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1. 发明授权

US5451671A Method of purifying 2',3'-dideoxynucleosides 失效
标题翻译： 2'，3'-双脱氧核苷的纯化方法
公开(公告)号：US5451671A
公开(公告)日：1995-09-19
申请号：US76964
申请日：1993-06-16
申请人： Hiroshi Shiragami , Masayuki Arai , Kunisuke Izawa , Yutaka Honda , Yasuhiro Tanaka , Toshihide Yukawa , Satoji Takahashi
发明人： Hiroshi Shiragami , Masayuki Arai , Kunisuke Izawa , Yutaka Honda , Yasuhiro Tanaka , Toshihide Yukawa , Satoji Takahashi
IPC分类号： C07H1/06 , C07H19/04 , C07H19/173
CPC分类号： C07H1/06 , C07H19/04
摘要： A crude 2',3'-dideoxynucleoside compound is purified by extracting with an organic solvent, or crystallizing, the 2',3'-dideoxynucleoside compound from a basic aqueous solution having a pH of not less than 12 containing the same. In another embodiment of purification a basic aqueous solution having a pH of not less than 11 of a crude 2',3'-dideoxynucleoside derivative is brought into contact with a nonpolar porous resin, whereby the derivative is adsorbed on the resin, and then the thus adsorbed derivative is desorbed with an aqueous alcoholic solution.2',3'-Dideoxynucleoside compounds which have utility as anti-AIDS drugs or anti-virus drugs can be isolated and purified in high purity and in high yield from their crude products containing impurities.
摘要翻译：粗制的2'，3'-二脱氧核苷化合物通过用有机溶剂萃取，或从含有其的pH不低于12的碱性水溶液中结晶2'，3'-二脱氧核苷化合物而纯化。在纯化的另一个实施方案中，使粗制的2'，3'-二脱氧核苷衍生物的pH不低于11的碱性水溶液与非极性多孔树脂接触，由此将衍生物吸附在树脂上，然后将因此吸附的衍生物用含水醇溶液解吸。具有作为抗艾滋病药物或抗病毒药物的作用的2'，3'-二脱氧核苷化合物可以从其含有杂质的粗产物中以高纯度和高产率分离和纯化。

2. 发明授权

US5399554A Readily soluble 2',3'-dideoxyinosine compositions 失效
标题翻译：易溶2'，3'-二脱氧肌苷组合物
公开(公告)号：US5399554A
公开(公告)日：1995-03-21
申请号：US5421
申请日：1993-01-19
申请人： Kimiyasu Sakamoto , Toshihide Yukawa
发明人： Kimiyasu Sakamoto , Toshihide Yukawa
IPC分类号： A61K31/195 , A61K31/70 , A61K47/18 , C07D473/18 , A61K31/52
CPC分类号： A61K31/70 , A61K47/183 , Y10S514/964
摘要： A readily soluble 2',3'-dideoxyinosine composition is prepared by combining 80 to 1 parts by weight of a basic amino acid and 20 to 99 parts by weight of 2',3'-dideoxyinosine. The greater solution velocity of this composition improves solubility for therapeutic uses.
摘要翻译：通过将80至1重量份的碱性氨基酸和20至99重量份的2'，3'-二脱氧肌苷组合，制备易溶的2'，3'-二脱氧肌苷组合物。该组合物的较大的溶液速度提高了治疗用途的溶解性。

3. 发明授权

US4789758A Process for the production of an N-protected-L-.alpha.-aspartyl-L-phenylalanine 失效
标题翻译：用于生产N-保护的-L-α-天门冬酰基-L-苯丙氨酸的方法
公开(公告)号：US4789758A
公开(公告)日：1988-12-06
申请号：US106801
申请日：1987-10-13
申请人： Tadashi Takemoto , Toshihide Yukawa , Kunio Hisamitsu
发明人： Tadashi Takemoto , Toshihide Yukawa , Kunio Hisamitsu
IPC分类号： C07K5/075 , C07C99/00
CPC分类号： C07K5/0613 , Y10S530/801
摘要： A process is described for the synthesis of N-protected-L-.alpha.-aspartyl-L-phenylalanine by both (a) the rection of an N-protected-L-aspartic anhydride and a R.sub.1 -L-phenylalanine, and (b) the reaction of an N-protected-L-aspartic anhydride and L-phenylalanine in an aqueous medium in the presence of R.sub.2, where R.sub.1 may be an alkali metal salt, alkaline earth metal salt, ammonium salt or organic amine salt, and R.sub.2 may be an ammonium salt or an alkali or alkaline earth metal salt of an inorganic or organic acid.
摘要翻译：描述了通过（a）N-保护的L-天冬氨酸酐和R1-L-苯丙氨酸的反应来合成N-保护的-L-天冬酰胺-L-苯丙氨酸的方法，和（b）在R2的存在下，N-保护的L-天冬氨酸酐和L-苯丙氨酸在水性介质中的反应，其中R1可以是碱金属盐，碱土金属盐，铵盐或有机胺盐，R2可以是无机或有机酸的铵盐或碱金属或碱土金属盐。

4. 发明授权

US5795585A Ruminant feed additive composition containing novel phosphoric acid-amino acid composite salt and water-soluble high-molecular substance 失效
标题翻译：含有新型磷酸 - 氨基酸复合盐和水溶性高分子物质的反刍动物饲料添加剂组合物
公开(公告)号：US5795585A
公开(公告)日：1998-08-18
申请号：US777052
申请日：1996-12-30
申请人： Toru Ikeda , Toshihide Yukawa
发明人： Toru Ikeda , Toshihide Yukawa
IPC分类号： A23K1/00 , A23K1/16 , A23K1/175 , A23K1/18 , C07C229/26 , A61K9/16
CPC分类号： C07C229/26 , A23K20/147 , A23K40/35 , A23K50/10
摘要： A ruminant feed additive composition comprises a phosphoric acid-amino acid composite salt and a water-insoluble salt of a polyvalent-metal-sensitive water-soluble high-molecular weight substance. The composite salt contains a basic amino acid, an alkaline-earth metal and phosphoric acid, and is insoluble in neutral or alkaline aqueous solution, but is soluble in acidic aqueous solution.
摘要翻译：反刍动物饲料添加剂组合物包含磷酸 - 氨基酸复合盐和多价金属敏感性水溶性高分子量物质的水不溶性盐。复合盐含有碱性氨基酸，碱土金属和磷酸，不溶于中性或碱性水溶液，但溶于酸性水溶液。

5. 发明授权

US5744178A Ruminant feed additive composition containing novel phosphoric acid-amino acid-polyvalent metal composite salt and gastric antacid 失效
标题翻译：含有新型磷酸 - 氨基酸 - 多价金属复合盐和胃酸的反刍动物饲料添加剂组合物
公开(公告)号：US5744178A
公开(公告)日：1998-04-28
申请号：US774362
申请日：1996-12-27
申请人： Toru Ikeda , Toshihide Yukawa , Hisamine Kobayashi , Hiroyuki Sato , Nobuyoshi Kitamura
发明人： Toru Ikeda , Toshihide Yukawa , Hisamine Kobayashi , Hiroyuki Sato , Nobuyoshi Kitamura
IPC分类号： A23K1/00 , A23K1/16 , A23K1/175 , A23K1/18
CPC分类号： A23K50/10 , A23K20/22 , A23K20/26 , A23K20/30 , A23K40/10 , A23K40/35
摘要： A ruminant feed additive composition in the form of a powder or granules comprises as active ingredients a gastric antacid, a phosphoric acid-amino acid-polyvalent metal composite salt and optionally a water-insoluble salt of a polyvalent metal-sensitive water-soluble high-molecular weight substance. The phosphoric acid-amino acid-polyvalent metal composite salt is composed of a phosphoric acid such as orthophosphoric acid, a polyphosphoric acid or a metaphosphoric acid, a basic amino acid such as lysine or methionine, an alkaline earth metal such as calcium or magnesium and, optionally, a polyvalent metal such as aluminum.
摘要翻译：粉末或颗粒形式的反刍动物饲料添加剂组合物包含作为活性成分的胃酸，磷酸 - 氨基酸 - 多价金属复合盐和任选的多价金属敏感性水溶性高分子金属盐的水不溶性盐，分子量物质。磷酸 - 氨基酸 - 多价金属复合盐由磷酸如正磷酸，多磷酸或偏磷酸，碱性氨基酸如赖氨酸或甲硫氨酸，碱土金属如钙或镁组成，以及，任选地，多价金属如铝。

6. 发明授权

US5225587A Method of producing .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride 失效
标题翻译：生产α-L-天冬氨酰-L-苯丙氨酸甲酯盐酸盐的方法
公开(公告)号：US5225587A
公开(公告)日：1993-07-06
申请号：US864133
申请日：1992-04-06
申请人： Katsumi Sugiyama , Kiyo Adachi , Toshihide Yukawa
发明人： Katsumi Sugiyama , Kiyo Adachi , Toshihide Yukawa
IPC分类号： C07K5/072 , C07K5/075
CPC分类号： C07K5/0613
摘要： A method of purifying .alpha.-L-aspartyl-L-phenylalanine methyl ester as a hydrochloride salt thereof which comprises:i) contacting a mixture of .alpha.-L-aspartyl-L-phenylanaline methyl ester and .beta.-L-aspartyl-L-phenylalanine methyl ester with an aqueous medium containing (a) hydrogen chloride in an amount not more than ca. 2 mol., per liter of said aqueous medium, but not less than 1 mol., per mole of said of said mixture of .alpha.-L-aspartyl-L-phenylalanine methyl ester and .beta.-L-aspartyl-L-phenylalanine methyl ester, and (b) an inorganic chloride selected from the group consisting of NaCl, KCl, NH.sub.4 Cl, CaCl.sub.2, and ZnCl.sub.2 in an amount of at least ca. 50 g., per liter of said aqueous medium, to form crystals of .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride, andii) recovering the .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride crystals therefrom.
摘要翻译：纯化α-L-天冬氨酰基-L-苯丙氨酸甲酯盐酸盐的方法，其包括：i）使α-L-天冬氨酰基-L-苯亚胺甲酯与β-L-天冬氨酰基-L-苯丙氨酸的混合物甲酯与含有（a）氯化氢的含水介质的量不大于约每摩尔所述所述α-L-天冬氨酰基-L-苯丙氨酸甲酯和β-L-天冬氨酰-L-苯丙氨酸甲酯的混合物每升所述水性介质2摩尔，但不小于1摩尔，和（b）选自NaCl，KCl，NH 4 Cl，CaCl 2和ZnCl 2的无机氯化物，其量至少约为。 50升，每升所述水性介质中，形成α-L-天冬氨酰基-L-苯丙氨酸甲酯盐酸盐的晶体，和ii）从其中回收α-L-天冬氨酰基-L-苯丙氨酸甲酯盐酸盐晶体。

7. 发明授权

US4780528A Tripeptides and sweetening agents containing the same 失效
标题翻译：含有相同的三肽和甜味剂
公开(公告)号：US4780528A
公开(公告)日：1988-10-25
申请号：US794788
申请日：1985-11-04
申请人： Tadashi Takemoto , Toyoto Hijiya , Toshihide Yukawa
发明人： Tadashi Takemoto , Toyoto Hijiya , Toshihide Yukawa
IPC分类号： A23L27/30 , C07K5/08 , C07K5/083 , C07K5/093 , C07K5/097 , C07C103/52
CPC分类号： C07K5/0819 , A23L27/31 , C07K5/0806 , C07K5/081 , C07K5/0821 , C07K5/0823 , Y02P20/55 , Y10S530/801
摘要： Tripeptide sweeteners represented by formula (I)X--Asp--Y--ORwhereinX is glycine or a D or DL-isomer of alanine, .alpha.-aminobutyric acid, serine, threonine, norvaline, asparagine, B-methyl aspartate, proline or pipecolic acid, andY is a D, L or DL-isomer of alanine, phenylalanine, phenylglycine, serine or .beta.-aminobutyric acid or a salt thereof, andR is methyl, ethyl, propyl or isopropyl, are disclosed.
摘要翻译：由式（I）X-Asp-Y-OR表示的三肽甜味剂，其中X是甘氨酸或丙氨酸，α-氨基丁酸，丝氨酸，苏氨酸，正缬氨酸，天冬酰胺，天冬氨酸B-甲酯，脯氨酸或哌啶的D或DL-异构体酸，Y是丙氨酸，苯丙氨酸，苯基甘氨酸，丝氨酸或β-氨基丁酸或其盐的D，L或DL-异构体，R是甲基，乙基，丙基或异丙基。

8. 发明授权

US5763657A Phosphoric acid-amino acid-polyvalent metal composite salt and ruminant feed additive composition 失效
标题翻译：磷酸 - 氨基酸 - 多价金属复合盐和反刍动物饲料添加剂组成
公开(公告)号：US5763657A
公开(公告)日：1998-06-09
申请号：US894703
申请日：1997-08-28
申请人： Toyoto Hijiya , Toru Ikeda , Kenichi Mori , Toshihide Yukawa , Tadashi Takemoto , Hajime Kamada
发明人： Toyoto Hijiya , Toru Ikeda , Kenichi Mori , Toshihide Yukawa , Tadashi Takemoto , Hajime Kamada
IPC分类号： A23K1/00 , A23K1/16 , A23K1/175 , A23K1/18 , C07C229/26 , C07C279/14 , C07C229/00
CPC分类号： C07C229/26 , A23K20/142 , A23K20/147 , A23K20/26 , A23K40/10 , A23K40/35 , A23K50/10 , C07C279/14 , Y10S426/807
摘要： The present specification discloses a ruminant feed additive composition which contains as an active ingredient a phosphoric acid-amino acid-polyvalent metal composite salt (final composite salt) which is insoluble in neutral or alkaline water and is soluble in acidic water and which can be obtained by treating a composite salt composed of a basic amino acid, magnesium and phosphoric acid with a salt of a divalent or trivalent (polyvalent) metal other than magnesium, or by treating the above-mentioned composite salt with the polyvalent metal salt and a condensed phosphoric acid component (alone) or the condensed phosphoric acid component and a phosphoric acid component (in combination), this composition taking the form of a powder or granules. The above-mentioned final composite salt can exhibit the excellent stability to neutral or slightly acidic water, namely, the low solubility therein in comparison with the intermediate composite salt, and it can have both the excellent insolubility of the basic amino acid in a rumen of a ruminant and the excellent elution thereof in an abomasum and lower digestive organs.
摘要翻译： PCT No.PCT / JP96 / 03420 Sec。 371日期1997年8月28日 102（e）日期1997年8月28日PCT 1996年11月21日PCT公布。第WO97 / 24314号公报日本1997年7月10日本说明书公开了一种反刍动物饲料添加剂组合物，其含有不溶于中性或碱性水并且可溶于酸性水的磷酸 - 氨基酸 - 多价金属复合盐（最终复合盐）作为活性成分并且可以通过用碱性氨基酸，镁和磷酸组成的复合盐与除了镁以外的二价或三价（多价）金属的盐处理或通过用多价金属处理上述复合盐来获得盐和缩合磷酸组分（单独）或缩合磷酸组分和磷酸组分（组合），该组合物为粉末或颗粒形式。上述最终的复合盐可以显示出对中性或微酸性水的优异的稳定性，即与中间复合盐相比，其溶解度低，并且可以具有优异的碱性氨基酸在瘤胃的不溶性反刍动物和在皱胃和下消化器官中的优异洗脱。

9. 发明授权

US4822907A Method for recovering .alpha.-L-aspartyl-L-phenylalanine methyl ester 失效
标题翻译： α-L-天冬氨酰-L-苯丙氨酸甲酯的回收方法
公开(公告)号：US4822907A
公开(公告)日：1989-04-18
申请号：US56907
申请日：1987-06-03
申请人： Katsumi Sugiyama , Takashi Yamashita , Toshihide Yukawa
发明人： Katsumi Sugiyama , Takashi Yamashita , Toshihide Yukawa
IPC分类号： C07K1/14 , C07K1/26 , C07K5/072 , C07K5/075 , C07C103/52
CPC分类号： C07K5/0613
摘要： A process for recovering .alpha.-L-aspartyl-L-phenylalanine methyl ester from a solution containing various methyl ester or demethylated derivatives of .alpha.-L-aspartyl-L-phenylalanine methyl ester and chloride ions is disclosed. This process uses a reverse osmosis membrane having a specific chloride inhibition rate to desalt and concentrate a solution containing a specified ratio of .delta.-L-aspartyl-L-phenylalanine methyl ester to its derivatives until a specific weight ratio of organic chloride ion to the sum of .alpha.-L-aspartyl-L-phenylalanine methyl ester and its derivatives is obtained. This desalted and concentrated solution is then contacted with an aqueous solvent containing methanol and hydrochloride acid to recover high yields of .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloride.
摘要翻译：公开了从含有α-L-天冬氨酰-L-苯丙氨酸甲酯和氯离子的各种甲酯或去甲基化衍生物的溶液中回收α-L-天冬氨酰基-L-苯丙氨酸甲酯的方法。该方法使用具有特定氯化物抑制速率的反渗透膜脱盐，并将含有特定比例的δ-L-天冬氨酰-L-苯丙氨酸甲酯的溶液浓缩至其衍生物，直到有机氯离子与总和的比重的α-L-天冬氨酰基-L-苯丙氨酸甲酯及其衍生物。然后将该脱盐浓缩溶液与含有甲醇和盐酸的含水溶剂接触，以回收高产率的α-L-天冬氨酰基-L-苯丙氨酸甲酯盐酸盐。

10. 发明授权

US4820861A Process for the production of N-formyl-alpha-L-aspartyl-L-phenylalanine methyl ester 失效
标题翻译：制备N-甲酰基-α-L-天冬氨酰基-L-苯丙氨酸甲酯的方法
公开(公告)号：US4820861A
公开(公告)日：1989-04-11
申请号：US931123
申请日：1986-11-17
申请人： Toshihide Yukawa , Haruo Kawasaki , Masao Nakamura , Takashi Yamashita , Toshiaki Tsuji
发明人： Toshihide Yukawa , Haruo Kawasaki , Masao Nakamura , Takashi Yamashita , Toshiaki Tsuji
IPC分类号： C07K1/06 , B01J31/04 , C07B61/00 , C07K5/06 , C07K5/075 , C07C101/02
CPC分类号： C07K5/0613
摘要： N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester is obtained by reacting L-phenylalanine methyl ester with N-formyl-L-aspartic acid anhydride in a reaction solvent containing acetic acid or acetic acid and formic acid in a complete mixing type continuous reaction mode.
摘要翻译： N-甲酰基-α-天冬氨酰基-L-苯丙氨酸甲酯通过L-苯丙氨酸甲酯与N-甲酰基-L-天冬氨酸酐在含有乙酸或乙酸的反应溶剂和甲酸的完全反应溶液中反应得到混合型连续反应方式。

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