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1. 发明授权

US5436239A Method of treating clostridium difficile colitis and cholera 失效
标题翻译：治疗艰难梭菌结肠炎和霍乱的方法
公开(公告)号：US5436239A
公开(公告)日：1995-07-25
申请号：US40444
申请日：1993-04-01
申请人： Richard L. Guerrant , Guodong Fang , Manasses C. Fonteles
发明人： Richard L. Guerrant , Guodong Fang , Manasses C. Fonteles
IPC分类号： A61K31/00 , A61K31/12 , A61K31/335 , A61K31/34 , A61K31/365 , A61K31/405 , A61K31/44 , A61K31/4439 , A61K31/47 , A61K31/55 , A61K31/551
CPC分类号： A61K31/551 , A61K31/00 , A61K31/12 , A61K31/335 , A61K31/365 , A61K31/405 , A61K31/44 , A61K31/4439 , A61K31/47 , A61K31/55
摘要： The invention relates to the treatment of antibiotic associated colitis, typically due to Clostridium difficile using the Platelet Activating Factor antagonists WEB 2170, SR 27417 or BN 52021, or the cyclooxygenase antagonist indomethacin. The PAF antagonists BN 52021 and SR 27417 and the cyclooxygenase antagonist indomethacin were effective in inhibiting the secretory effects caused by C. difficile Toxin A and by Cholera toxin.
摘要翻译：本发明涉及抗生素相关性结肠炎的治疗，通常由于使用血小板活化因子拮抗剂WEB 2170，SR 27417或BN 52021或环氧合酶拮抗剂吲哚美辛导致的艰难梭菌。 PAF拮抗剂BN 52021和SR 27417和环加氧酶拮抗剂吲哚美辛有效抑制艰难梭菌毒素A和霍乱毒素引起的分泌作用。

2. 发明授权

US5929095A Method of inhibiting secretory effects caused by Cholera 失效
标题翻译：抑制霍乱引起的分泌作用的方法
公开(公告)号：US5929095A
公开(公告)日：1999-07-27
申请号：US877748
申请日：1997-06-17
申请人： Richard L. Guerrant , Guodong D. Fang , Manasses C. Fonteles
发明人： Richard L. Guerrant , Guodong D. Fang , Manasses C. Fonteles
IPC分类号： A61K31/00 , A61K31/12 , A61K31/335 , A61K31/34 , A61K31/365 , A61K31/405 , A61K31/44 , A61K31/4439 , A61K31/47 , A61K31/55 , A61K31/551
CPC分类号： A61K31/551 , A61K31/00 , A61K31/12 , A61K31/335 , A61K31/365 , A61K31/405 , A61K31/44 , A61K31/4439 , A61K31/47 , A61K31/55
摘要： The administration of the PAF antagonists BN 52021 and SR 27417, in combination with cyclooxygenase antagonist indomethacin are disclosed as effective in inhibiting the secretory effects caused by Cholera toxin.
摘要翻译：公开了PAF拮抗剂BN 52021和SR 27417与环加氧酶拮抗剂吲哚美辛组合的施用，可有效抑制由霍乱毒素引起的分泌作用。

3. 发明授权

US5639750A Method of inhibiting secretory effects caused by cholera 失效
标题翻译：抑制霍乱引起的分泌作用的方法
公开(公告)号：US5639750A
公开(公告)日：1997-06-17
申请号：US477313
申请日：1995-06-07
申请人： Richard L. Guerrant , Guodong D. Fang , Manasses C. Fonteles
发明人： Richard L. Guerrant , Guodong D. Fang , Manasses C. Fonteles
IPC分类号： A61K31/00 , A61K31/12 , A61K31/335 , A61K31/34 , A61K31/365 , A61K31/405 , A61K31/44 , A61K31/4439 , A61K31/47 , A61K31/55 , A61K31/551
CPC分类号： A61K31/551 , A61K31/00 , A61K31/12 , A61K31/335 , A61K31/365 , A61K31/405 , A61K31/44 , A61K31/4439 , A61K31/47 , A61K31/55
摘要： The invention relates to the treatment fluid secretion caused by Cholera toxin that can be blocked through the administration of PAF antagonists BN 52021 and SR 27417.
摘要翻译：本发明涉及通过施用PAF拮抗剂BN 52021和SR 27417可以阻断由霍乱毒素引起的治疗液分泌。

4. 发明申请

US20120010187A1 BROAD SPECTRUM BENZOTHIOPHENE-NITROTHIAZOLIDE AND OTHER ANTIMICROBIALS 有权
标题翻译：广泛光谱苯并噻唑和其他抗生素
公开(公告)号：US20120010187A1
公开(公告)日：2012-01-12
申请号：US13257707
申请日：2010-03-16
申请人： Paul S. Hoffman , Richard L. Guerrant , Timothy L. Macdonald , Thomas Eric Ballard, JR.
发明人： Paul S. Hoffman , Richard L. Guerrant , Timothy L. Macdonald , Thomas Eric Ballard, JR.
IPC分类号： A61K31/427 , C07D417/12 , C07D417/14 , C07D409/12 , C07D333/44 , A61P31/04 , A61K31/4439 , A61K31/381 , A61K31/454 , A61K31/5377 , A61P31/00 , C07D277/58 , A61K31/426
CPC分类号： C07D417/14 , A61K31/381 , A61K31/426 , A61K31/427 , A61K31/4439 , C07D277/54 , C07D277/58 , C07D333/42 , C07D333/44 , C07D409/12 , C07D417/12 , Y02A50/47 , Y02A50/473 , Y02A50/491
摘要： The invention provides FIG. 1 novel antimicrobial chemical entities based on a nitrothiazolide backbone that exhibit antibacterial and antiparasitic action against a wide range of human pathogens. The new classes of compounds show extended action against Gram positive bacteria including MRSA drug resistant pathogens. In the Gram-positive organisms, they specifically target and functionally inhibit microbial attachment to surfaces and biofilm formation. In Gram-negative bacteria, including enteroaggregative E. coli strains, these compounds function as pilicides by inhibiting the assembly of pilin subunits into adhesive filaments. Several of these compounds show potent antimicrobial action against Gram positive bacteria, perhaps involving novel targets. Many of the benzothiophene derivatives exhibit antimicrobial activity in the low micrograms per ml range and in blocking biofilm formation in the nanomolar range; ranges considered are well within the range of utility as therapeutics.
摘要翻译：本发明提供图一种基于硝基噻唑烷骨架的新型抗菌化学物质，对广泛的人类病原体表现出抗菌和抗寄生虫作用。新类化合物对革兰氏阳性细菌（包括MRSA耐药病原体）具有延长的作用。在革兰氏阳性生物中，它们特异性靶向和功能性地抑制微生物附着于表面和生物膜形成。在包括肠聚集大肠杆菌菌株的革兰氏阴性菌中，这些化合物通过抑制丝氨酸亚基组装成粘合剂长丝而起二硅化物的作用。这些化合物中的几种显示出对革兰氏阳性细菌的强力抗微生物作用，可能涉及新的靶标。许多苯并噻吩衍生物以低微克每毫升范围表现出抗微生物活性，并阻止纳摩尔范围内的生物膜形成; 所考虑的范围完全在作为治疗剂的效用范围内。

5. 发明申请

US20150018330A1 BROAD SPECTRUM BENZOTHIOPHENE-NITROTHIAZOLIDE AND OTHER ANTIMICROBIALS 有权
标题翻译：广泛光谱苯并噻唑和其他抗生素
公开(公告)号：US20150018330A1
公开(公告)日：2015-01-15
申请号：US14446793
申请日：2014-07-30
申请人： Paul S. Hoffman , Richard L. Guerrant , Timothy L. MacDonald , Thomas Eric Ballard, JR.
发明人： Paul S. Hoffman , Richard L. Guerrant , Timothy L. MacDonald , Thomas Eric Ballard, JR.
IPC分类号： C07D417/14 , C07D333/44 , C07D409/12 , C07D277/58 , C07D417/12
CPC分类号： C07D417/14 , A61K31/381 , A61K31/426 , A61K31/427 , A61K31/4439 , C07D277/54 , C07D277/58 , C07D333/42 , C07D333/44 , C07D409/12 , C07D417/12 , Y02A50/47 , Y02A50/473 , Y02A50/491
摘要： The invention provides novel antimicrobial chemical entities based on a nitrothiazolide backbone that exhibit antibacterial and antiparasitic action against a wide range of human pathogens. The new classes of compounds show extended action against Gram positive bacteria including MRSA drug resistant pathogens. In the Gram-positive organisms, they specifically target and functionally inhibit microbial attachment to surfaces and biofilm formation. In Gram-negative bacteria, including enteroaggregative E. coli strains, these compounds function as pilicides by inhibiting the assembly of pilin subunits into adhesive filaments. Several of these compounds show potent antimicrobial action against Gram positive bacteria, perhaps involving novel targets. Many of the benzothiophene derivatives exhibit antimicrobial activity in the low micrograms per ml range and in blocking biofilm formation in the nanomolar range; ranges considered are well within the range of utility as therapeutics.
摘要翻译：本发明提供了基于硝基噻唑烷骨架的新型抗微生物化学物质，其对广泛的人类病原体表现出抗菌和抗寄生虫作用。新类化合物对革兰氏阳性细菌（包括MRSA耐药病原体）具有延长的作用。在革兰氏阳性生物中，它们特异性靶向和功能性地抑制微生物附着于表面和生物膜形成。在包括肠聚集大肠杆菌菌株的革兰氏阴性菌中，这些化合物通过抑制丝氨酸亚基组装成粘合剂长丝而起二硅化物的作用。这些化合物中的几种显示出对革兰氏阳性细菌的强力抗微生物作用，可能涉及新的靶标。许多苯并噻吩衍生物以低微克每毫升范围表现出抗微生物活性，并阻止纳摩尔范围内的生物膜形成; 所考虑的范围完全在作为治疗剂的效用范围内。

6. 发明授权

US08835644B2 Broad spectrum benzothiophene-nitrothiazolide and other antimicrobials 有权
标题翻译：广谱苯并噻吩 - 硝基噻唑等抗菌药物
公开(公告)号：US08835644B2
公开(公告)日：2014-09-16
申请号：US13257707
申请日：2010-03-16
申请人： Paul S. Hoffman , Richard L. Guerrant , Timothy L. Macdonald , Thomas Eric Ballard, Jr.
发明人： Paul S. Hoffman , Richard L. Guerrant , Timothy L. Macdonald , Thomas Eric Ballard, Jr.
IPC分类号： C07D277/58 , C07D417/12 , C07D417/14 , C07D277/54 , C07D333/42 , C07D409/12
CPC分类号： C07D417/14 , A61K31/381 , A61K31/426 , A61K31/427 , A61K31/4439 , C07D277/54 , C07D277/58 , C07D333/42 , C07D333/44 , C07D409/12 , C07D417/12 , Y02A50/47 , Y02A50/473 , Y02A50/491
摘要： The invention provides novel antimicrobial chemical entities based on a nitrothiazolide backbone that exhibit antibacterial and antiparasitic action against a wide range of human pathogens. The new classes of compounds show extended action against Gram positive bacteria including MRSA drug resistant pathogens. In the Gram-positive organisms, they specifically target and functionally inhibit microbial attachment to surfaces and biofilm formation. In Gram-negative bacteria, including enteroaggregative E. coli strains, these compounds function as pilicides by inhibiting the assembly of pilin subunits into adhesive filaments. Several of these compounds show potent antimicrobial action against Gram positive bacteria, perhaps involving novel targets. Many of the benzothiophene derivatives exhibit antimicrobial activity in the low micrograms per ml range and in blocking biofilm formation in the nanomolar range; ranges considered are well within the range of utility as therapeutics.
摘要翻译：本发明提供了基于硝基噻唑烷骨架的新型抗微生物化学物质，其对广泛的人类病原体表现出抗菌和抗寄生虫作用。新类化合物对革兰氏阳性细菌（包括MRSA耐药病原体）具有延长的作用。在革兰氏阳性生物中，它们特异性靶向和功能性地抑制微生物附着于表面和生物膜形成。在包括肠聚集大肠杆菌菌株的革兰氏阴性菌中，这些化合物通过抑制丝氨酸亚基组装成粘合剂长丝而起二硅化物的作用。这些化合物中的几种显示出对革兰氏阳性细菌的强力抗微生物作用，可能涉及新的靶标。许多苯并噻吩衍生物以低微克每毫升范围表现出抗微生物活性，并阻止纳摩尔范围内的生物膜形成; 所考虑的范围完全在作为治疗剂的效用范围内。

7. 发明申请

US20100035867A1 Inhibitors of Cyclic Nucleotide Synthesis and Their Use for Therapy of Various Diseases 审中-公开
标题翻译：环状核苷酸合成抑制剂及其用于各种疾病的治疗
公开(公告)号：US20100035867A1
公开(公告)日：2010-02-11
申请号：US12307150
申请日：2007-07-06
申请人： Richard L. Guerrant , Alexander Y. Kots , Ferid Murad , Byung-Kwon Choi
发明人： Richard L. Guerrant , Alexander Y. Kots , Ferid Murad , Byung-Kwon Choi
IPC分类号： A61K31/5415 , A61K31/519
CPC分类号： A61K31/519 , Y02A50/471 , Y02A50/473
摘要： We disclose a method of inhibiting activity of adenylyl cyclase or guanylyl cyclase in a mammal by administering to the mammal an amount of a composition effective to inhibit the activity, wherein the composition contains at least one compound selected from the group consisting of structural formulae (Ia) and (Ib) and salts thereof, wherein R1 is —H or has the structure —C(═O)R8; R2 is ═O or has the structure —OC(═O)R9; and R3, R4, R5, R6, and R7 are each independently selected from the group consisting of —H, —NO2, formula (I), -halogen, —OC(═O)R9, —OR9, —OH, —R8OH, —CH3, —OC(═O)CH2Ph, formulae (II), (III), (IV), —OPh, —CF3, —R8, —C(═O)OR9, -Ph, —R8Ph, formulae (V), (VI), (VII), (VIII), (IX), (X), (XI), (XII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII), (XIX), (XX), and (XXI), wherein each R8 is independently a linear or branched hydrocarbon group having from 1 to 4 carbon atoms and each R9 is independently a hydrocarbon group having from 1 to 2 carbon atoms. Administering the composition can be used to treat a disease in a mammal mediated by activity of adenylyl cyclase or guanylyl cyclase and effected by a toxin produced by a pathogenic organism or to reduce cyclic AMP or cyclic GMP levels in a mammal in need of reduction thereof. The composition can also be administered to mammalian cells in vitro. The above methods of inhibiting activity of adenylyl cyclase or guanylyl cyclase and treating diseases via such inhibition can be effective without prolonged treatment, have reversible effects, have low or no toxicity, are highly potent, are unlikely to have side effects, do not act on purinergic receptors, or can negate pathogenic toxins independently of whether the pathogenic organism survives.
摘要翻译：我们公开了通过向哺乳动物施用一定量的有效抑制活性的组合物来抑制腺苷酸环化酶或鸟苷酸环化酶的活性的方法，其中组合物含有至少一种选自结构式（Ia ）和（Ib）及其盐，其中R 1是-H或具有-C（-O）R 8的结构; R2是-O或具有-OC（-O）R9的结构; 并且R 3，R 4，R 5，R 6和R 7各自独立地选自-H，-NO 2，式（I）， - 卤素，-OC（-O）R 9，-OR 9，-OH，-R 8 OH ，-CH 3，-OC（-O）CH 2 Ph，式（II），（III），（IV），-OPh，-CF 3，-R 8，-C（ - ）OR 9，-Ph，-R 8 Ph，（ⅩⅢ），（ⅩⅣ），（ⅩⅤ），（ⅩⅥ），（ⅩⅦ），（ⅩⅥ），（ⅩⅥ），（XVIII），（XIX），（XX）和（XXI），其中每个R 8独立地为具有1至4个碳原子的直链或支链烃基，并且每个R 9独立地为具有1至2个碳原子的烃基原子施用组合物可用于治疗由腺苷酸环化酶或鸟苷酸环化酶的活性介导的哺乳动物疾病，并且由病原生物产生的毒素影响，或减少需要还原的哺乳动物中的环AMP或环GMP水平。组合物也可以在体外施用于哺乳动物细胞。上述抑制腺苷酸环化酶或鸟苷酸环化酶的活性和通过这种抑制作用治疗疾病的方法可以在没有延长治疗的情况下有效，具有可逆作用，具有低毒性或无毒性，高度有效，不会产生副作用，不起作用嘌呤能受体，或者可以否定致病性毒素，而不管病原菌是否存活。

8. 发明授权

US06649746B1 Biological production of stable glutamine, poly-glutamine derivatives in transgenic organisms and their use for therapeutic purposes 有权
标题翻译：转基因生物中稳定的谷氨酰胺，多谷氨酰胺衍生物的生物生物及其用于治疗目的
公开(公告)号：US06649746B1
公开(公告)日：2003-11-18
申请号：US09563096
申请日：2000-05-02
申请人： Michael P. Timko , Richard L. Guerrant
发明人： Michael P. Timko , Richard L. Guerrant
IPC分类号： C07H2104
CPC分类号： C07K14/00 , A61K38/00 , C07K2319/00
摘要： The invention provides a bioproduction of glutamine rich peptides. These peptides are used for rehydration and nutrition therapy in patients and for enhanced nutrition in animals. The peptides may be used as individual peptides or combined with other peptides in oligopeptides or proteins. Compositions of glutamine rich peptides and nucleic acid sequences for producing such peptides, as well as methods of production and use, are described.
摘要翻译：本发明提供了富含谷氨酰胺的肽的生物生产。这些肽用于患者的补液和营养治疗，并用于增强动物营养。肽可以用作单独的肽或与寡肽或蛋白质中的其它肽组合使用。描述了富集谷氨酰胺的组合物和用于产生这种肽的核酸序列，以及生产和使用方法。

9. 发明授权

US5561111A Stable glutamine derivatives for oral and intravenous rehydration and nutrition therapy 失效
标题翻译：稳定的谷氨酰胺衍生物用于口服和静脉补液和营养治疗
公开(公告)号：US5561111A
公开(公告)日：1996-10-01
申请号：US362914
申请日：1994-12-23
申请人： Richard L. Guerrant , Timothy L. MacDonald , Aldo A. M. Lima , Nathan M. Thielman , Thomas Miller
发明人： Richard L. Guerrant , Timothy L. MacDonald , Aldo A. M. Lima , Nathan M. Thielman , Thomas Miller
IPC分类号： A61K38/05 , A61K38/06 , A61K38/04
CPC分类号： A61K38/06 , A61K38/05
摘要： A method for the treatment of dehydration or nitrogen deficiency-based malnutrition is provided which involves administering to a patient in need thereof an effective amount of a compound selected from oligopeptides formed from the coupling of one or more amino acids with glutamine, the product of coupling glucose with glutamine, the product of coupling glucose and one or more amino acids with glutamine, or the product from acylating glutamine with a carboxylic acid having from 2 to 6 carbon atoms.
摘要翻译：提供了一种治疗脱水或基于缺氮的营养不良的方法，其涉及向有需要的患者施用有效量的选自由一种或多种氨基酸与谷氨酰胺偶联形成的寡肽的化合物，偶联产物葡萄糖与谷氨酰胺，将葡萄糖和一种或多种氨基酸与谷氨酰胺偶联的产物，或由具有2至6个碳原子的羧酸酰化谷氨酰胺的产物。

10. 发明授权

US4820714A Use of phospholipase inhibitors in the treatment of Clostridium difficile diarrhea 失效
标题翻译：磷脂酶抑制剂在难辨梭状芽胞杆菌腹泻治疗中的应用
公开(公告)号：US4820714A
公开(公告)日：1989-04-11
申请号：US858674
申请日：1986-05-02
申请人： Richard L. Guerrant , Aldo M. Lima
发明人： Richard L. Guerrant , Aldo M. Lima
IPC分类号： A61K31/23 , A61K31/44 , A61K31/225
CPC分类号： A61K31/00 , A61K31/23 , Y10S514/867
摘要： Hemorrhagic fluid secretion and histologic damage to the intestinal mucosa by C. difficile toxin is blocked by the use of phospholipase inhibitors.
摘要翻译：通过使用磷脂酶抑制剂阻止艰难梭菌毒素对出血性分泌和对肠粘膜的组织学损伤。

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