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    公开号:AU2005301975A1
    申请号:U2005301975
    申请日:2005-11-03
    公开日:2006-05-11
    发明作者:Mark Scialdone
    申请人:EI Du Pont de Nemours and Co；
    IPC主号:A01N43-16
    专利说明:
    WO2006/050519 PCT/US2005/040146 TITLE INSECT REPELLENT COMPOSITIONS COMPRISING DIHYDRONEPETALACTONE, AN ALCOHOL AND AN ESTER This application claims the benefit of U.S. Provisional Application No. 60/624,579, filed on November 3, 2004, which is incorporated in its entirety 10 as a part hereof for all purposes. Technical Field The present invention relates to the field of 15 insect repellency, and the use of dihydronepetalactone stereoisomers generally as repellent materials. Background 20 Repellent substances generally cause insects to be driven away from, or to reject, otherwise insect acceptable food sources or habitats. Most known repellents are only mildly toxic. A few of the known repellents, in fact, are not active poisons at all but 25 rather prevent damage to plants/animals or articles of manufacture by making insect food sources or living conditions unattractive or offensive. Most current commercial insect repellents contain the synthetic chemical N,N-diethyl-m-toluamide (DEET) as their 30 primary active ingredient. For instance, repellents sold under the major commercial brand names such as Off!®, Deep Woods Off!®, and Cutter® are all DEET based products and comprise 85% of insect repellent sales (Consumer Reports Buying Guide, 1994 Special Year- End 35 Issue). Further, Consumer Reports tests indicated that products with the highest concentration of DEET lasted the longest against mosquitoes. 1 WO2006/050519 PCT/US2005/040146 Despite being an effective repellent, however, this compound has certain drawbacks. Specifically, it possesses an unpleasant odor and imparts a greasy feel to the skin. Although it has recently been re 5 registered for use in the US by the EPA, concerns have been raised as to its safety, particularly when applied to children [Briassoulis, G.; Narlioglou, M.; Hatzis, T. (2001) Human & Experimental Toxicology 20(1), 8-14]. Studies have demonstrated that high concentrations of 10 DEET may give rise to allergic or toxic reactions in some individuals. Other disadvantages associated with DEET include that it (1) is a synthetic chemical having a limited spectrum of activity; (2) is a powerful plasticizer and will dissolve or mar many plastics and 15 painted surfaces; and (3) plasticizes the inert ingredients typically used in topical formulations in order to lengthen the time of effectiveness. This leads to DEET formulations with low user acceptability. 20 As a result of the above limitations, DEET-free products with repellent activity are finding favor with consumers, and demand for compositions containing natural products (versus synthetic chemicals such as DEET) is increasing. These DEET-free repellent 25 compounds require a combination of excellent repellency, high residual activity and relatively little or no toxicity to humans (or pets) and the environment. In response to these consumer demands, there is an on-going need to develop new repellent 30 compounds, which can be obtained from, or synthesized from, natural plant materials and which are pleasant toc use. Many plant species produce essential oils 35 (aromatic oils) that are used as natural sources of insect repellent and fragrant chemicals [Hay, R.K.M., Svoboda, K.P., Botany, in "Volatile Oil Crops: their biology, chemistry and production"; Hay, R.K.M., 2 WO2006/050519 PCT/US2005/040146 Waterman, P.G. (eds.); Longman Group UK Limited (1993)]. Citronella oil, known for its general repellence towards insects, is obtained from the graminaceous plants Cymbopogon winterianus and C. 5 nardus. Examples of plants used as sources of fragrant chemicals include Melissa officinalis (Melissa), Perilla frutescens (Perilla), Posostemon cablin (Patchouli) and various Lavandula spp. (Lavender). All of these examples of plants yielding oil of value to 10 the fragrance industry are members of the Labiatae (Lamiaceae) family. Plants of the genus Nepeta (catmints) are also members of this family, and produce an essential oil, which is a minor item of commerce. This oil is very rich in a class of monoterpenoid 15 compounds known as iridoids [Inouye, H. Iridoids. Methods in Plant Biochemistry 7:99-143 (1991)], more specifically the methylcyclopentanoid nepetalactones [Clark, L.J. et al. The Plant Journal, 11:1387-1393 (1997)] and derivatives. 20 Iridoid monoterpenoids have long been known to be effective repellents to a variety of insect species [Eisner, T. Science 146:1318-1320 (1964); Eisner, T. Science 148:966-968 (1965); Peterson, C. and J. Coats, 25 Pesticide Outlook 12:154-158 (2001); and Peterson, C. et al. Abstracts of Papers American Chemical Society, (2001) 222 (1-2) : AGRO73] . U.S. Patent 4,663,346 discloses insect repellants with compositions containing bicyclic iridoid lactones (e.g., 30 iridomyrmecin). Further, U.S. Patent 4,869,896 discloses use of these bicyclic iridoid lactone compositions in potentiated insect repellent mixtures with DEET. 35 Formal studies concerning the repellency of dihydronepetalactones, a class of iridoid monoterpenoids derived from nepetalactones (shown in Figure 1), have been much less conclusive and have 3 WO2006/050519 PCT/US2005/040146 failed to teach or imply that these compounds exert a repellent effect on the common insect pests of human society. For example, a study of the composition of the secretion from anal glands of the ant Iridomyrmex 5 nitidus showed that isodihydronepetalactone was present in appreciable amounts, together with isoiridomyrmecin [Cavill, G.W.K., and D.V. Clark. J. Insect Physiol. 13:131-135 (1967)]. Although isoiridomyrmecin was known at the time to possess good 'knockdown' 10 insecticidal activity, no evidence was provided in support of a similar activity for isodihydronepetalactone, and no investigation of this compound's repellent effect (as distinct from insecticidal activity) was made. 15 In a later publication by Cavill, G.W.K., et al. [Tetrahedron 38:1931-1938 (1982)], the presence of dihydronepetalactones in the defensive secretion of an ant was again reported, but the authors concluded that 20 the compound iridodial, rather than a dihydronepetalactone, was the basic repellent constituent. CHO CHO 25 Iridodial 30 4 WO2006/050519 PCT/US2005/040146 Most recently, Jefson, M., et al. [J. Chemical Ecology 9:159-180 (1983)] described the repellent effect of dihydronepetalactone. Initial repellency caused by the undiluted compound was measured with 5 respect to the ant species Monomorium destructor during feeding. After 25 seconds of exposure to the pure dihydronepetalactone, approximately 50-60% of the ants ceased to feed. However, further analyses of the repellency over a longer time course were not 10 presented, nor were analyses with anything other than the pure undiluted compound. Repellency observed over such short periods of time (seconds) with concentrated chemicals is insufficient to allow prediction of efficacy in practical applications such as in topical 15 insect repellents. There is consequently a continuing need for a biologically based compound having improved insect repellent properties (with respect to DEET) and which 20 is substantially non-toxic or only mildly toxic to humans. Preferred repellents will have activity against a wide variety of insects, including biting insects, wood-boring insects, noxious insects, household pests, and the like. Applicants have found 25 that dihydronepetalactones, and compositions thereof, perform well as a new class of effective insect repellent compounds without the disadvantageous properties characteristic of prior-art compositions. 30 Summary One embodiment of this invention is an insect repellent composition or article that contains a dihydronepetalactone, or a mixture of 35 dihydronepetalactone stereoisomers, represented by the general formula: 5 WO 2006/050519 PCT/US2005/040146 0 0 Another embodiment of this invention is a process for fabricating an insect repellent composition 5 or an insect repellent article of manufacture by providing as the composition or article, or incorporating into the composition or article, a dihydronepetalactone, or a mixture of dihydronepetalactone stereoisomers, as described above. 10 Yet another embodiment of this invention is the use of a dihydronepetalactone, or a mixture of dihydronepetalactone stereoisomers, as described above, or a composition thereof, as an insect repellent; and 15 thus an embodiment in which, in a method of repelling insects, the insects are exposed to a diihydronepetalactone, or a mixture of dihydronepetalactone stereoisomers, or a composition thereof, as described above. 20 Yet another embodiment of this invention is a formulated inset repellent composition that includes a dihydronepetalactone, or a mixture of dihydronepetalactone stereoisomers, as described above 25 and one or more of a carrier, an adjuvant and an additive. 6 WO2006/050519 PCT/US2005/040146 Brief Description of the Drawings Figure 1 shows the chemical structures of the naturally occurring iridoid (methylcyclopentanoid) nepetalactones. 5 Detailed Description A nepetalactone" is a compound having the general structure: 10 0 77a 1 20 6 3 4a 5 Four chiral centers are present within the methylcyclopentanoid backbone of nepetalactone at carbons 4, 4a, 7 and 7a as shown above; (7S) 15 nepetalactones are produced by several plants and insects. Dihydronepetalactones are known as minor constituents of the essential oils of several labiate plants of the genus Nepeta (Regnier, F.E., et al. (1967) Phytochemistry 6:1281-1289; DePooter, H.L., et 20 al. (1988) Flavour and Fragrance Journal 3:155-159; Handjieva, N.V. and S.S. Popov (1996) J. Essential Oil Res. 8:639-643). Dihydronepetalactones are defined by Formula 1: 25 30 7 WO 2006/050519 PCT/US2005/040146 O 2 91 0 8 7 6 4 5 Formula I 5 wherein 1, 5, 6 and 9 indicate the four chiral centers of the molecule and the structure encompasses all possible stereoisomers of dihydronepetalactone. The structures of dihydronepetalactone stereoisomers that 10 may be derived from (7S)-nepetalactones are shown below. 8 WO 2006/050519 PCT/US2005/040146 O (1S,5S,9S,6R)-5,9-dimethyl-3-oxabicyclo[4.3.0]nonan-2-one H - 0 0 O (1S,9S,5R,6R)-5,9-dimethyl-3-oxabicyclo[4.3.0]nonan-2-one 0 1HO (1S,5S,9S,6S)-5,9-dimethyl-3-oxabicyclo [4.3.0]nonan-2-one H O - 0 (1S,9S,6S,5R)-5,9-dimethyl-3-oxabicyclo [4.3.0]nonan-2-one H
    :
    H O - (9S,5S, 1R,6R)-5,9-dimethyl-3-oxabicyclo[4.3.0]nonan-2-one H - 0 O (9S, 1R,5R,6R)-5,9-dimethyl-3-oxabicyclo[4.3.0]nonan-2-one ~(9S,6S, 1R,5S)-5,9-dimethyl-3-oxabicyclo [4.3.0]nonan-2-one H - 0 O (9S,6S, 1R,5R)-5,9-dimethyl-3-oxabicyclo[4.3.0]nonan-2-one H - 0 (9S,6S, 1R,5R)-5,9-dimnethyl-3-oxabicyclol4.3.O]nonan-2-one H The term "dihydronepetalactones" or "dihydronepetalactone mixtures" refers to any mixture 5 of dihydronepetalactone stereoisomers. The molar or mass composition of each of these isomers relative to the whole dihydronepetalactone composition can be 9 WO2006/050519 PCT/US2005/040146 variable. Dihydronepetalactones are abbreviated as "DHN". A dihydronepetalactone will be understood to 5 encompass any and all dihydronepetalactone stereoisomers and mixtures thereof, unless a particular isomer or mixture is specified. When dihydronepetalactone is prepared from a naturally occurring source of nepetalactone some variation in 10 molar concentration of stereoisomers is expected. Preparation from a naturally occurring source is, however, a preferred method of preparation. Dihydronepetalactones are reported in the 15 literature as minor constituents of the essential oils of several labiate plants of the genus Nepeta [Regnier, F.E., et al., Phytochemistry 6:1281-1289 (1967); DePooter, H.L., et al., Flavour and Fragrance Journal 3:155-159 (1988); Handjieva, N.V. and S.S. Popov, J. 20 Essential Oil Res. 8:639-643 (1996)]. Additionally, dihydronepetalactones have been identified as constituents of the defensive secretions of certain insects, including rove beetles [Jefson, M., et al., J. Chem. Ecol. 9:159-180 (1983)] and ants, specifically 25 Iridomyrmex species [Cavill, G.W.K. and D.V. Clark. J. Insect Physiol. 13:131-135 (1967)]. In those species that possess dihydronepetalactones, it has been proposed that they are biosynthetically derived from the iridoid monoterpene iridodial. 30 The chemical synthesis of dihydronepetalactones and their related iridoid monoterpenoid compounds has been described and found to be conducted in a variety of ways. The following are useful references relating 35 to synthesis: 1)Abelman, M.M. et al. J. Am. Chem. Soc. 104(14):4030-2 (1982) 10 WO 2006/050519 PCT/US2005/040146 2) Fleming, I. and N.K. Terrett. Tetrahedron Lett. 25(44): 5103-5104 (1984); J. Chem. Soc., Perkin Trans. 1:2645-2650 (1998). 3) Lee, E. and C.H. Yoon. J. Chem. Soc., Chem. 5 Commun. 4: 479-81 (1994). 4) Nagata, H. and K. Ogasawara- Tetrahedron Lett. 40(36): 6617-6620 (1999). 5)Nangia, A. et al. Tetrahedron Lett. 35(22): 3755-8 (1994). 10 6) Tanimori, S. and M. Nakayama. Agric. Biol. Chem. 55(4): 1181-1184 (1991). 7)Uyehara, T. et al. J. Chem. Soc., Chem. Commun. 2:113-14 (1989); Tennen Yuki Kagobutsu Toronkai Koen Yoshishu 32: 441-6 (1990); J. 15 Org. Chem. 57(11): 3139-3145 (1992). 8) Wolinsky, J. and E.J. Eustace. J. Org. Chem. 37(21): 3376-8 (1972). 9) Wolinsky, J. and D.L. Nelson. Tetrahedron 25(17): 3767-74 (1969) 20 Regnier et al, op.cit., discloses the preparation of DHN from nepetalactone by the catalyzed hydrogenation of nepetalactone isolated from the essential oils of plants of the genus Nepeta 25 (catmints) . One preferred and convenient method for synthesis of dihydronepetalactone is thus by hydrogenation of nepetalactone obtained in relatively pure form from the essential oils isolated by various means from plants of the genus Nepeta (catmints) 30 Catalysts such as platinum oxide and palladium supported on strontium carbonate give dihydronepalactone in 24-90% yields (Regnier et al. op. cit. ). 35 The preferred process for producing the dihydronepetalactones represented by Formula I in the present invention, therefore, is by hydrogenation of nepetalactones from plants with oils of defined 11 WO2006/050519 PCT/US2005/040146 nepetalactone stereoisomer content, an industrially advantageous approach in terms of production cost and its biological basis. Other processes are as disclosed in U.S. 03/225,290 (WO 03/84946), which is incorporated 5 in its entirety as a part hereof for all purposes. Methods for isolation or extraction of essential oils include without limitation steam distillation, organic solvent extraction, microwave-assisted organic 10 solvent extraction, supercritical fluid extraction, mechanical extraction and enfleurage (initial cold extraction into fats followed by organic solvent extraction). 15 The essential oils isolated from different Nepeta species are well known to possess different proporticns of each naturally occurring stereoisomer of nepetalactone (Regnier et al. op. cit.; DePooter, et al. op.cit.; Handjieva et al op.cit.). Thus DHN 20 prepared from oil derived from any Nepeta species wiLl necessarily be a mixture of stereoisomers thereof, the constitution of that mixture depending upon the particular species of Nepeta from which it is derived. 25 As discussed herein above, four chiral centers are present within the methylcyclopentanoid backbone of the nepetalactone at carbons 4, 4a, 7 and 7a as shown: O 7 120 6 54a 5 30 12 WO2006/050519 PCT/US2005/040146 A total of eight pairs of dihydronepetalactone enantiomers are possible after hydrogenation of nepetalactone. Of these, the naturally occurring stereoisomers described thus far are (9S) 5 dihydronepetalactones. Preferred repellent materials in accordance with the present invention include a mixture of any or all of the possible stereoisomers of dihydronepetalactone. More preferred repellent materials include a mixture of (9S) 10 dihydronepetalactones. Most preferred are (9S) dihydronepetalactone stereoisomers derived from (7S) nepetalactones. This includes the compounds commonly known as cis,trans-nepetalactone, cis,cis nepetalactone, trans,cis-nepetalactone, and 15 trans,trans-nepetalactone, as illustrated in Figure 1. The predominant stereoisomers produced by N. cataria (cis,trans and trans,cis-) are preferred. Upon completion of the hydrogenation reaction, the 20 resulting mixture of isomer products may be separated by any conventional method (e.g., preparative liquid chromatography) to yield each highly purified pair of dihydronepetalactone diastereomers. This permits the use of various different diastereomers as are found to 25 be most effective against particular insects. It is preferable to isolate a specific nepetalactone isomer from a plant to convert to its corresponding pair of diastereomers by hydrogenation. 30 In addition to variation in nepetalactone stereoisomer content between different Nepeta species, intra-species variation is also known to exist. Plants of a given species may produce oils with different compositions depending on the conditions of their 35 growth or growth stage at harvest. In fact variation in oil composition independent of growth conditions or growth stage at harvest has been found in Nepeta racemosa, (Clark, L.J., et al. op.cit.). Plants of a 13 WO2006/050519 PCT/US2005/040146 single species exhibiting different oil compositions are termed chemotypes. In Nepeta racemosa, chemotypes exhibiting marked differences in the proportion of different nepetalactone stereoisomers exist. Thus, the 5 preferred process for producing specific dihydronepetalactone enantiomers is hydrogenation of an oil from a Nepeta chemotype known to contain specific nepetalactone stereoisomers. 10 Insects include any member of a large group of invertebrate animals characterized, in the adult state (non-adult insect states include larva and pupa) by division of the body into head, thorax, and abdomen, three pairs of legs, and, often (but not always) two 15 pairs of membranous wings. This definition therefore includes a variety of biting insects (e.g., ants, bees, black flies, chiggers, fleas, green head flies, mosquitoes, stable flies, ticks, wasps), wood-boring insects (e.g., termites), noxious insects (e.g., 20 houseflies, cockroaches, lice, roaches, wood lice), and household pests (e.g., flour and bean beetles, dust mites, moths, silverfish, weevils). A host is any plant or animal affected by insects. 25 Typically, hosts are considered to be insect-acceptable food sources or insect-acceptable habitats. An insect susceptible article is any item of commerce created by man, which is affected by insects. This may include buildings, furniture, and the like. Typically, these 30 articles of manufacture are considered to be insect acceptable food sources or insect-acceptable habitats. The terms "insect repellent", "insect repellent composition" or "repellent composition" will refer to a 35 compound or composition that deters insects from their preferred hosts or insect-suitable articles of manufacture. Most known repellents are not active poisons at all, but rather prevent damage to 14 WO2006/050519 PCT/US2005/040146 plants/animals or articles of manufacture by making insect food sources or living conditions unattractive or offensive. Typically, an insect repellent is a compound or composition that can be either topically 5 applied to the host, or is a compound or composition that may be incorporated into an insect susceptible article to produce an insect repellent article that deters insects from the nearby 3- dimensional space in which the host or article exists. In either case, the 10 effect of the insect repellent is to drive the insects away from or to reject (1) the host, thereby minimizing the frequency of insect "bites" to the host; and/or (2) the insect susceptible article, thereby protecting the article from insect damage. Repellents may be in 15 the form of gases (olfactory), liquids, or solids (gustatory). Some examples of well-known insect repellents include: benzil; benzyl benzoate; 2,3,4,5-bis(butyl-2 20 ene) tetrahydrofurfural (MGK Repellent 11); butoxypolypropylene glycol; N-butylacetanilide; normal butyl-6,6-dimethyl-5,6-dihydro-l,4-pyrone-2-carboxylate (Indalone); dibutyl adipate; dibutyl phthalate; di normal-butyl succinate (Tabatrex); N,N-diethyl-meta 25 toluamide (DEET); dimethyl carbate (endo,endo)-dimethyl bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate); dimethyl phthalate; 2-ethyl-2-butyl-l,3-propanediol; 2- ethyl 1,3-hexanediol (Rutgers 612); di-normal-propyl isocinchomeronate (MGK Repellent 326); 2 30 phenylcyclohexanol; p-methane-3,8-diol, and normal propyl N, N- diethylsuccinamate. Standard repellents for mosquitoes, ticks, and the like are citronella oil (discussed below), dimethyl phthalate, normal butylmesityl oxide oxalate and 2-ethyl hexanediol-l,3 35 (See, Kirk-Othmer Encyclopedia of Chemical Technology, 2 nd Ed., Vol. 11: 724-728; and The Condensed Chemical Dictionary, 8 th Ed., p 756). 15 WO2006/050519 PCT/US2005/040146 An insect repellent is any compound or composition that deters insects from a host. It will be appreciated that such usage makes no distinction among compounds that have highly ephemeral effects as 5 compared to those that exhibit long-term beneficial effects, and/or those that require very high surface concentrations before there is an observable effect on insect behavior. 10 The term "insect repellent" thus indicates a compound or composition conferring on a host protection from insects when compared to no treatment at all. Protection desirably results in a statistically significant reduction in numbers of insects, and may, 15 for example, be usefully determined by measuring mean complete protection time ("CPT") in tests in which insect behavior toward treated animals, including humans, and treated inanimate surfaces is observed. Mean CPT refers to the mean length of time over 20 repetitions of tests in which the time before the first landing, probing or biting (in the case of a biting insect) or crawling (in the case of a crawling insect such as a tick or chigger) on a treated surface is observed [see e.g. US EPA Office of Prevention, 25 Pesticides and Toxic Substances product performance test guidelines OPPTS 810.3700; and Fradin, M.S., Day, J.F. (2002) New England Journal of Medicine 347, 13 18]. In one exemplary embodiment of this invention, the insect repellent composition hereof has a mean CPT 30 that is statistically indistinguishable from that of DEET. In the test in which this condition of the respective mean CPT performances of a DHN composition and DEET are shown to be statistically 16 WO2006/050519 PCT/US2005/040146 indistinguisable, the test conditions (including amounts of active ingredients) utilized must of course be identical, or, if not identical, must differ only in ways that do not prevent utilization of the results for 5 the purposes of documenting the existence of the condition described. As noted above, DHN compares favorably in performance with DEET. Moreover, DHN is advantageously 10 prepared from naturally occurring nepetalactone derived from plants whereas DEET, and many other insect repellents, are not prepared from natural sources - an important consumer consideration when choosing an effective repellent. Preparation from natural sources 15 also offers the potential for low production costs. A useful property of DHN is that it provides a considerable improvement over the odor of DEET while exhibiting effective insect repellency. The DHN 20 compounds and compositions of this invention possess a pleasant fragrance. The fragrance notes of the DHN materials make them useful in imparting, altering, augmenting or enhancing the overall olfactory component of an insect repellent composition or article, for 25 example, by utilizing or moderating the olfactory reaction contributed by one or more other ingredients in the composition. Specifically, the DHN compositions of the invention may be utilized to either mask or modify the odor contributed by other ingredients in the 30 formulation of the final repellent composition or article, and/or to enhance consumer appeal of a product by imparting a characteristic perfume or aroma. 17 WO2006/050519 PCT/US2005/040146 In addition to the chemical compounds and compositions as described above, a variety of effective insect repellents contain essential oils and/or active ingredients of essential oils. "Essential oils" are 5 defined as any class of volatile oils obtained from plants possessing the odor and other characteristic properties of the plant. Examples of repellent compounds that are essential oils include: almond bitter oil, anise oil, basil oil, bay oil, caraway oil, 10 cardamom oil, cedar oil, celery oil, chamomile oil, cinnamon oil, citronella oil, clove oil, coriander oil, cumin oil, dill oil, eucalyptus oil, fennel oil, ginger oil, grapefruit oil, lemon oil, lime oil, mint oil, parsley oil, peppermint oil, pepper oil, rose oil, 15 spearmint oil (menthol), sweet orange oil, thyme oil, turmeric oil, and oil of wintergreen. Examples of active ingredients in essential oils are: citronellal, methyl salicylate, ethyl salicylate, propyl salicylate, citronellol, safrole, and limonene. 20 In contrast to an insect repellent, an insecticide is a compound or mixture that is capable of poisoning an insect via its oral ingestion, by contact with the insect cuticle, or by fumigant action through the air. 25 Thus, an insecticide is a type of pesticide designed to control insect life that is harmful to man (i.e., directly harmful as disease vectors, or indirectly harmful by destruction of crops, food products, or textile fabrics). Several well-known insecticides 30 include: inorganic compounds (such as arsenic, lead andc copper); naturally occurring organic compounds (such as rotenone, pyrethrins, nicotine, copper naphthenate and petroleum derivatives); and synthetic organic compounds (such as DDT, dieldrin, endrin, chlordane, lindane, 35 para-dichlorobenzene and parathion). A potentiated insect repellent composition is a repellent composition that produces a result 18 WO2006/050519 PCT/US2005/040146 substantially in excess of that which reasonably could be expected or predicted from the known effect of the components either alone or additively. In the present invention, a potentiated insect repellent composition 5 will typically include dihydronepetalactones or a mixture thereof, and at least one other insect repellent compound that is not itself dihydronepetalactone (sometimes referred to as a non dihydronepetalactone insect repellent compound). 10 An insect repellent composition can be used as a component of an insect repellent article, wherein an insect repellent article is an article of manufacture possessing insect repellency that is enhanced, altered, 15 or augmented by the presence thereon or therein of an insect repellent composition. As used herein with respect to insect repellency, the terms "alter" and "modify" in their various forms refer to a means of supplying or imparting insect repellency to a 20 composition, or augmenting the existing insect repellency characteristics where natural repellency is deficient in some regard, or supplementing the existing insect repellency to modify its quality, or character The term "enhance" is intended to mean the 25 intensification (without effecting a change in kind or quality of repellency) of one or more repellency properties in an insect repellent composition or insect repellent article. 30 The dihydronepetalactones of the present invention possess unique properties of insect repellency and are particularly effective against a wide spectra of common insect pests, including biting insects, wood-boring insects, noxious insects, and household-pests, and 35 other insects that interfere with human society. These insects include a variety of biting insects (e.g., ants, bees, black flies, chiggers, fleas, green head flies, mosquitoes, stable flies, ticks, wasps, horn 19 WO 2006/050519 PCT/US2005/040146 flies), wood-boring insects (e.g., termites), noxious insects (e.g., houseflies, cockroaches, lice, roaches, wood lice), and household pests (e.g., flour and bean beetles, dust mites, moths, silverfish, weevils). In 5 the case of mosquitoes, which convey pathogenic microbes, these repellent properties are additionally effective for preventing infection with such diseases One property that is important to overall insect 10 repellency is surface activity, as most (if not all) repellents contain both polar and non-polar regions in their structure- A second property is volatility. Insect repellents form an unusual class of compounds where evaporation of the active ingredient from the 15 host's skin surface or from the insect repellent article is necessary for effectiveness, as measured by the host's protection from insect bites or the article's protection from insect damage. In the case of a topical insect repellent, a certain minimum 20 concentration of repellent is needed in the air space directly above the skin surface of the host in order to repel insects, and this concentration is a measure of the potency of the repellent. However, evaporation rate is also affected by the rate of skin absorption- 25 in most cases, penetration into and through the skin is an undesirable mode of loss of compound from the skirt surface. Similar considerations must be made for insect repellent articles, concerning the minimum concentration of repellent required in the three 30 dimensional air space surrounding the article itself. A variety of strategies are available to researchers attempting to balance these properties of evaporation (and, optionally, penetration). First, Lt 35 is possible to find a single active ingredient having the right balance of physical properties. Alternatively, the active ingredient could be formulated with polymers and inert ingredients added to 20 WO2006/050519 PCT/US2005/040146 the active ingredient for the purpose of modifying the persistence of the active ingredient on the host's skin surface or within the insect repellent article. However, adding inert ingredients to the active 5 ingredient limits the number of molecules of active ingredient on the surface of the repellent film or article. Since a molecule must be on the surface in order to evaporate, the evaporation rate is lowered. This carries with it the negative consequence of 10 diluting the concentration of active ingredient that can be applied to the host's skin surface or that is present on the surface of an insect repellent article. This, in turn, reduces the overall potency of a formulation containing inert ingredients. In a third 15 alternative, the active ingredient can be contained in microcapsules to control rates of loss from thie host's skin surface or insect repellent article. Finally, another technique of limiting the evaporation rate of active ingredient is to synthesize a precursor 20 molecule, which slowly disintegrates on the skin surface or insect repellent article to release the active ingredient. For example, release of the active ingredient may 25 be, for example, by sub-micron encapsulation, in which the active ingredient is encapsulated surroundede) within a skin nourishing protein just the way air is captured within a balloon. The protein may be used at, for example, a 20% concentration. An application of 30 repellent contains many of these protein capsules that are suspended in either a water-based lotion, or water for spray application. After contact with skin the protein capsules begin to breakdown releasing the encapsulated dihydronepetalactone. The process 35 continues as each microscopic capsule is depleted then replaced in succession by a new capsule that contacts the skin and releases its active ingredient. The process may take up to 24 hours for one application. 21 WO 2006/050519 PCT/US2005/040146 Because protein's adherence to the skin is so effective, these formulas are very resistant to perspiration (sweat-off), and water. When applied they are dry and comfortable with no greasiness. This 5 system results in very effective protection, but it is only effective when used on skin because clothing does not have the capability to release the proteins. An alternative system uses a polymer to encase the repellent, which slows down early evaporation leaving 10 more dihydronepetalactone available for later evaporation. This system can often increase a repellent's length of effectiveness by 25% to 50% over comparable non-entrapped products, but often feels greasy because of the presence of the polymer. In 15 another alternative, a synergist is used to keep stimulating the evaporation of the dihydronepetalactone in the composition. Regardless of the particular strategy applied to 20 control volatility of an insect repellent, each repellent must have a minimum effective evaporation rate (MEER) from the skin surface or insect repellent article to maintain the necessary minimum concentration of repellent in the air space directly above the skin 25 surface/article for effective insect repellency. An evaporation rate greater than the minimum effective evaporation rate (MEER) results in a significant and undesirable mode of loss. The issue is further complicated, however, since the MEER will change as a 30 function of conditions in the field. Both the avidity or biting tendency of an insect and the concentration of insects in the host's environment must be considered. For example, as the avidity of mosquitoes increases, a higher MEER will be required. In an 35 environment having a low concentration of mosquitoes where those mosquitoes are not hungry, the MEER could be as low as 2, or more commonly, 5 or 6. In contrast, in an environment having a high concentration of hungry 22 WO2006/050519 PCT/US2005/040146 mosquitoes, the MEER might be as high as 12-15. Preferred in the present invention are insect compositions wherein the skin surface evaporation rate is at least equal to a minimum effective evaporation 5 rate over a period of time where a preferred period of time is about 5 hours. The effectiveness of DHN or any insect repellent depends upon the surface concentration of the active 10 ingredient on the host surface to which it is applied. Many compounds known in the art to exhibit insect repellency do so, however, only in relatively concentrated form. See, for example, McGovern et al in U.S. 4,416, 881, which discloses the use of repellent 15 concentrations of 6.25-25%. In other situations representative of the art, it is often found that concentrations of DEET much below 1% require repeated application to achieve an effective surface concentration, yet concentrations above 30% result in 20 excessive surface concentration, which is both wasteful and conducive to the production of undesirable side effects. A further advantage of this invention is consequently that DHN not only provides effective insect repellency at concentrations similar to those 25 employed for DEET, DHN may be employed at concentrations up to and including neat DHN (i.e. the composition hereof may, if desired, contain 100% by weight DHN). The property of effective repellency in DHN provides many options for economical utilization of 30 the DHN active ingredient over a wide range of levels of concentration. In one embodiment of this invention, DHN is incorporated in effective amounts into a composition 35 suitable for application to a host plant or animal, preferably to human skin. Suitable compositions include DHN and a vehicle or a carrier, preferably an alcohol such as iso-propyl alcohol, a lotion such as 23 WO2006/050519 PCT/US2005/040146 one of the numerous skin creams known in the art, or a silicaceous clay. Preferably the DHN is present ir the insect repellent composition of the invention at a concentration of about 0.1% to 30% by weight, 5 preferably about 0.5% to 20% by weight, and most preferably about 1% to 15% by weight. In this invention, a variety of carriers or diluents for the above-disclosed dihydronepetalactones 10 can be used. The carrier allows the formulation to be adjusted to an effective concentration of repellant molecules. When formulating a topical insect repellent, preferably, the repellant molecules are mixed in a dermatologically acceptable carrier. The 15 carrier may further provide water repellency, prevent skin irritation, and/or soothe and condition skin. Factors to consider when selecting a carrier(s) for any formulation of insect repellent include commercial availability, cost, repellency, evaporation rate, odor, 20 and stability. Some carriers can themselves have repellent properties. For the present invention, the specific choice of a carrier, if any, to be utilized in achieving the 25 desired intimate admixture with the final product can be any carrier conventionally used in insect repellent formulations. The carrier, moreover, should preferably also be one that will not be harmful to the environment. Accordingly, the carrier can be any one 30 of a variety of commercially available organic and inorganic liquid, solid, or semi- solid carriers or carrier formulations usable in formulating insect repellent products. For example the carrier may include silicone, petrolatum, lanolin or many of 35 several other well-known carrier components. Examples of organic liquid carriers include 1 iquid aliphatic hydrocarbons (e.g., pentane, hexane, heptane, 24 WO 2006/050519 PCT/US2005/040146 nonane, decane and their analogs) and liquid aromatic hydrocarbons. Examples of other liquid hydrocarbons include oils produced by the distillation of coal and the distillation of various types and grades of 5 petrochemical stocks, including kerosene oils, which are obtained by fractional distillation of petroleum. Other petroleum oils include those generally referred to as agricultural spray oils (e.g., the so-called light and medium spray oils, consisting of riddle 10 fractions in the distillation of petroleum and which are only slightly volatile). Such oils are usually highly refined and may contain only minute amounts of unsaturated compounds. Such oils, moreover, are generally paraffin oils and accordingly can be 15 emulsified with water and an emulsifier, diluted to lower concentrations, and used as sprays. TIall oils, obtained from sulfate digestion of wood pulp, like the paraffin oils, can similarly be used. Other organic liquid carriers can include liquid terpene hydrocarbons 20 and terpene alcohols such as alpha-pinene, clipentene, terpineol, and the like. Other carriers include silicone, petrolatum, lanolin, liquid hydrocarbons, agricultural spray oils, 25 paraffin oil, tall oils, liquid terpene hydr-ocarbons and terpene alcohols, aliphatic and aromatic alcohols, esters, aldehydes, ketones, mineral oil, higher alcohols, finely divided organic and inorganic solid materials. 30 Still other liquid carriers can include organic solvents such as aliphatic and aromatic alcohols, esters, aldehydes, and ketones. Aliphatic monohydric alcohols include methyl, ethyl, normal-propy-l, 35 isopropyl, normal-butyl, sec-butyl, and tert-butyl alcohols. Suitable alcohols include glycols (such as ethylene and propylene glycol) and pinacols. Suitable polyhydroxy alcohols include glycerol, arabLtol, 25 WO2006/050519 PCT/US2005/040146 erythritol, sorbitol, and the like. Finally, suitable cyclic alcohols include cyclopentyl and cyclolexyl alcohols. 5 Conventional aromatic and aliphatic esters, aldehydes and ketones can be used as carriers, and occasionally are used in combination with the above mentioned alcohols. Still other liquid carriers include relatively high-boiling petroleum products such 10 as mineral oil and higher alcohols (such as cetyl alcohol). Additionally, conventional or so-called "stabilizers" (e.g., tert-butyl sulfinyl dimethyl dithiocarbonate) can be used in conjunction with, or as a component of, the carrier or carriers comprising the 15 compositions of this invention. Solid carriers, which can be used in the compositions of the present invention include finely divided organic and inorganic solid materials. 20 Suitable finely divided solid inorganic carriers include siliceous minerals such as synthetic and natural clay, bentonite, attapulgite, fuller's earth, diatomaceous earth, kaolin, mica, talc, finely divided quartz, and the like, as well as synthetically prepared 25 siliceous materials, such as silica aerogels and precipitated and fume silicas. Examples of finely divided solid organic materials include cellulose, sawdust, synthetic organic polymers, and the Like. Examples of semi-solid or colloidal carriers include 30 waxy solids, gels (such as petroleum jelly), Lanolin, and the like, and mixtures of well-known liquid and solid substances which can provide semi-solid carrier products, for providing effective repellency within the scope of the instant invention. 35 Other carriers suitable for use in a composition of this invention, in addition to water, include one or more of the following: 26 WO2006/050519 PCT/US2005/040146 *Acetone *CIO-C18 Triglycerides *C12-C18 Acid Triglycerides *Dipropyl, Dibutyl, Diisocetyl, Diisopropyl or 5 Dimethyl Oxalate *Cyclo(ethoxy)methicone eAmyl, Methyl, Butyl, Ethyl, Ethoxyethanol, Ethoxydiglycol or Tetrahydrofurfuryl Acetate *Ethoxydiglycol 10 *Kerosene *Ethoxyethanol *Diacetin *Benzyl, Diacetone, Denatured ethyl, Tetrahydrofurfuryl or Oleyl Alcohol 15 *Benzyl Benzoate or Laurate *Ethylene Carbonate eEthyl Hexanediol *Oil of Bertholetta Excelsa Nut, Carthamus Tinctorius, Helianthus Annuus, Ricinus Commuris, 20 Aleurites Moluccana, Linum Usitatissimum, Cocos Nucifera, Zea Mays, Pinus Palustris, Sesamum Indicum, Glycine Soja, Helianthus Annuus, Prunus Amygdalus Dulcis, Olea Europaea, Elaeis Guineensis, Prunus Persica Kernel, Cucurbita Pepo, Brassica Carnpestris, 25 Oryza Sativa, Oryza Saliva, Carthamus Tinctorius, Juglans Regia or Triicum Vulgare *Dibutyl Phthalate or Sebacate *Furfural *Butoxy-diglycol, -propanol or -ethanol 30 *Diethoxyethyl Succinate *Diethyl Oxalate, Phthalate, Sebacate or Succinate en- or t-Butyl, Hexyl or Isopropyl Alcohol *Glycofurol *Gycol 35 *Butylene, Hexylene, Diethylene, Dipropylene, Pentylene, Propylene or Triethylene Glycol *C6~C20 linear, branched or cyclic alkane, alkanol or alkane polyol 27 WO2006/050519 PCT/US2005/040146 *Butyloctanol *Dihexyl, Diisobutyl, Diisodecyl, Ditridecyl, Dibutyl, Diisocetyl, Diisopropyl, Dipropyl or Diisoponyl Adipate 5 eButyrolactone *1,2,6-Hexanedol *Caprylic, Capric, Lauric or Stearic Triglyceride *Isoamyl, Isobutyl, Isopropy or Propyl Acetate *Isobutoxypropanol 10 oDiisopropyl Sebacate *Dimethoxydiglycol oIsobutyl, Methyl or Stearyl Benzoate *Isopropyl Laurate, Myristate, Palmitate or Stearate *Octyl, Lauryl, Myristyl, Palmitoyl or Stearyl Benzoate 15 oDimethyl Phthalate, Glutarate, Maleate, Adipate or Succinate *Dimethyl Sulfone *Dimethyl Ether *Dimethyl Isosorbide 20 oDioctyl Sebacate, Adipale, Phthalate or Succinate oMethylethylketone *3-Methoxybutanol *Dipentene *Methoxydigycol 25 oDiphenyl Methane oMethoxy-ethanol, -isopropanol or -methylbutanol *C4-C400 polyethylene, polypropylene, polyethylene/ether or polypropylene/ether glycol *Perfluorodecalin 30 *Methylal *Perfluorotetralin *Pheroxyisopropanol *Phenylpropanol *Methyl Hexyl Ether 35 *Methylpropanediol *Methyl Pyrrolidone *Methyl Butyl Ketone *Thiolanediol 28 WO2006/050519 PCT/US2005/040146 *Toluene *Propanediol *Triacetin *Tributyl Citrate 5 *Tributylcresylbutane * Propylene Carbonate *Tricaprin eTricaprylin *Trichloroethlane 10 *Triheptanoini *Trihydroxystearin *Triisononancin *Tiisostearinra *Trilaurin 15 *Trilinolein *Trilinolenin *Trimethylhecanol *Trimyristin *Trioctanoin 20 *Triolein *Tripalmitin *Trisebacin *Tristearin *Triundecanoin 25 *Xytene In addition to the above-mentioned materials, such as the liquid hydrocarbons, the carrier can contain conventional emulsifying agents which can be used for 30 causing the dihydronepetalactone compounds to be dispersed in, and diluted with, water for end-use application. Insect repellent compositions of the present 35 invention containing the dihydronepetalactones may also contain adjuvants known in the art of personal care product formulations, such as thickeners, buffering agents, chelating agents, preservatives, fragrances, 29 WO 2006/050519 PCT/US2005/040146 antioxidants, gelling agents, stabilizers, surfactants, emolients, coloring agents, aloe vera, waxes, other penetration enhancers and mixtures thereof, and therapeutically or cosmetically active agents. 5 Additionally, the compositions of the present invention may also contain other adjuvants such as one or more therapeutically or cosmetically active ingredients. Exemplary therapeutic or cosmetically 10 active ingredients useful in the compositions of the invention include fungicides, sunscreenirig agents, sunblocking agents, vitamins, tanning agents, plant extracts, anti-inflammatory agents, anti-oxidants, radical scavenging agents, retinoids, alpha- hydroxy 15 acids, emollients, antiseptics, antibiotics, antibacterial agents or antihistamines, and may be present in an amount effective for achieving the therapeutic or cosmetic result desired. 20 Additionally, the compositions of this invention may contain one or more other additives such as an antioxidant, an emulsion stabilizer, a preservative, a propellant, an emollient, a sunscreen agent, a surfactant, an emulsifying agent, a solubilizing agent 25 and/or an ultraviolet light absorber. Examples of materials that may function as such additives are set forth below. The compositions of this invention may include one 30 or more materials that may function as an antioxidant, such as reducing agents and free radical scavengers. Suitable materials that may function as an antioxidant include one or more of the following: 35 *Acetyl Cysteine *Ascorbic Acid *Ascorbyl Palmitate or Stearate et-Butyl Hydroquinone 30 WO2006/050519 PCT/US2005/040146 *Cysteine *Diamylhydroquinone *Dicetyl, Dilauryl, Dimyristyl, Distearyl or Ditridecyl Thiodipropionate 5 *Erythorbic Acid *2-Ethylhexyl, Lauryl, Myristyl, Palmitoyl or Stearyl 4-methoxycinnamate *Ethyl Ferulate *Ferulic Acid 10 *Hydroquinone ep-Hydroxyanisole *Hydroxylamine Sulfate *Magnesium Ascorbate *Magnesium Ascorbyl Phosphate 15 *Octyl Gallate *Octyl, Lauryl, Myristyl, Palmitoyl or Stearyl Salicylate *Octocrylene *Phloroglucinol 20 *Polyethylene glycol ether of tocopherol *Potassium Ascorbyl Tocopheryl Phosphate *Potassium Sulfite *Propyl Gallate *Rutin 25 *Sodium Ascorbate *Sodium Erythorbate *Sodium Sulfite *Sodium Thloglycolate *Sorbityl Furfural 30 *Tertiary butyl 4-methoxy phenol *Thiodiglycol *Thiodiglycolamide *Thioglycolic Acid *Thiolactic Acid 35 *Thiosalicylic Acid *Tocopherol *Tocopheryl Acetate *Tocopheryl Linoleate 31 WO2006/050519 PCT/US2005/040146 *Tocopheryl Nicotinate *Tocopheryl Succinate *Tris(Nonylpheny)Phosphite 5 The compositions of this invention may also include one or more materials that may function as an emulsion stabilizer. These materials would not act as primary emulsifiers, but would prevent or reduce the coalescence of emulsified droplets. This could be 10 accomplished, for example, by modifying the continuous or the disperse phase of the emulsion through electrical repulsion, from changes iri viscosity, or from film formation on the droplet surface. Suitable materials that may function as an emulsion stabilizer 15 include one or more of the following: *Cetyl Alcohol *Montmorillonite *Aluminum Caprylate, Stearate, Laurate, Palmitate, 20 Lanolate or Myristate *Cis-C 1 8 Glycol *Dodecylhexadecanol
    *H(OCH
    2
    CH
    2 )nOH where n = 350 to 160,000 *Pectin 25 *Glucose Pentaacetate *Glycol Oleate, Palmitate, Stearate or Ricinoleate *(Alkyl)cellulose *Hydroxyalkyl (alkyl)cellulose *Calcium Laurate, Myristate or Stearate 30 *Cl 0 -Cs 50 alcohol such as cetyl, myristyl, stearyl, tallow or lauryl alcohol *Polyvinyl Acetate *Lanolin *Styrene/maleic anhydride copolymer 35 *Xanthan gum The compositions of this invention may also include one or more materials that may function as a 32 WO2006/050519 PCT/US2005/040146 preservative, which would prevent or retard microbial growth and thus protect the composition (or products made therefrom) from spoilage or from inadvertent contamination by the consumer during use. Suitable 5 materials that may function as a preservative include one or more of the following: *Ammonium Benzoate or Propionate *Chloroxy enol 10 *Isobutylparaben *o, m or p-Cresol *Isodecylparaben *Benzoic Acid *Isopropyl Cresol, Paraben or Sorbate 15 *Benzotriazole *Benzyl Alcohol oMagnesium Benzoate *Benzylparaben *Dehydroacetic Acid 20 *Magnesium Propionate *5-Bromo-5-Nitro-l,3-Dioxane *Diazolidinyl Urea *Magnesium Salicylale *2-Bromo-2-Nitropropane-l,3-Diol 25 *Dibromopropamidine Diisothionate *Butyl Benzoate *Dimethyl Hydroxymethyl Pyrazole *Butylparaben oDimethylol Ethylene Thiourea 30 *Calcium Benzoate, Salicylate, Sorbate, Paraben or Propionate *Dimethyl Oxazolidine *Methyl Hydroxyl Hydantoin oMethyldibromo Glutaronitrile 35 *Methylisothiazolinone *Methylparaben *Ethylparaben *Chlorhexidine Diacetate, Digluconate or Dihydrochloride 33 WO2006/050519 PCT/US2005/040146 *Formaldehyde *Glutaral *Glyoxal *Chloroacetamide 5 *Hexamidine *Chlorobutanol *Hexamidine Diparaben *Phenol .p-Chloro-m-Cresol 10 *Hexamidine Paraben *Octyl, Lauryl, Myristyl, Palmitoyl or Stearyl Salicylate *Octyl, Lauryl, Myristyl, Palmitoyl or Stearyl Benzoate *Octocrylene 15 *Phenoxyethanol *Chlorophene *4Hydroxybenzoic Acid *Phenoxyethylparaben *P-Chlorophenol 20 *Hydroxymethyl Dioxoazabicyclooctane *Phenoxyisopropanol *Chlorothymol *Imidazolidinyl Urea *Phenyl Benzoate 25 *Phenyl Mercuric Acetate, Benzoate, Borate, Bromide or Chloride *Potassium Salicylate, Sorbate, Benzoate, Propylparaben, Butylparaben, Ethylparaben, Methylparaben, Paraben, Phenoxide, o-Phenylphenate 30 or Propionate *Propionic Acid *Propyl Benzoate *Phenylparaben *Propylparaben 35 *o-Phenylphenol. *Silver Borosilicate *Silver Magnesium Aluminum Phosphate *Sorbic Acid 34 WO2006/050519 PCT/US2005/040146 eSodium Hydroxymethylglycinate, Methylparaben, Paraben, Phenolsulfonate, Phenotide, o Phenylphenate, Propionate, Propylparaben, Pyrithione, Salicylate, Sorbate, Benzoate, 5 Butylparaben, p-Chloro-m-Cresol, Dehydroacetate, Ethylparaben, Formate or Hydroxyrnethane Sulfonate *Zinc Pyrithione The compositions of this invention may also 10 include one or more materials that may function as a propellant, which are chemicals used for expelling products from pressurized containers (aerosols) . The functionality of a propellant depends on its vapor pressure at ambient temperature and its compressibility. Liquids 15 or gases can be used as propellants as long as the pressure developed within the container is safely below the container's bursting pressure under normal storage and use conditions. Suitable materials that may function as a propellant include one or more of the 20 following: eButane
    *CH
    3 CClF 2 *Nitrogen 25 *Carbon Dioxide
    *CH
    3C
    F
    2 *Nitrous Oxide *Dimethyl Ether *Isobutane 30 *Pentane *Ethane *Isopentane *Propane
    *CH
    3
    CHF
    2 35 The compositions of this invention may also include one or more materials that may function as an emollient, which is a cosmetic ingredient that maintains the 35 WO2006/050519 PCT/US2005/040146 soft, smooth, and pliable appearance of skin. The purpose of an emollient is to remain on the skin surface or in the stratum corneum to act as a lubricant, to reduce flaking, and to improve the skin's appearance. Suitable 5 materials that may function as an emollient include one or more of the following: eAcetylated Lanolin or Lanolin Alcohol *Bisphenylhexamethicone 10 *Bertholetta Excelsa Nut Oil *Caprylic/Capric Glycerides *Butoxyethyl Stearate *Caprylic/Capric/Succinic Triglyceride *Acetylated Sucrose Distearate 15 *Acetyl Trihexyl Citrate *Butyl Isostearate, Myristate, Oleate or Stearate *Caprylyl Glycol *Acetyl Trioctyl Citrate *Cetearyl Octanoate or Palmitate 20 ePrunus Armenlaca Kernel Oil *Cetyl Acetate, Caprylate, Lactate, Laurate, Octanoate or Oleate eArachidyl Propionate *C14~C15 Alcohols 25 *Cetylarachidol *Argania Spinosa Oil *C12-C28 Alkyl Acetate, Benzoate or Lactate or Octanoate *Persea Gratissima Oil 30 *Orbignya Olelfera Oil *Melissa Officinalis Seed Oil *C24~C28 Alkyl Methicone *C12-C13 Alkyl Octanoate *Cetyl Glycol, Glycol Isostearate or Glycol 35 Palmitate *Benzyl Laurate *Bis-Diglyceryl Polyacyladipate-1 or -2 *Camellia Kissi Oil 36 WO2006/050519 PCT/US2005/040146 *Isostearyl, Myristyl, Lauryl, Isocetyl, Pentadecyl, Oleyl, Tridecyl or Undecyl Alcohol *Isostearyl Glyceryl Ether *Isostearyl Benzoate, Lactate, Neopentanoate, 5 Octanoate, Palmitate or Myristate eMethyl Stearate *Rosa Moschata Seed Oil *Hydroxycetylisostearate *Isatis Tinctoria Oil 10 *Isoamyl Laurate *Isobutyl Myristate, Palmitate, Pelargonate or Stearate *Isopropyl Laurate, Myristate, Palmitate or Stearate *Isotridecyl Isononanoate eMyristyl Isostearate, Lactate, Neopentanoate, 15 Octanoate or Propionate *Actinidia Chinensis Seed Oil *Isocetyl Isodecanoate, Palmitate or Stearate *Lanolin Lanolin Oil or Wax 20 *Isodecyl Citrate, Hydroxystearate, Laurate, Myristate, Neopentanoate, Palmitate or Stearate *Neopentyl Glycol Dicaprylate, Dicaprate, Dilaurate or Dioctanoate *Nonyl Acetate 25 *Lauryl Glycol *Octyl Acetoxystearate *Lauryl Isostearate or Lactate *Octyldecanol *Octyldodecanol 30 *Octyldodecyl Benzoate, Lactate, Neopentanoate or Octanoate *Octyl, Lauryl, Myristyl, Palmitoyl or Stearyl Benzoate Isohexadecane *Methyl Benzoate, Caproate, Caprylate, Caprate or 35 Glucose Dioleate *Isohexyl Neopentanoate, Palmitate or Laurate *Octyl Hydroxystearate, Laurate, Isopalmitate, Isostearate, Myristate, Neopentanoate, 01eate, 37 WO2006/050519 PCT/US2005/040146 Palmitate or Stearate eMethyl Glucose Isostearate, Laurate, Sesquicaprylate, Sesquicaprate, Sesquilaurate or Sesquistearate *Isopropyl Hydroxycetyl Ether 5 *Isopropyl Hydroxystearate, Isostearate, Lanolate, Laurate, Linoleate, Myristate or Oleate *2-Oleamido-l,3-Octadecanediol *Oleyl Acetate, Lactate or Oleate *Methyl Hydroxystearate, Laurate, Isostearate, 10 Myristate, Oleate, Palmitate or Pelargonate eIsopropyl Palmitate, Isopropyl or Stearate *Isosorbide Laurate *Passiflora Eduls Oil *Polyethyelene Glycol Glycerides 15 ePolyglyceryl Myristate, Oleate, Pentastearate or Ricinoleate ePolyglyceryl Oleyl Ether *Polyethylene Glycol Tricapryl Citrate, Tricetyl Citrate, Trilauryl Citrate, Trimyristyl Citrate or 20 Tristearyl Citrate *Polyethylene Glycol Castor Oil *Pentaerythrityl Dioleate, Distearate, Stearate, Tetrabenzoate or Trioleate *Polyglyceryl Sesquioleate, Stearate, Tetraoleate, 25 Tetrastearate, Caprate, Caprylate, Decalinoleate, Laurate or Isopalmitate ePropylene Glycol Hydroxystearate Stearate, Laurate, Linoleate, Myristate, Ricinoleate, Stearte, Oleate, Soyate or Caprylate 30 ePropylene Glycol Myristyl Ether or Myristyl Ether Acetate eSucrose Polyoleate, Polypalmate, Polystearate, Ricinoleate, Stearate, Triacetate, Polylaurate, Polylinoleate, Myristate, Oleate, Laurate or Palmitate 35 ePolypropylene Glycol Lauryl, Cetyl, Stearyl, Oleyl or Pentaerythrityl Ether *Tridecyl Neopentanoate, Octanoate, Stearate or Isononanoate 38 WO2006/050519 PCT/US2005/040146 eStearyl Acetate, Benzoate or Lactate eStearyl Glycol Isostearate or Citrate *Polypropylene Glycol/Polyethylene Glycol *Trimethylolpropane or Propene 5 *Trioctyl Trimellitate *Tris(Tributoxysiloxy)Methylsilane The compositions of this invention may also include one or more materials that may function as a 10 sunscreen agent. Under 58 Fed. Reg. 28194 (May 12, 1993), a sunscreen active ingredient is defined as an "ingredient that absorbs at least 85 percent of the radiation in the UV range at wavelengths from 290 to 320 nanometers, but may or may not transmit radiation at 15 wavelengths longer than 320 nanometers." Suitable materials that may function as a sunscreen agent include one or more of the following: *Aminobenzoic Acid ("PABA") 20 *Glyceryl Aminobenzoate (Glyceryl PABA) *Oxybenzone (Benzophenone-3) *Cinoxate eHomosalate *Octyl Dimethyl PABA 25 *Diethanolamine Methoxycinnamate *2-Ethylhexyl, Lauryl, Myristyl, Palmitoyl, or Stearyl 4-methoxycinnamate *Lawsone with Dihydroxyacetone * Phenylbenzimidazole Sulfonic Acid 30 eMenthyl Anthranilate *Red Petrolatum eDigalloyl Trioleate *Octocrylene * Sulisobenzone (Benzophenone-4) 35 *Dioxybenzone (Benzophenone-8) *Octyl Methoxycinnamate * Titanium Dioxide * Ethyl 4-[bis(Hydroxypropyl)] Aminobenzoate (Ethyl 39 WO2006/050519 PCT/US2005/040146 Dihydroxypropyl PABA) *Octyl Salicylate *Trolamine Salicylate 5 The compositions of this invention may also include one or more materials that may function as a surfactant, an emulsifying agent or a solubilizing agent. Such a material may be used to reduce surface tension, to form complex films on the surface of 10 emulsified droplets, to create a repulsive barrier on emulsified droplets to prevent their coalescence, to retard physical changes in emulsions throughout during shelf-life or to cause a solute to become part of a micelle formed by a surfactant. Suitable materials 15 that may function as a surfactant, an emulsifying agent or a solubilizing agent include one or more of the following: *C50-C650 linear or branched dihydroxy 20 polyoxyethylene/po lyoxypropylene block copolymer *C50~C650 branched polyhydroxy polyoxyethylene/polyoxypropylene block copolymer of ethylene diamine *C12-C330 ethoxylated alkyl phenol 25 *C16-C140 polyethylene glycol ether of C12~C60 alcohols eCarboxylic acid esters of C12~C330 ethoxylated alkyl phenol *Ester of C12-C40 Carboxlic Acid and C8~C40 30 Polyethylene Glycol *Ester of Caprylic or Capric Triglyceride and C8-C40 Polyethylene Glycol *Phosphoric acid esters of C12-C330 ethoxylated alkyl phenol 35 *Phosphoric acid esters and diesters of C16~C140 polyethylene glycol ether of C12-C60 alcohols *Abietic Acid *Calcium Stearoyl Lactylate 40 WO 2006/050519 - PCT/US2005/040146 eCetethyl Morpholinium Ethosutfate eCetrimonium Bromide, Chloride, Methosulfate or Tosylate *Cetyl Alcohol 5 *Cetyl Dimethicone Copolyol *Cetyl Glyceryl Ether/Glycerin Copolymer *Cetyl Phosphate eCetearyl Glucosicde *Dextrin Behenate, Laurate, Myristate, Palmitate or 10 Stearate eDicetyl Phosphate *Diethytaminoethyl Laurate or Stearate *Dimethyl Octynedi ol *Dimyristyl Phosphate 15 eGlyceryl Arachidate, Behenate, Caprylate, Caprate, Cocoate, Erucate, Hydrogenated Rosinate, Hydroxystearate, Isopalmitate, Isostearate, Isotridecanoate/Stearate/Adipate, Lanolate, Laurate, Oleate, Linoleate, Linolenate, Oleate, Montanate, 20 Myristate, Palmitate, Stearate, Palmitoleate, Ricinoleate or Uridecylenate eGlycol Octanoate eHydrogenated Lecithin *Hydrogenated Palm Glyceride 25 *Hydroxycetyl Phosphate *Hydroxyethyl Glyceryl Oleate and/or Stearate eLanolin *Laurtrimonium Chloride eLauryl Phosphate 30 *Lecithin eMannitan Laurate or Oleate *Myristoyl Methylalanine oPalmitic Acid eOctoxyglyceryl Behenate or Palmitate 35 *Pelargonic Acid *Pentaerythrityl Stearate *Phosphatidylcholi ne *Potassium Laurate, Myristate, Oleate, Lauryl 41 WO2006/050519 PCT/US2005/040146 Hydroxypropyl Sulfonate, Cetyl Phosphate, Lauryl Sulfate, Palmate, Palmitate, Ricinoleate or Stearate *Sodium Palmate, Palmitate, Phthalate Stearyl Amide, Ricinoleate, Stearate, Stearyl Sulfate, Trideceth 5 Sulfate, Tridecyl Sulfate, Undecylenate, Lauroyl Lactylate, Lauryl Phosphate, Myristate, Oleate, Oleoyl Lactylate, Behenoyl Lactylate, Caproyl Lactylate, Caprylate, Isostearoyl Lactylate or Laurate ePropylene Glycol Behenate, Caprylate, 10 Hydroxystearate, Isostearate, Laurate, Linoleate, Unolenate, Myristate, Oleate, Ricinoleate or Stearate *Sorbitan Caprylate, Diisostearate, Dioleate, Distearate, Isostearate, Laurate, Oleate, Palmitate, Sesquiisostearate, Sesquioleate, Sesquistearate, 15 Stearate, Triisostearate, Trioleate or Tristearate *Raffinose Oleate *Stearic Acid *Stearoyl Lactylic Acid *Stearyl Alcohol 20 *Sucrose Dilaurate, Distearate, Laurate, Myristate, Oleate, Palmitate, Polylaurate, Polylinoleate, Polyoleate, Polypalmate or Polystearate *C32-C82 polyethylene glycol ether of behenyl alcohol *C20-C106 polyethylene glycol ether of cetyl alcohol 25 *C28-C80 polyethylene glycol ether of cetyl or oleyl alcohol *C20-C70 polyethylene glycol ether of cetyl and/or stearyl alcohol eC20-C80 polyethylene glycol ether of cholesterol 30 *C16-C24 polyethylene glycol ether of decyl alcohol *C40-C80 polyethylene glycol ether of dihydrocholesterol *C20-C60 polyethylene glycol ether of isocetyl alcohol 35 *C18-C30 polyethylene glycol ether of isodecyl alcohol *C18-C40 polyethylene glycol ether of isolauryl alcohol 42 WO 2006/050519 PCT/US2005/040146 *C20-C120 polyethylene glycol ether of isostearyl alcohol *C12-C120 polyethylene glycol ether of glyceril caprate, caprylate, laurate, myristate, oleate, 5 palmitate or stearate *C14-C100 polyethylene glycol ether of lauryl alcohol *C16~C24 polyethylene glycol ether of myristyl alcohol *C20-C70 polyethylene glycol ether of oleyl alcohol 10 *C10-C100 polyethylene/polypropylene glycol ether of butyl alcohol *C20~C106 polyethylene/polypropylene glycol ether of cetyl alcohol *C20-C100 polyethylene/polypropylene glycol ether of 15 decyl alcohol *C14-CI00 polyethylene/polypropylene glycol ether of lauryl alcohol *Carboxylic acid ester of C20-C120 polyethylene glycol ether of isostearyl alcohol 20 *Carboxylic acid esters of C14-Cl00 polyethylene glycol ether of lauryl alcohol *Carboxylic acid ester of C16-C24 polyethylene glycol ether of myristyl alcohol *Citric acid diesters of C14-Cl00 polyethylene glycol 25 ether of lauryl alcohol *Isopropyl Laurate, Myristate, Palmitate or Stearate *Lauric acid ester of C30-C120 polyethylene glycol ether of sorbitol *Octyl, Lauryl, Myristyl, Palmitoyl or Stearyl 30 Salicylate *Phosphoric acid ester of C20-C106 polyethylene glycol ether of cetyl alcohol *Phosphoric acid ester of C20~C120 polyethylene glycol ether of isostearyl alcohol 35 *Phosphoric acid diesters of C14-Cl00 polyethylene glycol ether of lauryl alcohol *Phosphoric acid esters and/or diesters of C20-C70 polyethylene glycol ether of oleyl alcohol 43 WO2006/050519 PCT/US2005/040146 *Stearic acid ester of C15~C30 polyethylene glycol ether of glycerin *Stearic acid ester of C20-C60 polyethylene glycol ether of isocetyl alcohol 5 *Stearic acid ester of C20-C120 polyethylene glycol ether of isostearyl alcohol *Diethanolamine salt of phosphoric acid ester of C20-C106 polyethylene glycol ether of cetyl alcohol *Diethanolamine salt of phosphoric acid ester of 10 C20-C70 polyethylene glycol ether of cetyl and/or stearyl alcohol eDiethanolamine salt of Phosphoric acid ester of C20-C70 polyethylene glycol ether of oleyl alcohol *Disodium salt of citric acid ester of C14-Cl00 15 polyethylene glycol ether of lauryl alcohol *Disodium salt of phosphoric acid ester of C14-Cl00 polyethylene glycol ether of lauryl alcohol *Disodium salt of phosphoric acid ester of C20-C70 polyethylene glycol ether of oleyl alcohol 20 eMonoethanolamine salt of phosphoric acid ester of C20-C70 polyethylene glycol ether of cetyl and/or stearyl alcohol *C12-C120 polyethylene glycol diester of behenic, capric, caprylic, lauric, oleic, octanoic, palmitic 25 or stearic acid *Polyesters of C6-C40 polyglycerin and behenic, capric, caprylic, lauric, oleic, octanoic, palmitic or stearic acid. 30 The compositions of this invention may also include one or more materials that may function as an ultraviolet light absorber to protect a product made from the composition from chemical or physical deterioration induced by ultraviolet light. UV 35 absorbers, like sunscreen agents, have the ability to convert incident ultraviolet radiation into less damaging infrared radiation (heat). Suitable materials 44 WO2006/050519 PCT/US2005/040146 that may function as an ultraviolet light absorber include one or more of the following: *Acetaminosalol 5 *3-Benzylidene Camphor eStilbenedisulfonate eAllantoin PABA *Disodium Distyrylbiphenyl Disulfonate *Benzalphthalide 10 *Sulfonamide ODrometrizole *Benzophenone *Benzylidene Camphor Sulfonic Acid *Ethyl Dihydroxypropyl PABA 15 *Benzophenone substituted with one or more groups selected from hydroxyl, alkoxy, alkyl, halogen and sulfonate *Benzyl Salicylate *Ethyl Diisopropylcinnamate, Methoxycinnamate or 20 Urocanate eBumetrizole *Ethyl PABA *Butyl Methoxydibenzoylmethane *Butyl PABA 25 *Etocrylene *Cinoxate *Ferulic Acid *Glyceryl Octanoate Dimethoxycinnamate *Di-t-Butyl Hydroxybenzylidene Camphor 30 *Glyceryl PABA *Digalloyl Trioleate *Glycol Salicylate eDiisopropyl Methyl Cinnamate *Isoamyl p-Methoxycinnamate 35 *Disodium Bisethylphenyl Triaminotriazine *Isopropylbenzyl Salicylate *Isopropyl Dibenzoylmethane *Octyl Triazone 45 WO2006/050519 PCT/US2005/040146 *Sodium Urocanate *Isopropyl Methoxycinnamate *PABA *Menthyl Anthranilate or Salicylate 5 *Pentyl Dimethyl PABA *Terephthaylidene Dicamphor Sulfonic Acid *4-Methylbenzylidene Camphor *Phenylbenzimidazole Sulfonic Acid *Titanium Dioxide 10 *Octocrylene *Polyacrylamidomethyl Benzylidene Camphor *TriPABA Panthenol *Octrizole *Potassium Methoxycinnamate 15 eUrocanic Acid *Octyl Dimethyl PABA *Potassium Phenylbenzimidazole Sulfonate *Octyl Methoxycinnamate or Salicylate *Sodium Phenylbenzimidazole Sulfonate 20 A formulated mixture of one or more carriers, adjuvants and/or additives may be selected from the members of the groups thereof contained in the lists set forth above. They may also be selected from a 25 subgroup of the members of the foregoing lists formed by omitting any one or more members from the whole groups as set forth in the above lists. As a result, a mixture of carriers, adjuvants and/or additives may in such instance not only be made from one or more members 30 selected from any subgroup of any size that may be formed by all the various different combinations of individual members from the whole groups as set forth in the above lists, but may also be made in the absence of members that have been omitted from the whole groups 35 to form the subgroup. The subgroup formed by omitting various members from the whole group in the list above may, moreover, be an individual member of a whole group such that a carrier, adjuvant and/or additive is 46 WO2006/050519 PCT/US2005/040146 provided in the absence of all other members of the whole groups except the selected individual member. Dihydronepetalactones may be utilized in the 5 present invention individually or combined in any proportion. As is conventional in the art, the desired amount of an insect repellent composition to be added to a given insect susceptible article with properties of insect repellency is determined by the nature of the 10 product and other factors. These factors include both considerations of cost and the nature of the other ingredients in the insect repellent composition or repellent article, their amounts, and the desired repellency effect. In general, the composition of the 15 repellent should contain sufficient amounts of active insect repellant material to be efficacious in repelling the insect from the host over a prolonged period of time (preferably, for a period of at least several hours). 20 The amount of each dihydronepetalactone of Formula I or mixtures thereof in an insect repellent composition or repellent article that contains one or more of the carriers, adjuvants and/or additives as 25 described above will generally not exceed about 80% by weight based on the weight of the final product, however, greater amounts may be utilized in certain applications and this amount is not limiting. More preferably, a suitable amount of dihydronepetalactone 30 will be at least about 0.001% by weight and preferably about 0.01% up to about 50% by weight; and more preferably, from about 0.01% to about 20% weight percent, based on the weight of the composition or article. Specific compositions will depend on the 35 intended use. The dihydronepetalactone repellent compositions of the present invention can be formulated without a 47 WO2006/050519 PCT/US2005/040146 carrier and be effective. More often, however, the insect repellent composition will include a carrier and contain about 0.001-50% weight of the disclosed compounds, and such compound is usually iran intimate 5 mixture with the carrier to bring the active material into position for repelling common insect pests, such as biting insects, wood-boring insects, noxious insects, household pests, and the like. 10 The compositions of the invention may be formulated and packaged so as to deliver the product in a variety of forms including as a solution, suspension, cream, ointment, gel, film or spray, depending on the preferred method of use. The carrier may be an aerosol 15 composition adapted to disperse the dihydronepetalactone into the atmosphere by means of a compressed gas. Desirable properties of a topical insect repellent 20 article include low toxicity, resistance to loss by water immersion or sweating, low or no odcr or at least a pleasant odor, ease of application, and rapid formation of a dry tack-free surface film on the host's skin. In order to obtain these properties, the 25 formulation for a topical insect repellent article should permit insect-infested animals (e.g., dogs with fleas, poultry with lice, cows with ticks, and humans) to be treated with an insect repellent composition of the present invention by contacting the skin, fur or 30 feathers of such an animal with an effective amount of the repellent article for repelling the insect from the animal host. Thus, dispersing the article into the air or dispersing the composition as a liquid mist or fine dust will permit the repellent composition to fall on 35 the desired host surfaces. Likewise, directly spreading of the liquid/semi-solid/solid repellent article on the host is an effective method of 48 WO2006/050519 PCT/US2005/040146 ccntacting the surface of the host with an effective amount of the repellent composition. Embodiments of the present invention which may be 5 used as a topical insect repellent articles, include (but are not limited to): colognes, lotions, sprays, creams, gels, ointments, bath and shower gels, foam products (e.g., shaving foams), makeup, deodorants, shampoo, hair lacquers/hair rinses, and personal soap 10 compositions (e.g., hand soaps and bath/shower soaps). This invention also relates to the use of dihydronepetalactone mixtures as insect repellents in a variety of articles, which are susceptible to attack by 15 insects. These outdoor consumable products will generally, but not necessarily, comprise an insect repellent composition of the invention, but will ccntain an effective amount of dihydronepetalactone. Typical articles that can be improved by the use of 20 dihydronepetalactones and mixtures thereof include, but are not limited to: air fresheners, candles, other scented articles, fibers, sheets, cloth [e.g., for clothing, nettings (mosquito netting), and other fabrics], paper, paint, ink, clay, woods, furniture 25 (e.g., for patios and decks), carpets, sanitary goods, plastics, polymers, and the like. The dihydronepetalactone compositions of this invention may be blended with polymers, which may also 30 involve a controlled release systems. Compatible polymers may or may not be biodegradable. Exemplary polymers are high-density polyethylene or low-density polyethylene, biodegradable thermoplastic pclyurethanes, biodegradable ethylene polymers, and 35 poly(epsilon caprolactone) homopolymers and compositions containing the same as disclosed in U.S. 4,496,467, U.S. 4,469,613 and U.S. 4,548,764. 49 WO2006/050519 PCT/US2005/040146 Dihydronepetalactones are particularly advantageous for use as repellent materials in preparations of the present invention for a variety of 5 reasons. First, the compounds are cost effective to produce, an important consumer consideration when choosing an effective repellent. Many commercially 10 available repellent products are only effective in relatively concentrated form, including as much as 5-30% (or more) repellent in a carrier, based on total weight. U.S. 4,416, 881 to McGovern et al., for example, discloses repellent concentrations of 6.25-25% 15 repellent in a carrier. Secondly, the compounds are known natural compounds, thus overcoming concerns raised against synthetic chemicals such as DEET as the primary active 20 ingredient in repellent compositions. Finally, in addition to the natural repellent properties of the dihydronepetalactone mixtures thus prepared, the compositions also possess a unique and 25 pleasant fragrance. The fragrance notes of the subject compounds make them useful in imparting, altering, augmenting or enhancing the overall olfactory component of an insect repellent composition or article, for example, by utilizing or moderating the olfactory 30 reaction contributed by one or more other ingredients in the composition. Specifically, the dihydronepetalactones of the invention or mixtures thereof may be utilized to either mask or modify the odor contributed by other ingredients in the 35 formulation of the final repellent composition or article, and/ or to enhance consumer appeal of a product by imparting a characteristic perfume or aroma. It is expected that the pleasant fragrance of 50 WO2006/050519 PCT/US2005/040146 dihydronepetalactones will possess much greater appeal to consumers than other insect repellent compounds, particularly DEET. 5 Dihydronepetalactones and their uses are also described in U.S. SN 10/349,865, filed January 23, 2003, which is incorporated in its entirety as a part hereof for all purposes. 10 Where the composition of this invention is stated or described as comprising, including, containing, having, being composed of or being constituted by certain components, it is to be understood, unless the statement or description 15 explicitly provides to the contrary, that one or more components in addition to those explicitly stated or described may be present in the composition. In an alternative embodiment, however, the composition of this invention may be stated or described as consisting 20 essentially of certain components, in which embodiment components that would materially alter the principle of operation or the distinguishing characteristics of the composition are not present therein. In a further alternative embodiment, the composition of this 25 invention may be stated or described as consisting of certain components, in which embodiment components other than impurities are not present therein. Where the indefinite article "a" or "an" is 30 used with respect to a statement or description of the presence of a component in the composition of this invention, it is to be understood, unless the statement or description explicitly provides to the contrary, that the use of such indefinite article does not limit 35 the presence of the component in the composition to one in number. 51
    权利要求:
    Claims (12)
    [1] 1. An insect repellent composition comprising (a) a dihydronepetalactone, or a mixture of dihydronepetalactone stereoisomers, represented by the general formuiala: 10 O 0 (b) an alcohol selected from a (i) C6-C 2 0 linear, branched or cyclic alkanol and (ii) a C 10 o-Cso 50 alcohol, 15 and (c) an ester.
    [2] 2. A composition according to Claim 1 further comprising a C 6 -C 20 linear, branched or cyclic alkane polyol. 20
    [3] 3. A composition according to Claim 1 further comprising a C 4 -C 400 polyethylene glycol.
    [4] 4. A composition according to Claim 1 further 25 comprising a C 4 -C 4 00 polyethylene ether glycol.
    [5] 5. A composition according to Claim 1 further comprising a C16-C 140 polyethylene glycol ether of a C 12 ~C 60 alcohol. 30 52 WO 2006/050519 PCT/US2005/040146 5S A composition according to Claim 1 further comprising a C 1 G-C1 40 polyethylene glycol ether of a C 12 -C6o alcohol. 5
    [6] 6- A composition according to Claim 1 further comprising a paraben.
    [7] 7. A composition according to Claim 6 wherein the paraben is selected from the group consisting of 10 methylparaben, ethylparaben, propylparaben, isopropylparaben, butylparaben, isobutylparaben, isodecylparaben, benzylparaben and phenylparaben.
    [8] 8. A composition according to Claim 1 further 15 comprising water.
    [9] 9. A composition according to Claim 1 wherein the ester comprises an ester of a C 12 -C 40 carboxylic acid and a CB-C 40 polyethylene glycol. 20
    [10] 10. A composition according to Claim 1 wherein the ester is selected from the group consisting of (a) Amyl, Methyl, Butyl, Ethyl, 25 Ethoxyethanol, Ethoxydiglycol, Tetrahydrofurfuryl, Isoamyl, Isobutyl, Isopropyl or Propyl Acetate; (b) Isobutyl, Methyl, Stearyl, Octyl, Lauryl, Myristyl or Palmitoyl Benzoate; 30 (c) Dimethyl Phthalate, Glutarate, Maleate, Adipate or Succinate; (d) Octyl, Lauryl, Myristyl, Palmitoyl or 35 Stearyl Salicylate; (e) Glycol Oleate, Palmitate, Stearate or Ricinoleate; 53 WO2006/050519 PCT/US2005/040146 (f) Butyl Isostearate, Myristate or Oleate; 5 (g) Cetyl Acetate, Caprylate, Lactate, Laurate, Octanoate or Oleate; (h) Isostearyl Benzoate, Lactate, Neopentanoate, Octauicate, Palmitate or Myristate; 10 (i) Isoamyl Laurate; (j) Isobutyl Myristate, Palmitate, Pelargonate or Stearate; 15 (k) Isocetyl Isodecanoate, Palmitate or Stearate; (L) Isodecyl Citrate, Hydroxystearate, 20 Laurate, Myristate, Neopentanoate, Palmitate or Stearate; (m) Isopropyl Hydroxystearate, Isostearate, Lanolate, Laurate, Linoleate, Myristate, Oleate, 25 Palmitate or Stearate; (n) Methyl Hydroxystearate, Laurate, Isostearate, Myristate, Oleate, Palmitate, Stearate or Pelargonate; 30 (o) Polyglyceryl Myristate, Oleate, Pentastearate or Ricinoleate; (p) Stearyl Acetate, Benzoate or Lactate; 35 (q) Phospl-ioric acid esters and diesters of C 16 -C 14 0 polyethylene glycol ether of C 12 -C60 alcohols; 54 WO2006/050519 PCT/US2005/040146 (r) Glyceryl Caprylate, Caprate, Hydroxystearate, Isopalmitate, Isostearate, Lanolate, Laurate, Oleate, Linoleate, Linolenate, Myristate, Palmitate, Stearate or Ricinoleate; and 5 (s) Propylene Glycol Hydroxystearate, Isostearate, Stearate, Laurate, Linoleate, Myristate, Ricinoleate, Oleate or Caprylate. 10
    [11] 11. A composition according to Claim 1 formulated as a liquid.
    [12] 12. A composition according to Claim 1 formulated as a lotion. 15 55
    类似技术:
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    同族专利:
    公开号 | 公开日
    CA2584354A1|2006-05-11|
    KR20140103188A|2014-08-25|
    IL182629D0|2007-07-24|
    CA2584354C|2015-02-24|
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    US8748477B2|2014-06-10|
    BRPI0516881A|2008-09-23|
    JP2008519050A|2008-06-05|
    US20140288167A1|2014-09-25|
    US20060223878A1|2006-10-05|
    CN101090630A|2007-12-19|
    US9314021B2|2016-04-19|
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    法律状态:
    2009-11-05| MK1| Application lapsed section 142(2)(a) - no request for examination in relevant period|
    优先权:
    申请号 | 申请日 | 专利标题
    US62457904P| true| 2004-11-03|2004-11-03||
    US60/624,579||2004-11-03||
    PCT/US2005/040146|WO2006050519A1|2004-11-03|2005-11-03|Insect repellent compositions comprising dihydronepetalactone, an alcohol, and an ester|
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