WO2017003395A1 - Nanoencapsulated mosquito-, fly- and tick-repellent formulation - Google Patents

Nanoencapsulated mosquito-, fly- and tick-repellent formulation Download PDF

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Publication number
WO2017003395A1
WO2017003395A1 PCT/TR2016/000095 TR2016000095W WO2017003395A1 WO 2017003395 A1 WO2017003395 A1 WO 2017003395A1 TR 2016000095 W TR2016000095 W TR 2016000095W WO 2017003395 A1 WO2017003395 A1 WO 2017003395A1
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Prior art keywords
formulation
oil
agent
weight
nano
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PCT/TR2016/000095
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French (fr)
Inventor
Tuncay YILDIZTEKIN
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Entovest İlaç Ki̇mya Ve Teknoloji̇ Araştirma Merkezi̇ San. Ti̇c. Ltd. Şti̇.
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Publication of WO2017003395A1 publication Critical patent/WO2017003395A1/en

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Classifications

    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N25/00Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/26Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests in coated particulate form
    • A01N25/28Microcapsules or nanocapsules

Definitions

  • the present invention involves development of a repellent that contains natural ingredients, that has an extended effect period thanks to nano-capsule formulation type against mosquitoes that threaten human health and that can be sprayed directly onto skin again thanks to its new formulation type.
  • insects such as flies, mosquitoes and ticks.
  • the most low-cost and easiest one of such methods is to spray the chemicals that have repellent effect on insects like flies, mosquitoes and ticks or to apply them onto skin.
  • DEET diethyltoluamide
  • PMD (Para-menthane Diol) is a natural substance that is found in the leaves of Eucalyptus citriodora plant and has a menthol-like odor. As a mosquito repellent, PMD is supported as product type 19 (repellent) in EU Biocides 98/8. For this reason, it has been increasingly used recently. Aside from PMD, there are many other natural substances, which have repellent characteristics. However, since all herbal repellent oils including PMD (Para-menthane Diol) are volatile and they evaporate and lose their effects within minutes after they are sprayed, this poses problems for the application. Therefore, no long-term repellent effects that are desired can be achieved from use of this substance or all the other similar herbal repellent oils.
  • repellent used herein refers to synthetic and natural substances or various formulations that contain the formulation thereof, which are applied onto the skin or face and prevent insects such as flies, mosquitoes, ticks or bugs from coming/landing on to or moving on the surface where the substance is applied.
  • the present invention involves repellent formulations that contain various herbal oils, which have PMD (Para-menthane Diol) and/or repellent effect, alone or in combinations of two, three, four and five, etc. or in combination of all.
  • PMD Para-menthane Diol
  • lcaridin, DEET (N.N-diethyl-meta-toluamide) and IR3535® (3-(N-acetyl-N- butyi) amino propionic acid ethyl ester) and chemical molecules from the similar class are applied onto the skin as chemical spray repellents.
  • the chemical repellents from the prior art cause not only skin irritation and allergy and but also health problems through inhalation.
  • herbal PMD Geraniol, pyrethrum, Azadirachtin and/or Neem Oil, Citronella and derivatives, Lavender oil, eucalyptus oil, thyme oil, peppermint oil, cinnamon oil, turmeric oil, d-limonene or derivatives and numerous natural oil ready solutions (water based or alcohol based) are also used.
  • volatile herbal oils provide short-term protection, maximum 2 hours, against mosquitoes and other harmful insects even though they are safe to use. Considering that an average night sleep is 8 hours, there is no difference between using and not using these repellents. It is because the user must interrupt his or her sleep every two hours to reapply the herbal oil in order to prevent any mosquito problems, which is not possible for the user.
  • emulsifiers and solvents are used in spray repellents that contain chemical active agent and herbal active agent in the prior art. Since such auxiliary agents are also in contact with the skin when applying, their side effects should also be taken into consideration. In particular, it should be noted that some of such auxiliary agents have negative side effects, which requires seeking for alternatives.
  • both most of the auxiliary agents and the active agents are safe and natural substances that are extracted from herbs.
  • the products are not suitable for spraying and they cannot be applied by spraying since they are formulated as microcapsules that have particle diameters greater than ⁇ ⁇ which requires high viscosity in the formulations that leads non-sprayibility. Therefore, they have not been used in the industry.
  • Abovementioned problems, which are experienced in the state of the art related to the repellent substances that may be used in insect control against flies, mosquitoes and ticks and the formulations that contain such substances, have urged inventors to produce new solutions.
  • inventors aim at providing protection against mosquitoes (Aedes spp, Culex Spp, Anopheles spp, Culiseta spp. and all mosquito types), gnats (Phlebotomus spp), sandflies, flies and all types of tick using a natural and safe repellent.
  • Another object of the invention is to develop a natural herbal spray repellent that has an effect period as long as that of and that is safer than lcaridin, DEET N,N-diethyl-meta-toluamide) and IR3535® (3-(N-acetyl-N-butyl) amino propionic acid ethyl ester), which are chemicals used as mosquito repellents, instead of such chemicals.
  • the present invention aims at eliminating the health problems caused by chemical repellents.
  • Another object of the invention is to offer a new alternative solution for resistance of mosquitoes in the prior art, which shall also be effective on resisting populations.
  • Another object of the invention is to develop a natural herbal repellent that has a longer effect period thanks to nano-capsule formulation instead of simple herbal repellents that have short effect period.
  • Another object of the invention is to manufacture repellents that are safe enough to use on even three-month old babies, in the prior art, chemical products have approvals for use for ages 7 and over while the simple herbal solutions are allowed for use for ages 3 and over.
  • Another object of the invention is to achieve a natural nano-capsule formulation repellent against mosquitoes, gnats and ticks.
  • PMD Para- menthane Diol
  • Present invention involves a nano-capsule formulation containing PMD (Para-menthane Diol) as active agent, geraniol, azadirachtin, pyrethrum/ pyrethrin, neem oil, valerian oil, peppermint oil, rosemary oil, basil oil, cinnamon oil, lavender oil, turmeric oil, eucalyptus oil, thyme oil, garlic oil, citronella, citronella java, lemongrass and/or derivatives of such oils and/or one, several or all of general citrus oils as repellent agents, all or some of which are found in nano-capsule form.
  • emulsifier, solvent, carrier, capsulation agent, load exchanger, anti-freezing agent and co-solvent are used as auxiliary agents aside from the active agent in the formulation that contains repellent agent.
  • the invention in a way, relates to a repellent formulation against flies, mosquitoes, gnats or ticks and is characterized by (a) that it contains PMD (Para-menthane Diol), geraniol, azadirachtin, pyrethrum/ pyrethrin, neem oil, valerian oil, peppermint oil, rosemary oil, basil oil, cinnamon oil, lavender oil, turmeric oil, eucalyptus oil, thyme oil, garlic oil, citronella, citronella java, lemongrass, general citrus oils and/or one or several repellent active agents selected from a group consisting of such oils or their derivatives or all of the repellent active agent composing such group and (b) that it is in nano-capsule form.
  • PMD Para-menthane Diol
  • geraniol geraniol
  • azadirachtin azadirachtin
  • pyrethrum/ pyrethrin n
  • the present invention relates to a repellent formulation developed against flies, mosquitoes, gnats or ticks and is characterized by (a) that it contains PMD (Para-menthane Diol), geraniol, azadirachtin, pyrethrum/ pyrethrin, neem oil, valerian oil, peppermint oil, rosemary oil, basil oil, cinnamon oil, lavender oil, turmeric oil, eucalyptus oil, thyme oil, garlic oil, citronella, citronella java, lemongrass, general citrus oils and/or one or several repellent active agents selected from a group consisting of such oils or their derivatives or all of the repellent active agent composing such group and (b) that it is in nano-capsule form.
  • PMD Para-menthane Diol
  • geraniol geraniol
  • azadirachtin azadirachtin
  • pyrethrum/ pyrethrin neem
  • PMD Para-menthane Diol
  • PMD is used alone as a repellent agent in the formulations suitable to the invention.
  • PMD Para-menthane Diol
  • nano-capsule form in the formulation.
  • the total amount of the repellent agent ranges between 0.001 % and 99.99% by weight.
  • PMD Para-menthane Diol
  • the total amount of the repellent agent ranges between 0.001 % and 99.99% by weight.
  • the percentage ranges between 0.001% and 99.99% for the alternative or total of alternatives if more than one alternative is used.
  • one, several or all of such oils used as alternatives in the formulation as mentioned above may be used as synergists (effect booster) or as the 2 nd , 3 rd , 4 th ... active agent beside the PMD (Para-menthane Diol) in the formulation.
  • the synergist percentage may range between 0.00012% and 99.8%.
  • one or a combination selected among the group of geraniol, azadirachtin, pyrethrum/ pyrethrin, citronella, citronella java, lemon grass oil, turmeric oil, garlic oil, rosemary oil, lavender oil, valerian oil, thyme oil, basil oil, canola oil, nut oil, cinnamon oil, turmeric oil, eucalyptus oil, citrus oils and neem oil or other herbal oils having repellent affects are used as active agents as an alternative to PMD (Para-menthane Diol).
  • the percentage of alternative natural repellents range between 0.001% and 99.99% in the invention.
  • oils to be used as an alternative to PMD may either be used individually or in combination or in entirety. Furthermore one, several or all of these oils may be used together with the PMD (Para-menthane Diol) within the scope of this invention.
  • the present invention it is planned to achieve a product that is both non-toxic and suitable for spraying onto the skin, that can be sprayed and that can remain stable at lower viscosities since it has very small particle diameter by means of encapsulation of particles equal to or smaller than 10 ⁇ , preferably equal to or smaller than 0.1 um ( ⁇ 199 nm), with a natural additive by using nano-encapsulation method.
  • the suspension viscosity must be at least 700 cP in order that the particles that are larger than 1 ⁇ can suspend mechanically in the suspension. In lower viscosities, the user will have to shake the product before application since active agents composing the suspension will precipitate.
  • the size of the capsules achieved with the invention have been adjusted to be suitable to the triggers that produce ideal and fine sprays in order to allow for application onto the skin.
  • capsules that are larger than 0.1 micron cannot be easily sprayed through spray head.
  • an extra series of procedures have been performed to adjust the viscosity to allow for applying the product using spray heads.
  • studies have been conducted on both the viscosity and the capsule size; and a product that can be applied using all types of spray heads has been invented.
  • the invention involves formulation of natural herbal oils using nano-capsulation technique to achieve a repellent product.
  • the nano-capsule formulation type designed within the frame of the invention allow for achieving a long-term repellent effect of herbal oils and ideal viscosity to apply the product by using the spray technique.
  • the invention is also intended for developing the nano-capsule formulation type, in which herbal oils have never been tried as mosquito / fly / tick repellent.
  • the object of the invention is formulation type nano-capsule.
  • the purpose of developing the nano-capsule formulation type is to discover how to prolong the repellent effect and to render the viscosity of the formulation suitable for spraying. Such effect can also be achieved using the microcapsule method; however, microcapsule formulation type cannot be sprayed since it has high viscosity. Therefore, using the nano-capsule formulation type, both the repellent effect period has been prolonged and the product has been rendered suitable for application with spray method thanks to the type of formulation subject to the invention.
  • the invention is the first study ever on formulation of natural herbal oils using nano-capsule formulation type. In the prior art, herbal oils are developed as single solutions. Their effect periods are short and they contain numerous auxiliary chemicals aside from natural oils.
  • the invention also prevents the contents of the formula from penetrating into the skin thanks to nano-capsulation formulation technology.
  • a natural oil that has a single repellent active agent has been preferred for use.
  • natural oils that can be used as alternatives to PMD within the scope of the invention can be used together with PMD or in a single combination, which contains several or all of such oils.
  • the most basic property of the active agents to be used in the formulation is that they are active agent (oils) that are not soluble in water.
  • emulsifier, solvent, carrier, capsulation agent, load exchanger, anti- freezing agent and co-solvent are the auxiliary agents aside from the active agent in the formulation.
  • the emulsifier and other auxiliary agents used within the scope of the invention are safe substances that are also used in food products and that have food codex approvals. Such substances have no adverse effects on the skin.
  • the percentage of PMD (Para-methane Diol) used as the repellent active agent in the formulations suitable to the invention ranges between 0.001% and 99.00% by weight; it is preferably used by 0.001% to 75% and most preferably used by 1% to 15%, i.e. by 10%.
  • the formulations subject to the invention may contain at least one auxiliary agent selected from among emulsifier I, antifreeze, co-solvent, emulsifier II, capsulation agent I, capsulation agent II, solvent and carrier, or the combination thereof in addition to the active repellent agent.
  • auxiliary agent selected from among emulsifier I, antifreeze, co-solvent, emulsifier II, capsulation agent I, capsulation agent II, solvent and carrier, or the combination thereof in addition to the active repellent agent.
  • the emulsifier I to be used within the scope of the formulation subject to the invention ranges between 1% and 78% by weight; it is preferably used by 3% to 70% and most preferably used by 5% to 65%, i.e. by 10%.
  • the emulsifier 1 sorbitan esters and ethoxylates to be used in the formulation subject to the invention are, for example, selected from among Tween 20, Tween 80, Tween 60, Tween 40, Tween 21, Tween 65, Tween 61, Span 20, Span 40, Span 60, Span 80, Span 83, Span 85 and Span 120.
  • emulsifier 1 and/or emulsifier II can also be used in the production as emulsifier 1 and/or emulsifier II.
  • the emulsifier II to be used within the scope of the formulation subject to the invention ranges between 1 % and 80% by weight; it is preferably used by 3% to 75% and most preferably used by 5% to 70%, i.e. by 15%.
  • the emulsifier II Tristyrylphenol ethoxylate to be used in the formulation subject to the invention is, for example, selected from among Agnique TSP 15, Soprophor BSU, Soprophor CY/8 and Emulsogen TS 160.
  • the ideal emulsifier combination is sought to ensure formulation of the active agent as micro- emulsification.
  • the selected emulsifier I and emulsifier 11 are combined.
  • Other emulsifiers that can be used for the same purpose from among similar groups or different groups can also be used in the production.
  • the antifreeze agent to be used in the formulation subject to the invention is, for example, selected from among a group that is composed of monoethyleneglycol, diethyleneglycol, dipropyleneglycol and monopropyleneglycol.
  • the antifreeze agent to be used within the scope of the formulation subject to the invention ranges between 0.5% and 55% by weight; it is preferably used by 1% to 50% and most preferably used by 3% to 45%, i.e. by 5%.
  • the subject antifreeze agent is used as antifreeze and in order to support micro-emulsification.
  • Other glycols, glycol ethers and other molecules that can be used as antifreeze can also be used in the production within the scope of the invention.
  • the co-solvent to be used in the formulation subject to the invention is selected from among a group that consists of octanol, methanol, butanol, isopropanol, propanol and ethanol.
  • the co-solvent to be used within the scope of the formulation subject to the invention ranges between 0.75% and 75% by weight; it is preferably used by 3% to 70% and most preferably used by 5% to 65%, i.e. by 7%.
  • the capsulation agent to be used within the scope of the formulation subject to the invention ranges between 0.000001% and 65% by weight; it is preferably used by 0.0001% to 60% and most preferably used by 0.01% to 50%, i.e. by 0.75%.
  • the capsulation agent I to be used in the formulation subject to the invention is selected from among a group that consists of gelatin, gum Arabic, chitosan and maltodextrin.
  • the capsulation agent 1 mentioned herein is a natural component that dissolves in water and forms a capsule wall around the droplets that will be encapsulated. Natural agents and/or chemical agents that can form a capsulation wall can also be used as alternatives to the aforementioned agents within the scope of the invention.
  • the capsulation agent II to be used within the scope of the formulation subject to the invention ranges between 0.00002% and 54% by weight; it is preferably used by 0.0001% to 50% and most preferably used by 0.01% to 45%, i.e. by 0.60%.
  • the capsulation agent II to be used in the formulation subject to the invention may be selected from among a group that consists of sodium tripoliphosphate, citric acid, propionic acid and phosphoric acid.
  • the capsulation agent II mentioned herein is a capsulation initiator agent.
  • the capsulation process starts thanks to the load transfer around the emulsifier. All chemicals that can be used for the same purpose can be used as alternatives to the aforementioned agents within the scope of the invention.
  • the solvent agent to be used within the scope of the formulation subject to the invention ranges between 0.0000014% and 58% by weight; it is preferably used by 0.00001% to 55% and most preferably used by 0.0001 % to 52%, i.e. by 0.5%.
  • the solvent agent to be used in the formulation subject to the invention may be selected from among a group that consists of acetic acid and citric acid.
  • the solvent agent mentioned herein helps increase the solubility of the capsulation agent in water.
  • Other chemicals or natural substances that help increase the solubility of the capsulation agent in water can be used as alternatives to the aforementioned agents within the scope of the invention.
  • the carrier agent to be used within the scope of the formulation subject to the invention ranges between 1% and 99% by weight; it is preferably used by 3% to 95% and most preferably used by 5% to 93%, i.e. by 55%.
  • the carrier agent to be used in the formulation subject to the invention is water.
  • the carrier agent mentioned herein is the carrier medium.
  • Other carrier agents known in the technique can also be used as an alternative to water.
  • the formulation suitable to the invention can be prepared following the below-mentioned steps:
  • a solution containing the capsulation agent I is prepared
  • Emulsifier mixture is prepared

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  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
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  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
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Abstract

The present invention involves development of a repellent that contains natural ingredients, that has an extended effect period thanks to nano-capsule formulation type against flies, mosquitoes, ticks, gnats, sandflies, all types of flies and ticks that threaten human health and that can be sprayed directly onto skin again thanks to its new formulation type.

Description

NANOENCAPSULATED MOSQUITO-, FLY- AND TICK-REPELLENT
FORMULATION
FIELD OF THE INVENTION
The present invention involves development of a repellent that contains natural ingredients, that has an extended effect period thanks to nano-capsule formulation type against mosquitoes that threaten human health and that can be sprayed directly onto skin again thanks to its new formulation type.
Several methods are used as a protection against harms of insects such as flies, mosquitoes and ticks. The most low-cost and easiest one of such methods is to spray the chemicals that have repellent effect on insects like flies, mosquitoes and ticks or to apply them onto skin.
The most commonly used synthetic substance as a protection against insects like flies, mosquitoes and ticks is diethyltoluamide known as DEET. However, this commonly used substance has a toxic effect on users and may cause serious irritation. Furthermore, it is reported that those who are exposed to this substance also suffer from seizures, insomnia and mood disorders.
PMD (Para-menthane Diol) is a natural substance that is found in the leaves of Eucalyptus citriodora plant and has a menthol-like odor. As a mosquito repellent, PMD is supported as product type 19 (repellent) in EU Biocides 98/8. For this reason, it has been increasingly used recently. Aside from PMD, there are many other natural substances, which have repellent characteristics. However, since all herbal repellent oils including PMD (Para-menthane Diol) are volatile and they evaporate and lose their effects within minutes after they are sprayed, this poses problems for the application. Therefore, no long-term repellent effects that are desired can be achieved from use of this substance or all the other similar herbal repellent oils.
The term "repellent" used herein refers to synthetic and natural substances or various formulations that contain the formulation thereof, which are applied onto the skin or face and prevent insects such as flies, mosquitoes, ticks or bugs from coming/landing on to or moving on the surface where the substance is applied.
The present invention involves repellent formulations that contain various herbal oils, which have PMD (Para-menthane Diol) and/or repellent effect, alone or in combinations of two, three, four and five, etc. or in combination of all.
BACKGROUND OF THE INVENTION
In the prior art, lcaridin, DEET (N.N-diethyl-meta-toluamide) and IR3535® (3-(N-acetyl-N- butyi) amino propionic acid ethyl ester) and chemical molecules from the similar class are applied onto the skin as chemical spray repellents.
Authorities do not allow use of chemical spray repellents used in the prior art on babies and children. Furthermore, use of such repellents on adults requires great attention and care.
The chemical repellents from the prior art cause not only skin irritation and allergy and but also health problems through inhalation.
Since chemical containing repellents used in the prior art are used for long periods without any rotation, insects resist to such repellents in certain geographies.
Despite the health problems they may cause, the chemical repellents used in the prior art are preferred for their fly-mosquito repelling effects for long-term, approximately 4-6 hours. Since they have a long period of effect, these products dominate 90% of the spray/aerosol repellent market. In other words, 90 out of 100 people have to use such chemical repellents. That is to say, chemical repellents cause users to ignore the diseases that will result from the health risks such chemical repellents cause. Besides, there are no available chemical spray repellents suitable for use on babies as a protection against mosquitos and flies. Such data has led to an increase in researches looking into ways of effective and safe protection against mosquitos and other harmful insects.
In the other prior art, herbal PMD, Geraniol, pyrethrum, Azadirachtin and/or Neem Oil, Citronella and derivatives, Lavender oil, eucalyptus oil, thyme oil, peppermint oil, cinnamon oil, turmeric oil, d-limonene or derivatives and numerous natural oil ready solutions (water based or alcohol based) are also used.
However, volatile herbal oils provide short-term protection, maximum 2 hours, against mosquitoes and other harmful insects even though they are safe to use. Considering that an average night sleep is 8 hours, there is no difference between using and not using these repellents. It is because the user must interrupt his or her sleep every two hours to reapply the herbal oil in order to prevent any mosquito problems, which is not possible for the user.
In the prior art, both chemical repellents and natural herbal repellents used as sprays or aerosols are developed as water-based ready solutions, alcohol-based ready solutions or gaseous aerosols. In the prior art, alcohol is used generally in the formulation of both chemical and natural repellents. It requires evidence that such alcohol, used aside from the repellent active agent, has no health risks.
Likewise, in addition to the active agent, emulsifiers and solvents are used in spray repellents that contain chemical active agent and herbal active agent in the prior art. Since such auxiliary agents are also in contact with the skin when applying, their side effects should also be taken into consideration. In particular, it should be noted that some of such auxiliary agents have negative side effects, which requires seeking for alternatives.
In the present invention, both most of the auxiliary agents and the active agents are safe and natural substances that are extracted from herbs.
In the prior art, there were no difference between using and not using herbal repellents since they have brief and short-term effects. The fact that they are released to the market despite their negative attributes put users through unnecessary financial loss.
In the prior art, even though the spectrum is achieved with chemicals in the invention, the fact that it cannot be used in children and it causes possible health problems in adults make it impossible to benefit from the spectrum sufficiently. In the prior art, herbal repellents with simple solutions have weak effects on ticks whereas its effect on mosquitoes have a rather short term.
In the prior art, studies have been conducted to improve the effectiveness of the products by using different manufacturing methods. In this context, micro-encapsulation method was adopted in production. However, it is not safe to use such products on skin since oil droplets having particle diameter greater than 1 μιη are encapsulated with polymerization of toxic isocyanate groups such as Toluen diisocyanate.
Furthermore, in the prior art, the products are not suitable for spraying and they cannot be applied by spraying since they are formulated as microcapsules that have particle diameters greater than Ι μιη which requires high viscosity in the formulations that leads non-sprayibility. Therefore, they have not been used in the industry. Abovementioned problems, which are experienced in the state of the art related to the repellent substances that may be used in insect control against flies, mosquitoes and ticks and the formulations that contain such substances, have urged inventors to produce new solutions.
OBJECT OF THE INVENTION
By looking at the state of the art, inventors aim at providing protection against mosquitoes (Aedes spp, Culex Spp, Anopheles spp, Culiseta spp. and all mosquito types), gnats (Phlebotomus spp), sandflies, flies and all types of tick using a natural and safe repellent.
Another object of the invention is to develop a natural herbal spray repellent that has an effect period as long as that of and that is safer than lcaridin, DEET N,N-diethyl-meta-toluamide) and IR3535® (3-(N-acetyl-N-butyl) amino propionic acid ethyl ester), which are chemicals used as mosquito repellents, instead of such chemicals.
In a sense, the present invention aims at eliminating the health problems caused by chemical repellents.
Another object of the invention is to offer a new alternative solution for resistance of mosquitoes in the prior art, which shall also be effective on resisting populations.
Another object of the invention is to develop a natural herbal repellent that has a longer effect period thanks to nano-capsule formulation instead of simple herbal repellents that have short effect period.
Another object of the invention is to manufacture repellents that are safe enough to use on even three-month old babies, in the prior art, chemical products have approvals for use for ages 7 and over while the simple herbal solutions are allowed for use for ages 3 and over.
Another object of the invention is to achieve a natural nano-capsule formulation repellent against mosquitoes, gnats and ticks.
Inventors have surprisingly determined that the nano-capsule formulation containing PMD (Para- menthane Diol) as active agent, geraniol, azadirachtin, pyrethrum/ pyrethrin, neem oil, valerian oil, peppermint oik rosemary oil, basil oil, cinnamon oil, lavender oil, turmeric oil, eucalyptus oil, thyme oil, garlic oil, citronella, citronella java, lemongrass and/or derivatives of such oils and/or one, several or all of general citrus oils has overcome the problems that exists in the state of the art. DETAILED DESCRIPTION OF THE INVENTION
Present invention involves a nano-capsule formulation containing PMD (Para-menthane Diol) as active agent, geraniol, azadirachtin, pyrethrum/ pyrethrin, neem oil, valerian oil, peppermint oil, rosemary oil, basil oil, cinnamon oil, lavender oil, turmeric oil, eucalyptus oil, thyme oil, garlic oil, citronella, citronella java, lemongrass and/or derivatives of such oils and/or one, several or all of general citrus oils as repellent agents, all or some of which are found in nano-capsule form. Within the scope of the invention, emulsifier, solvent, carrier, capsulation agent, load exchanger, anti-freezing agent and co-solvent are used as auxiliary agents aside from the active agent in the formulation that contains repellent agent.
The invention, in a way, relates to a repellent formulation against flies, mosquitoes, gnats or ticks and is characterized by (a) that it contains PMD (Para-menthane Diol), geraniol, azadirachtin, pyrethrum/ pyrethrin, neem oil, valerian oil, peppermint oil, rosemary oil, basil oil, cinnamon oil, lavender oil, turmeric oil, eucalyptus oil, thyme oil, garlic oil, citronella, citronella java, lemongrass, general citrus oils and/or one or several repellent active agents selected from a group consisting of such oils or their derivatives or all of the repellent active agent composing such group and (b) that it is in nano-capsule form.
On the other hand, the present invention relates to a repellent formulation developed against flies, mosquitoes, gnats or ticks and is characterized by (a) that it contains PMD (Para-menthane Diol), geraniol, azadirachtin, pyrethrum/ pyrethrin, neem oil, valerian oil, peppermint oil, rosemary oil, basil oil, cinnamon oil, lavender oil, turmeric oil, eucalyptus oil, thyme oil, garlic oil, citronella, citronella java, lemongrass, general citrus oils and/or one or several repellent active agents selected from a group consisting of such oils or their derivatives or all of the repellent active agent composing such group and (b) that it is in nano-capsule form. in a preferred application of the invention, PMD (Para-menthane Diol) is used alone as a repellent agent in the formulations suitable to the invention. In a preferred application of the invention, PMD (Para-menthane Diol) is found in nano-capsule form in the formulation.
In formulations suitable to the invention, some or all of PMD (Para-menthane Diol) or its alternatives as a repellent agent may be found by weight in nano-capsule form.
In the formulation suitable to the invention, the total amount of the repellent agent ranges between 0.001 % and 99.99% by weight. In another application of the invention, PMD (Para-menthane Diol) is used as a repellent active agent in the formulation subject to the invention. As an alternative to such active agent; geraniol, azadirachtin, pyrethrum/ pyrethrin, neem oil, valerian oil, peppermint oil, rosemary oil, basil oil, cinnamon oil, lavender oil, turmeric oil, eucalyptus oil, thyme oil, garlic oil, citronella, citronella java, !emongrass and derivatives of such oils or general citrus oils and one, several or all of the aforementioned oils can be used in combination. In case of using alternative oils, the percentage ranges between 0.001% and 99.99% for the alternative or total of alternatives if more than one alternative is used.
From another angle in the invention, one, several or all of such oils used as alternatives in the formulation as mentioned above may be used as synergists (effect booster) or as the 2nd, 3rd, 4th... active agent beside the PMD (Para-menthane Diol) in the formulation. The synergist percentage may range between 0.00012% and 99.8%.
In another preferred application of the invention; one or a combination selected among the group of geraniol, azadirachtin, pyrethrum/ pyrethrin, citronella, citronella java, lemon grass oil, turmeric oil, garlic oil, rosemary oil, lavender oil, valerian oil, thyme oil, basil oil, canola oil, nut oil, cinnamon oil, turmeric oil, eucalyptus oil, citrus oils and neem oil or other herbal oils having repellent affects are used as active agents as an alternative to PMD (Para-menthane Diol). The percentage of alternative natural repellents range between 0.001% and 99.99% in the invention.
The oils to be used as an alternative to PMD (Para-menthane Diol) may either be used individually or in combination or in entirety. Furthermore one, several or all of these oils may be used together with the PMD (Para-menthane Diol) within the scope of this invention.
Within the scope of the invention, slow release of volatile natural oils was ensured using nano- capsule formulation technique, and the effect period of a single application was increased over 8 hours. Such result achieved from the invention has extended the effect period of natural oils by more than 4 times.
In the present invention, it is planned to achieve a product that is both non-toxic and suitable for spraying onto the skin, that can be sprayed and that can remain stable at lower viscosities since it has very small particle diameter by means of encapsulation of particles equal to or smaller than 10 μιη, preferably equal to or smaller than 0.1 um (<199 nm), with a natural additive by using nano-encapsulation method. In the known technique, the suspension viscosity must be at least 700 cP in order that the particles that are larger than 1 μηι can suspend mechanically in the suspension. In lower viscosities, the user will have to shake the product before application since active agents composing the suspension will precipitate.
In the known technique, it is not possible to spray the liquids that have viscosity greater than 200 cP using standard spray guns. Therefore, sprayable suspensions that have to be produced in lower viscosities will precipitate since they will not be stable at such viscosity. For this reason, spray suspensions must be shaken before use. As a result, the manufacturer is forced to choose between a spray product that must be shaken before use and a non-spray product that can be used without shaking.
The size of the capsules achieved with the invention have been adjusted to be suitable to the triggers that produce ideal and fine sprays in order to allow for application onto the skin. In general, capsules that are larger than 0.1 micron cannot be easily sprayed through spray head. Aside from minimizing the capsule size to 0.1 micron within the frame of the invention, an extra series of procedures have been performed to adjust the viscosity to allow for applying the product using spray heads. In other words, studies have been conducted on both the viscosity and the capsule size; and a product that can be applied using all types of spray heads has been invented.
The invention involves formulation of natural herbal oils using nano-capsulation technique to achieve a repellent product. The nano-capsule formulation type designed within the frame of the invention allow for achieving a long-term repellent effect of herbal oils and ideal viscosity to apply the product by using the spray technique.
The invention is also intended for developing the nano-capsule formulation type, in which herbal oils have never been tried as mosquito / fly / tick repellent.
The object of the invention is formulation type nano-capsule. The purpose of developing the nano-capsule formulation type is to discover how to prolong the repellent effect and to render the viscosity of the formulation suitable for spraying. Such effect can also be achieved using the microcapsule method; however, microcapsule formulation type cannot be sprayed since it has high viscosity. Therefore, using the nano-capsule formulation type, both the repellent effect period has been prolonged and the product has been rendered suitable for application with spray method thanks to the type of formulation subject to the invention. The invention is the first study ever on formulation of natural herbal oils using nano-capsule formulation type. In the prior art, herbal oils are developed as single solutions. Their effect periods are short and they contain numerous auxiliary chemicals aside from natural oils.
The invention also prevents the contents of the formula from penetrating into the skin thanks to nano-capsulation formulation technology.
With the present invention, volatility of volatile repellent oils has been prevented thanks to nano- capsule, long-term effect has been obtained with slow release depending on time and the targeted result has been achieved. Since the combinations achieved using capsulation (microencapsulation) techniques other than nano-encapsulation have high viscosity, they are not suitable for spraying.
In a preferred application of the invention, a natural oil that has a single repellent active agent has been preferred for use. In another sense, natural oils that can be used as alternatives to PMD within the scope of the invention can be used together with PMD or in a single combination, which contains several or all of such oils. The most basic property of the active agents to be used in the formulation is that they are active agent (oils) that are not soluble in water. Within the scope of the invention, emulsifier, solvent, carrier, capsulation agent, load exchanger, anti- freezing agent and co-solvent are the auxiliary agents aside from the active agent in the formulation.
The emulsifier and other auxiliary agents used within the scope of the invention are safe substances that are also used in food products and that have food codex approvals. Such substances have no adverse effects on the skin.
The percentage of PMD (Para-methane Diol) used as the repellent active agent in the formulations suitable to the invention ranges between 0.001% and 99.00% by weight; it is preferably used by 0.001% to 75% and most preferably used by 1% to 15%, i.e. by 10%.
The formulations subject to the invention may contain at least one auxiliary agent selected from among emulsifier I, antifreeze, co-solvent, emulsifier II, capsulation agent I, capsulation agent II, solvent and carrier, or the combination thereof in addition to the active repellent agent.
The emulsifier I to be used within the scope of the formulation subject to the invention ranges between 1% and 78% by weight; it is preferably used by 3% to 70% and most preferably used by 5% to 65%, i.e. by 10%. The emulsifier 1 sorbitan esters and ethoxylates to be used in the formulation subject to the invention are, for example, selected from among Tween 20, Tween 80, Tween 60, Tween 40, Tween 21, Tween 65, Tween 61, Span 20, Span 40, Span 60, Span 80, Span 83, Span 85 and Span 120.
Depending on the emulsification of the repellent active agent molecule, other emulsifiers suitable for use in other cosmetic and food products can also be used in the production as emulsifier 1 and/or emulsifier II.
The emulsifier II to be used within the scope of the formulation subject to the invention ranges between 1 % and 80% by weight; it is preferably used by 3% to 75% and most preferably used by 5% to 70%, i.e. by 15%.
The emulsifier II Tristyrylphenol ethoxylate to be used in the formulation subject to the invention is, for example, selected from among Agnique TSP 15, Soprophor BSU, Soprophor CY/8 and Emulsogen TS 160.
The ideal emulsifier combination is sought to ensure formulation of the active agent as micro- emulsification. The selected emulsifier I and emulsifier 11 are combined. Other emulsifiers that can be used for the same purpose from among similar groups or different groups can also be used in the production.
The antifreeze agent to be used in the formulation subject to the invention is, for example, selected from among a group that is composed of monoethyleneglycol, diethyleneglycol, dipropyleneglycol and monopropyleneglycol.
The antifreeze agent to be used within the scope of the formulation subject to the invention ranges between 0.5% and 55% by weight; it is preferably used by 1% to 50% and most preferably used by 3% to 45%, i.e. by 5%.
The subject antifreeze agent is used as antifreeze and in order to support micro-emulsification. Other glycols, glycol ethers and other molecules that can be used as antifreeze can also be used in the production within the scope of the invention.
The co-solvent to be used in the formulation subject to the invention is selected from among a group that consists of octanol, methanol, butanol, isopropanol, propanol and ethanol.
The co-solvent to be used within the scope of the formulation subject to the invention ranges between 0.75% and 75% by weight; it is preferably used by 3% to 70% and most preferably used by 5% to 65%, i.e. by 7%.
The capsulation agent to be used within the scope of the formulation subject to the invention ranges between 0.000001% and 65% by weight; it is preferably used by 0.0001% to 60% and most preferably used by 0.01% to 50%, i.e. by 0.75%.
The capsulation agent I to be used in the formulation subject to the invention is selected from among a group that consists of gelatin, gum Arabic, chitosan and maltodextrin.
The capsulation agent 1 mentioned herein is a natural component that dissolves in water and forms a capsule wall around the droplets that will be encapsulated. Natural agents and/or chemical agents that can form a capsulation wall can also be used as alternatives to the aforementioned agents within the scope of the invention.
The capsulation agent II to be used within the scope of the formulation subject to the invention ranges between 0.00002% and 54% by weight; it is preferably used by 0.0001% to 50% and most preferably used by 0.01% to 45%, i.e. by 0.60%. The capsulation agent II to be used in the formulation subject to the invention may be selected from among a group that consists of sodium tripoliphosphate, citric acid, propionic acid and phosphoric acid.
The capsulation agent II mentioned herein is a capsulation initiator agent. The capsulation process starts thanks to the load transfer around the emulsifier. All chemicals that can be used for the same purpose can be used as alternatives to the aforementioned agents within the scope of the invention.
The solvent agent to be used within the scope of the formulation subject to the invention ranges between 0.0000014% and 58% by weight; it is preferably used by 0.00001% to 55% and most preferably used by 0.0001 % to 52%, i.e. by 0.5%.
The solvent agent to be used in the formulation subject to the invention may be selected from among a group that consists of acetic acid and citric acid.
The solvent agent mentioned herein helps increase the solubility of the capsulation agent in water. Other chemicals or natural substances that help increase the solubility of the capsulation agent in water can be used as alternatives to the aforementioned agents within the scope of the invention.
The carrier agent to be used within the scope of the formulation subject to the invention ranges between 1% and 99% by weight; it is preferably used by 3% to 95% and most preferably used by 5% to 93%, i.e. by 55%.
The carrier agent to be used in the formulation subject to the invention is water.
The carrier agent mentioned herein is the carrier medium. Other carrier agents known in the technique can also be used as an alternative to water.
The formulation suitable to the invention can be prepared following the below-mentioned steps:
1. A solution containing the capsulation agent I is prepared
2. Emulsifier mixture is prepared
3. Oil phase is added and micro-emulsification is achieved
4. The solution containing the capsulation agent II is added and the capsulation process is started.
Below given by the inventors is an example of the formulations subject to the invention. Such example is given only for the purpose of describing the invention, the scope of which is not limited to such example.
Example:
Para-menthane Diol Repellent active agent 10%
Tween 80 Emulsifier I 10%
Emulsogen TS 160 Emulsifier II 15%
Diethylene glycol Antifreeze 5%
Ethanol Co-solvent 7%
Chitosan Capsulation Agent I 0.75%
Na-Tripolyphosphate Capsulation Agent 11 0.60%
Acetic acid Solvent 0.5%
Water Carrier 51.15% 1. The solution containing the chitosan is prepared
2. PMD phase is added and micro-ernulsification is achieved.
3. The solution containing the Na-tripolyphosphate is prepared and the capsulation process is started.

Claims

1. A formulation that has repellent effect against flies, mosquitoes, gnats or ticks,
• characterized in that the formulation contains PMD (Para-menthane Diol), geraniol, azadirachtin, pyrethrum/ pyrethrin, neem oil, valerian oil, peppermint oil, rosemary oil, basil oil, cinnamon oil, lavender oil, turmeric oil, eucalyptus oil, thyme oil, garlic oil, citronella, citronella java, lemongrass, general citrus oils or one, several or all of such oils selected from among a group that is composed of the aforementioned oils or their derivatives as repellent active agent or contains all of the repellent active agents that compose such group and
• the formulation is in nano-capsule form.
2. A formulation, according to Claim 1, characterized in that, the repellent active agent found in the formulation ranges between 0.001% and 99.99% by weight.
3. A formulation, according to Claim 1, characterized in that, the repellent active agent generally preferred is Para-menthane Diol (PMD).
4. A formulation, according to Claim 1, 2 or 3, characterized in that, the capsulation agent and most of the auxiliary agents used in accordance with the specifications are selected from among safe and natural substances.
5. A formulation, according to Claim 3, characterized in that, the para-menthane diol used as the repellent active agent is found in nano-capsule form.
6. A formulation, according to Claim 4, characterized in that, the Para-menthane diol can both be in nano-capsule form in entirety and in nano-capsule form in part by weight and in free form as combination by weight for the other part.
7. A formulation, according to Claim 3 or 4, characterized in that, the para-menthane diol found in the formulation ranges between 0.001+ and 99.99% by weight.
8. A formulation, according to any one of the Claim 3 to 5, characterized in that, geraniol, azadirachtin, pyrethrum/ pyrethrin, neem oil, valerian oil, peppermint oil, rosemary oil, basil oil, cinnamon oil, lavender oil, turmeric oil, eucalyptus oil, thyme oil, garlic oil, citronella, citronella java, lemongrass and/or derivatives of such oils and/or one, several or all of general citrus oils are used as synergist oils (effect booster) beside the para- menthane diol (PMD) that is used as the active agent.
9. A formulation, according to Claim 1 or 8, characterized in that, the other alternative oils to be used in accordance with the specifications and/or all of the synergists may be in nano-capsule form whereas a part of them can be found in nano-capsule form by weight and the other part may be found in free form in combination.
10. A formulation, According to Claim 8, characterized in that, the synergist oil is found by 0.
00012% to 99.8%.
1 1. A formulation, according to any one of the previous Claims, characterized in that, the nano-capsules composing the formulation is equal to or smaller than 10 μπι, and preferably equal to or smaller than 0.1 μιη.
12. A formulation, according to any one of the previous Claims, characterized in that, the nano-capsule formulation has a viscosity that is rendered suitable for use in standard spray tools.
13. A formulation, according to any one of the previous Claims, characterized in that, the effect period of the nano-capsule formulation has been extended by at least twice.
14. A formulation, according to Claims 11, 12 and 13, characterized in that, the formulation is developed to have particles that will not penetrate into the skin.
15. A formulation, according to any one of the previous Claims, characterized in that, the formulation contains at least one auxiliary agent from among or a combination of emulsifier 1, antifreeze, co-solvent, emulsifier II, capsulation agent I, capsulation agent II, solvent and carrier in addition to the repellent active agent.
16. A formulation, according to Claim 15, characterized in that, the emulsifier I is used by 1% to 78% by weight.
17. A formulation, according to Claim 15 or 16, characterized in that, the emulsifier I sorbitan esters and ethoxylates are, for example, selected from among Tween 20, Tween 80, Tween 60, Tween 40, Tween 21, Tween 65, Tween 61, Span 20, Span 40, Span 60, Span
80, Span 83, Span 85 and Span 120.
18. A formulation, according to Claim 15, characterized in that, the emulsifier II is used by l% to 80% by weight.
19. A formulation, according to Claim 15 or 18, characterized in that, the emulsifier II Tristyrylphenol ethoxylate is, for example, selected from among Agnique TSP 15,
Soprophor BSU, Soprophor CY/8 and Emulsogen TS 160.
20. A formulation According to any one of the Claims 16 to 19, characterized in that, the emulsifier I and emulsifier II are combined.
21. A formulation, according to Claim 15, characterized in that, the antifreeze agent is used by 0.5% to 55% by weight.
22. A formulation, according to Claims 15 or 21, characterized in that, the antifreeze agent is, for example, selected from among a group that is composed of monoethyleneglycol, diethyleneglycol, dipropyleneglycol and monopropyleneglycol.
23. A formulation, according to Claim 15, characterized in that, the co-solvent is used by 0.75% to 75% by weight.
24. A formulation, according to any one of the Claims 15 or 23, characterized in that, the co- solvent is, for example, selected from among a group that consists of octanol, methanol, butanol, isopropanol, propanol and ethanol.
25. A formulation, according to Claim 15, characterized in that, the capsulation agent I is used by 0.000001% to 65% by weight.
26. A formulation, according to any one of the Claims 15 or 25, characterized in that, the capsulation agent II is, for example, selected from among a group that consists of gelatin, gum Arabic, chitosan and maltodextrin.
27. A formulation, according to Claim 15, characterized in that, the capsulation agent II is used by 0.00002% to 54% by weight.
28. A formulation, according to any one of the Claims 15 or 27, characterized in that, the capsulation agent II is selected from among a group that consists of sodium Na- tripoliphosphate, citric acid, propionic acid and phosphoric acid.
29. A formulation, according to Claim 15, characterized in that, the solvent agent is used by
0.0000014% to 58% by weight.
30. A formulation, according to any one of the Claims 15 or 29, characterized in that, the solvent agent is selected from among a group that consists of acetic acid and citric acid.
31. A formulation, according to Claim 15, characterized in that, the carrier agent is used by 1% to 99% by weight.
32. A formulation, according to any one of the Claims 15 or 31, characterized in that, the carrier agent is water.
33. A method for the production of a formulation, according to any one of the Claims 1 to 32, characterized in that, the formulation consists of the following steps: • A solution containing the capsulation agent 1 is prepared
• Emulsifier mixture is prepared
• Oil phase is added and micro-emulsification is achieved
• The solution containing the capsulation agent II is added and the capsulation process is started.
34. A formulation, according to any one of the Claims 1 to 32, characterized in that, the formulation is used to repel flies, mosquitoes, ticks, gnats, sandflies, all types of flies and ticks that threaten the health of humans and animals.
PCT/TR2016/000095 2015-07-02 2016-07-04 Nanoencapsulated mosquito-, fly- and tick-repellent formulation WO2017003395A1 (en)

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CN108125929A (en) * 2017-12-11 2018-06-08 中国农业科学院兰州畜牧与兽药研究所 It is a kind of12C6+The method that ion beam irradiation prepares Herba Origani Vulgaris quintessence oil microcapsules
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CN112043612A (en) * 2020-08-19 2020-12-08 广州市浪奇实业股份有限公司 Low-sensitivity mosquito-proof composition without organic solvent
CN112089635A (en) * 2020-08-19 2020-12-18 广州市浪奇实业股份有限公司 Organic solvent-free anti-mosquito composition from food additive source
WO2022150277A1 (en) * 2021-01-06 2022-07-14 S. C. Johnson & Son, Inc. Spatial insect repellent compositions
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