# Patent

## Title
Mixtures of sabadilla alkaloids and neem oil and uses thereof

## Abstract

The present invention is directed to pesticidal mixtures comprising sabadilla alkaloids and neem oil and methods of controlling pests including insects and mites by application of pesticidal mixtures comprising sabadilla alkaloids and neem oil.

## Background
FIELD OF THE INVENTION
The present invention is directed to pesticidal mixtures comprising sabadilla alkaloids and neem oil and methods of controlling pests including insects and mites by application of pesticidal mixtures comprising sabadilla alkaloids and neem oil.
BACKGROUND OF THE INVENTION
Arthropod pests are one of the major threats to human welfare and exert continued stress on the food supply and transmit a broad array of medical and veterinary diseases. Synthetic insecticides played a significant role and, in many ways, ushered in modern agriculture and pest control. However, the widespread use of synthetic insecticides also created numerous environmental challenges. The acute effects of synthetic pesticides on professional applicators and other end users are well-known but the chronic long-term human health effects can be equally serious. Further, the use of synthetic insecticides has led to the development of resistant insect populations. Insecticide resistance is a complex phenomenon underlined by a diverse array of physiological mechanisms. Major mechanisms that are responsible for the development of insecticide resistance are metabolic detoxification, target site mutation, reduced cuticular penetration and behavioral avoidance.
Integrated Pest Management (“IPM”) is a holistic approach to pest management. A fundamental aspect of insecticide utilization under the broader framework of IPM is the management of insecticide resistance (IRM) by the utilization of insecticide combinations that reduce the rate of resistance development. A combination of insecticides with different modes of action is fundamentally a concept based upon the idea of redundant killing of target insects. Insects adapted to one of the active ingredient in the combination product will still be killed by the other active ingredient. Mixtures can also reduce the amount of pesticides applied in the environment and the environmental impact associated with pesticide applications.
Most botanical insecticides are readily biodegradable and significantly less harmful to the environment and users than synthetic insecticides. The very short environmental persistence, usually less than 24 hours, of plant derived insecticides is favorable to the survival of non-target, beneficial parasites and predators which are important components of IPM. Unlike conventional insecticides which are typically based on a single active ingredient, plant derived insecticides usually comprise an array of chemical compounds that affect both behavioral and physiological functions of the target arthropods. The probability of pest resistance developing to plant derived insecticides is less than that for synthetic pesticides because these mixtures may have a variety of modes of action.
One effective naturally derived pesticide is found in the tissues of many of the plants of the genus Schoenocaulon, commonly referred to as sabadilla. The species with the longest history of use, and the most readily available, is Schoenocaulon officinale. The plant is indigenous to Central and South America and its seeds have been used for centuries for their insecticidal properties. The seeds contain several alkaloids including veratridine and cevadine, both of which are known to be active against arthropods.
Neem oil (also known as margosa oil) is another naturally derived pesticide extracted from the seed of the neem tree (Azadirachta indica). Azadirachtin is another naturally derived pesticide extracted from the neem tree seed. Azadirachtin is effective against over 200 species of insects by dissuading feeding and disrupting growth. Neem oil acts primarily as a suffocant. Further, neem oil demonstrates very low toxicity to mammals and is biodegradable.
Thus, there is a need in the art for pesticide combinations that contain naturally derived pesticides that decrease health concerns to humans and also decrease the risk of the development of pesticide resistance.
SUMMARY OF THE INVENTION
In one aspect, the present invention is directed to pesticidal mixtures of sabadilla alkaloids and neem oil.
In another aspect, the present invention is directed to methods of controlling pests, including insects and mites, comprising applying an effective amount of a mixture of sabadilla alkaloids and neem oil.
In a preferred aspect, the sabadilla alkaloids are derived from Schoenocaulon officinale. 


DETAILED DESCRIPTION OF THE INVENTION
Applicant unexpectedly discovered that pesticidal mixtures of sabadilla alkaloids and neem oil provided enhanced pesticidal activity compared to either pesticide alone. Further, Applicant discovered that pesticidal mixtures of sabadilla alkaloids and neem oil were capable of controlling a large variety of arthropods.
The present invention is directed to pesticidal mixtures comprising an effective amount of sabadilla alkaloids and neem oil.
Sabadilla alkaloids may be derived from any species of Schoenocaulon. The genus Schoenocaulon includes the following species: S. calcicola, S. caricifolium, S. comatum, S. conzattii, S. dubium (alt. S. gracile), S. framei, S. ghiesbreghtii (alt. S. drummondii, S. yucatanense), S. ignigenum, S. intermedium, S. jaliscense, S. macrocarpum (alt. S. lauricola), S. madidorum, S. megarrhizum, S. mortonii, S. oaxacense, S. obtusum, S. officinale, S. pellucidum, S. plumosum, S. pringlei, S. rzedowskii, S. tenorioi, S. tenue, S. tenuifolium, S. texanum, and S. tigrense. In a preferred embodiment the sabadilla alkaloids are derived from S. officinale. In another preferred embodiment the sabadilla alkaloids are veratridine and cevadine
As used herein, all numerical values relating to amounts, weight percentages and the like are defined as “about” or “approximately” each particular value, namely, plus or minus 10%. For example, the phrase “at least 5% by weight” is to be understood as “at least 4.5% to 5.5% by weight.” Therefore, amounts within 10% of the claimed values are encompassed by the scope of the claims.
The term “effective amount” means the amount of the formulation that will control the target pest. The “effective amount” will vary depending on the mixture concentration, the type of pest(s) being treated, the severity of the pest infestation, the result desired, and the life stage of the pest during treatment, among other factors. Thus, it is not always possible to specify an exact “effective amount.” However, an appropriate “effective amount” in any individual case may be determined by one of ordinary skill in the art.
In a preferred embodiment, the ratio of sabadilla alkaloids to neem oil is from about 1:1,000 to about 2:1, more preferably from about 1:500 to about 1:1, yet more preferably from about 1:334 to about 1:1 and most preferably from about 1:334 to about 1:9, from about 1:80 to about 1:1, from about 1:80 to about 1:5 or from about 1:160 to about 1:5.
In another preferred embodiment, the pesticidal mixtures of the present invention may contain one or more excipients selected from the group consisting of solvents, anti-caking agents, stabilizers, defoamers, slip agents, humectants, dispersants, wetting agents, thickening agents, emulsifiers, penetrants, adjuvants, synergists, polymers, propellants and/or preservatives.
The present invention is further directed to methods of controlling a pest comprising applying a pesticidal mixture comprising an effective amount of sabadilla alkaloids and neem oil to the pest or the pest's environment.
In a preferred embodiment, the pest is selected from an insect and a mite.
In an embodiment, the pest controlled is selected from the group consisting of aphids (Homoptera), whiteflies (Hemiptera), thrips (Thysanoptera), bed bugs (Hemiptera), fleas (Siphonaptera), caterpillars/worms (Lepidoptera), beetles (Coleoptera), cockroaches (Blattodea), flies (Diptera), ants (Hymenoptera), mosquitoes (Culicidae) and mites (Acari).
In a preferred embodiment, the pest controlled are selected from the group consisting of common bed bugs (Cimex lectularius), green peach aphids (Myzus persicae), house fly (Musca domestica), yellow fever mosquito (Aedes aegypti), southern house mosquito (Culex quinquefasciatus), African malaria mosquito (Anopheles gambiae), common malaria mosquito (Anopheles quadrimaculatus) and German cockroach (Blattella germanica).
The pesticidal mixtures of the present invention can be applied by any convenient means. Those skilled in the art are familiar with the modes of application including spraying, brushing, soaking, in-furrow treatments, or side-dressing.
In a preferred embodiment, sabadilla alkaloids are applied to the pest or the pest's environment at a rate from about 1 to about 1,000 grams per hectare (“g/HA”), preferably from about 10 to about 700 g/HA and most preferably from about 22 to about 105 g/HA.
In a preferred embodiment, neem oil is applied to the pest or the pest's environment at a rate from 10 to about 10,000 g/HA, more preferably from about 500 to about 8,000 g/HA and most preferably from about 918 to about 7,344 g/HA.
In another preferred embodiment, the pesticidal mixtures of the present invention comprise from about 0.01% to about 1% w/w sabadilla alkaloids, more preferably from about 0.025% to about 0.5% w/w and most preferably from about 0.05% to about 0.5% w/w, from about 0.05% to about 0.1% w/w or from about 0.025% to about 0.1% w/w.
In another preferred embodiment, the pesticidal mixtures of the present invention comprise from 0.1% to about 10% w/w neem oil, more preferably from about 0.5% to about 4% w/w.
As used herein, “control” a pest or “controlling” pest(s) refers to killing, incapacitating, repelling, or otherwise decreasing the negative impact of the pest on plants or animals to a level that is desirable to the grower or animal.
As used herein, “pest's environment” refers to any area that the pest is present during any life stage. One environment likely to be treated by the methods of the present invention includes the plants that the pest is living on and the surrounding soil. The pest's environment may also include harvested plants, gardens, fields, greenhouses, or other buildings, and various indoor surfaces and structures, such as furniture including beds, and furnishings including books, clothing, etc.
The articles “a,” “an” and “the” are intended to include the plural as well as the singular, unless the context clearly indicates otherwise. For example, the methods of the present invention are directed to controlling “pest”, but this can include control of a multiple pests (such as a more than one insect or more than one insect species or more than one mite or more than one mite species).
The following examples are intended to illustrate the present invention and to teach one of ordinary skill in the art how to use the extracts of the invention. They are not intended to be limiting in any way.
EXAMPLES
Example 1—German Cockroach
In this study, the response of the German cockroach (Blattella germanica) to application of a 1:80, 1:10, 1:8 and 1:1 ratio of sabadilla (S. officinale) alkaloids to neem oil will be observed. Specifically, sabadilla alkaloids and neem oil will be applied to the pest at the respective rates of: 1) 0.05% w/w to 0.5% w/w, 2) 0.5% w/w to 0.5% w/w, 3) 0.05% w/w to 4% w/w and 4) 0.5% w/w to 4% w/w.
The results of the study are predicted to show more than an additive effect. One can determine that the response is more than additive using the following formula: % Cexp=A+B−(AB/100).
Example 2—Bed Bugs
In this study, the response of the bed bug (Cimex lectularius) to application of a 1:80, 1:10, 1:8 and 1:1 ratio of sabadilla (S. officinale) alkaloids to neem oil will be observed. Specifically, sabadilla alkaloids and neem oil will be applied to the pest at the respective rates of: 1) 0.05% w/w to 0.5% w/w, 2) 0.5% w/w to 0.5% w/w, 3) 0.05% w/w to 4% w/w and 4) 0.5% w/w to 4% w/w.
The results of the study are predicted to show enhanced pesticidal activity.
Example 3—Mosquito
In this study, the response of the mosquito to application of a 1:80, 1:40, 1:10 and 1:5 ratio of sabadilla (S. officinale) alkaloids to neem oil will be observed. Specifically, sabadilla alkaloids and neem oil will be applied to the pest at the respective rates of: 1) 0.05% w/w to 0.5% w/w, 2) 0.1% w/w to 0.5% w/w, 3) 0.05% w/w to 4% w/w and 4) 0.1% w/w to 4% w/w.
The results of the study are predicted to show enhanced pesticidal activity.
Example 4—House Fly
In this study, the response of the house fly (Musca domestica) to application of a 1:160, 1:40, 1:20 and 1:5 ratio of sabadilla (S. officinale) alkaloids to neem oil will be observed. Specifically, sabadilla alkaloids and neem oil will be applied to the pest at the respective rates of: 1) 0.025% w/w to 0.5% w/w, 2) 0.1% w/w to 0.5% w/w, 3) 0.025% w/w to 4% w/w and 4) 0.1% w/w to 4% w/w.
The results of the study are predicted to show enhanced pesticidal activity.
Example 5—Whiteflies
In this study, the response of the whitefly to application of a 1:334, 1:70, 1:42 and 1:9 ratio of sabadilla (S. officinale) alkaloids to neem oil will be observed. Specifically, sabadilla alkaloids and neem oil will be applied to the pest at the respective rates of: 1) 22 g/HA to 918 g/HA, 2) 105 g/HA to 918 g/HA, 3) 22 g/HA to 7.344 g/HA and 4) 105 g/HA to 7.344 g/HA.
The results of the study are predicted to show enhanced pesticidal activity.
Example 6—Mites
In this study, the response of the mite to application of a 1:334, 1:70, 1:42 and 1:9 ratio of sabadilla (S. officinale) alkaloids to neem oil will be observed. Specifically, sabadilla alkaloids and neem oil will be applied to the pest at the respective rates of: 1) 22 g/HA to 918 g/HA, 2) 105 g/HA to 918 g/HA, 3) 22 g/HA to 7.344 g/HA and 4) 105 g/HA to 7.344 g/HA.
The results of the study are predicted to show enhanced pesticidal activity.

## Claims

1. A pesticidal mixture comprising an effective amount of an active ingredient consisting of sabadilla alkaloids and of neem oil, wherein the concentration ratio of sabadilla alkaloids to neem oil is from about 1:1,000 to about 1:1 and wherein the sabadilla alkaloids are veratridine and cevadine.

2. The mixture of claim 1, wherein the sabadilla alkaloids are derived from Schoenocaulon officinale.

3. The mixture of claim 1, wherein the sabadilla alkaloid is present in the mixture at a concentration from about 0.01% to about 1% w/w, wherein w/w denotes weight by total weight of the mixture.

4. The mixture of claim 1, wherein the sabadilla alkaloid is present in the mixture at a concentration from about 0.025% to about 0.5% w/w, wherein w/w denotes weight by total weight of the mixture.

5. The mixture of claim 1, wherein the neem oil is present in the mixture at a concentration from about 0.1% to about 10% w/w, wherein w/w denotes weight by total weight of the mixture.

6. The mixture of claim 1, wherein the neem oil is present in the mixture at a concentration from about 0.5% to about 4% w/w, wherein w/w denotes weight by total weight of the mixture.

7. A method of controlling a pest comprising applying a pesticidal mixture comprising an effective amount of an active ingredient consisting of sabadilla alkaloids and neem oil to the pest or the pest's environment, wherein the concentration ratio of sabadilla alkaloids to neem oil is from about 1:1,000 to about 1:1 and wherein the sabadilla alkaloids are veratridine and cevadine.

8. The method of claim 7, wherein the pest is at least one of an insect and a mite.

9. The method of claim 7, wherein the pest is selected from the group consisting of Homoptera, Hemiptera, Thysanoptera, Hemiptera, Siphonaptera, Lepidoptera, Coleoptera, Blattodea, Diptera, Hymenoptera, and Acari.

10. The method of claim 7, wherein the pest is selected from the group consisting of Cimex lectularius, Myzus persicae, Musca domestica, Aedes aegypti, Culex quinquefasciatus, Anopheles gambiae, Anopheles quadrimaculatus and Blattella germanica.

11. The method of claim 7, wherein the sabadilla alkaloid is applied at a rate from about 1 to about 1,000 grams per hectare.

12. The method of claim 7, wherein the sabadilla alkaloid is applied at a rate from about 10 to about 700 grams per hectare.

13. The method of claim 7, wherein the sabadilla alkaloid is applied at a rate from about 22 to about 105 grams per hectare.

14. The method of claim 7, wherein the neem oil is applied at a rate from about 10 to about 10,000 grams per hectare.

15. The method of claim 7, wherein the neem oil is applied at a rate from about 500 to about 8,000 grams per hectare.

16. The method of claim 7, wherein the neem oil is applied at a rate from about 918 to about 7,344 grams per hectare.

17. The pesticidal mixture of claim 1, wherein the concentration ratio of sabadilla alkaloids to neem oil is from about 1:500 to about 1:1.

18. The pesticidal mixture of claim 17, wherein the concentration ratio of sabadilla alkaloids to neem oil is from about 1:80 to about 1:1.

19. The pesticidal mixture of claim 18, wherein the concentration ratio of sabadilla alkaloids to neem oil is from about 1:80 to about 1:5.

20. The method of claim 9, wherein the pest is selected from the group consisting of aphids, whiteflies, thrips, bed bugs, fleas, caterpillars, worms, beetles, cockroaches, flies, ants, and mites.

21. The method of claim 10, wherein the pest is selected from the group consisting of common bed bugs, green peach aphids, house fly, yellow fever mosquito, southern house mosquito, African malaria mosquito, common malaria mosquito and German cockroach.