rexresearch.com



Anandasankar RAY, et al.

Mosquito Repellant








http://www.kitepatch.com

"The Kite™ uses our patent-pending compounds that block mosquitoes’ ability to track humans for up to 48 hours..."



[ viz., butanol, 2,3-butadiene, & butanone, guava & citrus volatiles, &c. -- see the patent excerpts below ]



http://ucrtoday.ucr.edu/16352
July 16, 2013
Research Leads to Affordable Technology to Fight Mosquito-borne Diseases

By

Iqbal Pittalwala

Discoveries from UC Riverside are the foundation for Olfactor Labs to develop an easy-to-wear patch that makes humans invisible to mosquitoes

RIVERSIDE, Calif. — Technology that hampers mosquitoes’ host-seeking behavior, identified at the University of California, Riverside in 2011, has led to the development of the world’s first product that blocks mosquitoes’ ability to efficiently detect carbon dioxide, their primary method of tracking human blood meals.

The initial research was performed in the laboratory of Anandasankar Ray, an associate professor of entomology, and was featured on the cover of the journal Nature.  Ray’s lab identified volatile odor molecules that can impair, if not completely disrupt, mosquitoes’ carbon dioxide detection machinery.

The intellectual property was licensed to Olfactor Laboratories Inc., a company that grew around the technology, expanded the research, filed additional patents, and developed related technologies that led to the mosquito-warding product.

Called the Kite Mosquito Patch, the product marks a significant advancement in the global fight against mosquito-borne diseases such as malaria, West Nile virus and dengue fever.  The patch delivers mosquito-repelling compounds in a simple, affordable and scalable sticker that can be used by individuals in regions impacted by malaria and other mosquito-borne diseases.

“UCR is committed to strengthening and expanding its ties with industry partners,” said Michael Pazzani, the vice chancellor for research and economic development.  “Olfactor Laboratories Inc. is a great example of how UCR innovations result in new industries, which, in turn, lead to the development of products impacting the lives of people around the globe.”

Simple and affordable, Kite is a colorful sticker, small enough to be worn virtually without notice.  It disburses the non-toxic compounds that provide individuals with up to 48 hours of protection from mosquitoes. Estimated to cost a fraction of existing repellents, Kite is applied to clothing and can be used by people of all ages, including infants and pregnant mothers.

“I am very excited to see how Olfactor Labs has rapidly taken our initial discovery to a product that can have great value in the war against mosquitoes and disease,” Ray said. “I am most impressed that they have designed something affordable and convenient for use in Africa and around the world. I am rooting for this to become a game changer in lowering instance of malaria, dengue, filariasis and other dangerous diseases.”

Kite’s technology is the culmination of years of development work on a class of odor molecules, all of which are non-toxic compounds approved for human consumption by the U.S. Food and Drug Administration.

“The Kite Mosquito Patch isn’t just another mosquito product, but a powerful alternative to most products on the market, enabling people to live normal lives with a new level of protection against contracting mosquito-borne diseases,” said Michelle Brown, the chief scientist and vice president of Olfactor Laboratories, Inc.

Initial funding for the technology came to Ray’s lab from the Bill and Melinda Gates Foundation and the National Institutes of Health.  Olfactor Laboratories Inc. has funding from the National Institute of Health, agreements with the Walter Reed Army Institute for Research and the U.S. Department of Agriculture to test a range of technologies developed at the company relating to mosquito and other vector insects.  The Kite Mosquito Patch is one of a number of new products with the ‘Kite’ product family, all of which use non-toxic compounds to repel, kill or lure vector insects.

“Kite will provide a new level of protection to, for example, children in Uganda, for the elderly in Mali, and hikers in Seattle or Sarasota seeking a safer, socially responsible solution,” said Grey Frandsen, project lead and chief marketing officer at Innovation Economy Crowd (ieCrowd), a crowd-powered platform aimed at transforming innovations into solutions. Olfactor Laboratories Inc. is an ieCrowd company.

The first Kite Mosquito Patches will be tested in districts of Uganda hardest hit by malaria. In 2010 an estimated 219 million cases of malaria occurred worldwide and 660,000 people died, 91 percent in the African Region.



http://www.olfactorlabs.com/

Technology

Development of a novel class of spatial, non-insecticidal insect repellents that manipulates the primary mechanism used in host-seeking is underway at Olfactor Laboratories, Inc. (OLI), an ieCrowd Company. Blood-feeding insects such as mosquitoes, which spread malaria, dengue and filariasis, track their prey through carbon dioxide (CO2) emissions in breath using their olfactory neurons (sense of smell). Researchers from the University of California, Riverside (UCR) demonstrated in the internationally renowned scientific journal Nature (2011) that the CO2 receptor in mosquito can be activated or inhibited by small molecules. After licensing this technology from UCR, OLI has generated its own patent-pending library of compounds that activate or inhibit the carbon dioxide receptor neuron. This patent-pending technology, which is supported by the National Institute of Health, represents a revolutionary paradigm shift in the war against vector insects and the diseases they transmit.

With the ability to activate as well as inhibit the CO2 receptor with small molecules, OLI is focused on two separate applications to be utilized in vector control:

1) Development of spatial, non-insecticidal repellents that will block the ability of the insect to sense CO2.

2) Development of cost-effective, efficient lures that will mimic CO2 for use in surveillance traps.

Due to our stringent safety profile prescreening process, OLI active ingredients for non-insecticidal repellents and CO2 mimics are approved for use by the US Food and Drug Administration (FDA) as flavors and fragrances. Many of these active ingredients are highly aromatic which will allow greater flexibility for use in delivery devices, making our products amenable for use throughout the world.



kitepatch.com doesn't acknowledge the inventor :



[ Excerpts ]

WO2013059364

METHODS FOR ASSESSING REPELLANT QUALITY OF ORGANIC MATERIALS AND METHODS AND COMPOSITIONS FOR REPELLING ARTHROPODS
    
Inventor:
RAY ANANDASANKAR [US]
BOYLE SEAN MICHAEL [US]     
Applicant:
UNIV CALIFORNIA [US]     

The disclosure provides methods and compositions for modifying psyllid behavior. In addition, the disclosure provides methods and volatile odorants useful for repelling or attracting psyllids.

TECHNICAL FIELD

[0002] The disclosure provides compounds useful as insect repellents and compositions comprising such repellents. The disclosure further provides compounds useful as insect attractants and compositions comprising such attractants. The disclosure further provides compounds useful as insect traps.

BACKGROUND

[0003] Numerous insects are vectors for disease. Mosquitoes in the genus Anopheles are the principle vectors of malaria, a disease caused by protozoa in the genus Trypanosoma. Aedes aegypti is the main vector of the viruses that cause Yellow fever and Dengue. Other viruses, the causal agents of various types of encephalitis, are also carried by Aedes spp. mosquitoes. Wuchereria bancrofti and Brugia malayi, parasitic roundworms that cause filariasis, are usually spread by mosquitoes in the genera Culex, Mansonia, and Anopheles.

[0004] Horse flies and deer flies may transmit the bacterial pathogens of tularemia (Pasteurella tularensis) and anthrax (Bacillus anthracis), as well as a parasitic roundworm (Loa loa) that causes loiasis in tropical Africa.

[0005] Eye gnats in the genus Hippelates can carry the spirochaete pathogen that causes yaws (Treponema pertenue), and may also spread conjunctivitis (pinkeye). Tsetse flies in the genus Glossina transmit the protozoan pathogens that cause African sleeping sickness (Trypanosoma gambiense and T. rhodesiense). Sand flies in the genus Phlebotomus are vectors of a bacterium (Bartonella bacilliformis) that causes Carrion's disease (oroyo fever) in South America. In parts of Asia and North Africa, they spread a viral agent that causes sand fly fever (pappataci fever) as well as protozoan pathogens (Leishmania spp.) that cause Leishmaniasis.

[0006] Most blood feeding insects, including mosquitoes, sandflies, Testse flies, use olfactory cues to identify human hosts. This group of hematophagous insects can transmit a wide assortment of deadly human diseases that together cause more suffering and deaths globally than any other disease condition. Diseases transmitted by such insects include malaria, dengue fever, yellow fever, West Nile virus, filariasis, river blindness, epidemic polyarthritis, Leshmaniasis, trypanosomiasis, Japanese encephalitis, St.Louis Encephalitis amongst others.

[0007] The olfactory system can detect and discriminate amongst an extremely large number of volatile compounds in the environment, and this is critical for important behaviors like finding hosts, finding food, finding mates, and avoiding predators. To detect this wide variety of volatiles, most organisms have evolved extremely large families of receptor genes that typically encode 7-transmembrane proteins expressed in the olfactory neurons. Little is known, however, about what structural characteristics of small volatile molecules are important for behavior modification. The predicted odors provided herein are able to manipulate the olfactory-based behavior of an organism by making use of computationally identified important structural characteristics.

[0008] Volatile chemical space is immense. Odors in the environment that have been catalogued in some plant sources alone number more than a couple thousand. A very small proportion of chemical space has been systematically tested for the ability to modify behavior, and a very small fraction of odor receptors, whose sequences are known, have been tested for their ability to be affected by behavior modifying odors. The complete 3-D structures of odor receptor proteins have not yet been determined, thus modeling of odor- protein interactions is not yet possible except in rare instances. Furthermore, were a 3-D receptor structure to become available, application of one odor-receptor interaction to study others may be confounded by the possibility of multiple ligand binding sites in a single receptor, as well as the sequence divergence amongst different odor receptors. The disclosure was identified by intelligent and rapid screening of untested volatile chemical space through computational identification of important characteristics shared between known behavior modifying compounds, circumventing many of the previously described obstacles. Additionally, one can screen potential odors for toxicological safety. The disclosure has been used to identify molecular features important in mosquito avoidance. The identified features were then used to screen a vast chemical space, predicting odors that interrupt host- seeking behavior.

[0009] Several repellent compounds have been identified to date. These compounds range from naturally occurring extracts to commercially manufactured compounds. The degree of protection, duration of protection, and safety of these odors varies greatly. The gold standard of these compounds generally considered DEET.

[0010] DEET (N,N-diethyl-3-methylbenzamide) has been used for insect repellency for over 50 years. Protection is generally provided by direct application to the skin in concentrations ranging from 3 to 100 percent (Household products database of NLM). While results vary across experiments, DEET has been shown to act as an irritant and in some cases may cause skin reactions. In a recent study DEET has also just recently been shown to inhibit acetylcholinesterase in humans, which is an important neurotransmitter. DEET is also known to dissolve several products including certain plastics, synthetic fabrics, painted or varnished surfaces. How DEET is detected by arthropods is currently unknown. Several candidate methods have been proposed, but sufficient evidence that any of these methods is the direct avoidance-inducing pathway has not been demonstrated. As an example, it has been demonstrated that Culex quinquefasciatus are able to directly detect DEET through a short trichoid sensillum in a dose dependent manner. It has also been proposed that Drosophila are able to detect DEEN through gustatory receptors. It is possible that mosquitoes recognize this compound through a combination of olfactory and gustatory pathways.

[0011] Several other terpenoid compounds with repellent properties including thujone, eucalyptol, and linalool have also been identified. These compounds were shown to directly activate a trichoid sensillum housed odor receptor, which is also activated by DEET, only more strongly than DEET itself.

[0012] Icaridin, which is also called picaridine, is also used as an insect repellent.

Similarly to DEET it  acts as a repellent to several different insect species. Icaridin has the added benefit of not melting plastics. It has been found to be as effective as DEET at repelling insects, while being less irritating than DEET.

[0031] The disclosure further provides an arthropod repelling composition including two or more compounds listed in Table 1; two or more compounds listed in the Table 2; or two or more compounds selected from the group consisting of methyl N,N-dimethyl anthranilate, ethyl anthranilate, butyl anthranilate, or 2,3-dimethyl-5-isobutyl pyrizine. In some embodiments, the repelling composition is formulated as a lotion, cream, dust, cosmetic, perfume, spray, paste, slow-release granule, paint, treated clothing, treated netting, treated building material, or incense. In some embodiments, the arthropod is an insect. In some embodiments, the arthropod is of the order Diptera. In some embodiments, the arthropod is of the genus Drosophila. In some embodiments, the arthropod is a mosquito. In some embodiments, the mosquito is of the species Aedes aegypti.
 
Compounds and Compositions for Insect Repellents, Masking Agents, and Traps

[0081] The disclosure provides methods for identifying and the identified compositions of volatile odorants that modulate the electrophysiological response of neuron in various insect disease vectors including Drosophila melanogaster, Culex quinquefasciatus, An. gambiae and Aedes aegypti mosquitoes. In some embodiments, the odorants can completely inhibit the electrophysiological response of the neuron at very low concentrations.

[0087] In some embodiments, the repelling composition includes two or more compounds listed in Table 1; two or more compounds listed in the Table 2; or two or more compounds selected from the group consisting of methyl [N,N-dimethyl anthranilate, ethyl anthranilate, butyl anthranilate, or 2,3-dimethyl-5-isobutyl pyrizine.
 


[ Excerpts ]

WO2013056176
ODORS FOR PSYLLID TRAPPING, REPELLING AND CONTROL
    
Inventor:
RAY ANANDASANKAR [US]
FORSTER LISA

TECHNICAL FIELD

[0002] The disclosure relates methods and compositions for attracting and repelling psyllids, such as, for example, Asian Citrus Psyllids (ACPs), and inhibiting the spread of Huanglongbing disease in plants and trees.

BACKGROUND

[0003] Citrus greening, also called Huanglongbing (HLB) or yellow dragon disease, is a disease of citrus. This bacterial disease is thought to have originated in China in the early 1900's. The disease is primarily spread by two species of psyllid insects. One species, the Asian citrus psyllid, Diaphorina citri, has been present in Florida since 1998. The bacteria that cause HLB itself are not harmful to humans but the disease is damaging to the citrus crops. There are three strains of the bacteria: an Asian version, an African version, and a recently described American strain discovered in Brazil.

[0004] The Asian strain, Candidatus Liberibacter asiaticus, was found in Florida in early September, 2005. As a result, HLB is becoming a major threat to the U.S. citrus industry. Other than tree removal, there are no known effective controls once a tree is infected and there has been no known cure for the disease. Infected trees may produce misshapen, unmarketable, bitter fruit. HLB reduces the quantity and quality of citrus fruits, eventually rendering infected trees useless. In areas of the world affected by HLB the average productive lifespan of citrus trees has dropped from 50 or more years to 15 or less. The trees in the orchards usually die 3-5 years after becoming infected and require removal and replanting. An infected tree produces fruit that is unsuitable for sale as fresh fruit or for juice.

[0005] Citrus plants infected by the HLB bacteria may not show symptoms for years following infection. Initial symptoms frequently include the appearance of yellow shoots on a tree. As the bacteria move within the tree, the entire canopy progressively develops a yellow color.

[0006] The most characteristic symptoms of HLB are a blotchy leaf mottle and vein yellowing that develop on leaves attached to shoots, providing the overall yellow appearance. These foliar symptoms may superficially resemble a zinc deficiency although the green and yellow contrast is not as vivid with greening as it is with zinc deficiency or another disease, citrus variegated chlorosis. Leaves with HLB have a mottled appearance that differs from nutrition-related mottling in that greening-induced mottling usually crosses leaf veins. Nutrition related mottles usually are found between or along leaf veins and leaves may be small and upright.

[0007] Fruit from diseased trees are small, often misshapen, and typically some green color remains on ripened fruit. On Mandarin orange, fruit may develop an uneven ripening such that they appear half orange and half yellow. This symptom is the origin of the common name "greening." Yields are almost minimal, and any developed fruit is rendered worthless due to small size, poor color, and bad taste.

[0008] Among the volatiles released by guava and garlic chive leaves that induce repellence to ACP, dimethyl disulfide (DMDS) has been assayed in a small plot field trial and led to reduction in ACP densities for up to three weeks. This field trial was performed on an low psyllid density area (average: 3-4 ACP/10 trees) and resulted in only 65% reduction in ACP densities which indicates DMDS treatment may not be effective as a repellent to effectively control ACP in citrus plantations. Additionally, DMDS has strong and unpleasant odor and its toxic effect (DMDS-MSDS) may also preclude deployment of DMDS in citrus producing areas.

[0009] Methyl salicylate is another compound that has been identified as both an ACP attractant and repellent. Methyl salicylate is a chemical released in high amounts by citrus plants under physical stress, leading to ACP repellency in laboratory behavioral assays. On the other hand, at lower concentration ACP is attracted to it in lab behavior assays. It is not known whether this compound will serve as an attractant or repellent in the field. [0010] Therefore, there is a need for psyllid (e.g. , Asian Citrus Psyllid) trapping, repelling, and control agents that are environmentally safe, inexpensive, and usable in conjunction with other control methods. This is the object of the methods disclosed herein.

SUMMARY

[0011] The disclosure provides a comprehensive set of odor receptor neuron ligands for the psyllid set forth in the tables herein.

[0012] The disclosure provides an insect repellent comprising: a compound selected from the group consisting of a selected citrus volatile, a selected guava volatile, a selected synthetic compound, and any combination thereof. In one embodiment, the citrus volatile is selected from the group consisting of Sabinene, a-Humulene, [beta]-Caryophyllene, ([Epsilon])-[beta]- Ocimene, Myrcene, Terpinolene, a-Terpinol, p-Cymene, [delta]-3-Carene, Octanal, E-2-Hexenal, Limonene (+), [gamma]-Terpinene, Citral, Citronellal, Limonene (-), Acetic Acid, Pentyl Acetate, Acetophenone, Isobutyl Acetate, 3-Methyl- l-Butanol, 1-Hexanol, Ethyl Butyrate, Dipropyldisulfide, (Z)-2-Hexanol, Propionic acid, (+)-Carvone, Methyl Butyrate, a- Terpinene, Nonanal, and (Z)-3-Hexen- l-ol. In another embodiment, the guava volatile is selected from the group consisting of (Z)-3-Hexenal, Benzaldehyde, and (E,E)-2,4- Hexadienal. In yet another embodiment, the synthetic compound is selected from the group consisting of Methyl Salicylate and Isobutyric Acid. In further embodiments, the insect repellent or ligand is formulated as a lotion, a cream, a spray or a dust. In yet a further embodiment, the insect repellent or ligand comprises a vaporizer, a treated mat, treated outerwear, an oil, a candle, or a wicked apparatus.

[0013] The disclosure also provides an insect trap comprising a compound selected from the group consisting of a citrus volatile, a guava volatile, a synthetic compound, and any combination thereof. In one embodiment, the citrus volatile is selected from the group consisting of Sabinene, a-Humulene, [beta]-Caryophyllene, (E)-P-Ocimene, Myrcene, Terpinolene, a-Terpinol, p-Cymene, [delta]-3-Carene, Octanal, E-2-Hexenal, Limonene (+), [gamma]- Terpinene, Geranial (Syn. Citral), Citronellal, Limonene (-), Acetic Acid, Pentyl Acetate, Acetophenone, Isobutyl Acetate, 3-Methyl- l-Butanol, 1-Hexanol, Ethyl Butyrate, Dipropyldisulfide, (Z)-2-Hexanol, Propionic acid, (+)-Carvone, Methyl Butyrate, a- Terpinene, Nonanal, and (Z)-3-Hexen- l-ol. In another embodiment, the guava volatile is selected from the group consisting Z-3-Hexenal, Benzaldehyde, and (E,E)-2,4-Hexadienal. In yet another embodiment, the synthetic compound is selected from the group consisting of Methyl Salicylate and Isobutyric Acid. In various other embodiments, the insect trap comprises a trapping agent emitted from vaporizers, treated mats, treated pods, absorbed material, cylinders, oils, candles, wicked apparatus, fans, within or near trap entrances. In yet another embodiment, of the insect trap the trapping agent is a liquid source that can evaporate to form vapors within or near trap entrances. In another embodiment, the insect trap is suction based, light based, electric current based.

[0014] The disclosure also provides a method of repelling an insect pest, comprising applying to an object, in an amount effect to repel said insect pest, a compound identified herein.

[0015] The disclosure also provides a method of repelling psyllids, comprising applying to an object a compound selected form the group consisting of a citrus volatile, a guava volatile, a natural volatile, a synthetic volatile, and any combination thereof. In one embodiment, the psyllid comprises the Asian Citrus Psyllid. In another embodiment, the psyllid comprises the Asian Citrus Psyllid Diaphorina citri. In another embodiment, the object is a citrus plant. In another embodiment, the repellant is applied to a citrus plant. In another embodiment, the applying comprises application of the repellant to an article, which article is suspended on a citrus plant.

[0016] The disclosure provides for a method of attracting a psyllid comprising exposing the psyllid with an attracting composition comprising one or more compounds listed in Table 1. The disclosure also provides for a method of attracting a psyllid comprising exposing the psyllid with a psyllid attracting composition comprising two or more compounds each independently selected from the group consisting of a C10-C15 terpene; a C10-C15 terpenoid; a C6-C8 alcohol; a C5-C7 ester; a C7-C10 compound containing an aromatic ring; a C6-C10 aldehyde; a C5-C8 ketone; and a S2-S3, C6 sulfur compound. In some embodiments, the attracting composition comprises two or more compounds listed in Table 1. In other embodiments the attracting composition comprises p-cymene, ethyl butyrate, and myrcene. In other embodiments, the attracting composition comprises acetophenone, p-cymene, ethyl butyrate, and myrcene. In other embodiments the attracting composition comprises one or more compounds selected from the group consisting of myrcene, [delta]-3-carene, terpinolene, ([Epsilon])-[beta]-[omicron][omicron][iota][eta][iota][epsilon][eta][epsilon], [beta]-caryophyllene, [alpha]-humulene, and D- limonene. In other embodiments, the attracting composition comprises [delta]-3-carene and terpinolene. In other embodiments, the attracting composition comprises (E)^-ocimene, [beta]- caryophyllene, and cc-humulene. In other embodiments, the attracting composition comprises [delta]-3-carene, terpinolene, [beta]-caryophyllene, and cc-humulene. In other embodiments, the attracting composition comprises myrcene, [delta]-3-carene, (E)^-ocimene, and D-limonene. In other embodiments, the attracting composition comprises myrcene, [delta]- 3-carene, terpinolene, (E)^-ocimene, [beta]-caryophyllene, cc-humulene, and D-limonene. In other embodiments, the psyllid attracting composition comprises a vapor, and wherein the vapor is emitted from a vaporizer, treated mat, treated pod, absorbed material, cylinder, oil, candle, wicked apparatus, or fan. In other embodiments, the psyllid attracting composition comprises a liquid, and wherein the liquid evaporates to a vapor within or near a psyllid trap entrance. In other embodiments, the exposing the psyllid with the psyllid attracting composition is carried out using suction, light, an electric current, or any combination thereof. In other embodiments, the psyllid is an Asian Citrus Psyllid (Diaphorina citri), an African Citrus Psyllid (Trioz erytreae), a Pear Psyllid (Cacopsylla (Psylla) pyri), a Carrot Psyllid (Trioza apicalis), a Potato Psyllid (Bactericera (Paratrioza) cockerelli), and a psyllid of the family Psyllidae (Hemiptera). In other embodiments, the psyllid is an Asian Citrus Psyllid (Diaphorina citri). The disclosure also provides for an insect attractant composition comprising any compound disclosed above. In some embodiments, the insect attractant composition further comprises one or more compounds selected from the group consisting of (+)-carvone; 1-hexanol; and nonanal.

[0017] The disclosure also provides for a method of repelling a psyllid comprising exposing the psyllid with a psyllid repelling composition comprising one or more compounds each independently selected from the group consisting of a C4-C6 diketone; a C4 lactone; a C8-15 ester; a C2-C5 carboxylic acid; a C2-6 amine; and a C5-C6, N1-N2 heterocycle. In some embodiments, the psyllid repelling composition comprises one or more compounds selected from the group consisting of perillaldehyde; ethyl hexanoate; n- octyl acetate; isobutyric acid; propionic acid; acetic acid; pentanoic acid; 2,3-butanedione; [beta]-butyrolactone; N-methylpiperidine; dimethyl amine; putrescine dihydrochloride; hexylamine; pentylamine; pyridine; (+)-carvone; 1-hexanol; and nonanal. In other embodiments, the psyllid repelling composition comprises one or more compounds selected from the group consisting of (+)-carvone; 1-hexanol; and nonanal. In other embodiments, wherein the psyllid repelling composition comprises one or more compounds selected from the group consisting of hexylamine, pentylamine, pyridine, 2-phenylethanamine, and dimethylamine. In other embodiments, wherein the psyllid repelling composition comprises one or more compounds selected from the group consisting of acetic acid and propionic acid. In other embodiments, wherein the psyllid repelling composition comprises one or more compounds selected from the group consisting of hexylamine, pentylamine, pyridine, 2-phenylethanamine, dimethylamine, acetic acid, and propionic acid. In other embodiments, the psyllid repelling composition comprises one or more compounds selected from the group consisting of perillaldehyde; ethyl hexanoate; n-octyl acetate; isobutyric acid; propionic acid; acetic acid; pentanoic acid; 2,3-butanedione; [beta]-butyrolactone; N- methylpiperidine; dimethyl amine; putrescine dihydrochloride; hexylamine; pentylamine; and pyridine; and one or more compounds selected from the group consisting of (+)- carvone; 1-hexanol; and nonanal. In other embodiments, the psyllid repelling composition is formulated as a lotion, cream, spray, or dust. In other embodiments, the exposing the psyllid with the psyllid repelling composition is carried out using a vaporizer, a treated mat, treated outerwear, an oil, a candle, or a wicked apparatus. In other embodiments, the exposing the psyllid with the psyllid repelling composition comprises applying to an object an effective amount of the psyllid repelling composition to repel the psyllid. In other embodiments, the exposing comprises applying the psyllid repelling composition on or near a plant. In other embodiments, the exposing comprises applying the psyllid repelling composition to an article, and wherein the article is suspended on a citrus plant. In other embodiments, the psyllid is an Asian Citrus Psyllid (Diaphorina citri), an African Citrus Psyllid (Trioza erytreae), a Pear Psyllid (Cacopsylla (Psylla) pyri), a Carrot Psyllid (Trioza apicalis), a Potato Psyllid (Bactericera (Paratrioza) cockerelli), and a psyllid of the family Psyllidae (Hemiptera). In other embodiments, the psyllid is an Asian Citrus Psyllid {Diaphorina citri). The disclosure also provides for an insect repellant composition comprising a compound of any one of above compounds. In some embodiments, the insect repellant composition comprises one or more compounds selected from the group consisting of (+)-carvone; 1-hexanol; and nonanal.



WO2011130726
LIGANDS FOR ODOR RECEPTORS AND OLFACTORY NEURONS
  


WO2010102049
INSECT REPELLENT AND ATTRACTANTS
    
Inventor:
RAY ANANDASANKAR [US]
TURNER STEPHANIE LYNN

BACKGROUND

[0003] Numerous insects are vectors for disease. Mosquitoes in the genus Anopheles are the principle vectors of malaria, a disease caused by protozoa in the genus Trypanosoma . Aedes aegypti is the main vector of the viruses that cause Yellow fever and Dengue. Other viruses, the causal agents of various types of encephalitis, are also carried by Aedes spp. mosquitoes. Wuchereria bancrofti and Brugia malayi, parasitic roundworms that cause filariasis, are usually spread by mosquitoes in the genera Culex, Mansonia, and Anopheles .

[0004] Horse flies and deer flies may transmit the bacterial pathogens of tularemia (Pasteurella tularensis) and anthrax (Bacillus anthracis) , as well as a parasitic roundworm (Loa loa) that causes loiasis in tropical Africa.

[0005] Eye gnats in the genus Hippelates can carry the spirochaete pathogen that causes yaws (Treponema pertenue) , and may also spread conjunctivitis (pinkeye) . Tsetse flies in the genus Glossma transmit the protozoan pathogens that cause African sleeping sickness (Trypanosoma gambiense and T. rhodesiense) . Sand flies in the genus Phlebotomus are vectors of a bacterium (Bartonella bacilli formis) that causes Carrion's disease (oroyo fever) in South America. In parts of Asia and North Africa, they spread a viral agent that causes sand fly fever (pappataci fever) as well as protozoan pathogens (Leishmania spp.) that cause Leishmaniasis .

SUMMARY

[0006] The disclosure provides an insect repellent comprising: a compound selected from the group consisting of a 4 to 6 carbon aldehyde, a 5 to 8 carbon alcohol, a 3 to 8 carbon mono- or di- ketone, and any combination thereof. In one embodiment, the 4 to 6 carbon aldehyde is selected from the group consisting of butanal, penatanal, and hexanal . In another embodiment, the 5 to 8 carbon alcohol is selected from the group consisting pentanol, hexanol, cyclohexanol, Z3-hexen-l-ol, Z2-hexen-l-ol, l-hexen-3-ol, 1-hepten- 3-ol, 3-hexanol, and 2-hexanol. In a further embodiment, the 3 to 8 carbon mono- or di-ketones is selected from a butanedione (2,3- butanedione) and pentanedione . In a specific embodiment, the compound is 2, 3-butanedione . The compound may be formulated into a replellent for topical application such as in the form of a lotion, cream, spray or dust. In another embodiment, the repellent comprises a vaporizer, a treated mat, treated outerwear, an oil, a candle, or a wicked apparatus.

[0007] The disclosure also provides an insect trap comprising a compound selected from the group consisting of a 4 to 6 carbon aldehyde, a 5 to 8 carbon alcohol, a 3 to 8 carbon mono- or di- ketone, and any combination thereof. In one embodiment, the 4 to 6 carbon aldehyde is selected from the group consisting of butanal, penatanal, and hexanal. In another embodiment, the 5 to 8 carbon alcohol is selected from the group consisting pentanol, hexanol, cyclohexanol, Z3-hexen-l-ol, Z2-hexen-l-ol, l-hexen-3-ol, 1-hepten- 3-ol, 3-hexanol, and 2-hexanol. In a further embodiment, the 3 to 8 carbon mono- or di-ketones is selected from a butanedione (2,3- butanedione) and pentanedione.

[0008] The disclosure also provides a method of repelling an insect pest, comprising applying to a subject, in an amount effect to repel said insect pest, a compound selected from the group consisting of a 4 to 6 carbon aldehyde, a 5 to 8 carbon alcohol, a 3 to 8 carbon mono- or di-ketone, and any combination thereof. In one embodiment, the 4 to 6 carbon aldehyde is selected from the group consisting of butanal, penatanal, and hexanal. In another embodiment, the 5 to 8 carbon alcohol is selected from the group consisting pentanol, hexanol, cyclohexanol, Z3-hexen-l-ol, Z2-hexen-1-ol, l-hexen-3-ol, l-hepten-3-ol, 3-hexanol, and 2-hexanol. In a further embodiment, the 3 to 8 carbon mono- or di-ketones is selected from a butanedione (2, 3-butanedione) and pentanedione . [0009] The disclosure also provides a method of repelling an insect pest, comprising applying to a subject an active compound in an amount effective to repel the insect pest; wherein said insect pest is selected from the group consisting of flies and mosquitoes; and wherein the compound is selected from the group consisting of a 4 to 6 carbon aldehyde, a 5 to 8 carbon alcohol, a 3 to 8 carbon mono- or di-ketone, and compositions comprising any combination thereof .

[0010] The disclosure provides a method of repelling mosquitoes, comprising applying to a subject an effective amount of a repellant comprising a compound selected from the group consisting of a 4 to 6 carbon aldehyde, a 5 to 8 carbon alcohol, and a 3 to 8 carbon mono- or di-ketone.

[0011] In various embodiments of the disclosure a subject can be treated with the repellent of the disclosure. In some embodiment, the subject is a human. In other embodiment, the subject is a domesticated or livestock animal. The methods and compositions of the disclosure can be used to modify the CO2 homing activity of mosquitoes or repel mosquitoes. The mosquitoes can be selected from the group consisting of Tiger mosquitoes, Aedes aboriginis, Aedes Aegypti, Aedes, albopictus, Aedes cantator, Aedes sierrensis, Aedes sollicitans, Aedes squamiger, Aedes sticticus, Aedes vexans, Anopheles quadrimaculatus, Culex pipiens, and Culex quinquefaxciatus .

DETAILED DESCRIPTION

[0035] The disclosure provides a class of volatile odorants that can inhibit the electrophysiological response of the CO2 neuron in various insect disease vectors including Drosophila melanogaster, Culex qumquefasciatus, An. gambiae and Aedes aegypti mosquitoes. In some embodiment, the odorants can completely inhibit the electrophysiological response of the CO2 neuron at very low concentrations .

[0050] The compounds and compositions of the disclosure can be used as antagonist to mask the chemoattractant activity of CO2. The compounds and compositions can be used as attractants alone or in combination with an insecticide, trap, or other mechanical, electrical or chemical that kills the insect or prevents its escape . [0051] Compounds useful in the methods, compositions and devices of the disclosure include, but are not limited to, 4 to 6 carbon aldehydes (e.g., butanal, penatanal, hexanal) , 5 to 8 carbon alcohols (e.g., pentanol, hexanol, cyclohexanol, Z3-hexen-l-ol, Z2- hexen-1-ol, l-hexen-3-ol, l-hepten-3-ol, 3-hexanol, 2-hexanol and the like), and 3 to 8 carbon mono- or di-ketones (e.g., butanedione (2, 3-butanedione) , pentanedione and the like) . Additional related compounds having similar structure can be assayed using the methods described herein to determine if they have antagonistic effects or agonistic effects. For example, compounds having 2-8 carbon atoms and an aldehyde, ketone or alcohol can be assayed using electrophysiology measurement described herein.

 
0060] The volatile compounds of the disclosure have masking and repellant effects by impairing the ability to find a host via long-range cues from CO2 plumes emitted from human breath will be exploited to protect larger area. [0061] The disclosure provides a method of controlling insect attraction to a subject, the method comprising the step of inhibiting gustatory receptor activation (e.g., CO2 sensing gustatory receptors) in the insect or overstimulating the receptor with an antagonist (or a combination of antagonists) selected from the group consisting of 4 to 6 carbon aldehydes (e.g., butanal, penatanal, hexanal) , 5 to 8 carbon alcohols (e.g., pentanol, hexanol, cyclohexanol, Z3-hexen-l-ol, Z2-hexen-l-ol, l-hexen-3-ol, l-hepten-3-ol, 3-hexanol, 2-hexanol and the like) , and 3 to 8 carbon mono- or di-ketones (e.g., butanedione (2, 3-butanedione) , pentanedione and the like) , wherein inhibiting expression alters insect responsiveness to carbon dioxide, thereby controlling insect attraction to the subject.

[0062] In one embodiment, the gustatory receptor is Gr21a, Gr63a, or a homologue or ortholog thereof, or a combination thereof. In another embodiment, the gustatory receptor is GPRgr22, GPRgr24, or a homologue thereof, or a combination thereof

[0063] In another embodiment, this disclosure provides a method of inhibiting, preventing or reducing the incidence of insect-borne disease in a subject, the method comprising the step of overstimulating or antagonizing a CO2 receptor in an insect with a compounds or combination of compounds selected from the group consisting of 4 to 6 carbon aldehydes (e.g., butanal, penatanal, hexanal), 5 to 8 carbon alcohols (e.g., pentanol, hexanol, cyclohexanol, Z3-hexen-l-ol, Z2-hexen-l-ol, l-hexen-3-ol, l-hepten- 3-ol, 3-hexanol, 2-hexanol and the like) , and 3 to 8 carbon mono- or di-ketones (e.g., butanedione (2, 3-butanedione) , pentanedione and the like) , wherein the receptor response to carbon dioxide is modified and attraction to the subject inhibited, thereby inhibiting, preventing or reducing the incidence of insect-borne disease in a subject.

[0064] In one embodiment, the disease is malaria, dengue, yellow fever, river blindness, lymphatic filariasis, sleeping sickness, leishmaniasis, epidemic polyarthritis, West Nile virus disease or Australian encephalitis.

[0065] In one embodiment, the method of inhibiting, preventing or reducing the incidence of insect-borne disease is via exposing the insect to an agent the antagonizes the C02 receptor or neuron in the insect.
[0066] An active compounds or compounds of the disclosure (e.g., 4 to 6 carbon aldehydes (e.g., butanal, penatanal, hexanal) , 5 to 8 carbon alcohols (e.g., pentanol, hexanol, cyclohexanol, Z3- hexen-1-ol, Z2-hexen-l-ol, l-hexen-3-ol, l-hepten-3-ol, 3-hexanol, 2-hexanol and the like) , and 3 to 8 carbon mono- or di-ketones (e.g., butanedione (2, 3-butanedione) , pentanedione and the like)) may be produced in accordance with techniques known to those skilled in the art, or where novel may be produced by variations of known techniques which will be apparent to those skilled in the art.

[0071] The compositions may comprise various combinations of compounds as well as varying concentrations of the compound depending upon the insect to be repelled or masked, the type of surface that the composition will be applied to, or the type of trap to be used. Typically the active ingredient compound of the disclosure (e.g., 4 to 6 carbon aldehydes (e.g., butanal, penatanal, hexanal) , 5 to 8 carbon alcohols (e.g., pentanol, hexanol, cyclohexanol, Z3-hexen-l-ol, Z2-hexen-l-ol, l-hexen-3-ol, l-hepten-3-ol, 3-hexanol, 2-hexanol and the like) , and 3 to 8 carbon mono- or di-ketones (e.g., butanedione (2, 3-butanedione) , pentanedione and the like) ) will be present in the composition in a concentration of at least about 0.0001% by weight and may be 10, 50, 99 or 100% by weight of the total composition. The repellant carrier may be from 0.1% to 99.9999% by weight of the total composition. The dry formulations will have from about 0.0001-95% by weight of the pesticide while the liquid formulations will generally have from about 0.0001-60% by weight of the solids in the liquid phase.

...Using a T-maze choice assay the experiment demonstrated that wild-type Drosophila show a robust avoidance behavior to 0.67% CO2 (Figure 15a) . Inclusion of either 1-hexanol or 2, 3-butanedione with CO2 results in a reduction in mean avoidance behavior, although to varying degrees; avoidance to CO2 is abolished in the presence of 2, 3-butanedione (Figure 15a) . In wild-type Drosophila, however, a number of ORN classes are activated by 1-hexanol and 2, 3-butanedione . This raises the possibility that behavioral avoidance to CO2 may be overcome by activation of these other classes of ORNs, rather than by inhibition of C02-responsive neurons. To distinguish between these possibilities, the behavior of 0r83b<2> mutant flies in which most of the ORNs are non-functional, but electrophysiological responses to CO2 are not affected were examined (Figures 15b, lla) . Consistent with the electrophysiological analysis, flies lacking Or83b have a robust avoidance response to CO2 (Figure 15b) , which is comparable to the level observed for wild type flies (Figure 15a) . Avoidance is significantly reduced with the addition of either 1-hexanol or 2, 3-butanedione with CO2 (Figure 15b) . Taken together these results demonstrate that 1-hexanol and 2, 3-butanedione can effectively inhibit CO2-mediated innate avoidance behavior by inhibiting the CO2 receptor .
   



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