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81. 发明授权

US5801047A Method for making stable extracellular tyrosinase and synthesis of polyphenolic polymers therefrom 失效
标题翻译：制备稳定的细胞外酪氨酸酶和由其合成多酚聚合物的方法
公开(公告)号：US5801047A
公开(公告)日：1998-09-01
申请号：US471993
申请日：1995-06-06
申请人： Guy Richard della-Cioppa , Stephen John Garger, Jr. , Richard Barry Holtz , Michael Jay McCulloch , Genadie Gleb Sverlow
发明人： Guy Richard della-Cioppa , Stephen John Garger, Jr. , Richard Barry Holtz , Michael Jay McCulloch , Genadie Gleb Sverlow
IPC分类号： C12N15/09 , C08G61/00 , C08H99/00 , C12N20060101 , C12N1/21 , C12N9/02 , C12N9/96 , C12N15/53 , C12P20060101 , C12P7/00 , C12P17/00 , C12P21/08 , C12R1/48 , C12N1/20
CPC分类号： C12Y110/03001 , C08G61/00 , C12N9/0059 , C12N9/0071 , C12P17/00 , C12Y114/18001
摘要： A process for the in vitro production of chemically modified polyphenolic polymer (PPP). First, stable, highly active extracellular tyrosinase is produced from genetically transformed microorganism such as Streptomyces antibioticus. The tyrosinase is then incubated with a reaction substrate such as 1-tyrosine, hydrolyzed protein, or an oligopeptide in combination with 1-tyrosine. The ratio of the oligopeptide/tyrosine combination as well as variation in the concentration of tyrosinase can be used to modify the color, the molecular size, and the spectral absorbance properties of the PPP produced. Alternatively, or additionally, oxidants such as hydrogen peroxide or hypochlorite can be used to modify the color of the PPP, regardless of the method used to produce the PPP, and the PPP can subsequently be fractionated using molecular weight cut-off ultrafiltration. Organic solvents can also be used in the method of making PPP to produce PPPs having variable but reproducible physical properties.
摘要翻译：一种体外生产化学改性多酚聚合物（PPP）的方法。首先，稳定的，高活性的细胞外酪氨酸酶由遗传转化的微生物如抗链霉菌（Streptomyces antibioticus）产生。然后将酪氨酸酶与1-酪氨酸，水解蛋白质或寡肽与1-酪氨酸组合的反应底物孵育。寡肽/酪氨酸组合的比例以及酪氨酸酶浓度的变化可用于改变生产的PPP的颜色，分子大小和光谱吸收性质。或者或另外，可以使用氧化剂如过氧化氢或次氯酸盐来改变PPP的颜色，而不管用于生产PPP的方法如何，并且随后可以使用分子量截止超滤对PPP进行分级。有机溶剂也可用于制备PPP以产生具有可变但可再现的物理性质的PPP的方法。

82. 发明授权

US5703051A Therapeutic uses of melanin 失效
标题翻译：黑色素的治疗用途
公开(公告)号：US5703051A
公开(公告)日：1997-12-30
申请号：US988739
申请日：1992-12-10
申请人： David L Berliner , Robert L. Erwin , David R. McGee
发明人： David L Berliner , Robert L. Erwin , David R. McGee
IPC分类号： A61K31/53 , A61K9/12 , A61K31/40 , A61K31/41 , A61K31/69 , A61K31/70 , A61K31/711 , A61K31/787 , A61K31/795 , A61K33/20 , A61K38/00 , A61K38/22 , A61K38/43 , A61K38/44 , A61K39/395 , A61K45/00 , A61K47/48 , A61K48/00 , A61K51/00 , A61P25/00 , A61P25/16 , A61P25/18 , A61P25/28 , A61P27/02 , A61P43/00 , C12N9/02 , C12P17/00 , C12P17/18 , C12R1/465 , A61K47/06 , A61K47/46
CPC分类号： C12P17/00 , A61K31/40 , A61K31/69 , A61K33/22 , A61K38/185 , A61K38/22 , A61K47/48415 , A61K47/4843 , A61K48/00 , C12N9/0059 , C12N9/0071 , C12Y110/03001 , C12Y114/18001 , A61K38/00
摘要： The invention is directed to the treatment of degenerative diseases of tissues which have lost melanin and which share a common embryological basis as tissues of the nervous system by the administration of an active substance which causes an increased concentration of melanin in the tissue. Such active substances include melanin, melanin variants, melanin analogs, melanin derivatives, tyrosinase, tyrosinase gene, melanin-concentrating hormone and combinations thereof. Examples of such diseases include Parkinson's disease, Alzheimer's disease, retinitis pigmentosa, schizophrenia and dementia. The invention is also useful in assisting in the repair of neurons in a mammal having neuron damage by administering an effective amount of an active substance which causes an increased concentration of melanin in the neuron to aid in nerve repair. The invention is further useful in protecting a mammal from a toxin-induced disease or from the adverse effects of a toxin by administering an effective amount of the active substance described above.
摘要翻译：本发明涉及通过施用导致组织中黑色素浓度增加的活性物质而失去黑色素的组织的退行性疾病的治疗，其通过神经系统的组织共享共同的胚胎学基础。这些活性物质包括黑色素，黑色素变体，黑色素类似物，黑色素衍生物，酪氨酸酶，酪氨酸酶基因，黑色素浓缩激素及其组合。这些疾病的实例包括帕金森病，阿尔茨海默病，色素性视网膜炎，精神分裂症和痴呆。本发明还可用于通过施用有效量的活性物质来辅助具有神经元损伤的哺乳动物的神经元的修复，所述活性物质引起神经元中黑色素浓度增加以帮助神经修复。本发明还可用于通过施用有效量的上述活性物质来保护哺乳动物免受毒素诱发的疾病或毒素的不利影响。

83. 发明授权

US5552307A Method of using an elicitor to increase production of metabolites in biological cells 失效
标题翻译：使用激发剂增加生物细胞中代谢产物的方法
公开(公告)号：US5552307A
公开(公告)日：1996-09-03
申请号：US334794
申请日：1994-11-04
申请人： Bezalel Kessler , Chaim Frenkel , Daphna Frenkel , Abraham Kessler
发明人： Bezalel Kessler , Chaim Frenkel , Daphna Frenkel , Abraham Kessler
IPC分类号： C12N5/00 , C12P17/00 , C12P33/00 , C12N5/02
CPC分类号： C12P17/00 , C12N5/0025 , C12P33/00
摘要： A method for culturing fungal and plant cells in a culture medium containing an elicitor to increase production of a metabolite produced by the cells. For example, tobacco leaves produce the metabolite nicotine and the nicotine is produced in significantly greater amounts when the tobacco is cultured in a elicitor-containing medium. The elicitor is an oxidized Bovine Serum Albumin (BSA), or a glycosylated BSA, or an oxidized lysozyme, or glycosylated lysozyme or azetidine-2-carboxylic acid. Further, metabolite production is increased 1000% over the production of the metabolite when an elicitor is not added during the culturing method.
摘要翻译：一种在含有诱导剂的培养基中培养真菌和植物细胞以增加由细胞产生的代谢产物的方法。例如，当烟草在含有诱导剂的培养基中培养时，烟草叶产生代谢物尼古丁，并且产生的尼古丁显着更大的量。激发剂是氧化牛血清白蛋白（BSA）或糖化BSA，或氧化溶菌酶，或糖基化溶菌酶或氮杂环丁烷-2-羧酸。此外，当在培养方法中不加入诱导剂时，代谢产物的产生比代谢物的产生增加1000％。

84. 发明授权

US5541080A Method for preparing L-alpha-amino acids 失效
标题翻译：制备L-α-氨基酸的方法
公开(公告)号：US5541080A
公开(公告)日：1996-07-30
申请号：US69277
申请日：1993-05-28
申请人： Charles J. Sih
发明人： Charles J. Sih
IPC分类号： C12P13/04 , C12P17/00 , C12P41/00 , C12Q1/34 , C07B57/00 , C12Q1/37
CPC分类号： C12P13/04 , C12P17/00 , C12P41/003
摘要： A process is provided for preparing an L-.alpha.-amino acid from a 5(4H)-oxazolone precursor. The precursor is subjected to a two-step process sequence in which the precursor is first contacted with a methanolytically active lipase in the presence of methanol in a non-polar solvent to enantioselectively solvolyze the precursor and produce an intermediate optically active methyl ester of the desired .alpha.-amino acid. This ester is then contacted with a protease in the presence of water to enantioselectively cleave the ester and accomplish an enzymatic kinetic resolution to prepare the product L-.alpha.-amino acid in high optical purity.
摘要翻译：提供了从5（4H） - 恶唑酮前体制备L-α-氨基酸的方法。将前体进行两步工艺顺序，其中前体首先在甲醇在非极性溶剂存在下与甲醇分解活性脂肪酶接触，以对映体选择性溶剂化前体，并产生所需的中间体旋光活性甲酯 α-氨基酸。然后在水存在下将该酯与蛋白酶接触，以对映选择性地裂解酯，并实现酶动力学拆分以制备高光学纯度的产物L-α-氨基酸。

85. 发明授权

US5466592A Method for making stable, extracellular tyrosinase and synthesis of polyphenolic polymers therefrom 失效
标题翻译：制备稳定的细胞外酪氨酸酶和从其中合成多酚聚合物的方法
公开(公告)号：US5466592A
公开(公告)日：1995-11-14
申请号：US154171
申请日：1993-11-17
申请人： Guy R. della-Cioppa , Stephen J. Garger, Jr. , Richard B. Holtz , Michael J. McCulloch , Genadie G. Sverlow
发明人： Guy R. della-Cioppa , Stephen J. Garger, Jr. , Richard B. Holtz , Michael J. McCulloch , Genadie G. Sverlow
IPC分类号： C12N15/09 , C08G61/00 , C08H99/00 , C12N20060101 , C12N1/21 , C12N9/02 , C12N9/96 , C12N15/53 , C12P20060101 , C12P7/00 , C12P17/00 , C12P21/08 , C12R1/48 , C12N9/48 , A61K7/42 , C12N9/74 , C12P21/06
CPC分类号： C12Y110/03001 , C08G61/00 , C12N9/0059 , C12N9/0071 , C12P17/00 , C12Y114/18001
摘要： A process for the in vitro production of chemically modified polyphenolic polymer (PPP). First, stable, highly active extracellular tyrosinase is produced from genetically transformed microorganism such as Streptomyces antibioticus. The tyrosinase is then incubated with a reaction substrate such as l-tyrosine, hydrolyzed protein, or an oligopeptide in combination with l-tyrosine. The ratio of the oligopeptide/tyrosine combination as well as variation in the concentration of tyrosinase can be used to modify the color, the molecular size, and the spectral absorbance properties of the PPP produced. Alternatively, or additionally, oxidants such as hydrogen peroxide or hypochlorite can be used to modify the color of the PPP, regardless of the method used to produce the PPP, and the PPP can subsequently be fractionated using molecular weight cut-off ultrafiltration. Organic solvents can also be used in the method of making PPP to produce PPPs having variable but reproducible physical properties.
摘要翻译：一种体外生产化学改性多酚聚合物（PPP）的方法。首先，稳定的，高活性的细胞外酪氨酸酶由遗传转化的微生物如抗链霉菌（Streptomyces antibioticus）产生。然后将酪氨酸酶与反应底物如1-酪氨酸，水解蛋白质或寡肽与1-酪氨酸组合孵育。寡肽/酪氨酸组合的比例以及酪氨酸酶浓度的变化可用于改变生产的PPP的颜色，分子大小和光谱吸收性质。或者或另外，可以使用氧化剂如过氧化氢或次氯酸盐来改变PPP的颜色，而不管用于生产PPP的方法如何，并且随后可以使用分子量截止超滤对PPP进行分级。有机溶剂也可用于制备PPP以产生具有可变但可再现的物理性质的PPP的方法。

86. 发明授权

US5280096A Substantially pure diol and triol stereoisomers, method of preparation and polymers thereof 失效
标题翻译：基本纯二醇和三醇立体异构体，制备方法及其聚合物
公开(公告)号：US5280096A
公开(公告)日：1994-01-18
申请号：US922716
申请日：1992-07-31
申请人： Cary J. Morrow , Joe S. Wallace
发明人： Cary J. Morrow , Joe S. Wallace
IPC分类号： C12P7/18 , C12P7/22 , C12P11/00 , C12P17/00 , C12P41/00 , C08F12/02 , C08F112/02
CPC分类号： C12P7/22 , C12P11/00 , C12P17/00 , C12P41/004 , C12P7/18
摘要： Optically active polymers are of the formula ##STR1## wherein R and R.sup.1 are different from each other and are selected from the group consisting of (C.sub.1 -C.sub.20)alkyl, (C.sub.2 -C.sub.20)alkenyl, (C.sub.2 -C.sub.20)alkynyl, (C.sub.3 -C.sub.22) cycloalkyl and (C.sub.6 -C.sub.22)aryl, the alkyl, alkenyl and alkynyl further including an atom selected from the group consisting of N, O and S in the chain, the alkyl, alkenyl and alkynyl further including a substituent selected from the group consisting of (C.sub.1 -C.sub.4)alkyl and halogen atoms, the cycloalkyl and aryl further including an atom selected from the group consisting of N, O and S in the ring, and the cycloalkyl and aryl further including a substituent selected from the group consisting of (C.sub.1 -C.sub.10)alkoxy, aryloxy, halogen atoms, NO.sub.2 and NHCOR.sup.4 wherein R.sup.4 is selected from the group consisting of (C.sub.1 -C.sub.6)alkyl, (C.sub.2 -C.sub.6)alkenyl, (C.sub.2 -C.sub.6)alkynyl and (C.sub.6 -C.sub.10)aryl; R.sup.2 is selected from the group consisting of --CO--, --CO--R.sup.3 --CO--, (CH.sub.2).sub.q, --C.sub.6 H.sub.4 --, 4,4'-biphenylene and --OCNH--R.sup.3 --NHCO-- wherein R.sup.3 is selected from the group consisting of (C.sub.1 -C.sub.10)alkyl, (C.sub.2 -C.sub.10)alkenyl, (C.sub.2 -C.sub.10)alkynyl, (C.sub.4 -C.sub.20)aryl and (C.sub.3 -C.sub.20)cycloalkyl and q is from 1 to 12; m is from 1 to 10,000; and p is from 0 to m. The polymer is formed from a stereochemically pure compound.
摘要翻译：光学活性聚合物具有下式：其中R和R 1彼此不同，并且选自（C 1 -C 20）烷基，（C 2 -C 20）烯基，（C 2 -C 20）炔基，（C 3 -C 20） -C 22）环烷基和（C 6 -C 22）芳基，所述烷基，烯基和炔基还包括在所述链中选自N，O和S的原子，所述烷基，烯基和炔基还包括选自由（C 1 -C 4）烷基和卤素原子组成的基团，环烷基和芳基还包括在环中选自N，O和S的原子，并且环烷基和芳基还包括选自以下的取代基：的（C 1 -C 6）烷氧基，芳氧基，卤素原子，NO 2和NHCOR 4，其中R 4选自（C 1 -C 6）烷基，（C 2 -C 6）烯基，（C 2 -C 6）炔基和（C 6 -C 10））芳基; R2选自-CO - ， - CO-R3-CO-，（CH2）q，-C6H4-，4,4'-联亚苯基和-OCNH-R3-NHCO-，其中R3选自由（C1-C10）烷基，（C2-C10）烯基，（C2-C10）炔基，（C4-C20）芳基和（C3-C20）环烷基组成，q为1至12; m为1〜10,000; p为0〜m。聚合物由立体化学纯的化合物形成。

87. 发明授权

US5225435A Soluble melanin 失效
标题翻译：可溶性黑色素
公开(公告)号：US5225435A
公开(公告)日：1993-07-06
申请号：US674489
申请日：1991-03-25
申请人： John M. Pawelek , Seth J. Orlow
发明人： John M. Pawelek , Seth J. Orlow
IPC分类号： A23L1/275 , A61K8/72 , A61K31/785 , A61Q17/04 , C09B69/10 , C12P17/00 , C12P17/10
CPC分类号： C12P17/00 , A23L5/43 , A23L5/47 , A61K31/785 , A61K8/72 , A61Q17/04 , C09B69/104 , C12P17/10
摘要： A melanin that is soluble in an aqueous solution at a pH of at least 5 to 9 at a temperature of 0 to 100.degree. C. The melanin is further characterized by being capable of being filtered through at least a 0.45 micron size filter. Still further, the melanin is characterized by having a molecular weight of greater than 10,000 kilodaltons. The melanin is useful for providing a naturally-appearing tan to mammalian skin and hair. Such melanin can be produced by combining dopachrome and 5,6-dihydroxyindole (or allowing dopachrome to spontaneously form 5,6-dihydroxyindole) and an appropriate enzyme or by combining 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid or by incubating 5,6-dihydroxyindole-2-carboxylic acid alone. The melanin is also useful for providing a sun-screen to mammalian skin and hair, to treat post-inflammatory hypo- and hyperpigmentation, to tint glass and plastic, to protect industrial materials against ultraviolet damage, and as a coloring agent in foodstuffs such as coffee, tea, soda, whiskey and liquors.
摘要翻译：在0至100℃的温度下，在至少5至9的pH下可溶于水溶液的黑色素。黑色素的进一步特征在于能够通过至少0.45微米尺寸的过滤器过滤。此外，黑色素的特征在于具有大于10,000千道尔顿的分子量。黑色素可用于向哺乳动物皮肤和头发提供天然存在的棕褐色。这种黑色素可以通过组合多巴色胺和5,6-二羟基吲哚（或允许多巴色素自发形成5,6-二羟基吲哚）和合适的酶或通过将5,6-二羟基吲哚和5,6-二羟基吲哚-2-羧酸或通过单独孵育5,6-二羟基吲哚-2-羧酸。黑色素还可用于向哺乳动物皮肤和头发提供防晒剂，以治疗炎症后期和色素沉着过度，使玻璃和塑料变色，以保护工业材料免受紫外线损伤，以及作为食品中的着色剂，例如咖啡，茶，苏打水，威士忌和烈酒。

88. 发明授权

US5216116A Soluble melanin 失效
标题翻译：可溶性麦芽糖
公开(公告)号：US5216116A
公开(公告)日：1993-06-01
申请号：US525944
申请日：1990-05-18
申请人： John M. Pawelek
发明人： John M. Pawelek
IPC分类号： A61K8/72 , A61K31/405 , A61Q17/04 , A61Q19/04 , C08G63/685 , C12P17/00 , C12P17/10 , C08G63/06
CPC分类号： A61Q17/04 , A61K8/72 , A61Q19/04 , C08G63/6852 , C12P17/00 , C12P17/10
摘要： A melanin that is soluble in an aqueous solution at a pH of at least 5 to 9 at a temperature of 0.degree. to 100.degree. C. The melanin is further characterized by being capable of being filtered through at least a 0.45 micron size filter. Still further, the melanin is characterized by having a molecular weight of greater than 10,000 kilodaltons. The melanin is useful for providing a naturally-appearing tan to mammalian skin and hair. The melanin is also useful for providing a sun-screen to mammalian skin and hair.
摘要翻译：在0至100℃的温度下，可溶于pH至少为5至9的水溶液的黑色素。黑色素的进一步特征在于能够通过至少0.45微米尺寸的过滤器过滤。此外，黑色素的特征在于具有大于10,000千道尔顿的分子量。黑色素可用于向哺乳动物皮肤和头发提供天然存在的棕褐色。黑色素也可用于向哺乳动物的皮肤和头发提供防晒霜。

89. 发明授权

US5112807A Compound "Leualacin", its preparation and its use in the treatment of cardiovascular disorders 失效
标题翻译：化合物“利昔康宁”，其制备及其在治疗心血管疾病中的应用
公开(公告)号：US5112807A
公开(公告)日：1992-05-12
申请号：US403117
申请日：1989-09-05
申请人： Kiyoshi Hamano , Kouhei Furuya , Kazuhiko Tanzawa , Takeshi Kagasaki , Masaaki Miyamoto , Takeshi Kinoshita
发明人： Kiyoshi Hamano , Kouhei Furuya , Kazuhiko Tanzawa , Takeshi Kagasaki , Masaaki Miyamoto , Takeshi Kinoshita
IPC分类号： C07D273/00 , C07D273/08 , C07K11/02 , C12P17/00
CPC分类号： C07D273/00 , C07K11/02 , C12P17/00 , C12R1/645 , Y10S435/911 , Y10S514/821 , Y10S514/929 , Y10S530/80
摘要： A new compound, which we have named "Leualacin" has the formula (I): ##STR1## and may be prepared by cultivation of a microorganism of the genus Hapsidospora, especially Hapsidospora irregularis. The compound may be used for the treatment and prophylaxis of cardiovascular diseases and disorders, especially hypertension.

90. 发明授权

US5104798A Microbiological oxidation of methyl groups in heterocycles 失效
标题翻译：甲基组合物在微生物中的氧化作用
公开(公告)号：US5104798A
公开(公告)日：1992-04-14
申请号：US650589
申请日：1991-02-05
申请人： Andreas Kiener
发明人： Andreas Kiener
IPC分类号： C12N9/04 , C12P7/40 , C12P17/00 , C12P17/12 , C12R1/40
CPC分类号： C12P7/40 , C12P17/00 , Y10S435/877
摘要： A microbiological process for the oxidation of methyl groups in aromatic 5- or 6-member ring heterocycles to the corresponding carboxylic acid. The heterocycle serves as the substrate and exhibits no substituent on the carbon atoms adjacent to the methyl groups to be oxidized. The reaction of the heterocycle takes place by means of microorganisms of the genus Pseudomonas utilizing toluene, xylene, or cymene. The enzymes of the microorganisms have been previously induced.
摘要翻译：用于将芳族5-或6-元环杂环中的甲基氧化成相应羧酸的微生物过程。杂环用作底物，并且在与待氧化的甲基相邻的碳原子上不显示取代基。杂环的反应通过使用甲苯，二甲苯或甲基异丙苯的假单胞菌属的微生物进行。以前已经诱导了微生物的酶。

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