The invention relates to a process for the preparation of highly soluble individual or combined sweet glycosides from a Stevia rebaudiana Bertoni plant extract, and more particularly for preparation of highly soluble rebaudioside A.
It is well known that Rebaudioside A exhibits so called polymorphism (Zell et al., 2000). Rebaudioside A amorphous, anhydrous and solvate forms differ significantly from each other in terms of solubility which is one of the main criteria for the commercial viability of a sweetener. In this regard, as shown in Table 1, the hydrate form of Rebaudioside A displays the lowest solubility (Prakash et al., 2008). It was shown that Rebaudioside A may transform from one polymorph form to another at certain conditions (U.S. pat. appl. Ser. No. 11/556,049).
Patent application WO/2010/118218 describes a process of producing highly soluble rebaudioside A by preparing a highly soluble hydrated crystalline form. However the described methodology utilizes low throughput techniques such as evaporative crystallization or hot filtration/centrifugation of slurries which can be hard to accomplish in large industrial scale.
On the other hand it is known (Prakash et al., 2008) that rebaudioside A amorphous forms prepared by spray drying display high solubility as well. However spray drying of rebaudioside A is a very challenging and low throughput task because generally spray drying requires concentrated feed solutions (about 50% solids content). Rebaudioside A concentrated solutions prepared by simple dissolution are very unstable and tend to crystallize very fast. These concentrated solutions (>10%) prepared by common solubilization methods such as heating under normal conditions crystallize shortly after cooling down to room temperature. Thus spray drying of such solutions requires special equipment capable of maintaining the solution at elevated temperature.
On the other hand extended exposure of rebaudioside A to high temperature both in solid form and in aqueous solutions results in hydrolytic decomposition of the material (Prakash et al., 2008).
Therefore a high throughput process of manufacturing highly soluble Rebaudioside A or other steviol glycosides on an industrial scale without needing a sophisticated equipment setup will offer certain advantages compared to other techniques known to art.
The invention is directed to a method for producing a sweetener comprising the steps of providing a Stevia sweetener powder and solubilizing it in the water under gradient temperature treatment conditions, to produce a highly stable concentrated solution, and spray drying the highly stable concentrated solution to obtain a highly soluble Stevia sweetener powder.
Hereinafter the term “steviol glycoside(s)” will mean Rebaudioside A, Rebaudioside B, Rebaudioside C, Rebaudioside D, Rebaudioside E, Rebaudioside F, Stevioside, Steviolbioside, Dulcoside A, Rubusoside, or other glycoside of steviol and combinations thereof.
Hereinafter, unless specified otherwise, the solubility of material is determined in RO (reverse osmosis) water at room temperature. Where the solubility is expressed as “%” it to be understood as number of grams of material soluble in 100 grams of solvent.
It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.
A process for the preparation of highly soluble Stevia sweetener, particularly Rebaudioside A, is described herein.
Crystalline Rebaudioside A has an inherently very low solubility, ranging from about 1%-2%. As described above, Rebaudioside A exhibits polymorphism, resulting in a variety of forms with very different characteristics and handling properties. The hydrate form has very low solubility (less than 0.2%), and is therefore not commercially viable as a sweetener. The solvate form has a solubility typically greater than 30%, but this form has only of scientific interest and cannot be used for food or beverage applications because the level of residual alcohol (1-3%) makes it unfit for use in foods and beverages. The anhydrous form has a solubility reported in literature of a maximum of up to about 30% solubility. The amorphous form has as solubility generally greater than 30%, but for its preparation, the crystalline form has to be dissolved in the water at very high concentrations (approx. 50%) which is not achievable by common solubilization techniques.
Typical spray drying techniques involve the use of a highly concentrated, and yet stable, starting solution to achieve the highest output possible. As noted above, crystalline Rebaudioside A has a very low solubility, so to create a stable solution (one which will not crystallize at room temperature), the solution has to be very dilute. Spray drying very dilute solutions is not economically efficient as the output of the spray dried powder will be very low. The need exists, therefore, for a process in which a high solubility Rebaudioside A is obtained by a process which does not require significantly diluted Rebaudioside A solution in order for the solution to be stable at room temperature.
In one embodiment of the present invention, an initial material, comprising sweet glycoside(s) of the Stevia rebaudiana Bertoni plant extract, which includes Stevioside, Rebaudioside A, Rebaudioside B, Rebaudioside C, Rebaudioside D, Rebaudioside E, Rebaudioside F, Steviolbioside, Dulcoside A, Rubusoside or other glycoside of steviol and combinations thereof, was combined with water at a ratio of about 1:1 (w/w).
The obtained mixture was further subjected to a gradient heat treatment which resulted in high stability and high concentration solution. The gradient of about 1° C. per minute was used in heating the mixture. The mixture was heated to the temperature of about 110-140° C., preferably about 118-125° C. and was held at maximum temperature for about 0-120 min, preferably about 50-70 min.
After the heat treatment the solution was cooled down to room temperature at gradient of about 1° C. per minute. 24-hour incubation of this high stability and high concentration solution did not show any crystallization.
The solution was spray dried by a laboratory spray drier operating at about 175° C. inlet temperature and about 100° C. outlet temperature. A highly soluble amorphous form of rebaudioside A was obtained with greater than about 30% solubility in water at room temperature.
The following examples illustrate preferred embodiments of the invention. It will be understood that the invention is not limited to the materials, proportions, conditions and procedures set forth in the examples, which are only illustrative.
100 g of rebaudioside A containing Stevioside 0.2%, Rebaudioside C 0.3%, Rebaudioside F 0.3%, Rebaudioside A 97.7%, Rebaudioside D 1.0%, and Rebaudioside B 0.3%, all percentages being on a percent dry weight basis, and having water solubility of 0.6% was mixed with 100 g of water and boiled on a laboratory heater until complete dissolution. Upon complete dissolution, the solution was cooled to room temperature to make Solution #1.
100 g of rebaudioside A containing Stevioside 0.2%, Rebaudioside C 0.3%, Rebaudioside F 0.3%, Rebaudioside A 97.7%, Rebaudioside D 1.0%, Rebaudioside B 0.3%, all percentages being on a percent dry weight basis, and having water solubility of 0.6% was mixed with 100 g of water and incubated in autoclave (AMA 270, Astell Scientific, UK), at 121° C. for 1 hour. Upon completion of incubation period the obtained clear solution was cooled to room temperature to make Solution #2.
100 g of rebaudioside A containing Stevioside 0.2%, Rebaudioside C 0.3%, Rebaudioside F 0.3%, Rebaudioside A 97.7%, Rebaudioside D 1.0%, Rebaudioside B 0.3%, all percentages being on a percent dry weight basis, and having water solubility of 0.6% was mixed with 100 g of water and incubated in thermostatted oil bath. The temperature was increased at 1° C. per minute to 121° C. The mixture was maintained at 121° C. for 1 hour and then the temperature was decreased to room temperature (25° C.) at 1° C. per minute to make Solution #3.
Rebaudioside A Solution #1, Solution #2 and Solution #3 prepared according to EXAMPLE 1, EXAMPLE 2 and EXAMPLE 3, respectively, were assessed in terms of their stability at room temperature (25° C.). The results are summarized in Table 2.
It can be seen that the solution prepared by temperature gradient method shows greater stability against crystallization.
Rebaudioside A Solution #1, Solution #2 and Solution #3 prepared according to EXAMPLE 1, EXAMPLE 2 and EXAMPLE 3, respectively, were dried using YC-015 laboratory spray drier (Shanghai Pilotech Instrument & Equipment Co. Ltd., China) operating at 175° C. inlet and 100° C. outlet temperature. Solution #1 and Solution #2 had to be maintained at 80° C. to prevent premature crystallization whereas Solution #3 was maintained at room temperature. The Solution #1 yielded Sample #1, Solution #2 yielded Sample #2 and Solution #3 yielded Sample #3.
The obtained amorphous powder samples were compared for solubility (Table 3).
The process of the present invention resulted in a Rebaudioside A polymorph which demonstrated high degree of solubility in water. Although the foregoing embodiments describe the use of Rebaudioside A, it is to be understood that any Stevia-based sweetener may be used and prepared in accordance with this invention, and all Stevia-based sweeteners are contemplated to be within the scope of the present invention.
Although the invention and its advantages have been described in detail, it should be understood that various changes, substitutions and alterations can be made herein without departing from the spirit and scope of the invention as defined by the appended claims. Moreover, the scope of the application is not intended to be limited to the particular embodiments of the invention described in the specification. As one of ordinary skill in the art will readily appreciate from the disclosure of the invention, the compositions, processes, methods, and steps, presently existing or later to be developed that perform substantially the same function or achieve substantially the same result as the corresponding embodiments described herein may be utilized according to the invention.
This application is a continuation application of U.S. patent application Ser. No. 13/984,315, filed on Aug. 28, 2013, the contents of which are incorporated by reference herein, which is a U.S. national phase application of International Application No. PCT/US2012/024585, filed Feb. 10, 2012, which claims the benefit of U.S. Provisional Patent Application No. 61/441,443, filed Feb. 10, 2011.
Number | Name | Date | Kind |
---|---|---|---|
3723410 | Persinos | Mar 1973 | A |
4082858 | Morita et al. | Apr 1978 | A |
4171430 | Matsushita et al. | Oct 1979 | A |
4219571 | Miyake | Aug 1980 | A |
4361697 | Dobberstein et al. | Nov 1982 | A |
4454290 | Dubois | Jun 1984 | A |
4590160 | Nishihashi et al. | May 1986 | A |
4599403 | Kumar | Jul 1986 | A |
4612942 | Dobberstein et al. | Sep 1986 | A |
4657638 | le Grand et al. | Apr 1987 | A |
4892938 | Giovanetto | Jan 1990 | A |
4917916 | Hirao et al. | Apr 1990 | A |
5112610 | Kienle | May 1992 | A |
5576042 | Fuisz | Nov 1996 | A |
5779805 | Morano | Jul 1998 | A |
5962678 | Payzant et al. | Oct 1999 | A |
5972120 | Kutowy et al. | Oct 1999 | A |
6031157 | Morita et al. | Feb 2000 | A |
6080561 | Morita et al. | Jun 2000 | A |
6204377 | Nishimoto et al. | Mar 2001 | B1 |
6228996 | Zhou et al. | May 2001 | B1 |
6706304 | Ishida et al. | Mar 2004 | B1 |
7807206 | Magomet et al. | Oct 2010 | B2 |
7838044 | Abelyan et al. | Nov 2010 | B2 |
7862845 | Magomet et al. | Jan 2011 | B2 |
8257948 | Markosyan | Sep 2012 | B1 |
20020132320 | Wang et al. | Sep 2002 | A1 |
20030161876 | Hansson et al. | Aug 2003 | A1 |
20030232118 | Erchenfeld et al. | Dec 2003 | A1 |
20030236399 | Zheng et al. | Dec 2003 | A1 |
20060083838 | Jackson | Apr 2006 | A1 |
20060134292 | Abelyan et al. | Jun 2006 | A1 |
20060142555 | Jonnala et al. | Jun 2006 | A1 |
20070082102 | Magomet et al. | Apr 2007 | A1 |
20070082103 | Magomet et al. | Apr 2007 | A1 |
20070116800 | Prakash | May 2007 | A1 |
20070116819 | Prakash | May 2007 | A1 |
20070116820 | Prakash | May 2007 | A1 |
20070116821 | Prakash | May 2007 | A1 |
20070116822 | Prakash | May 2007 | A1 |
20070116823 | Prakash | May 2007 | A1 |
20070116824 | Prakash | May 2007 | A1 |
20070116825 | Prakash | May 2007 | A1 |
20070116826 | Prakash | May 2007 | A1 |
20070116827 | Prakash | May 2007 | A1 |
20070116828 | Prakash | May 2007 | A1 |
20070116829 | Prakash | May 2007 | A1 |
20070116830 | Prakash | May 2007 | A1 |
20070116831 | Prakash | May 2007 | A1 |
20070116832 | Prakash | May 2007 | A1 |
20070116833 | Prakash | May 2007 | A1 |
20070116834 | Prakash | May 2007 | A1 |
20070116835 | Prakash | May 2007 | A1 |
20070116836 | Prakash | May 2007 | A1 |
20070116837 | Prakash | May 2007 | A1 |
20070116838 | Prakash | May 2007 | A1 |
20070116839 | Prakash | May 2007 | A1 |
20070116840 | Prakash | May 2007 | A1 |
20070116841 | Prakash | May 2007 | A1 |
20070128311 | Prakash | Jun 2007 | A1 |
20070134390 | Prakash | Jun 2007 | A1 |
20070134391 | Prakash | Jun 2007 | A1 |
20070224321 | Prakash | Sep 2007 | A1 |
20070292582 | Prakash | Dec 2007 | A1 |
20080064063 | Brandle et al. | Mar 2008 | A1 |
20080102497 | Wong et al. | May 2008 | A1 |
20080107775 | Prakash | May 2008 | A1 |
20080107776 | Prakash | May 2008 | A1 |
20080107787 | Prakash | May 2008 | A1 |
20080108710 | Prakash | May 2008 | A1 |
20080111269 | Politi et al. | May 2008 | A1 |
20080226797 | Lee et al. | Sep 2008 | A1 |
20080292764 | Prakash | Nov 2008 | A1 |
20080292765 | Prakash | Nov 2008 | A1 |
20080292775 | Prakash et al. | Nov 2008 | A1 |
20080300402 | Yang et al. | Dec 2008 | A1 |
20090017185 | Catani | Jan 2009 | A1 |
20090053378 | Prakash | Feb 2009 | A1 |
20090074935 | Lee | Mar 2009 | A1 |
20090079935 | Harris et al. | Mar 2009 | A1 |
20090142817 | Norman et al. | Jun 2009 | A1 |
20090226590 | Fouache et al. | Sep 2009 | A1 |
20100055752 | Kumar | Mar 2010 | A1 |
20100056472 | Duan et al. | Mar 2010 | A1 |
20100057024 | Bernard | Mar 2010 | A1 |
20100099857 | Evans | Apr 2010 | A1 |
20100112159 | Abelyan et al. | May 2010 | A1 |
20100120710 | Watanabe et al. | May 2010 | A1 |
20100137569 | Prakash et al. | Jun 2010 | A1 |
20100189861 | Abelyan et al. | Jul 2010 | A1 |
20100227034 | Purkayastha et al. | Sep 2010 | A1 |
20100255171 | Purkayastha et al. | Oct 2010 | A1 |
20100278993 | Prakash et al. | Nov 2010 | A1 |
20100316782 | Shi et al. | Dec 2010 | A1 |
20110030457 | Valery et al. | Feb 2011 | A1 |
20110033525 | Liu | Feb 2011 | A1 |
20110092684 | Abelyan et al. | Apr 2011 | A1 |
20110104353 | Lee | May 2011 | A1 |
20110111115 | Shi et al. | May 2011 | A1 |
20110124587 | Jackson et al. | May 2011 | A1 |
20110160311 | Prakash et al. | Jun 2011 | A1 |
20110189360 | Yoo | Aug 2011 | A1 |
20110195169 | Markosyan et al. | Aug 2011 | A1 |
20120164678 | Stephanopoulos et al. | Jun 2012 | A1 |
20120214752 | Markosyan | Aug 2012 | A1 |
Number | Date | Country |
---|---|---|
210701736 | Jul 2008 | BR |
1049666 | Mar 1991 | CN |
1100727 | Mar 1995 | CN |
1112565 | Nov 1995 | CN |
1192447 | Sep 1998 | CN |
1238341 | Dec 1999 | CN |
1349997 | May 2002 | CN |
101200480 | Jun 2008 | CN |
101591365 | Dec 2011 | CN |
2486806 | Aug 2012 | EP |
52005800 | Jan 1977 | JP |
52083731 | Jul 1977 | JP |
52100500 | Aug 1977 | JP |
52136200 | Nov 1977 | JP |
54030199 | Mar 1979 | JP |
54132599 | Oct 1979 | JP |
55039731 | Mar 1980 | JP |
55081567 | Jun 1980 | JP |
55092400 | Jul 1980 | JP |
65120770 | Sep 1980 | JP |
65138372 | Oct 1980 | JP |
55162953 | Dec 1980 | JP |
65159770 | Dec 1980 | JP |
56099768 | Aug 1981 | JP |
56109568 | Aug 1981 | JP |
56121453 | Sep 1981 | JP |
56121454 | Sep 1981 | JP |
56121455 | Sep 1981 | JP |
56160962 | Dec 1981 | JP |
57002656 | Jan 1982 | JP |
57005663 | Jan 1982 | JP |
57046998 | Mar 1982 | JP |
57075992 | May 1982 | JP |
57086264 | May 1982 | JP |
58020170 | Feb 1983 | JP |
58028246 | Feb 1983 | JP |
58028247 | Feb 1983 | JP |
58212759 | Dec 1983 | JP |
58212760 | Dec 1983 | JP |
59045848 | Mar 1984 | JP |
62166861 | Jul 1987 | JP |
63173531 | Jul 1988 | JP |
H0195739 | Apr 1989 | JP |
1131191 | May 1989 | JP |
3262458 | Nov 1991 | JP |
6007108 | Jan 1994 | JP |
6192283 | Jul 1994 | JP |
7143860 | Jun 1995 | JP |
7177862 | Jul 1995 | JP |
8000214 | Jan 1996 | JP |
9107913 | Apr 1997 | JP |
2000236842 | Sep 2000 | JP |
2002262822 | Sep 2002 | JP |
2004344071 | Dec 2004 | JP |
2010516764 | May 2010 | JP |
20070067199 | Jun 2007 | KR |
20080071605 | Aug 2008 | KR |
20090021386 | Mar 2009 | KR |
2111969 | May 1998 | RU |
2123267 | Dec 1998 | RU |
2156083 | Sep 2000 | RU |
2167544 | May 2001 | RU |
2198548 | Feb 2003 | RU |
2005089483 | Sep 2005 | WO |
2006072878 | Jul 2006 | WO |
2006072879 | Jul 2006 | WO |
2008091547 | Jul 2008 | WO |
WO-2008112957 | Sep 2008 | WO |
2009108680 | Sep 2009 | WO |
2010118218 | Oct 2010 | WO |
2011059954 | May 2011 | WO |
2011153378 | Dec 2011 | WO |
2012082493 | Jun 2012 | WO |
2012082677 | Jun 2012 | WO |
2013022989 | Feb 2013 | WO |
2013036366 | Mar 2013 | WO |
Entry |
---|
JECFA “Steviol Glycosides” FAO JECFA Monographs 5 (2008) pp. 1-4. |
Emperor's Herbologist “Stevioside Comparison” pp. 1-5 Jan. 22, 2010 http://emperorsherbologist.com/steviacompare.php (Year: 2010). |
A-Glucosyltransferase Treated Stevia, Japan's Specifications and Standards for Food Additives, VIII edition, 2009, p. 257. |
Ahmed, et al., “Use of p-Bromophenacyl Bromide to Enhance Ultraviolet Detection of Water-Soluble Organic Acids (Steviolbioside and Rebaudioside B) in High-Performance Liquid Chromatographic Analysis”, Journal of Chromatography, vol. 192, 1980, 387-393. |
Chang, S. S. et al., “Stability Studies of Stevioside and Rebaudioside A in Carbonated Beverages”, Journal of Agricultural and Food Chemistry, vol. 31, 1983, 409-412. |
Chen, et al., “Enrichment and separation of rebaudioside A from stevia glycosides by a novel adsorbent with pyridyl group”, Science in China, vol. 42, No. 3, 1999 , 277-282. |
Chen, et al., “Selectivity of polymer adsorbent in adsorptive separations of stevia diterpene glycisides”, Science in China, vol. 41, No. 4, 1998 , 436-441. |
Chen, et al., “Studies on the adsorptive selectivity of the polar resin with carbonyl group on rebaudioside A”, Acta Polymeric Scnica, No. 4, 1999 , 398-403. |
Crammer, et al., “Sweet glycosides from the Stevia plant”, Chemistry in Britain, Oct. 1986, 915-916, 918. |
Darise et al., “Enzymic Transglucosylation of Rubusoside and the Structure-Sweetness Relationship of Steviol Bisglycosides,” Agric. Biol. Chem. vol. 48(10), 1984, 2483-2488. |
Dubois et al., “Diterpenoid Sweeteners. Synthesis and Sensory Evaluation of Stevioside Analogues with Improved Organoleptic Properties,” J. Med. Chem. vol. 28, (1985) 93-98. |
Fuh, “Purification of steviosides by membrane and ion exchange process”, Journal of Food Science, vol. 55, No. 5, 1990, 1454-1457. |
Fukunaga et al., “Enzymic Transglucosylation Products of Stevioside: Separation and Sweetness-evaluation,” Agric. Biol. Chem. vol. 53(6) (1989) 1603-1607. |
Fullas et al., “Separation of natural product sweetening agents using overpressured layer chromatography,” Journal of Chromatography, vol. 464 (1989) 213-219. |
Hale, et al., “Amylase of Bacillus Macerans”, Cereal Chemistry, vol. 28, No. 1, Jan. 1951, 49-58. |
Hartel, Richard “Crystallization in Foods” Handbook of Industrial Crystallization Elsevier 2002, pp. 287 and 293-296. |
International Search Report and Written Opinion of PCT/US20101055960, pp. 1-11, dated Jan. 2011. |
International Search Report and Written Opinion of PCT/US2011/036063, dated Aug. 5, 2011, pp. 1-7. |
International Search Report and Written Opinion of PCT/US2011/047498, dated Dec. 22, 2011, pp. 1-8. |
International Search Report and Written Opinion of PCT/US2011/047499, dated Dec. 22, 2011, pp. 1-8. |
International Search Report and Written Opinion of PCT/US2011/064343, pp. 1-17, dated Jan. 2, 2013. |
International Search Report and Written Opinion of PCT/US20111028028, pp. 1-8, dated May 2011. |
International Search Report and Written Opinion of PCT/US20111033734, pp. 1-8, dated Jul. 2011. |
International Search Report and Written Opinion of PCT/US20111033737, pp. 1-8, dated Jul. 2011. |
International Search Report and Written Opinion of PCT/US20111033912, pp. 1-6, dated Jul. 2011. |
International Search Report and Written Opinion of PCT/US20111035173, pp. 1-7, dated Aug. 2011 |
International Search Report and Written Opinion of PCT/US2012/024585, pp. 1-8, dated Jun. 2012. |
International Search Report and Written Opinion of PCT/US2012/024722, pp. 1-8, dated May 2012. |
International Search Report and Written Opinion of PCT/US2012/030210, pp. 1-10, dated Jul. 2012. |
International Search Report and Written Opinion of PCT/US2012/043294, pp. 1-7 , dated Sep. 2012. |
International Search Report and Written Opinion of PCT/US2012/051163, pp. 1-9, dated Oct. 2012. |
International Search Report and Written Opinion of PCT/US2012/052659, pp. 1-9, dated Nov. 2012. |
International Search Report and Written Opinion of PCT/US2012/052665, pp. 1-3, dated Nov. 2012. |
International Search Report and Written Opinion of PCT/US20131030439 pp. 1-10, dated May 2013. |
Jaitak, et al., “An Efficient Microwave-assisted Extraction Process of Stevioside and Rebaudioside-A from Stevia Rebaudiana (Bertoni)”, Phytochem. Anal. vol. 20, 2009 , 240-245. |
Kennelly, “Sweet and non-sweet constituents of Stevia rebaudiana”, Stevia: The genus Stevia, Taylor & Francis, 2002, 68-85. |
Kinghorn, “Overview”, Stevia: The genus Stevia, Taylor & Francis, 2002, 1-17. |
Kitahata, S. et al., “Production of Rubusoside Derivatives by Transgalactosylation of Various b-Galactosidases”, Agric. Biol. Chem., vol. 53, No. 11 1989 , 2923-2928. |
Kobayashi, et al., “Dulcoside A and B, New diterpene glycosides from Stevia Rebaudiana”, Phytochemistry, vol. 16, 1977 , 1405-1408. |
Kochikyan, et al., “Combined Enzymatic Modification of Stevioside and Rebaudioside A”, Applied Biochemistry and Microbiology, vol. 42, No. 1, 2006, 31-37. |
Kohda, et al., “New sweet diterpene glucosides from Stevia Rebaudiana”, Phytochemistry, vol. 15, 1976 , 981-983. |
Kovylyaeva, et al., “Glycosides from Stevia rebaudiana”, Chemistry of Natural Compounds, vol. 43, No. 1, 2007 , 81-85. |
Liu, et al., “Study of stevioside preparation by membrane separation process”, Desalination, vol. 83, 1991 , 375-382. |
Lobov, S. V. et al., “Enzymic Production of Sweet Stevioside Derivatives: Transglucosylation of Glucosidases”, Agric. Biol. Chem., vol. 55, No. 12, 1991 , 2959-2965. |
Montovaneli, et al., “The effect of temperature and flow rate on the clarification of the aqueous Stevia-extract in fixed-bed column with zeolites”, Brazilian Journal of Chemical Engineering, vol. 21, No. 3, 2004, 449-458. |
Moraes, et al., “Clarification of Stevia rebaudiana (Bert.) Bertoni extract adsorption in modified zeolites”, Acta Scientiarum, vol. 23, No. 6, 2001 , 1375-1380. |
Ohta et al., “Characterization of Novel Steviol Glycosides from Leaves of Stevia rebaudiana Morita,” J. Appl. Glycosi., vol. 57, 199-209, 2010. |
Ohtani et al. “Chapter 7. Methods to improve the taste of the sweet principles of Stevia rebaudiana.” The Genus Stevia, edited by A. Douglas Kinghorn, CRC Press 2001, Taylor and Francis, London and New York, pp. 138-159. |
Phillips, K. C. , “Stevia: steps in developing a new sweetener”, In T.H. Grenby, Editor, Developments in Sweeteners-3, Elsevier 1987 , 1-43. |
Pol, et al., “Comparison of two different solvents employed for pressurised fluid extraction of stevioside from Stevia rebaudiana: methanol versus water”, Anal Bioanal Chem vol. 388 2007 , 1847-1857. |
Prakash et al., “Development of rebiana, a natural, non-caloric sweetener,” Jul. 1, 2008, Food and Chemical Toxology, vol. 46, Is. 7, Sup. 1, p. S75-S82. |
Richman et al., “Fuctional genomics uncovers three glucosyltransferases involved in the synthesis of the major sweet glucosides of Stevia rebaudiana,” The Plant Journal, vol. 41 (2005) 56-67. |
Sakamoto et al., “Application of 13C Nmr Spectroscopy to Chemistry of Natural Glycosides: Rebaudioside-C, a New Sweet Diterpene Glycoside of Stevia Rebaudiana”, Chem. Pharm. Bull., vol. 25, 1977, 844-846. |
Shi, et al., “Synthesis of bifunctional polymeric adsorbent and its application in purification of Stevia glycosides”, Reactive & Functional Polymers, vol. 50, 2002, 107-116. |
Shibata et al., “Glucosylation of Steviol and Steviol-Glucosides in Extracts from Stevia rebaudiana Bertoni,” Plant Physiol. vol. 95, (1991) 152-156. |
Starratt, et al., “Rebaudioside F, a diterpene glycoside from Stevia Rebaudiana”, Phytochemistry, vol. 59, 2002 , 367-370. |
Sweet Green Fields, LLC, “Notice to the U.S. Food and Drug Administration (FDA) that the use of Rebiana (Rebaudiosid A) derived from Stevia rebaudiana, as a Food Ingredient is Generally Recognized as Safe (GRAS),” Jan. 15, 2009, http://www.accessdataida.gov/scriptsficn/gras_notices/grn000282.pdf (obtained from the WEB on May 8, 2012) entire document esp. p. 22, Table 1, pp. 1-97. |
Tanaka, O. , “Improvement of taste of natural sweeteners”, Pure & Appl. Chem., vol. 69, No. 4, 1997, 675-683. |
Teo, et al., “Validation of green-solvent extraction combined with chromatographic chemical fingerprint to evaluate quality of Stevia rebaudiana Bertoni”, J. Sep. Sci, vol. 32, 2009, 613-622. |
United Nations' Food and Agriculture Organization/Joint Expert Committee on Food Additives (2010) Steviol Glycosides,Compendium of Food Additive Specifications, FAO JECFA Monographs 10, 17-21. |
Van der Maarel et al., “Properties and applications of starch-converting enzymes of the a-amylase family,” Journal of Biotechnology, vol. 94 (2002) 137-155. |
Vasquez, Stimulation of the Gerbil's Gustatory Receptors by Some Potently Sweet Terpenoids, J. Agric. Food Chem., vol. 41, 1305-1310, 1993. |
Yamamoto, K. et al., “Effective Production of Glycosyl-steviosides by a-1,6 Transglucosylation of Dextrin Dextranase”, Biosci_Biotech. Biochem. vol. 58, No. 9, 1994 , 1657-1661. |
Yoda, et al., “Supercritical fluid extraction from Stevia rebaudiana Bertoni using CO2 and CO2+ water: extraction kinetics and identification of extracted components”, Journal of Food Engineering, vol. 57, 2003 , 125-134. |
Zell, et al., “Investigation of Polymorphism in Aspartame and Neotame Using Solid-State NMR Spectroscopy”, Tetrahedron, vol. 56, 2000, 6603-6616. |
Zhang, et al., “Membrane-based separation scheme for processing sweetener from Stevia leaves”, Food Research International, vol. 33, 2000 , 617-620. |
Hancock B C et al, “What is the true solubility advantage for amorphous pharmaceuticals?”, Pharmaceutical Research, Springer New York LLC, US, (Apr. 1, 2000), vol. 17, No. 4, doi:10.1023/A:1007516718048, ISSN 0724-8741, pp. 397-404, XP009086748 [A] 1-11. |
Kikuchi K et al, “Readily soluble sweetening agent prepn.—by processing mixt. of stevioside, prods. from Stevia Rebaudiana Bertonis and water in vacuum drying facility to shape in granular form”, WPI / Thomson,, (Apr. 13, 1989), vol. 1989, No. 21, XP002714589 [A] 1-11. |
Number | Date | Country | |
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20160360775 A1 | Dec 2016 | US |
Number | Date | Country | |
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61441443 | Feb 2011 | US |
Number | Date | Country | |
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Parent | 13984315 | US | |
Child | 15250550 | US |