JP5196702B2 - スクラロース精製のための抽出法 - Google Patents
スクラロース精製のための抽出法 Download PDFInfo
- Publication number
- JP5196702B2 JP5196702B2 JP2003574668A JP2003574668A JP5196702B2 JP 5196702 B2 JP5196702 B2 JP 5196702B2 JP 2003574668 A JP2003574668 A JP 2003574668A JP 2003574668 A JP2003574668 A JP 2003574668A JP 5196702 B2 JP5196702 B2 JP 5196702B2
- Authority
- JP
- Japan
- Prior art keywords
- sucralose
- solvent
- impurities
- extraction
- ethyl acetate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
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- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 title claims description 176
- 239000004376 Sucralose Substances 0.000 title claims description 174
- 235000019408 sucralose Nutrition 0.000 title claims description 173
- 238000000605 extraction Methods 0.000 title claims description 85
- 238000000746 purification Methods 0.000 title description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical group CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 179
- 239000002904 solvent Substances 0.000 claims description 161
- 239000012535 impurity Substances 0.000 claims description 100
- 238000000034 method Methods 0.000 claims description 81
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 41
- 239000007864 aqueous solution Substances 0.000 claims description 30
- 239000007788 liquid Substances 0.000 claims description 17
- 238000012546 transfer Methods 0.000 claims description 14
- 239000000284 extract Substances 0.000 claims description 8
- 230000014759 maintenance of location Effects 0.000 claims description 6
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 14
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- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
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- 150000001875 compounds Chemical class 0.000 description 11
- 150000003445 sucroses Chemical class 0.000 description 10
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- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
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- NUFKRGBSZPCGQB-FLBSXDLDSA-N (3s)-3-amino-4-oxo-4-[[(2r)-1-oxo-1-[(2,2,4,4-tetramethylthietan-3-yl)amino]propan-2-yl]amino]butanoic acid;pentahydrate Chemical compound O.O.O.O.O.OC(=O)C[C@H](N)C(=O)N[C@H](C)C(=O)NC1C(C)(C)SC1(C)C.OC(=O)C[C@H](N)C(=O)N[C@H](C)C(=O)NC1C(C)(C)SC1(C)C NUFKRGBSZPCGQB-FLBSXDLDSA-N 0.000 description 2
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- FFWSICBKRCICMR-UHFFFAOYSA-N 5-methyl-2-hexanone Chemical compound CC(C)CCC(C)=O FFWSICBKRCICMR-UHFFFAOYSA-N 0.000 description 2
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Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H5/00—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium
- C07H5/02—Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
- C07H1/06—Separation; Purification
Description
本発明は、スクラロース(sucralose)精製のための新規抽出法に関する。本発明は、本発明の方法によって製造されたスクラロース調製物を含む組成物にも関する。
スクロースの数百倍の甘味度(sweetness intensity)を有する甘味料であるスクラロース(4,1’,6’−トリクロロ−4,1’,6’−トリデオキシガラクトスクロース)は、スクロースから、その4位、1’位、及び6位のヒドロキシル基を塩素と置換することによって誘導される。特定のヒドロキシル基と塩素原子とを選択的に置換し、一方で反応性の高い第一級ヒドロキシル基を含む他のヒドロキシル基を保存させる必要があることに起因して、スクラロースの合成は、技術的に興味深い。この合成に対する多数のアプローチが開発されている。例えば、米国特許第4,362,869号;同第4,826,962号;同第4,980,463号;及び同第5,141,860号(これらは、本明細書中に、参考として明白に援用される)を参照のこと。しかしながら、そのようなアプローチは、代表的に、スクラロースに加えて、種々のレベルの他の塩素化糖化合物を含む生成物を提供する。多くの努力がスクラロースの合成に向けられてきたが、これまで、混入物の複合混合物から高純度の形態のスクラロースを単離することは、比較的注目を受けていなかった。初期に報告された仕事は、代表的に、合成混合物からの直接的なスクラロースの結晶化に関連し、これは高い不純物レベルの物質を生じるプロセスであった。スクラロースは、しばしば、合成混合物からシリカゲルクロマトグラフィーによって精製される。例えば、米国特許第5,128,248号(これは、本明細書中に参考として明白に援用される)を参照のこと。この手順は、そのシリカゲルの使用に起因して、高純度スクラロースの大容量での商業的生産に適さない。さらに、スクラロースからハロゲン化糖不純物を除去するための他の試みには、比較的注目が集まらなかった。これらの不純物の効率的な除去は、重要である。なぜなら、非常に低い濃度でさえ、これらは、スクラロースの甘味、味、及びフレーバー修飾特性に悪影響を与え得るからである。
本発明の1つの実施形態は、第一の溶媒中にスクラロースと不純物を含む組成物から不純物を除去するための方法に関し、この方法は、第二の少なくとも部分的に不混和性の溶媒を用いて、組成物の液体抽出を実施し、この第二の溶媒中への不純物の除去をもたらす工程、ならびに第三の少なくとも部分的に不混和性の溶媒を用いてこの組成物の第二の抽出を実施し、この第三の溶媒へのスクラロースの移動及び第一の溶媒中の不純物の保持をもたらす工程を含む。
本明細書中に記載される特定の方法論、プロトコル、pH及び試薬などが変化し得るので、本発明が、これらに限定されないことが理解される。本明細書中で用いられる用語が特定の実施形態のみを記載する目的で用いられ、そして本発明の範囲を限定することを意図しないことも理解されるべきである。本明細書中及び添付の特許請求の範囲において用いられる場合、単数形「a」、「an」及び「the」は、文脈が明確にそうでないことを示さない限り、複数形の参照を含む。従って、例えば、「溶媒(a solvent)」に対する参照は、1つ以上の溶媒に対する参照であり、そして当業者に公知のその等価物などを含む。
芳香族:本明細書中で用いられる場合、共鳴共役二重結合構造を有する環状化合物(例えば、ベンゼン、トルエン、またはキシレンなど)を含む溶媒を含む。
図1を参照して、本発明の液体−液体抽出法の1つの実施形態を示す。第一に、スクラロース水溶液100を液体−液体抽出容器(extractor vessel)150へと充填し得、そして約1:3.5の比率(酢酸エチル:水溶液)の比の酢酸エチルの容量を用いて抽出し得る。不純物及び少量の残存スクラロースを、より極性の弱い酢酸エチルの流れ200を用いて除去し得、一方で、大部分のスクラロースは、液体−液体抽出容器150中の水溶液中に残存する。必要に応じて、任意の水性バックウォッシャー250中で、酢酸エチルの流れ200を水でバックウォッシュして、酢酸エチルの流れ200から任意の残存スクラロースを回収し得る。次いで、酢酸エチル溶媒の流れ400を用いて、より極性の弱い不純物をこの系からパージし得る。次に、液体−液体抽出容器150中で、任意の残存する水性バックウォッシュ300を第一の水溶液と合わせ得る。例えば、約3:1〜約4:1の酢酸エチル:水の比の酢酸エチルを用いて、スクラロースを抽出し得る。大部分のスクラロースが、より極性の弱い酢酸エチルの流れ500に移動し、そしてより極性の強い不純物が、水相中に残存する。次いで、酢酸エチル溶媒の流れ500を、蒸留器350に充填して、この系に存在する残存する水600を除去し得る。酢酸エチルの流れ700中の精製したスクラロースを、結晶器450に供給し得、この結晶器から精製した結晶化スクラロースを回収し得、そして任意の残存する不純物を酢酸エチル溶媒800を用いて除去し得る。
図2は、液体−液体抽出法の別の実施形態を記載する。第一に、不純物を有するスクラロース水溶液1000を、第一のKarrカラム1500に充填し得る。ここで、それは、水飽和酢酸エチル2000と、0.35:1の比(酢酸エチル:水)で合わせられ得る。第一のKarrカラム1500から以下の2つの別個の相を得ることが出来る:スクラロースを含有する水相、ならびに残存スクラロースと不純物を含有する酢酸エチル相。酢酸エチルの流れ3000を、第二のKarrカラム2500に導入し得る。ここで、それを、水4000と、0.7:1の比(酢酸エチル:水)で合わせ、残存スクラロースを回収し得る。再び、第二のKarrカラム2500中に以下の2つの別個の相が形成される:回収された残渣スクラロースを含有する水相及び酢酸エチル相。第二のKarrカラム2500からの水の流れ5000が、第一のKarrカラム1500からの水相と合わせられ得る。次いで、酢酸エチル溶媒の流れ9000を用いて、より極性の弱い不純物を、この系からパージする。合わせた水の流れ6000は、Scheibelカラム3500に導入され得、そして酢酸エチル7000と約3:1の比(酢酸エチル:水)で合わせられ得る。水の流れ6000からのスクラロースは、より極性の弱い酢酸エチル7000に移動する。酢酸エチルストリーム8000中の精製されたスクラロースを、結晶器4500に供給し得、この結晶器から、精製したスクラロースを回収し得る。
さらなる説明なしで、当業者は、前述の記載を用いて、本発明を完全に利用することが出来ると考えられる。以下の実施例は単なる例示であり、いかなる様式においても、残りの開示部分を限定するものではない。
6−O−アセチル前駆体のアルカリ脱アシル化及び引き続く中和によって得られたスクラロース水溶液を、42インチの内径及び50フィートの攪拌時高さ(agitated height)を有するKarrカラムに導入した。このカラムに、水飽和酢酸エチルを0.35:1の比率(0.35部の酢酸エチル:1部のスクラロース水溶液)で導入した。このカラムから、2つの相を得た。酢酸エチル相を、42インチの内経及び58フィートの攪拌時高さを有するKarrカラムに導入した。水相:酢酸エチル相の比が0.7:1.0となるように、水もこのカラムに導入した。このバックウォッシュから得られた水溶液を、元の供給液と合わせ、そして第一の抽出に供給した。第一の酢酸エチル抽出由来の水相を、56インチの内経及び33フィートの攪拌時の高さを有するScheibelカラム(Koch、Inc.、Kansas City、MO)へと導入した。このカラムは、24段階の分離セクションを含んでいた。3:1の比率(酢酸エチル:水)の酢酸エチルも、このカラムに導入した。酢酸エチル相を除去し、そして結晶化によってこの酢酸エチル相からスクラロースを回収した。表3は、第一のKarrカラムから回収した酢酸エチル相中に存在する不純物のデータを提供する。表4は、Scheibelカラムにおける抽出後の水相中に残存する不純物のデータを提供する。
Claims (11)
- スクラロースと不純物を含む組成物から不純物を除去するための方法であって、該方法は、以下の工程を含み:
(a)酢酸エチルである第二の少なくとも部分的に不混和性の溶媒を用いて、水を含む第一の溶媒中に、スクラロースと不純物を含む該組成物の、第一の液体抽出を実施し、該第二の溶媒への該不純物の除去をもたらす工程;ならびに
(b)酢酸エチルである第三の少なくとも部分的に不混和性の溶媒を用いて、工程(a)で得られた、第一の溶媒中にスクラロースと不純物を含む該組成物の、第二の液体抽出を実施し、該第三の溶媒へのスクラロースの移動及び該第一の溶媒中の該不純物の保持をもたらす工程;
前記工程(a)が、前記第二の溶媒への前記不純物の少なくとも一部の除去をもたらし、
前記工程(b)が、前記第三の溶媒への前記スクラロースの大部分の移動及び前記第一の溶媒中の前記不純物の相当部分の保持をもたらす方法。 - 前記スクラロースを回収する工程をさらに含む、請求項1に記載の方法。
- 前記回収工程が、前記スクラロースを結晶化する工程を含む、請求項2に記載の方法。
- 前記第一の溶媒が水である、請求項1に記載の方法。
- 前記第二の溶媒:前記第一の溶媒の比率が、1:2〜1:5である、請求項1に記載の方法。
- 前記比率が1:3〜1:4である、請求項5に記載の方法。
- 前記工程(a)及び(b)が、バッチ抽出、連続抽出、及び連続向流抽出からなる群より選択される抽出法を含む、請求項1に記載の方法。
- 請求項1に記載の方法であって、該方法は、以下の工程をさらに含み:
(c)工程(a)において、前記第一の液体抽出の後に、水を用いて、工程(a)における第一の液体抽出により不純物を含むこととなった第二の溶媒の抽出を実施し、水溶液への、該第二の溶媒中に存在するスクラロースの移動をもたらす工程;ならびに
(d)工程(b)を実施する前に、工程(c)において得られた水溶液と、工程(a)において回収された水溶液とを、合わせる工程;
前記工程(c)が、前記水溶液への前記第二の溶媒中に存在するスクラロースの相当部分の移動をもたらすものである方法。 - 前記スクラロースを回収する工程をさらに含む、請求項8に記載の方法。
- 前記回収工程が、前記スクラロースを結晶化することを含む、請求項9に記載の方法。
- 前記工程(c)が、バッチ抽出、連続抽出、及び連続向流抽出からなる群より選択される抽出法を含む、請求項8に記載の方法。
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US10/092,715 | 2002-03-08 | ||
US10/092,715 US7049435B2 (en) | 2002-03-08 | 2002-03-08 | Extractive methods for purifying sucralose |
PCT/US2003/006627 WO2003076453A1 (en) | 2002-03-08 | 2003-03-06 | Extractive methods for purifying sucralose |
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EP (2) | EP1483278B1 (ja) |
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CA (1) | CA2481405A1 (ja) |
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Families Citing this family (44)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6890581B2 (en) * | 2002-04-05 | 2005-05-10 | Tate & Lyle Public Limited Company | Methods for buffer stabilized aqueous deacylation |
CA2558683A1 (en) * | 2004-03-05 | 2005-09-22 | Sunil Srivastava | High-intensity sweetener-polyol compositions |
US20080125584A1 (en) * | 2004-12-10 | 2008-05-29 | Rakesh Ratnam | Salts Assisted Selective Extraction Of 6-Acetyl- 4,1' , 6' Trichlorogalactosucrose And 4,1', 6' Trichlorogalactosucrosse From Aqueous Reaction Mixture |
US20060188629A1 (en) * | 2005-01-21 | 2006-08-24 | Greg Liesen | Method for the purification of sucralose |
CN102124017A (zh) * | 2005-06-01 | 2011-07-13 | V.B.医疗保险私人有限公司 | 利用溶剂萃取法纯化氯化蔗糖衍生物的方法 |
WO2007052302A2 (en) * | 2005-08-30 | 2007-05-10 | Pharmed Medicare Pvt. Ltd. | Removal of pyridine and pyridine analogs from reaction mass containing sucrose esters |
US9101160B2 (en) | 2005-11-23 | 2015-08-11 | The Coca-Cola Company | Condiments with high-potency sweetener |
US7741477B2 (en) * | 2006-01-10 | 2010-06-22 | Alembic Limited | Process for purification of sucralose |
US9012626B2 (en) * | 2006-06-19 | 2015-04-21 | The Coca-Cola Company | Rebaudioside a composition and method for purifying rebaudioside a |
US8791253B2 (en) * | 2006-06-19 | 2014-07-29 | The Coca-Cola Company | Rebaudioside A composition and method for purifying rebaudioside A |
JP2009542625A (ja) * | 2006-07-06 | 2009-12-03 | アレムビック・リミテッド | 高純度スクラロースの改良製造法 |
US8017168B2 (en) | 2006-11-02 | 2011-09-13 | The Coca-Cola Company | High-potency sweetener composition with rubisco protein, rubiscolin, rubiscolin derivatives, ace inhibitory peptides, and combinations thereof, and compositions sweetened therewith |
US8030481B2 (en) | 2007-05-21 | 2011-10-04 | The Coca-Cola Company | Stevioside polymorphic and amorphous forms, methods for their formulation, and uses |
US8436156B2 (en) * | 2008-01-04 | 2013-05-07 | Tate & Lyle Technology Limited | Method for the production of sucralose |
KR20100130219A (ko) * | 2008-03-20 | 2010-12-10 | 테이트 앤드 라일 테크놀러지 리미티드 | 3급 아미드 용매로부터 산을 제거하는 방법 |
US8436157B2 (en) * | 2008-03-26 | 2013-05-07 | Tate & Lyle Technology Limited | Method for the production of sucralose |
US20090299055A1 (en) * | 2008-04-03 | 2009-12-03 | Tate & Lyle Technology Limited | Purification of Sucralose Containing Feed Streams for Sucralose Crystallization |
AR071134A1 (es) * | 2008-04-03 | 2010-05-26 | Tate & Lyle Technology Ltd | Cristalizacion de sucralosa a partir de chorros que contienen sucralosa |
US20090259036A1 (en) * | 2008-04-03 | 2009-10-15 | Tate & Lyle Technology Limited | Extraction of less polar impurities from sucralose containing aqueous feed streams |
US8497367B2 (en) * | 2008-04-03 | 2013-07-30 | Tate & Lyle Technology Limited | Sucralose purification process |
WO2009137193A2 (en) * | 2008-04-03 | 2009-11-12 | Tate & Lyte Technology Ltd | Effect of carbohydrate concentration on sucralose extraction efficiency |
GB2468936B (en) | 2009-03-27 | 2011-09-07 | Mohamad Rami Radwan Jaber | Chlorination of sucrose-6-esters |
GB2469157B (en) | 2009-03-30 | 2011-07-06 | John Kerr | Process for removing dimethylamine during sucralose production |
GB2469158B (en) | 2009-03-31 | 2011-09-28 | Peter J Seaberg | Base-assisted formation of tin-sucrose adducts |
US8609805B2 (en) | 2009-04-15 | 2013-12-17 | Invista North America S.A R.L. | Copolyether glycol manufacturing process |
GB2474311B (en) * | 2009-10-12 | 2012-10-17 | Tate & Lyle Technology Ltd | Low temperature, single solvent process for the production of sucrose-6-ester |
GB2474310B (en) | 2009-10-12 | 2012-02-29 | Tate & Lyle Technology Ltd | Process for the production of sucrose-6-ester |
GB201110520D0 (en) | 2011-05-10 | 2011-08-03 | Tate & Lyle Technology Ltd | Extraction of carboxylic acids with tin compounds |
AU2012323934B2 (en) * | 2011-10-14 | 2017-06-29 | Lexington Pharmaceuticals Laboratories, Llc | Chlorination of carbohydrates and carbohydrate derivatives |
CN102391319B (zh) * | 2011-10-14 | 2015-01-07 | 山东三和维信生物科技有限公司 | 三氯蔗糖的结晶方法 |
CN102391320B (zh) * | 2011-12-23 | 2014-03-19 | 盐城捷康三氯蔗糖制造有限公司 | 溶剂热回流纯化三氯蔗糖的方法 |
US10227367B2 (en) | 2013-12-16 | 2019-03-12 | Tate & Lyle Technology Limited | Chlorination of sucrose-6-esters |
WO2016020635A1 (en) | 2014-08-08 | 2016-02-11 | Tate & Lyle Technology Limited | Chlorination of sucrose-6-esters |
CN104387427A (zh) * | 2014-10-30 | 2015-03-04 | 安徽金禾实业股份有限公司 | 一种三氯蔗糖的生产方法 |
GB2536480B (en) | 2015-03-17 | 2019-09-04 | Tate & Lyle Tech Ltd | DMF Distillation |
CN104861003A (zh) * | 2015-04-24 | 2015-08-26 | 吉安市新琪安科技有限公司 | 一种三氯蔗糖母液的处理方法 |
GB2551591B (en) * | 2016-06-23 | 2019-08-07 | Tate & Lyle Tech Ltd | Liquid-liquid extraction of DMF |
AR110314A1 (es) * | 2016-12-07 | 2019-03-20 | Monsanto Technology Llc | Procesos para la purificación, recuperación, y conversión de sales de clorofenol y preparación y recuperación de productos preparados a partir de las mismas |
CN106674292B (zh) * | 2016-12-09 | 2019-02-22 | 福建科宏生物工程股份有限公司 | 一种三氯蔗糖水结晶母液的提纯处理方法 |
CN108264527A (zh) * | 2018-01-15 | 2018-07-10 | 山东三和维信生物科技有限公司 | 一种提高三氯蔗糖纯度的方法 |
CN109315745A (zh) * | 2018-10-28 | 2019-02-12 | 四川泰之味食品有限公司 | 一种泡椒花生及其制备方法 |
CN111499672B (zh) * | 2019-01-30 | 2021-07-20 | 山东新和成精化科技有限公司 | 一种用于纯化三氯蔗糖的萃取方法 |
MX2023003704A (es) | 2020-09-30 | 2023-05-09 | Anhui Jinhe Ind Co Ltd | Método de purificación de sucralosa. |
MX2023005617A (es) * | 2020-11-13 | 2023-05-29 | Anhui Jinhe Ind Co Ltd | Metodo para purificar sucralosa. |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB2065646B (en) * | 1979-12-18 | 1983-10-05 | Tate & Lyle Ltd | Crystalline 4,1',6'-trichloro-4,1',6'-trideoxygalactosucrose |
ZA807578B (en) * | 1979-12-18 | 1981-11-25 | Tate & Lyle Patent Holdings | Crystalline 4,1',6'-trichloro-4,1',6'-trideoxy-galactosucrose |
EP0031651B1 (en) | 1979-12-20 | 1983-03-23 | TATE & LYLE PUBLIC LIMITED COMPANY | Process for the preparation of 4,1',6'-trichloro-4,1',6'-trideoxy-galactosucrose |
DE3165986D1 (en) * | 1980-07-08 | 1984-10-18 | Tate & Lyle Plc | Process for the preparation of 4, 1',6'-trichloro-4,1',6'-trideoxygalactosucrose (tgs) |
CA1183133A (en) | 1980-10-28 | 1985-02-26 | Tate & Lyle Public Limited Company | Sweet chlorine-substituted disaccharides |
GB8525871D0 (en) | 1985-10-21 | 1985-11-27 | Tate & Lyle Plc | Chemical compound |
GB8822673D0 (en) | 1988-09-27 | 1988-11-02 | Tate & Lyle Plc | Selective acylation of sugars |
GB2222827B (en) * | 1988-09-16 | 1992-08-19 | Tate & Lyle Plc | Chlorination of sugars |
GB8822674D0 (en) | 1988-09-27 | 1988-11-02 | Tate & Lyle Plc | Preparation of acylated sucrose derivatives |
NZ234143A (en) | 1989-06-28 | 1991-10-25 | Mcneil Ppc Inc | Aqueous pharmaceutical suspension formulation for administering substantially insoluble pharmaceutical agents |
US4980463A (en) | 1989-07-18 | 1990-12-25 | Noramco, Inc. | Sucrose-6-ester chlorination |
US5034551A (en) | 1990-04-23 | 1991-07-23 | Noramco, Inc. | Process for recovery of organotin esters from reaction mixtures containing the same and re-use of the recovered organotin compounds |
NZ240818A (en) | 1990-12-14 | 1993-08-26 | Mcneil Ppc Inc | Liquid sucralose concentrate compositions containing preservative, buffer and liquid |
US5272137A (en) | 1992-02-14 | 1993-12-21 | Mcneil-Pfc, Inc. | Aqueous pharmaceutical suspension for pharmaceutical actives |
US5397588A (en) | 1992-06-18 | 1995-03-14 | Mcneil-Ppc, Inc. | Reduced calorie fruit spreads |
US5270071A (en) | 1992-06-18 | 1993-12-14 | Mcneil-Ppc, Inc. | Reduced calorie fruit spreads |
US5354902A (en) | 1992-10-26 | 1994-10-11 | Mcneil-Ppc, Inc. | Stabilized sorbic acid or salt thereof |
CA2110313C (en) | 1992-12-01 | 2004-10-26 | Edward John Roche | Pharmaceutical compositions containing a guanidinothiazole compound and antacids |
US5530106A (en) * | 1993-03-12 | 1996-06-25 | Mcneil-Ppc, Inc. | Recovery of sucralose intermediates |
EP0620001A1 (en) | 1993-04-16 | 1994-10-19 | McNEIL-PPC, INC. | Aqueous pharmaceutical suspension and process for preparation thereof |
CA2128820A1 (en) | 1993-07-27 | 1995-01-28 | Walter G. Gowan, Jr. | Rapidly disintegrating pharmaceutical dosage form and process for preparation thereof |
US5674522A (en) | 1993-10-07 | 1997-10-07 | Mcneil-Ppc, Inc. | Beverage concentrate for drug delivery |
US5498709A (en) * | 1994-10-17 | 1996-03-12 | Mcneil-Ppc, Inc. | Production of sucralose without intermediate isolation of crystalline sucralose-6-ester |
US5593696A (en) | 1994-11-21 | 1997-01-14 | Mcneil-Ppc, Inc. | Stabilized composition of famotidine and sucralfate for treatment of gastrointestinal disorders |
WO1998035974A1 (en) * | 1997-02-13 | 1998-08-20 | Mcneil-Ppc Inc. | Chromatographic purification of chlorinated sucrose |
AU753587B2 (en) | 1997-11-14 | 2002-10-24 | Johnson & Johnson Consumer Companies, Inc. | Highly flavored dental floss |
EP1109461B1 (en) | 1998-07-07 | 2004-10-06 | McNEIL-PPC, INC. | Method of improving sweetness delivery of sucralose |
US6090401A (en) | 1999-03-31 | 2000-07-18 | Mcneil-Ppc, Inc. | Stable foam composition |
US6211246B1 (en) | 1999-06-10 | 2001-04-03 | Mcneil-Ppc, Inc. | Rapidly absorbed liquid compositions |
US6277409B1 (en) | 2000-02-11 | 2001-08-21 | Mcneil-Ppc, Inc. | Protective coating for tablet |
US6258381B1 (en) | 2000-02-11 | 2001-07-10 | Mcneil-Ppc, Inc. | Tablet and process for making the same |
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EP1483278B1 (en) | 2012-01-11 |
CN1318437C (zh) | 2007-05-30 |
RU2004129749A (ru) | 2005-04-20 |
KR20040099305A (ko) | 2004-11-26 |
EP2039699A3 (en) | 2010-11-17 |
US7049435B2 (en) | 2006-05-23 |
EP1483278A1 (en) | 2004-12-08 |
IL163662A0 (en) | 2005-12-18 |
AR038901A1 (es) | 2005-02-02 |
JP2005526075A (ja) | 2005-09-02 |
EP2039699A2 (en) | 2009-03-25 |
RU2326887C2 (ru) | 2008-06-20 |
KR101024882B1 (ko) | 2011-03-31 |
AU2003216515A1 (en) | 2003-09-22 |
WO2003076453A1 (en) | 2003-09-18 |
AU2003216515B2 (en) | 2008-07-10 |
ATE540962T1 (de) | 2012-01-15 |
BR0308261A (pt) | 2005-01-04 |
TW200408647A (en) | 2004-06-01 |
US20030171574A1 (en) | 2003-09-11 |
MXPA04009842A (es) | 2005-06-17 |
CA2481405A1 (en) | 2003-09-18 |
CN1646551A (zh) | 2005-07-27 |
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