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European Patent Office of Opposition to That Patent, in Accordance with the Implementing Regulations (19) TZZ_¥_T (11) EP 1 863 466 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/16 (2006.01) A61K 31/194 (2006.01) 09.08.2017 Bulletin 2017/32 A61K 36/28 (2006.01) A61K 36/81 (2006.01) A61K 36/9068 (2006.01) A23L 2/02 (2006.01) (2006.01) (2006.01) (21) Application number: 06769774.8 A23L 2/56 A23G 3/34 A23G 3/36 (2006.01) A23G 3/48 (2006.01) A23G 4/06 (2006.01) A61K 45/06 (2006.01) (22) Date of filing: 03.03.2006 A23L 27/00 (2016.01) A23L 27/14 (2016.01) A23L 33/105 (2016.01) A23L 27/20 (2016.01) A61K 36/61 (2006.01) (86) International application number: PCT/US2006/008016 (87) International publication number: WO 2006/112961 (26.10.2006 Gazette 2006/43) (54) SYNERGISTIC SALIVATION COMPONENTS SYNERGISTISCHE SPEICHELFLUSSKOMPONENTEN COMPOSANTS A EFFET SYNERGIQUE AUGMENTANT LA SALIVATION (84) Designated Contracting States: • SPENCE, David J. AT BE BG CH CY CZ DE DK EE ES FI FR GB GR New Jersey (US) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • GREEN, Carter B. SK TR New York 10980 (US) (30) Priority: 03.03.2005 US 594004 P (74) Representative: Carpmaels & Ransford LLP One Southampton Row (43) Date of publication of application: London WC1B 5HA (GB) 12.12.2007 Bulletin 2007/50 (56) References cited: (73) Proprietor: Takasago International Corporation EP-A1- 1 293 131 WO-A-2005/044778 (USA) WO-A2-2004/043906 CN-A- 1 128 636 Rockleigh, NJ 07647 (US) US-A- 4 639 368 (72) Inventors: • DATABASE WPI Week 198235 Thomson • MANLEY, Charles Scientific,London, GB; AN1982-73237E &JP S57 New Jersey 07456 (US) 118518 A (OKANO K) 23 July 1982 (1982-07-23) Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations. Notice of opposition shall not be deemed to have been filed until the opposition fee has been paid. (Art. 99(1) European Patent Convention). EP 1 863 466 B1 Printed by Jouve, 75001 PARIS (FR) EP 1 863 466 B1 Description FIELD OF THE INVENTION 5 [0001] The present application relates to food or beverage additives that enhance salivation upon consumption of the food or beverage. BACKGROUND OF THE INVENTION 10 [0002] The term "dry mouth" (a/k/a, xerostomia) describes an oral condition in which salivary production and/or flow is reduced. Dry mouth may result from one or more of a number of underlying conditions. In many cases, for example, dry mouth occurs due to a natural decrease of saliva production that occurs upon aging. The ability to produce saliva by people in their sixties is typically one-eight of that in young adults. Dry mouth may also affect people with speaking or digestive difficulties or result as a side effect of medication, for example medications used to treat depression and 15 other psychiatric conditions. Dry mouth or xerostomia is also associated with rheumatoid arthritis, diabetes, kidney failure, infection with HIV (the virus that causes AIDS), trauma to the salivary glands, or their ducts or nerves and radiation treatment for mouth or throat cancer. [0003] A sufficient level of salivation is important for good oral hygiene and taste sensation. Dry mouth is conducive to the growth of microorganisms that cause halitosis or bad breath. Accordingly, many breath freshening products include 20 formulations that increase saliva flow in the oral cavity. Dry mouth decreases taste sensation and, thus, may decrease the ability to taste and enjoy food and beverages. Increased saliva flow, conversely, promotes taste sensation and, thus, may increase the ability to taste and enjoy foods and beverages. [0004] Unfortunately, ingredients added to increase salivation in the food or beverages often cause the food or beverage to have an unpleasant taste. There remains a need for salivation component(s) that are effective to increase salivation 25 without negatively affecting the taste of the product to which the salivation agent is added. Similarly, there remains a need for more effective salivation components(s) so that salivation is increased at lower use levels. There is also a need for improved treatment of subjects who suffer from xerostomia, and to inhibit xerostomia in those subjects who have, or at risk of developing this condition. [0005] CN 1128636 discloses ingredients for preparing a cold tea drink which is purported to dispel the cold, promote 30 the secretion of saliva, quench the thirsty, and be beneficial to the stomach. [0006] WO 2004/043906 relates to the use of N-isobutylamide 2E, 4E-decadien acid (transpellitorin) in the form of an aromatic substance, in particular as a saliva stimulating aromatic substance for food, buccal hygiene or gustatory prep- arations. [0007] WO 2005/044778 discloses the use of an alkene carboxylic acid N alkylamide as an acrid agent, as a warming 35 agent, as a sharp-tasting substance, for inducing a temperature-independent feeling of warmth, for enhancing or imitating the flavor of ethanol or for inducing salivation. [0008] US 4639368 discloses a chewing gum composition adapted to supply a medicament to the oral cavity for local application thereto or for buccal absorption of said medicament which comprises a chewing gum base, an orally admin- istrable medicament, a taste masking generator of carbon dioxide and optionally a taste bud desensitizing composition. 40 [0009] JP S57 118518 discloses a nutritive agent comprising tea, Chinpi, alcohol, extract of Japanese persimmon fruit leaves, Coptis japonica root, Phellodendron amurense bark and further mixed with acids and chlorophyll. [0010] EP 1293131 discloses a throat care agent which promotes the secretion of saliva, promoting the secretion of a large amount of mucin which is a bactericidal component contained in the saliva, inhibiting the adhesion of pathogenic bacteria to the throat, and removing them from the throat to keep it refreshed. 45 SUMMARY OF THE INVENTION [0011] The present application relates to compositions comprising a) a food acid and ii) a tingling sensate. The com- positions have a pleasant taste and promote salivation in products to which they have been added, such as foods, and 50 beverages. [0012] The tingling sensate is selected from spilanthol, sanshool, hydroxy α-sanshool, hydroxyl β-sanshool, hydroxy γ-sanshool, sanshool I, sanshool II, sanshoamide, chavicine, piperine, echinacea extract, northern prickly ash extract, Nepalese spice timur extract, 4-(1-menthoxymethyl)-2-phenyl-1,3-dioxolane, n-isobutyldeca-trans-2-trans-4-dienamide, n-cyclopropyl,trans-2-cis-6-nonadienamide, n-ethyl trans-2-cis-6-nonadienamide and jambu oleoresin. In a preferred 55 embodiement, the tingling sensate is spilanthol that is obtained from jambu oleoresin. [0013] The food acid is selected from acetic acid, adipic acid, aspartic acid, benzoic acid, caffeotannic acid, citric acid, iso-citric acid, citramalic acid, formic acid, fumaric acid, galacturonic acid, glucuronic acid, glyceric acid, glycolic acid, ketoglutaric acid, α-ketoglutaric acid, lactic acid, lactoisocitric acid, malic acid, oxalacetic acid, oxalic acid, pyruvic acid, 2 EP 1 863 466 B1 quinic acid, shikimic acid, succinic acid, tannic acid, and tartaric acid. In a preferred embodiment, the food acids is selected from citric acid, lactic acid, malic acid, succinic acid, fumaric acid, tartaric acid, ascorbic acid or adipic acid. I n a particularly preferred embodiment, the food acid is succinic acid. [0014] The present application also provides a method of increasing the salivation effect of a food or beverage when 5 consumed by a human comprising or consisting essentially of, the step of adding (a) a food acid and (b) a tingling sensate to the food or beverage. Examples of foods or beverages in which the salivation cocktail may be added include, but are not limited to, carbonated fruit beverages, sport beverages, carbonated cola drinks, wine coolers, cordials, flavored water, powders for drinks, hard candy, soft candy, taffy, chocolates, sugarless candies, chewing gum, bubble gum, condiments, spices and seasonings, dry cereal, oatmeal, granola bars, alcoholic beverages, energy beverages, juices, 10 teas, coffees, salsa, gel beads, film strips for halitosis, gelatin candies, pectin candies, starch candies, lozenges, cough drops, throat lozenges, throat sprays, toothpastes and mouth rinses. [0015] The present disclosure also provides a method of treating, and a method of inhibiting xerostomia comprising administering a food, beverage, candy, or pharmaceutical dosage form that includes one of the salivation cocktails described in this application to a subject in need thereof. The application also provides a food, beverage, candy, or 15 pharmaceutical dosage form that includes one of the salivation cocktails described in this application for use in a method to treat or inhibit xerostomia. The present application also provides for the use of any of the salivation cocktails described in the this application in the manufacture of a medicament for use in treating or inhibiting xerostomia in a subject. DETAILED DESCRIPTION 20 [0016] It has been found that the salivation effect of a tingling sensate(e.g., spilanthol) is synergistically enhanced when it is combined with a food acid. Accordingly, significantly lower amounts of tingling sensate are necessary to achieve a similar or even an increased salivation effect when combined with a food acid. While it was previously known that common food acids (e.g., citric acid, lactic acid, malic acid, succinic acid, fumaric acid, tartaric acid, ascorbic acid 25 and adipic acid) and jambu oleoresin, individually, can increase salivation, it was not known that the combination of a food acid and a tingling sensate such as spilanthol synergistically increase salivation.
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