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Patent Issued for Compositions for and Methods of Controlling Olfactory Responses to Odorants

July 29, 2014



By a News Reporter-Staff News Editor at Life Science Weekly -- According to news reporting originating from Alexandria, Virginia, by NewsRx journalists, a patent by the inventors Vodyanoy, Vitaly J. (Auburn, AL); Scharpf, Lewis G. (Auburn, AL); Samoylov, Alexandre (Auburn, AL); Viswaprakash, Nilmini (Auburn, AL); Globa, Ludmila Petrovna (Auburn, AL); Morrison, Edward E. (Auburn, AL), filed on September 21, 2012, was published online on July 15, 2014 (see also Auburn University).

The assignee for this patent, patent number 8778409, is Auburn University (Auburn, AL).

Reporters obtained the following quote from the background information supplied by the inventors: "In the human world, olfaction serves to heighten or discriminate our aesthetic sense, while in other animals it is an important survival sense, upon which the well-being and sometimes the safety of the animal itself is dependent on. The partial or complete loss of smell (anosmia) affects approximately 2.5 million people in the United States and poses serious health risks as the presence of rancid food; toxic odors and smoke often go undetected. The clinical treatment of anosmia will require a better understanding of the mechanisms that regulate differentiation, proliferation and the injury response of the precursor, the multi-potent neuronal stem cells in the olfactory epithelium (OE). Olfactory receptor neurons (ORN) are the only mammalian neurons which undergo continuous neurogenesis through their life, suggesting that a neuronal stem cell exists in this system.

"An aroma compound, also known as odorant, aroma, fragrance, flavor, is a chemical compound that has a smell or odor. A chemical compound has a smell or odor when two conditions are met: the compound needs to be volatile, so it can be transported to the olfactory system in the upper part of the nose, and it needs to be in a sufficiently high concentration to be able to interact with one or more of the olfactory receptors. Typically, odorants are small molecules in a range of 40 to 400 Daltons.

"Aroma compounds can be found in food, wine, spices, perfumes, fragrance oils, and essential oils. For example, many aroma compounds form biochemically during ripening of fruits and other crops. In wines, most form as byproducts of fermentation. Odorants can also be added to a dangerous odorless substance, like natural gas, as a warning. Many of the aroma compounds also play a significant role in the production of flavorants, which are used in the food service industry to flavor, improve and increase the appeal of their products.

"The olfactory mucosa is an organ made up of the olfactory epithelium and mucus. The mucus protects the olfactory epithelium and allows odors to dissolve so that they can be detected by olfactory receptor neurons. In mammals, the olfactory mucosa is located on the roof of the nasal cavity, above and behind the nostrils.

"Cells in the olfactory mucosa have been shown to have a degree of plasticity. Because of this, these cells hold potential for therapeutic applications, have been used in clinical trials for adult stem cell therapeutic treatments, and have been successfully harvested for future applications.

"The olfactory epithelium is a specialized epithelial tissue inside the nasal cavity that is involved in smell. In humans, the olfactory epithelium measures about 1 inch wide by 2 inches long (about 2 cm by 5 cm) and lies on the roof of the nasal cavity about 3 inches (about 7 cm) above and behind the nostrils. The olfactory epithelium is the part of the olfactory system directly responsible for detecting odors.

"The tissue is made of three types of cells: the olfactory receptor neurons, which transduce the odor to electrical signals, the supporting cells, which protect the neurons and secrete mucus, and the basal cells, which are a type of stem cell that divide into olfactory receptor neurons to replace dead receptor neurons. The olfactory epithelium is divided into four zones from ventral to dorsal. Each olfactory receptor is expressed throughout one zone.

"In mammals, odorants are inhaled through the nose where they contact the olfactory epithelium. Olfactory receptor neurons in the olfactory epithelium transduce molecular features of the odorants into electrical signals which then travel along the olfactory nerve into the olfactory bulb. Axons from the olfactory sensory neurons converge in the olfactory bulb to form tangles called glomeruli (singular glomerulus). Inside the glomulerus, the axons contact the dendrites of mitral cells and several other types of cells. Mitral cells send their axons to a number of brain areas, including the piriform cortex, the medial amygdala, and the entorhinal cortex. The piriform cortex is probably the area most closely associated with identifying the odor. The medial amygdala is involved in social functions such as mating and the recognition of animals of the same species. The entorhinal cortex is associated with memory. The exact functions of these higher areas are a matter of scientific research and debate.

"Olfactory receptors belong to class A of the G protein-coupled receptor. In vertebrates, the olfactory receptors are located in the cilia of the olfactory sensory neurons. In insects, olfactory receptors are located on the antennae. Sperm cells also express odor receptors, which are thought to be involved in chemotaxis to find the egg cell.

"It is believed that rather than binding to specific ligands like most receptors, olfactory receptors bind to structures on odor molecules. Once the odorant has bound to the odor receptor, the receptor undergoes structural changes and it binds and activates the olfactory-type G protein on the inside of the olfactory receptor neuron. The G protein (Golf and/or Gs) in turn activates the lyase adenylate cyclase, which converts ATP into cyclic AMP (cAMP). The cAMP opens ion channels that allow calcium and sodium ions to enter into the cell, depolarizing the olfactory receptor neuron and beginning an action potential which carries the information to the brain.

"There are a wide range of different odor receptors, with as many as 1,000 in the mammalian genome. Olfactory receptors may make up as much as 3% of the genome. Only a portion of these potential genes form functional odor receptors. According to an analysis of the Human genome project, humans have 347 functional genes coded for olfactory receptors. The reason for the large number of different odor receptors is to provide a system for detecting as many different odors as possible. Even so, each odor receptor does not correspond to just one odor. Each individual odor receptor is broadly tuned to be activated by a number of similar structures. Like the immune system, this system allows molecules that have never been encountered before to be characterized. Also, most odors activate more than one type of odor receptor. This aspect provides for the identification of an almost limitless number of different molecules.

"Damage to the olfactory system can occur for a number of different reasons. For example, damage to the olfactory system can occur by traumatic brain injury, cancer, inhalation of toxic fumes, or neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. These conditions can cause anosmia (complete loss of ability to detect odors) or hyposmia (partial loss of the ability to detect odors). Even old age can cause anosmia or hyposmia; in fact most people suffer from some degree of hyposmia with aging.

"The ability to smell is important not only to the survival of human beings, but is also an important aspect of a fulfilling life experience. The loss of smell can have a far reaching impact on a person's metal health and overall quality of life. Therefore, there is a continued need to develop techniques for maintaining, enhancing or improving the ability to smell odorants, especially for those people who exhibit anosmia. There is also a need to develop techniques for reducing the ability to smell an odorant or odorants, especially when the odorant or odorants are non-toxic but still unpleasant."

In addition to obtaining background information on this patent, NewsRx editors also obtained the inventors' summary information for this patent: "The present invention is directed to compositions, systems and methods for modifying an olfactory response to one or more odorants. In accordance with the embodiments of the invention, a composition (also referred to herein as a metal composition) includes metal in the form of metal clusters, metal compounds, metal particles or a combination thereof. The metal, when applied to the olfactory tissue, associates with or binds with G-protein coupled to receptors located in the cilia. This association or binding modulates the cascade of events that ultimately leads to the sensation of smell.

"The metal, in accordance with an embodiment of the invention, is in the form of metal nanoparticles. The metal nanoparticles are able to include any metal element or combination of metal elements including, but not limited to, Ag, Pd, Rh, Cu, Pt, Ni, Fe, Ru, Os, Mn, Cr, Mo, Au, W, Co, Ir, Zn and Cd metal elements. In some embodiments, the metal nanoparticles are crystalline metal nanoparticles having a molar concentration in the composition that is in the range of 10.sup.-15 to 10.sup.-9 Moles.

"In accordance with the embodiments of the invention the composition also includes a delivery medium. The delivery medium is able to be a liquid, a powder, an emulsion, a suspension, a vapor or any suitable delivery medium for holding, storing and applying the metal to an olfactory tissue, such as an olfactory mucosa membrane. In some embodiments, the delivery medium is substantially liquid or vapor. The delivery medium is also able to include stabilizers, preservatives and/or surfactants to provide a formulation that is suitable for application to the olfactory tissue. For example, the delivery medium is able to include one or more of a fatty acid, an amino acid, an ester, an ether, a polyether, an amine and a carboxylic acid.

"The delivery medium is also able to include a biological component, which helps the metal interact with the olfactory tissue. For example, the delivery medium is able to include an olfactory binding protein.

"In accordance with yet further embodiments of the invention, the composition includes one or more odorants. Suitable odorants include any number of synthetic or natural odorants. Suitable odorants include, but are not limited to, aromatics, ketones, alcohols, aldehydes, esters, amines, thiols, terpenes, essential oils and combinations thereof.

"A system in accordance with the embodiments of the invention includes a delivery means, such as packaging or a dispenser for dispensing, applying or administering the composition, such as described above, to the olfactory tissue. The composition is able to be dispensed, applied or administered in the form of an aerosol spray, an aerated spray, liquid droplets, vapor or a plume of powder. Accordingly, suitable delivery means, packaging or dispensers include pressurized spray containers, a pump or squeeze spray container, dropper-bottle containers and powder adapted inhalers.

"In accordance with the method of the invention, a metal composition, such as described above, is formed and packaged or stored. As described above the metal composition is able to include one or more stabilizers, preservatives, surfactants or odorants. Where the metal composition is a medicating composition, the composition is packaged with a suitable applicator or dispenser, such that the metal composition is able to be applied to olfactory tissues through a nasal passage. The composition of the present invention is able to be used to enhance or suppress sensitivity of olfactory senses to fragrances and other odorants.

"In accordance with further methods of the invention a metal composition, such as described above, is applied to a surface of an object which contains an odorant. For example, a metal composition of the present invention can be sprayed on flowers to enhance the peoples sensitivity to the flower odorant or odorants."

For more information, see this patent: Vodyanoy, Vitaly J.; Scharpf, Lewis G.; Samoylov, Alexandre; Viswaprakash, Nilmini; Globa, Ludmila Petrovna; Morrison, Edward E.. Compositions for and Methods of Controlling Olfactory Responses to Odorants. U.S. Patent Number 8778409, filed September 21, 2012, and published online on July 15, 2014. Patent URL: http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2=HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2Fsrchnum.htm&r=1&f=G&l=50&s1=8778409.PN.&OS=PN/8778409RS=PN/8778409

Keywords for this news article include: Auburn University, Cells, Emerging Technologies, Nanoparticle, Nanotechnology, Neurons.

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Source: Life Science Weekly


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