US 20110223256A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2011/0223256A1 Zhang et al. (43) Pub. Date: Sep. 15, 2011 (54) METHOD FOR STABILIZING FILAVONOID Publication Classification AQUEOUS DISPERSION (51) Int. Cl. A6IR 9/14 (2006.01) (75) Inventors: Naijie Zhang, Ridgefield, CT (US); A63L/352 (2006.01) Vincent E.A. Rinaldi, Bethel, CT A63L/335 (2006.01) (US); Peter S. Given, JR., A63L/05 (2006.01) Ridgefield, CT (US) A6II 3L/22 (2006.01) A63L/7048 (2006.01) (73) Assignee: STOKELY-VAN CAMP, INC., A6IP33/6 (2006.01) Chicago, IL (US) (52) U.S. Cl. ......... 424/493: 514/456; 514/450; 514/734; 514/679; 514/27 (21) Appl. No.: 13/036,161 (57) ABSTRACT A method for Suspending microparticulated water insoluble (22) Filed: Feb. 28, 2011 bioactive compound in a beverage by incorporating solubi lized or dispersed microparticulated compound and at least one dispersion stabilizer into a beverage. A composition com Related U.S. Application Data prising solubilized or dispersed microparticulated water (60) Provisional application No. 61/312,694, filed on Mar. insoluble bioactive compound and a dispersion stabilizer 11, 2010. agent. E= 5. I Probe = 2f )A Aag = 50X Reference ag. = Curtiew. = r Feate = 24-327-2. late 14 Patent Application Publication Sep. 15, 2011 Sheet 1 of 4 US 2011/0223256 A1 &&. S SS E = i. Sigra A = WPSE G3 a = 9a urn I Prote = 201 A Aag = 5x Reference Aag = Cutiew, = . Fs are = 92-2-928-2 s. are: 2 SS = . Signal A = WPSG3 arrer = a Pa I Probe - 408 EA Aag = 6. KX Reference Aag = Out Dow. M = 5. Fis a = 92-928. F if date 52 Patent Application Publication Sep. 15, 2011 Sheet 3 of 4 US 2011/0223256 A1 gz'61-I Patent Application Publication Sep. 15, 2011 Sheet 4 of 4 US 2011/0223256 A1 NIGEHEJSEHNINE?NIHWNNILITE 9." 61-I axaSN S X S d X X) X: yar OK ~—,—————” NIWTIO'H[\ONILEOHEITO Xayatay X US 2011/0223256 A1 Sep. 15, 2011 METHOD FOR STABILIZING FILAVONOID BRIEF DESCRIPTION OF THE DRAWINGS AQUEOUS DISPERSION 0007 FIGS. 1A and 1B compare amorphous quercetin and crystalline quercetin, respectively. FIELD OF THE INVENTION 0008 FIGS. 2A and 2B show the results of a quercetin 0001. The present invention relates generally to a method stability study by FTIR and Carbon-13 NMR, respectively. for dispersing and Stabilizing water insoluble bioactive com 0009 FIG.3 shows samples of stable aqueous dispersions pounds in a liquid medium and a composition containing prepared in accordance with the present invention. flavonoid and a Suspension agent. DETAILED DESCRIPTION OF THE INVENTION BACKGROUND 0010. The present invention relates to a method for stabi lizing Suspended microparticulated water insoluble bioactive 0002 Biologically active (bioactive) compounds such as compounds such as quercetin particles in a liquid medium, flavonoids in general, are used as nutritional Supplements to Such as a beverage, and further to a composition containing provide, for example, antioxidants. Most of bioactive com solubilized or dispersed compound particles and at least one pounds are highly rigid and crystalline and water insoluble. dispersion stabilizer. Beverages, prepared with solubilized or Quercetin, in particular, is considered a powerful antioxidant. dispersed a bioactive compound and a dispersion stabilizer, A number of studies showed that quercetin is effective for the contain fine, stable dispersions. prevention of various diseases. 0011. The water insoluble bioactive compounds may be 0003 Flavonoids may be extracted from plants. For polyphenols, flavanoids, alkaloids, aldehyde, aryl ketone, example, quercetin is a natural, plant-derived, flavonoid. In benzofuranoid, benzopyranoid, diterpenoid, phenylpro particular, quercetin is the aglycone form of a number of other panoid, polyketide, sesquiterpenoid, monoterpenoid, and/or flavonoid glycosides, such as rutin and quercitrin, found in may be derived from plants, herbs, or botanicals. See for citrus fruit, cranberries, blueberries, buckwheat, onions, and example, Naturally Occurring Bioactive Compounds Edited other vegetables, fruits, and greenplants. The chemical struc by Mahendra Rai, Maria Cecillia Carpinella, 2006. Bioactive ture of quercetin is illustrated below: Compounds in Foods. Edited by John Gilbert and Hamide Z. Senyuva. Bioactive Compounds From Plants, Volume 154, John Wiley and Sons, 1990. OH 0012 Suitable polyphenols include quercetin, eriocitrin, OH neoeriocitrin, narirutin, naringin, hesperidin, hesperetin, neo hesperidin, neoponcirin, poncirin, rutin, isorhoifolin, rhoifo lin, dioSmin, neodiosmin, Sinensetin, nobiletin, tangeritin, HO O catechin, catechin gallate, epigallocatechin, epigallocatechin gallate, anthocyanin, heptamethoxyflavone, curcumin, res Veratrol, naringenin, tetramethoxyflavone, kaempferol, and OH rhoifolin. OH O 0013 Suitable flavonoids and other bioactive compounds include quercetin, flavonones, flavones, dihydroflavonols, flavonols, flavandiols, leucoanthocyanidins, flavonol glyco 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H sodes, flavonone glycosides, isoflavonoids, and neofla vonoids. In particular, the favonoids may be, but not limited chromen-4-one to, quercetin, eriocitrin, neoeriocitrin, narirutin, maringin, 0004. It is desired to use flavonoids as a nutritional supple hesperidin, hesperetin, neohesperidin, neoponcirin, poncirin, ment in food products such as beverages. Often such fla rutin, isorhoifolin, rhoifolin, dioSmin, neodiosmin, sinense vonoids are difficult to disperse and mix into beverage prod tin, nobiletin, tangeritin, catechin, catechin gallate, epigallo ucts at efficacious concentrations. Often such flavonoids will catechin, epigallocatechin gallate, oolong tea polymerized simply settle to the bottom of the container holding the bev polyphenol, anthocyanin, heptamethoxyflavone, daidzin, erage. For example, quercetin is typically obtained as a pow daidzein, biochaminn A, prunetin, genistin, glycitein, gly der and is insoluble in water. When added to liquid media, citin, genistein, 6.7.4 trihydroxyisoflavone, morin, apigenin, quercetin usually agglomerizes and settles to the bottom of Vitexin, balcalein, apin, cupressuflavone, datiscetin, dios the beverage, thereby resulting in a product that is not visually metin, fisetin, galangin, gossypetin, geraldol, hinokiflavone, appealing to the consumer. primuletin, pratol, luteolin, myricetin, orientin, robinetin, 0005. Therefore, a need exists in the food and beverage quercetagetin, and hydroxy-4-flavone. industry to provide the consumer with a food product con 0014 Suitable compounds derived from plants, herbs, or taining bioactive compounds Such as quercetin wherein the botanicals include pyrrolizildine, alkaloids, and artemisinin. bioactive compound is stabilized in an aqueous Suspension. 0015 For ease of discussion, the application will be dis cussed in terms of quercetin. However, it is intended that the BRIEF SUMMARY process steps and compositions apply to all suitable bioactive compounds described above and below. 0006. The present invention relates to a method for stabi 0016. In one aspect of the invention, quercetin is solubi lizing Suspended quercetin or other Suspended water lized or dispersed prior to adding the quercetin to an aqueous insoluble bioactive compounds in a beverage and a composi Solution containing a dispersion stabilizer. tion for a beverage containing stabilized Suspended quercetin 0017. An aqueous dispersion of quercetin through solubi or other water insoluble bioactive compounds. lization reduces particle size, density, rigidity, and crystalline US 2011/0223256 A1 Sep. 15, 2011 structure resulting in increasing dispersion stability. SEM 0027 Subsequently, water is added to dilute the concen results show dispersed quercetin in gellan gum has amor trated dispersion to yield a stable quercetin dispersion having phous structure (FIG. 1A) compared to crystalline quercetin a concentration between 0.001-5.0 wt.%. The pH of the (FIG. 1B). diluted dispersion is adjusted to less than 7.0, typically 2.5 to 0018. The chemical stability of quercetin during heating solubilizing process in polyols is determined by analytical 6. characterization. Quercetin dispersion with or without gellan 0028. The at least one dispersion stabilizer can be a gum is isolated and purified from beverage. FIGS. 2A and 2B biopolymer or a modified polysaccharide Such as gellangum, show that the spectra of FT-IR and carbon-13 NMR, respec pectin, carrageenan, ghatti gum, acacia gum, guar gum, Xan tively, of quercetin dispersions through solubilization are than gum, locust gum, agar, starch, alginate, cellulose, pro identical with that of starting material quercetin. The results tein, hydrolyzed protein, modified starch, carboxyl methyl indicate that there is no structure change of quercetin during cellulose (CMC) or the combination thereof. heating solubilization process. 0029 Preferably the biopolymers are charged polymers 0019 Quercetin is solubilized by dissolving quercetin in Such as carboxyl-containing polymers and Sulfate-containing a) hot alcohol. Such as hot ethanol or polyols, orb) an alkaline polymers. It was discovered that anionic or cationic biopoly solution having a pH above 7 or c) a mixture of alcohol and mers such as pectin, gellan gum, carrageenan, gum arabic, alkaline Solution, to form solubilized quercetin Solution hav ghatti gum, CMC, whey protein isolate showed better disper ing 1 to 15 wt % quercetin. Suitable alcohols include, but not sion stability than non-ionic polymers. It is believed that limited to, ethanol, isopropyl alcohol, isobutyl