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Patent Literature on Mosquito Repellent Inventions Which Contain Plant Essential Oils – a Review

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Patent Literature on Mosquito Repellent Inventions Which Contain Plant Essential Oils – a Review 598 Reviews Patent Literature on Mosquito Repellent Inventions which Contain Plant Essential Oils – A Review Authors Adrian Martin Pohlit1,3, Norberto Peporine Lopes3, Renata Antonaci Gama4, Wanderli Pedro Tadei2, Valter Ferreira de Andrade Neto4 Affiliations 1 Natural Products Department, National Institute for Amazon Research, Manaus, Brazil 2 Health Sciences Department, National Institute for Amazon Research, Manaus, Brazil 3 Department of Chemistry and Physics, College of Pharmaceutical Sciences, São Paulo University, Ribeirão Preto, Brazil 4 Department of Microbiology and Parasitology, Rio Grande do Norte Federal University, Natal, Brazil Key words Abstract were each cited in approximately 1/3 of all pat- l" botanical repellents ! ents. Camphor [Cinnamomum camphora (L.) J. l" natural products Bites of mosquitoes belonging to the genera Presl], cinnamon (Cinnamomum zeylanicum l" ‑ plant based repellents Anopheles Meigen, Aedes Meigen, Culex L. and Blume), clove [Syzygium aromaticum (L.) Merr. & l" repellent essential oils Haemagogus L. are a general nuisance and are re- L.M. Perry], geranium (Pelargonium graveolens l" mosquito repellents sponsible for the transmission of important trop- LʼHér.), lavender (Lavandula angustifolia Mill.), ical diseases such as malaria, hemorrhagic dengue lemon [Citrus × limon (L.) Osbeck], lemongrass and yellow fevers and filariasis (elephantiasis). [Cymbopogon citratus (DC.) Stapf] and pepper- Plants are traditional sources of mosquito repel- mint (Mentha × piperita L.) EOs were each cited ling essential oils (EOs), glyceridic oils and repel- in > 10% of patents. Repellent chemicals present lent and synergistic chemicals. A Chemical Ab- in EO compositions or added as pure “natural” in- stracts search on mosquito repellent inventions gredients such as geraniol, limonene, p-men- containing plant-derived EOs revealed 144 active thane-3,8-diol, nepetalactone and vanillin were patents mostly from Asia. Chinese, Japanese and described in approximately 40% of all patents. Korean language patents and those of India (in About 25% of EO-containing inventions included English) accounted for roughly 3/4 of all patents. or were made to be used with synthetic insect Since 1998 patents on EO-containing mosquito control agents having mosquito repellent proper- repellent inventions have almost doubled about ties such as pyrethroids, N,N-diethyl-m-tolua- received July 2, 2010 every 4 years. In general, these patents describe mide (DEET), (±)-p-menthane-3,8-diol (PMD) revised Dec. 28, 2010 repellent compositions for use in topical agents, and dialkyl phthalates. Synergistic effects involv- accepted January 3, 2011 cosmetic products, incense, fumigants, indoor ing one or more EOs and synthetic and/or natural Bibliography and outdoor sprays, fibers, textiles among other components were claimed in about 10% of all pat- DOI http://dx.doi.org/ applications. 67 EOs and 9 glyceridic oils were in- ents. Scientific literature sources provide evi- 10.1055/s-0030-1270723 dividually cited in at least 2 patents. Over 1/2 of all dence for the mosquito repellency of many of the Published online February 15, 2011 patents named just one EO. Citronella [Cymbopo- EOs and individual chemical components found Planta Med 2011; 77: 598–617 gon nardus (L.) Rendle, C.winterianus Jowitt ex in EOs used in patented repellent inventions. © Georg Thieme Verlag KG Bor] and eucalyptus (Eucalyptus LʼHér. spp.) EOs Stuttgart · New York · ISSN 0032‑0943 Correspondence Introduction 1 million deaths caused by malaria mainly in Afri- Prof. Dr. Valter Ferreira ! can children [1]. Human malaria is caused by in- de Andrade Neto Laboratory of Malaria Mosquito vectors of severe fections by unicellular protozoan parasites Plas- and Toxoplasmosis Biology tropical diseases modium falciparum Welch, P. vivax Grassi & Felet- Department of Microbiology Severe human tropical diseases such as malaria, ti, P. malariae Feletti & Grassi and P. ovale Ste- and Parasitology Rio Grande do Norte Federal dengue and yellow fevers and filariasis are trans- phens which are transmitted by about 20 Anoph- University (UFRN) mitted by the bites of infected hematophagous fe- eles spp. Another important disease is dengue Campus Universitário male mosquitoes belonging to the genera Aedes hemorrhagic fever which is a viral infection Lagoa Nova CEP 59072-970 Natal – RN Meigen, Anopheles Meigen, Culex L. and Haemago- caused by several Flavivirus spp. (Flaviviridae) Brazil gus L. (Diptera: Culicidae). For example, about 3.3 whose most important vector is Aedes (Stego- Phone: + 558432153437, billion people − 1/2 of the worldʼs population – myia) aegypti L. Dengue and dengue hemorrhagic ext. 225, 226 Fax:+558432119210 are at risk of contracting malaria. In 2008, there fevers threaten an estimated 2.5 billion people [email protected] were more than 247 million cases and more than − 2/5 of the worldʼs population – and an estimated Pohlit AM et al. Patent Literature on… Planta Med 2011; 77: 598–617 Reviews 599 50 million people contract the disease per year. Around 500000 pinene, p-cymene and γ-terpinene among other active com- dengue patients, most of whom are children, require hospitaliza- pounds [8]. According to a recent review of the scientific litera- tion each year and around 2.5% of those affected die [2]. Another ture, the most frequently studied repellent EOs are those ob- serious tropical disease which threatens about 1 billion people in tained from species belonging to the genera Cymbopogon Spreng., 80 countries is filariasis or elephantiasis. This disease already af- Ocimum L. and Eucalyptus LʼHér. spp. and a number of mosquito fects an estimated 120 million people and severely incapacitates repellent EOs have been identified in recent years having known and deforms 40 million people worldwide. Filariasis is caused by active repellent chemical components [7]. Mosquito repellency is infections by several roundworm species of which Wuchereria believed to be due to the synergistic interactions of the chemical bancrofti Cobbold (Filariidea: Onchocercidae) is the most impor- components in EOs. Furthermore, strong synergistic effects be- tant and is transmitted by the bites of the common house mos- tween EOs and isolated natural or synthetic substances have quito Cx. pipiens L. complex, Cx. quinquefaciatus Say, Aedes and been reported [7]. Anopheles spp. [3,4]. Yellow fever is an arbovirus of the Flavivirus The United States Environmental Protection Agency [9] has regis- genus (Flaviviridae) which is transmitted from monkeys in the tered citronella EO, eucalyptus EO and other plant oils as safe and jungle to humans and then from human to human by mosqui- effective ingredients for use in topical insect repellents. However, toes. The most significant yellow fever mosquito vector is Ae. ae- caution is recommended in the use of EOs in general due to a gypti. Despite the existence of effective vaccines, there are an es- number of potential toxic effects [7]. Among the important toxic timated 200000 cases of yellow fever and approximately 30000 effects of EOs are mutagenicity and genotoxicity. Another toxic deaths attributed to this disease each year [5]. In public health in- effect is the allergenicity of EO chemical components which are itiatives which aim to limit or eradicate these and other tropical controlled in the European Community and elsewhere. Interest- diseases, mosquito vector control methods such as repellence fig- ingly, a number of repellent and insecticidal plant EOs and their ure prominently among those which are employed. chemical constituents have been evaluated using a variety of methods and are believed to be non-mutagenic [10]. Synthetic mosquito repellents DEET and alkyl phthalates A number of commercial repellent products have been developed For more than 50 years, the synthetic compound DEET (N,N-di- over the past decades which utilize derivatives of plants such as ethyl-m-toluamide), has been the most effective single repellent EOs, fractions and their isolated chemical components and syn- for mosquito species and is the basis for many commercial repel- thetic components. Thus, it is important to have a comprehensive lent products on the market. Despite reports of severe toxic prop- knowledge of the commercially significant uses of EOs in mosqui- erties which can dramatically affect adults and especially young to repellent inventions and to the best of our knowledge the pat- children including dermatitis, allergic reactions, neurological ent literature on this topic has not been reviewed. The aim of the (seizures, coma) and cardiovascular toxicity, the risk of serious present review is to explore and analyze patent literature on toxic effects from DEET is considered slight. Nevertheless, DEET mosquito repellent inventions which make use of or are based should always be used at the lowest effective dose possible. Also, wholly on plant EOs and/or their chemical components. A sec- dimethyl and di-n-butyl phthalates (DMP and DBP, respectively), ondary aim is to analyze the scientific bases and relevancy of the which are effective mosquito repellents and were widely used in use of plant EOs and chemical components of these oils in pa- the last century, are no longer generally recommended for use as tented mosquito repellent formulations. mosquito repellents due to their toxicity [6]. Plants as sources of mosquito control agents Chemical Abstracts Search Criteria Plants have historically been valuable sources of agents for the ! control of insects [3,7]. They
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