) and knockdown (KT₅o) values were estimated using Probit analysis. Results

The results are provided in Table 5 below.

Table 5

As shown, the coil was unable under the conditions tested to provide a quick knockdown of resistant mosquitos. However, both dose levels of metofluthrin and dimefluthrin were able to provide effective knockdown of mosquitos and were similarly effective (as the 95% confidence limits overlap). As such, cones of the type disclosed here are effective at deterring and killing mosquitos even where they are from a resistant strain.

Example 5

Effect of burning speed

Cones (dosed with ~ 5 mg of metofluthrin) formulated to have various burning speed were evaluated in a large chamber (30 m³). The burning speed of cone was altered by (a) changing the cone composition by addition of potassium nitrate to accelerate the burning speed and (b) varying the cone size. Details of the formulations are set out in Table 6 below.

Table 6

The estimated evaporation rate is -60%.

Mosquito Coil (Malaysian Standard) Test Method

A smouldering coil was clipped onto a metal holder. After recording its initial weight, the coil was immediately introduced into the large chamber. This was followed immediately by the release of 100 female mosquitoes into the chamber. After the mosquito release, time was kept so that the timing for knockdown could be observed. The coil was allowed to burn continuously in the chamber. Mosquitoes knocked down (those that turned upside down) were counted at intervals for up to 2 hours. At the end of the observation period, the coil was weighed again to allow calculation of the burning rate.

Cone Test Method

The biological efficacy of the cones from Table 5 was evaluated in the same large chamber at 0 hour (initial), 4 hour and 8 hours. Prior to testing, one cone was placed onto a metal plate in the middle of the chamber floor. Then the sample was ignited from the tip of the cone. The flame was quickly extinguished and the cone was left to smoulder until the whole cone was consumed. a) Initial release of mosquitoes

As an initial step, 10 female mosquitoes were released into the chamber immediately after ignition (0 hour). Further releases were made every 1 minute release up to 10 minutes. On each occasion 10 female mosquitoes were released into the chamber (total insect per chamber =1 10). b) Delayed release of mosquitoes

A fresh batch of insects (100 female mosquitoes) was released into the chamber after 4 hours and again after 8 hours.

Knockdown time was measured from immediately after insects were released. Mosquitoes knocked down (turned upside down) were counted at appropriate intervals for up to 2 hours.

KT so values (from the knockdown data) were estimated using Probit Analysis.

The results are shown in Table 7.

Table 7

The test data presented in Table 7 shows that the cone with a burning time of 20 to 30 minutes provided particularly good knockdown efficacy for both immediate and extended protection (not less than 8 hours) against mosquito. Cones with a shorter burning time still provide protection after an extended period but to a slightly lesser extent. Cones with a burning time longer than 20 to 30 minutes provide slightly a lesser level of protection initially. A comparison to the reference coil shows that an adequate level of protection is provided both initially and for an extended period for all cone formulations. Example 6

Incense cones dosed with ~5 mg of one of renofluthrin, meperfluthrin and heptafluthrin respectively were manufactured (using the recipe and method of Example 1 ) and evaluated using the typical room method (in a large chamber of 30 m³). The burning time of the dosed incense cone was from 20 to 30 minutes, with an evaporation rate of at least 60%. Details of the tests are described in more detail below.

Mosquito Coil (Malaysian Standard) Test Method

A smoldering coil was clipped onto a metal holder. After recording its initial weight, the coil was immediately introduced into a large chamber, followed by immediate release of 100 female mosquitoes ( Aedes aegypti, susceptible strain) into said chamber. After the mosquitoes were released, the timing for knockdown observation was commenced immediately. The coil was allowed to burn continuously in the chamber. Knockdown mosquitoes (those that turned upside down) were counted at appropriate intervals for up to 2 hours. At the end of the observation period, the coil was weighed again to calculate the burning rate.

Cone Test Method

Biological efficacy of dosed incense cones were evaluated in the large chamber at 0 hours (initial) and at 8 hours. Prior to testing, a dosed incense cone was placed onto a metal plate at the middle of the chamber floor (containing one of the active ingredients). The cone was then ignited from the tip. The flame was quickly extinguished and the cone was left to smoulder until it had completely burnt off. a) Immediate release of mosquitoes

For the initial test right after the ignition (0 hour), 100 female mosquitoes ( Aedes aegypti, susceptible strain) were released immediately into the chamber. b) Delayed release of mosquitoes

For the 8 hours delayed-release test, 100 female mosquitoes ( Aedes aegypti, susceptible strain) were released into the chamber after 8 hours. The knockdown time was commenced immediately after the insects were released. The number of mosquitoes knocked down (turned upside down) were counted at appropriate intervals for up to 2 hours. The KT₅o values (from the knockdown data) were estimated using Probit Analysis. Results

^#1 Delayed release: Fresh batch of insects (100 female mosquitoes of Aedes aegypti) were released into the chamberat 8 hours.

Table 8 It was observed that an incense cone dosed with ~5mg of renofluthrin, meperfluthrin and heptafluthrin respectively, at a burning rate of 0.09 to 0.14 mg/minute, showed faster knockdown efficacy than the Malaysian Standard reference coil.

Claims

1. An insect repellent composition comprising:

a vapour-active pyrethroid;

a flammable bulk material; and

a binder;

wherein the vapour-active pyrethroid is selected from one or more of the group selected from metofluthrin, transfluthrin, dimefluthrin, meperfluthrin, renofluthrin and heptafluthrin, and the vapour-active pyrethroid is present in an amount so as to provide a release rate, such that:

2. The composition of claim 1 , wherein the pyrethroid is metofluthrin and the release rate is from 0.05 to 0.30 mg per minute.

3. The composition of claim 1 , wherein the pyrethroid is dimefluthrin and the release rate is from 0.05 to 0.50 mg per minute.

4. The composition of claim 1 , wherein the pyrethroid is transfluthrin and the release rate is from 0.15 to 0.45 mg per minute.

5. The composition of claim 1 , wherein the pyrethroid is meperfluthrin and the release rate is from 0.04 to 0.40 mg per minute.

6. The composition of claim 1 , wherein the pyrethroid is renofluthrin and the release rate is from 0.05 to 0.50 mg per minute.

7. The composition of claim 1 , wherein the pyrethroid is heptafluthrin and the release rate is from 0.05 to 0.50 mg per minute.

8. The composition of any one of the preceding claims, wherein the pyrethroid is provided in the form of the compound per se.

9. The composition of any one of claims 1 to 7, wherein the pyrethroid is provided in the form of an emulsifiable concentrate or as a microemulsion.

10. The composition of any one of the preceding claims, wherein the flammable bulk material is a powdered form of a substance selected from one or more of the group consisting of wood, sawdust, paper, cardboard, coconut shell, flour made from leaves or other nutshells, jute, sugarcane bagasse, rice husks, tea refuse, coffee refuse, charcoal, and pyrethrum marc.

1 1 . The composition of Claim 10, wherein the flammable bulk material is a substance selected from one or more of the group consisting of wood flour, coconut shell powder, charcoal powder, and pyrethrum marc.

12. The composition of any one of the preceding claims, wherein the flammable bulk material is provided in an amount of from 70 to 90% w/w.

13. The composition of any one of the preceding claims, wherein the binder is selected from one or more materials selected from Joss powder, a-starch, Makko powder, tabu powder, carboxymethyl cellulose, guar gum, tapioca starch, tamarind starch, and tamarind kernel powder.

14. The composition of claim 13, wherein the binder is Joss powder and/or a-starch

15. The composition of any one of the preceding claims, wherein the binder is provided in an amount of from 5 to 40% w/w.

16. The composition of any one of the preceding claims, further comprising a preservative.

17. The composition of claim 16, wherein the preservative is selected from one or more materials selected from sodium dehydroacetate, potassium sorbate and sodium benzoate.

18. The composition of either one of claims 16 or 17, wherein the preservative is provided in an amount of from 0.1 to 1 .0% w/w.

19. The composition of any one of the preceding claims further comprising at least one emulsifying agent.

20. The composition of any one of the preceding claims further comprising at least one accelerant or oxygen supplier for the fuel.

21 . The composition of any one of the preceding claims further comprising at least one retardant.

22. The composition of any one of the preceding claims, further comprising at least one colouring agent and/or perfume.

23. A method of preparing an insect repellent composition as defined in any one of the preceding claims comprising the steps of:

a) providing a vapour-active pyrethroid;

b) providing a flammable bulk material;

c) providing a binder;

d) optionally, providing a preservative;

e) optionally, providing at least one additive selected from the group consisting of emulsifying agents, accelerants or oxygen suppliers for the fuel, retardants, colouring agents, and perfumes; and

f) mixing the vapour-active pyrethroid, flammable bulk material and binder, and optionally the preservative and/or the at least one additive, with the addition of water.

24. The method of claim 23 further comprising the step of forming the composition into an article.

25. An article comprising an insect repellent composition as defined in any one of claims 1 to 22.

26. The article of claim 25, wherein the composition comprises a pyrethroid in the form of an emulsifiable concentrate or a microemulsion.

27. The article of either one of claims 25 or 26 wherein the article is self-supporting.

28. The article of claim 27 wherein the article is generally cone-shaped.

29. The article of any one of claims 25 to 28 which weighs from 0.5 to 5.0g.

30. The article of claim 29 which weighs from 0.8g to 3.0g.

31 . The article of claim 30 which weighs from 1 .0 to 2.0g.

32. The article of any one of claims 25 to 31 which is configured to burn for from 10 to 60 minutes.

33. The article of claim 32 which is configured to burn for 15 to 40 minutes.

34. The article of claim 33 which is configured to burn for from 20 to 30 minutes.

35. A kit comprising an article as defined in claim 25 which is not self-supporting, and further comprising a base for supporting the article.

36. A method of repelling insects, wherein the method involves igniting an insect repellent composition as defined in any one of claims 1 to 22 or an article as defined in any one of claims 25 to 34 to repel insects.

37. The method of Claim 36, wherein the insect is selected from one or more of the group consisting of mosquitos, biting midges, sand flies, black flies, house flies, bush flies, march flies, horse flies, bees, wasps, ants, cockroaches, leeches, ticks and mites.

38. The method of Claim 37, wherein the insect is a mosquito.

39. The method of Claim 38 wherein the mosquito is a mosquito that is resistant to D- allethrin.