TWI236376B - Topical organic ectoparasiticidal compositions - Google Patents

Abstract

This invention provides topical ectoparasiticidal formulations comprising an ectoparasiticide, preferably a pyrethroid or a spinosyn, a spreading agent that is a (C3-C6) branched alkyl (C10-C20) alkanoate, preferably isopropyl myristate, and optionally a miscibilizing agent compatible with organic solvent systems, and methods of controlling an ectoparasite infestation on certain animals comprising topically applying such formulations to the animal.

Description

1236376

V. Description of the Invention (1) The present invention relates to a topical organic ectoparasite formulation. Ectoparasites, such as fleas, fly flies, lice, ticks, and mites, < severely affect the yield of the animal industry. In addition, these ectoparasites bow and pet, and other animal diseases and discomfort. Ectoparasites are usually controlled by locally applying insecticides or mixtures of insecticides to animals. Topical ectoparasite control agents are typically applied as liquid formulations. Formulations can be applied by spot, piercing or spraying, by hand-held spraying or rapid injection, by back-line spraying, or by pouring.

A particular problem with topical formulations is poor movement from the application site. For example, in the sheep industry, the treatment of ectoparasites # is usually performed early in the season within 24 hours after shearing, or less late in the season and when the wool is longer. Especially in early season treatments, when topical formulations are applied to the midline or backline of an animal's back, the formulations of insecticidal ingredients currently available on the market are extremely poorly moved from the application location. Within the first 10 days, typically less than 10% of the insecticide applied spread from the application site. As a result, animal skins and / or hairs in a wide range of areas receive an insecticidal killer concentration. These areas are still vulnerable to damage from ectoparasites. In order to overcome the insufficient control caused by the poor movement of the killer bomber, a relatively large amount of killer agent is usually applied in the industry. This implementation increases undesired masters = insecticide residues are present in certain animal products (such as wool and medium), increasing the possibility of border pollution. It also increases undesired and unwanted pesticide exposure to animal treatment. The dangers of farmers and farmers. = Research on the mobility of Jiaotong University insecticides, it has recently been noticed that the use of solvents as the two 'compounds' can reduce the amount of insecticides in the formulation and achieve the same effect. So far In determining that a solvent can substantially enhance use

1236376 V. Description of the invention (2) The deployment of insecticides applied by point or pouring method is rarely successful. ^ The present invention provides insecticidal formulations, which can be applied topically to animals and have the advantage of allowing active ingredients to spread on the skin and / or hair of the animal to be treated, thereby providing the advantage of a wider coverage of insecticides. Therefore, these formulations can provide greater inhibition or extinguishment of ectoparasites in smaller amounts of insecticides. The topical ectoparasite-killing formulation of the present invention comprises an ectoparasite-killing agent, a spreading agent, and optionally a miscible agent. The present invention more specifically relates to a topical ectoparasitic formulation comprising from about 0.1 to about 25% by weight of an ectoparasite killer and from about 25 to about 99.9% by weight of one (C3 -C6) a branched alkyl (C1G-C2G) alkanoate spreading agent, and a miscible agent compatible with an organic solvent system having a selectivity of about 70% by weight. An example of a topical ectoparasite formulation of the present invention is where the ectoparasite killer is spinosyn, or a physiologically acceptable derivative or salt thereof. The present invention also includes a method of controlling ectoparasites infecting small anti-infestation animals or pets, including topically applying a spinosinol containing about 0.1 to about 25% by weight, or a physiologically acceptable derivative or salt thereof. , About 25 to 99.9% by weight of isopropyl myristate, and 0 to about 70% by weight of a miscible formulation compatible with organic solvent systems in animal hair or / or skin . The present invention also relates to a product comprising a packaging material and a topical formulation for controlling ectoparasite infestation of small anti-foul animals or pets, which is included in the packaging material, wherein the formulation includes a single-agent formulation for topical use, including 0.1 to about 25% by weight of an ectoparasite killer, and about 25 to about 99.9% by weight of a (C3-C6) branched alkyl group

O: \ 65 \ 65511.ptd Page 6 1236376 V. Description of the invention (3) (C1 ()-C2〇) alkanoic acid ester spreading agent, and a kind of organic solvent system with a selectivity of about 70% by weight A miscible content; and wherein the packaging material includes a label or packaging insert with instructions for topical application of the agent to animals. This product, or kit, is especially suitable when the pet is a dog or cat. The time of administration of this agent is generally every 30 days. Each set typically contains a sufficient number of doses to control ectoparasite infestation over a period of several months. The present invention further provides a topical formulation for controlling ectoparasite infestation in small ruminants or pets, comprising a spinoxin, or a derivative or salt thereof, and a spreading agent, substantially as described above, reference Either instance. Examples of small anti-domestic animals or pets are sheep, goats, or camels (came 11i d). The term pet includes dogs, cats, horses, and other humans who own and maintain close relationships and become part of the human-animal chain. Animal. As used herein, the term π control π table can improve or eliminate the current infection or prevent infection of susceptible hosts. Many insecticides can be used in the formulations of the invention. In fact, any ectoparasite compound that is soluble in a (C3-C6) branched alkyl (C1G-C2G) alkanoate vehicle and can be applied locally can be incorporated into these formulations as an insecticidal ingredient. Insecticides are typically effective against a wide range of pest species, including acaricides, antiparasites, insect growth regulators, and can inhibit or kill flies, flying insects, and others that only temporarily fall on farmed animals Compound of temporary π pests. Examples of useful species of insecticides are spinosin, organic phosphates,

O: \ 65 \ 65511.ptd Page 7 1236376 V. Description of the invention (4) Organochlorine, carbamate, and pyrethrum. Specific useful insecticidal compounds include tetraethylpyrophosphate (TEPP), mevinphos' disulfoton, azonphosmethyl, parathion, and sylparasson ( methylparathion, chlorfenvinphos, cichlorvos, diazinon, dimethoate, trichlorfon, chlorothion, malathion, dragon Ronnel, abate, baygon, carbarvl, mobam, temik, zectran, methoxychlor , Aldrin, dieldrin, endrin, heptachlor, chlordane, lindane, mirex, nicotine, rotanno (R〇tenoids), pyrethrums, spinoxin, and synthetic pyrethroids, including cypermethr i η are better insecticides that can be used in these formulations Spinozin or pyrethroids, such as cyphenidine (07-6161; 111 ^ 11). Spinozin is particularly good. Spinosyns (also known as the ^ 3 453 factor) is an agricultural killer's contact agent for the southern armyworm and other insects of the order Lepidoptera, and cotton aphids, and the same wings Other insects of the order Homoptera show activity (see, for example, US 5,571,901). Spinozin is also known to have some ectoparasiticidal activity, that is, in vitro, for insect members of the order Diptera, mosquito larvae, and black fly larvae

Page 8 1236376

Insects, and maggots, are active, and they have transient systemic activity against larvae and maggots in guinea pigs and sheep. For these tests, spinosinoxin was administered in an aqueous solution of polyvinylpyrrolidone or in polyethylene glycol (see US Pat. No. 5,571,901, Col. 26-32). Spinocinoxin is a macro bamboo that is made of natural bamboo, which is produced by fermentation of SaccharopolySp0ra spinosa. Many factors are produced by fermentation, including Shi negative Youxin A and Shi negative 5 Youxin D (also known as A83543A and A8354D). Shi Ning δ Youxin A and Shi Ning Youxin D are the two most effective insecticides Spinozin. A product that mainly contains these two spinosinoxins is commercially available from the trade name π Spinolox (s p i η s a d) π. Shi Ning 5 You Xin A is a younger brother Ife Xin who was isolated and identified by Saccharopolyspora spinosa fermented meat. Examination of the fermentation broth revealed that S spinosa produces many types of spinosin, called spinosin a to H and j. Other negative-sinusins, from K to W, have been identified by various strains of S. spinosa. Various histamines are different in the form of substitution on the amine group of forosamine, and select positions on the tetracyclic system and 2N, 3N, 4N- (tri-0-fluorenyl) rhamnosyl group .

Boeck et al. Describe Spinozin A-Η and J (which are referred to as A83543 factors A, B, C, D, E, F, G, H, and J), and their salts, in U.S. Patent 5,362, 634 (issued November 8, 1994), 5, 496, 932 (issued March 5, 1996), and 5,571,901 (issued November 5, 1996) Mynderse et al. Mentioned Spinozin LN (which Called A8 354 3 factors L, M, and N), its n-difluorenyl derivatives and salts thereof, in US Patent 5,202,242 (issued April 13, 1993); and Turner et al. Mentioned Spino Xin qt (which is called

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1236376 V. Description of the invention (6) A83543 factors Q, R, S and T), its n-difluorenyl derivatives and their salts; in US Patent 5,591,606 (issued on January 7, 1997), And 5,631,155 (issued on May 29, 1997). Spinnock 1 (, 0,?, 11, V'W and Y are described in, for example, Carl V. DeAmicis, James E. Dripps, Chris J. Hatton and Laura I. Karr, American Chemical Society's Symposium Series: Phytochemicals for Pest Control, Chapter 11, " Physical and

Biological Properties of Spinosyns: Novel Macro 1 i de Pest-Control Agents from Fermentation ", pages 146-154 (1997) ° Spinozin can be separated into a salt form, which can also be used in the formulation Φ of the present invention. Salts are prepared using standard procedures for salt preparation. For example, Spinoxin A can be neutralized with an appropriate acid to form an acid addition salt. Representatives of suitable acid addition salts include organic and inorganic acids such as sulfuric acid, hydrogen acid, phosphoric acid, acetic acid, succinic acid, citric acid, lactic acid, maleic acid, fumaric acid, cholic acid, and paranaphthalene. Acid, mucinic acid, glutamic acid, camphoric acid, glutaric acid, glycolic acid, dare acid, tartaric acid, gallic acid, lauric acid, stearic acid, salicylic acid, sulfonic acid, benzenesulfonic acid, sorbic acid, Acids such as picric acid, phenylarsinic acid and cinnamic acid are salts formed by the reaction. The term " spinnose or derivative thereof " as used herein refers to each spinnose factor (spinnose a, b, c, d, e, f, g, h, k, l, m, n, 〇, p, Q, R, s, t, v, w, or y), and one or more Spinoxin factors, N-difluorenyl derivatives, or combinations thereof. For convenience, this article The term "spinnosein" used in the term "spinnosein," or "spinnose"

O: \ 65 \ 65511.ptd Page 10 1236376 V. Description of the invention (7) Biological or salt, or a combination thereof. As used in this article, the "Sinoxolide pi list mainly contains the Spinoxin mixture containing Spinoxin A and D. Spinoxin is known to have excellent human and animal safety and toxicology. Because it is good for animals And the low toxicity of humans, Spinozin is considered to be environmentally friendly and "green" insecticide. It is best to mix Spinozin to maintain this "green" situation. Spinozin has recently been found to be used to fight or control parasites other than sheep and pets. Therefore, Spinoxin formulations with low toxicity and increased stability are potentially valuable in combating ectoparasites and diseases commonly carried by these pests. The formulation of the present invention further comprises a (C3-C6) branched alkyl (C1Q-C2Q) alkyl ester. This ingredient is an organic solvent and is used as a spreading agent. Spreading agents can increase the spread of active ingredients and assist in substantially evenly distributing the animal's hair and / or skin surface areas. Spread solvent systems should be safe, non-toxic, environmentally friendly, and non-flammable. (c3-c6) branched alkyl (C1G-C2 ()) alkanoates include all branched chain isomers of c3-c6 alkyl. Examples are isopropyl, isobutyl, isopentyl (C1Q-C2Q) alkanoate moiety includes C1Q-C2Q fatty alkanoate, including, but not limited to, decanoate (C1G), undecanoate (cn), dodecanoic acid Ester (c12), tridecanoate (c13), tetradecanoate (c14), pentadecanoate (C15), hexadecanoic acid S (C16), heptadecanoic acid S (C17), octadecanoic acid Vinegar (C18), and eicosanate (C2Q). The spreading agent is preferably (c3-c6) branched alkyl (C1G-C2Q) alkanoate. In these solvents, c3- branched alkyl c14-alkane Ester is particularly useful. A preferred spreading agent is isopropyl myristate (IPM).

O: \ 65 \ 65511.ptd Page 11 1236376 V. Description of the invention (8) The formulation can optionally contain a miscible. Miscible agents can help dissolve active ingredients and must be compatible with organic solvent systems. The term " compatible with organic solvent systems " means that a miscible agent does not form more than one phase when mixed with (C3-C6) branched alkyl (C1Q-C2Q) ester components. Miscible agents suitable for use in these formulations are generally (Ci-C3Q) organic acids. These organic acids are typically linear saturated fatty acids, but can also be low molecular weight organic acids such as formic acid, acetic acid, propionic acid, and benzoic acid. The choice of miscibility depends on the insecticide in the formulation. When the insecticide ingredient is a spinoxin, examples of suitable miscible agents are gallic acid, acetic acid, propionic acid, butyric acid, valeric acid, hexanoic acid, phenylarsinic acid, heptanoic acid, caprylic acid, nonanoic acid, decanoic acid. Acid, undecanoic acid, lauric acid, tridecanoic acid, myristic acid, pentadecanoic acid, palmitic acid, heptaic acid, stearic acid, oleic acid, arachidic acid, behenic acid, behenic acid, Hexadecanoic acid, icosanoic acid, icosanoic acid, psylic acid (psy 1 1 icacid), and hexacosanoic acid. Other useful miscible agents are (h-C3Q) thiosulfuric acid, sweet and bitter 1 _ C3Q) thiophosphonic acid, and (i _ C3.) Thiocarboxylic acid. In formulations containing spinoxin in isopropyl myristate, such as oleic acid is a particularly useful miscible because it can help dissolve spinoxin Solvent solution), and it is compatible with isopropyl myristate. Compounds other than (G-C3 ()) organic acids are also miscible agents useful in the formulations of the present invention. Generally, the miscible compounds that can be used in these formulations are: 1) compatible with selected organic solvent ingredients, and 2) soluble active ingredients without substantially altering the spreading properties of the formulations.

O: \ 65 \ 65511.ptd Page 12 1236376 V. Description of the invention (9) When the insecticide is a Spinoxin and the Spinoxin ingredient is Spinoxin 'D or Spinoxin (that is, Spinox Mixture of Nosing A and D), it is particularly important that the miscible agent can sufficiently dissolve Spinoxin D. In technical-grade sinoxol, factor D is generally the factor that causes solubility problems when preparing formulations containing sinoxol. Examples of miscible agents that can be used in the present invention to contain senoparin-containing ectoparasite formulations include, but are not limited to, benzalcohol, ethylene glycol phenyl ether, D-fluorene (1 i monene), N-fluorene -2 -D Biloprotidine, and methylated soybean oil, and methyl esters of soybean oil, such as SOYGOLD 1000 (AG Environmental Products LLC) 〇 The formulation of the present invention may also contain other optional ingredients, such as anti- Oxidants, UV-absorbing compounds or light stabilizers, viscosity modifiers, antimicrobials, dyes, fragrances, deodorants, and physiologically or dermatologically acceptable carriers, diluents, excipients, or adjuvants Agent. Such agents are known in the art. For example, one or more antioxidants may be added to the formulation in an amount effective to prevent oxidation of the ingredients of the formulation and ensure degradation. Potentially useful antioxidants include primary oxidants, which are free radical scavengers, such as hindered resins (phe η ο 1 ics) and secondary amines, and secondary antioxidants, such as linoleates and thioesters, which are used as peroxides Decomposing agent. The preferred antioxidants used in these formulations are blends of primary and secondary antioxidants, including specifically blends of phenol resins and sub-basic acids. There are many commercially available antioxidant products designed to stabilize polymers, including antioxidant formulations, and synergistic compositions comprising primary and secondary antioxidants. Examples of commercially available antioxidants that can be used in the formulations of the invention include I r g a η ο X ® antioxidants available from C i b a G e i g y,

O: \ 65 \ 65511.ptd Page 13 1236376 V. Description of the Invention (10)-Vanox® antioxidants available from R · T · Vanderbilt, and Naugard® antioxidants available from Uniroyal Chem i ca 1 s. When the formulation includes an antimicrobial ingredient, it should be present in an amount effective to prevent the growth of microorganisms in the formulation. The formulations of the present invention are generally prepared by thoroughly mixing or blending the ingredients. For example, a useful zenox formulation is a zenox compound with a top concentration of 2 mg per milliliter. A formulation was prepared containing 99.1% by weight of IP Μ'0 · 6% by weight s% oleic acid 'and 0.3% by weight of Snosox technical grade (§ 9% active ingredient). This formulation is added from a proper amount of Sinomox to a PM solvent and mixed or stirred, oleic acid is incorporated into the IPM / Sinomox mixture, and mixing or stirring is continued until Sinomox completely dissolves to form the final formulated product. Manufacturing. An optional addition step is to filter the final formulation to remove any impurities or foreign materials. '

The formulations of the invention are administered topically to animals. Local control methods include spot or pouring treatments, in which the formulation is placed directly on one of the considered skin and / or hair surface areas of the animal and can be spread on the remaining skin or hair surface area of the animal. The point or pouring method generally involves the formulation being initially placed on the animal's back midline (ie, head's, neck, shoulders, or back). Typically placed in a dorsal midline surface area that constitutes less than 10% of the animal's overall surface area. For example, a typical wash treatment involves applying about 4 to about 50 ml of a liquid ectoparasite formulation to a narrow strip of the animal's backline, from the shoulders to the tail or hips. For spot or water treatment to control the parasites (such as Yi) existing on the entire surface of the animal, the active ingredients of the ectoparasite must be spread by a narrow strip of topline to cover the entire surface of the animal. The formulation of the invention has this excellent spreading effect

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1236376 V. Description of the invention (11) Fruit. Of course, they can be applied to skin areas that constitute more than 10% of the animal's surface area, but this application limits the advantages provided by these formulations. Another advantage of these formulations is that they provide a wide range of ectoparasite killing without the need for more than one week or up to two weeks of application. Example 1 Wetting test of various solvent systems To determine the organic solvent that can be used as a spreading agent, a solvent system capable of dissolving at least 1% by weight of Cinoxil was used for hair wetting, and about 1 ml of the solvent system was applied dropwise ( Screening solvent, no active ingredients) on a piece of rabbit fur made by the county at an angle of about 45 °. A solvent system that wets rabbit hair and does not run off before wetting rabbit hair is considered to be screened. Table I describes the ability of the selected organic solvents to wet rabbit hair. Table_I. Solvent and water-based surfactant tincture system 濶 The ability of rabbit fur on rabbit skin to be made _ organically soluble 丨 J_ Fully wetted isopropyl myristate methyl laurate dipropylene glycol methyl ether lactate Ester methyl caprate methyl oleate ethyl octanoate ethyl hexanol oleate non-wetting triacetin N-methylpyrrolidone propylene glycol

Page 15 1236376 V. Description of the invention

Non-polar solvents that cannot be mixed with water

As shown in Table I, but the dipropylene miscible 'can also be fully wetted. Example 2 Formulation test of formulations The test was performed to determine the ability of various solvents to assist the spread of active ingredients. Worm, (V, M case WQ 95242 1 9 teaches that lanolin part (F1) can provide "excellent agent spread in sheep, when cloth ratio" .: Experiments are performed to compare the content of _hair fat part: two of the formulation Spreading properties. Determination of the uc_labeled buisness destroyer has a combination of "(^^ nnethrin)", when used for the test with lanolin and a gluten = 诏 中 牯, spread by the midline of the sheep's back The amount and rate. Contains * g / Zaisheng Bu Sai Ning Jia 100 Mi [i4C] Prepared in Bu Sai: Lanolin part π, ... isopropyl acid:,: octanoic acid / capric glycerine vinegar. Each preparation 1ml / 5kg of body weight 1 was applied to the backline of 3 sheep. After treatment, the 8th day to 14th day was pulled down from the backline of each sheep to the side along the meridian. Collect 12x12 mm squares, and collect wool = middle / hair area, also wipe. After 14 days of treatment, & set flat application hair, and collect fat samples on the back and around the kidneys. The amount of each sample-cyphenidin is counted by liquid scintillation Measurements. For most measurements, isopropyl myristate is given $ — Sai ϊϊ 脂 1 fat, F1 provides the least spread. When the vehicle η lanolin keep learning, just 2 centimeters meridian displayed after the initial administration of p - Race of deltamethrin

1236376 V. Description of the invention (13) The concentration increases with time. When the vehicle was isopropyl myristate, the amount of f-cynexin measured at all meridians increased over time after application. Octyl stearate and tricaprylic / capric glyceride give moderate spread, which is not as good as the spread provided by IPM formulations. Tissue residues were similar for each formulation, but the tricaprylic / capric glyceride formulations showed the highest residual amounts. After two weeks, F1 was measured as a very poor spreading agent. Caprylic acid stearic acid and tricaprylic acid / capric acid glyceride provided better spreading properties, while isopropyl myristate gave most Good exhibition cloth. Example 3 Φ ϋ fat and IPM. 配. | ^ ^ Parasite efficacy test to test the comparison of Ciproxil in F1 lanolin part compared to the formulation in isopropyl myristate against sheep lice Effect. Contain two mg / ml and 10 mg / ml of two F formulations and one formulation containing 2 Cangquan and 2 liters of Ciproxil in isopropyl myristate see below / milli a) F 1 formulation ( 2mg / ml) &: 81.11% F1 18.62% Solvent (50/50 petroleum ether / acetone) Only ·% Synox Technical Grade has 89% activity 100% (weight / weight) Formulation density = 0.84 G / ml b) F1 formulation (10 mg / ml) 80 · 26% F1 18 · 42% solvent (50/50 petroleum ether / acetone) L ... 32% Zanox technical grade has 89% active

I 1236376 V. Description of the invention (14) 100% formulation density = 0.84 g / ml c) IPM formulation (2 mg / ml) 99.123% IPM 0.613% oleic acid 0.264% Cinox technical grade has 89% activity 100% formulation density = 0.85 g / ml. Each formulation was applied by pouring to cotton and 卩 f 〇 诺诺 formulations at a dosage of 0 (ie, vehicle only), 0.4 and 2 mg / ml immediately after shearing. Kg 针 人 # 右 杀 1 土 PM formulation was tested at a dose of 0.4 mg / kg. A dose of 2 mg / kg of Znoxil / F1 was administered using a 10 mg / ml formulation, while a dose of 0.4 mg / kg was administered using a 2 mg / ml formulation. Counting is performed on all parts of the sheep, including head and neck. These lice counts were performed before treatment and approximately every week for the next 8 weeks. The results of this study are summarized in Table II.

O: \ 65 \ 65511.ptd Page 18 1236376 Description of the invention (15) Table II. Comparison of the efficacy of Cigna killing ectoparasites in sheep lice counts (average) in F1 and IPM formulations Day 0 lice count 1 2 3 4 5 6 7 8 F1 643 only 428 328 350 237 245 159 156 145 0.4 mg / kg Ciproxil / F1 622 391 213 211 159 118 103 69 68 2 mg / kg Cinox / F1 582 146 86 48 2 13 4 3 2 0.4 mg / kg cynox / IPM 575 138 81 68 47 32 13 25 21

As shown in Table II, the results show that the efficacy of Ciproxil in IPM at a dose of 0.4 mg / kg is better than that of Ciproxil in F1 at a dose of 0.4 mg / kg, which is almost equal to Ciproxil was administered in F 1 at a dose of 2 mg / kg. Zinoxol can significantly control sheep lice in IPM, including head and neck control. It shows that IPM enhances Zinoxol to spread from the midline of the back to the head, neck, and other body surface areas. Example 4 Efficacy of Zinuo in various organic solvents on sheep lice The efficacy of other sheep lice was studied to compare the efficacy of IPM and other organic solvent systems containing organic solvent blends as spreading agents. The formulations tested have the following composition: a) I P M formulation

Page 19 1236376 V. Description of the invention (16)

99. 12 ° / 〇 IPM 0.61% oleic acid 0.27% Ciproxil technical grade (89% active) b) 〇P / I P M f Zhou Yidudou 79. 78% octyl palmitate (OP)

19. 95% IPM 0. 27% Synox technology grade (89% active) c) GTCC / 0P formulation 79. 78% tricaprylic acid / capric glyceride (GTCC) 1 9. 95% octyl soft ester 0 · 27% Ciproxil technical grade (89%) activity d) GTCC / IPM / OP formulation

6 9. 8 1% trioctanoic acid / capric acid glyceride 14. 96 ° / 〇 IPM 14.96% hexadecyl octanoate (CAP) 0.27% Synapox technical grade (89%) activity

e) 0P / IPM / 0SU Blend 6 9. 8 1 Octyl palmitate 14. 96% IPM 14.96% dioctyl succinate (0SU) 0.27% Snosox technical grade (89% activity) f ) TPM / LWG / GTCC formulation 59.84% tripropylene glycol methyl ether (TPM) 19.95% liquid lanolin (LWG)

O: \ 65 \ 65511.ptd Page 20 1236376 V. Description of the invention (17). 19.95% tricaprylic acid / capric glycerol g 0.27% Snosox technical grade (8 9% activity) g) TPM / OSU Formulation 79.78% tripropylene glycol ether 19.95% dioctyl succinate 0.27% Cinox technical grade (89% active) Lice counts were performed on all parts of the sheep, including head and neck. These lice counts were performed before treatment and approximately every week for the next 12 weeks. The results of this study are summarized in Tables II and II. Table III: The efficacy of Ciproxil in organic solvent formulations for sheep lice lice count (average) Weekly lice count before treatment 1 2 4 6 8 12 Control 253 197 128 163 206 162 204 IPM 268 33 23 18 20 18 18 ΟΡ / ΙΡΜ 271 71 51 83 90 71 184 GTCC / OP 257 32 28 40 52 46 106 GTCC / IPM / CAP 278 28 16 24 25 22 33 OP / TPM / OSU 259 33 19 23 22 19 40 TM / LWG / GTCC 267 53 29 39 34 27 48 TPM / OSU 259 58 38 64 62 66 119 As shown in Table 11 I, Ciproxil was the most effective treatment among the 7 formulations tested in IP M. Great correlation exists in the results and fields of the spread experiment

Page 21 1236376 V. Description of the invention (18) Between the results of efficacy experiments. The formulations given by Zanox in I PM have excellent distribution characteristics and have proven to have significant long-term protection and inhibitory effects on sheep infected by ectoparasites. Examples 5-11 illustrate various formulations of the invention. Example 5: Ciproxil / IPM / acetic acid formulation 5.65% Ciproxil (88.5% activity)

3% acetic acid 91. 35% IPM Example 6: Zynox / IPM / Caprylic acid formulation 5.65% Zynox (88. 5% activity)

7. 5% octanoic acid 86.85% IPM Example 7: Ciproxil / IPM / lauric acid to adjust the amount of hexamethylene 5. 65% Ciproxil (88. 5% activity)

10. 15% lauric acid 84.2% IPM Example 8: Cinosin / IPM / oleic acid formulation 5. 65% Cinosin (88. 5% activity)

16. 5% oleic acid 77. 85 ° / 〇 IPM Example 9: Cinoxil / IPM / Phenolic acid formulation 5.65% Cinox (88.5% activity)

3.76% acetic acid 9 0.5 5 ° / 〇 IPM

O: \ 65 \ 65511.ptd Page 22 1236376 V. Description of the invention (19) Example 1 0: Ciproxil / IPM / NMP formulation 5. 65% Ciproxil (88. 5% activity) 4 0.0% 1 -Methyl-2-orbolobinone (NMP)

54.35% IPM Example 11: Heng-Seminin / IPM / Recipient 1. 18% Homo-Seminin (84.7% activity)

98. 8 2 ° / 〇IPM Example 5-10 The formulation can be weighed in a suitable container by Zynox, added with I PM and stirred to produce a slurry, then the final ingredients are added and stirred until a clear solution is produced. preparation. In the formulation of Preparation Example 11, f-Xaminin is an oily liquid and requires gentle heating (about 40-50 ° C) to be suitable for mixing into the organic solvent phase. No phase separation occurs during cooling

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______ f month day i ¥ ^ r / βΡ " 36376 曱 Please date: from a: J:; I case number: 89116159 category · / / 46 / κ, Γ l '义 卜 久 4 兰 tfa 士 & 丄 古》 , F \ C \ f \ J ^ S / {r〇 '丨 乂 cu: ..: ^ π': _., ..: '. … ': .- ,,: ... Guang Guang \ Ώ < 1 Ί ri-J invention patent specification, invention name Chinese local organic ectoparasite killer composition English TOPICAL ORGANIC ECTOPARASITICIDAL COMPOSITIONS inventor name (Chinese) James Webb Cassom 2. Paul Townsmanship 3. William Webster Thompson Name (English) L JAMES WEB KASSEBAUM 2. PAUL THOMAS PUGH 3. WILLIAM WEBSTER THOMPSON Nationality i. United States 2. United States 3. United States residence , Residence __ Department succession! 8 Li Wen No. 9221 3. Wu Guo Indianapolis, Indianapolis, Indiana, 5521 Overbrook Road, applicant name (name) (in Chinese) Eli Lilly and Company (name) ( English 3 l.ELI LILLY AND COMPANY ____ —Is the United States ----- " Residence, Residence (Office) i · Wu Guo, Indianapolis, Indiana, Eli Lilly, Inc., a representative human character name (Chinese) 1 · Peter G. Shi Junge ---------- " Name of Representative '(English) 1. PETER G. STRINGER — ^ -----

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Claims (1)

1236376 Case No. 89116159 〇c η 6. Scope of patent application1. A kind of Spinozin (s to 99.9 weight agent, and up to 70.2. According to the application (C 3-C 6) points 3. Shen burning base (ci 2-ci 6 4. According to claim a miscible benzoic acid, pimelic acid, myristic acid, arachidic acid, triconic acid ectoparasite killing composition, containing 0.1 to 2 5% by weight of pinosyn), or a physiologically acceptable derivative or salt thereof, 25% of one (C3-C6) branched alkyl (C1G-C2〇) sulphuric acid® is intended to distribute an organic solvent system of 5% by weight Compatible miscible. The composition of item 1 of the patent scope, wherein the spreading agent is a burning base (C12-C16) ester. The composition of the item 2 of patent scope, where (C3-C6 Branch) alkanoate is isopropyl myristate. The composition of claim 1, 2, or 3, further comprising a compound selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid, valeric acid, hexanoic acid, acid, caprylic acid, nonanoic acid, capric acid, undecanoic acid, and laurel Acid, Decanoic acid, Pentadecanoic acid, Palmitic acid, Heptaic acid, Stearic acid, Oil, Docosalic acid, Docosalic acid, Hexahexanoic acid, Twenty-nine, Psyllic acid , Hexadecanoic acid, or N-fluorenyl-2-orbital-pyrrolidone ° or a combination of 3 items, which additionally contains 5. According to the first patent application scope, an effective amount of an antimicrobial agent. 6. The composition according to item 1 of the scope of patent application, which can be combined with a single agent for topical application and packaging materials to form a product, wherein the packaging material includes a label with instructions for topical application of the single agent to small ruminants or pets Or packaging inserts. 7-The composition according to item 1, 2 or 3 of the scope of patent application, wherein the miscible is oleic acid. O: \ 65 \ 65511-940114.ptc Page 25