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1. 发明申请

WO2003075904A2 ARTEMISININS WITH IMPROVED STABILITY AND BIOAVAILABILITY FOR THERAPEUTIC DRUG DEVELOPMENT AND APPLICATION 审中-公开
标题翻译：具有改进的治疗药物开发和应用的稳定性和生物利用度的ARTEMISININ
公开(公告)号：WO2003075904A2
公开(公告)日：2003-09-18
申请号：PCT/US2003/006283
申请日：2003-02-28
申请人： WRAIR , HARTELL, Mark, G. , BHATTACHARJEE, Apurba, K. , HICKS, Rickey, P. , VANHAMONT, John, E. , MILHOUS, Wilbur, K.
发明人： HARTELL, Mark, G. , BHATTACHARJEE, Apurba, K. , HICKS, Rickey, P. , VANHAMONT, John, E. , MILHOUS, Wilbur, K.
IPC分类号： A61K31/00
CPC分类号： B82Y5/00 , A61K31/55 , A61K31/724 , A61K47/6951 , Y02A50/411 , Y10S514/895
摘要： A stable form of artemisinin wherein an artelinic acid or artesunic acid is complexed with cyclodextrin analogs, preferably, β-cyclodextrin. The complexed cyclodextrin artemisinin formulation shields the peroxide portion of the artemisinin backbone from hydrolytic decomposition rendering it stable in solution. Artelinic acid and cyclodextrin are placed into contact with one another to yield a 2:1 molecular species. Artesunic acid and cyclodextrin yield a 1:1 molecular species. The complexed cyclodextrin artemisinin formulation is effective for the treatment of malaria and is stable in solution for long periods of time.
摘要翻译：青蒿素的稳定形式，其中木糖酸或青蒿琥酯与环糊精类似物（优选β-环糊精）络合。络合的环糊精青蒿素配方将青蒿素骨架的过氧化物部分屏蔽水解分解，使其在溶液中稳定。将阿魏酸和环糊精彼此接触以产生2:1的分子种类。青蒿琥酯和环糊精产生1：1的分子种类。络合的环糊精青蒿素制剂对于治疗疟疾是有效的，并且在溶液中长时间稳定。

2. 发明申请

WO2008133984A4 COMBINATIONS OF GENE DELETIONS FOR LIVE ATTENUATED SHIGELLA VACCINE STRAINS 审中-公开
标题翻译：遗传性灭活疫霉菌株遗传基因的组合
公开(公告)号：WO2008133984A4
公开(公告)日：2009-03-05
申请号：PCT/US2008005342
申请日：2008-04-25
申请人： US ARMY WRAIR , VENKATESAN MALABI M , RANALLO RYAN T , BARNOY SHOSHANA
发明人： VENKATESAN MALABI M , RANALLO RYAN T , BARNOY SHOSHANA
IPC分类号： A61K39/02
CPC分类号： A61K39/0283 , A61K2039/522
摘要： Shigella vaccine strains whose primary attenuating feature is deletion of the virG(icsA) gene and additional two or more deletions in setAB(shET1), senA(shET2), senB(shET2- 2), stxAB, and msbB2 genes. Thus, the vaccine strain will have three or more deletions in the identified genes, will be safer, and will reduce or eliminate symptoms of fever and diarrhea in humans. The following specific vaccine strains have been constructed: WRSS3 (?senA, ?senB, ?virG, ?msbB2), WRSf2G15 (?virG, ?setAB, ?senA, ?senB, ?msbB2), and WRSd5 (?virG, ? stxAB, ?senA, ?senB, ?msbB2).
摘要翻译：志贺氏菌疫苗菌株，其主要减毒特征是virG（icsA）基因的缺失和在setAB（shET1），senA（shET2），senB（shET2-2），stxAB和msbB2基因中的另外两个或更多个缺失。因此，疫苗株在鉴定的基因中将具有三个或更多个缺失，将更安全，并且将减少或消除人类发烧和腹泻的症状。已经构建了以下具体的疫苗株：WRSS3（？senA，？senB，？virG，？msbB2），WRSf2G15（？virG，？setAB，？senA，？senB，？msbB2）和WRSd5（？virG，？stxAB ，？senA，？senB，？msbB2）。

3. 发明申请

WO2007038392A2 ANTIBODIES WITH SIMULTANEOUS SUBSITE SPECIFICITIES TO PROTEIN AND LIPID EPITOPES 审中-公开
标题翻译：抗体同时具有蛋白质和脂类表位特异性
公开(公告)号：WO2007038392A2
公开(公告)日：2007-04-05
申请号：PCT/US2006/037185
申请日：2006-09-22
申请人： WALTER REED ARMY INSTITUTE OF RESEARCH (WRAIR) , ALVING, Carl, R.
发明人： ALVING, Carl, R.
CPC分类号： C07K16/1063 , A61K39/12 , A61K39/21 , A61K2039/545 , A61K2039/55555 , A61K2039/55572 , A61K2039/6018 , C07K16/1045 , C07K16/18 , C07K16/468 , C07K2317/31 , C07K2317/33 , C07K2317/76 , C12N2740/16034 , C12N2740/16134
摘要： Antibodies and method of making antibodies, either monoclonal or polyclonal wherein said antibodies have dual or multi-specific binding capacity to more than one type of antigenic epitope. The antibodies have simultaneous or independent recognition subsites to each of the epitopes. Antigenic epitopes include lipids, peptides, proteins, amino acid sequences, sugars and carbohydrates. Monoclonal antibodies and a method of making monoclonal antibodies of the invention include monoclonal antibodies that are broadly neutralizing to HIV-I or other envelop viruses wherein the monoclonal antibody has subsites that simultaneously recognize protein and lipid epitopes from the virus.
摘要翻译：抗体和制备单克隆或多克隆抗体的方法，其中所述抗体对超过一种类型的抗原表位具有双特异性或多特异性结合能力。抗体对每个表位具有同时或独立的识别位点。抗原表位包括脂质，肽，蛋白质，氨基酸序列，糖和碳水化合物。单克隆抗体和制备本发明单克隆抗体的方法包括广泛中和HIV-1或其他包膜病毒的单克隆抗体，其中单克隆抗体具有同时识别来自病毒的蛋白质和脂质表位的亚位点。

4. 发明申请

WO2007146288A2 METHODS FOR THE FORMULATION AND MANUFACTURE OF ARTESUNIC ACID FOR INJECTION 审中-公开
标题翻译：制备和制备用于注射的ARTESENIC酸的方法
公开(公告)号：WO2007146288A2
公开(公告)日：2007-12-21
申请号：PCT/US2007/013781
申请日：2007-06-12
申请人： WALTER REED ARMY INSTITUTE OF RESEARCH (WRAIR) , ELLIS, William, Y. , LIM, Peter , MANIAR, Manaj
发明人： ELLIS, William, Y. , LIM, Peter , MANIAR, Manaj
CPC分类号： A61K9/0019 , A61K31/357 , Y02A50/411
摘要： A method for the manufacture of a sterile intravenous or intramuscular formulation of artesunic acid and the formulation are the subject of this invention. First the artesunic acid powder is sterilized with ethylene oxide and placed into a sterile container. The contained sterilized powder is then dissolved in sterile sodium phosphate buffered solution to produce an injectable intravenous or intramuscular formulation. The sodium phosphate dissolves and dilutes the artesunic acid powder without caking or frothing resulting in an improved drug product. The invention also relates to the formulation and a method of treating a patient with either uncomplicated or severe and complicated malaria.
摘要翻译：用于制造无菌静脉内或肌肉内青蒿琥酯和制剂的制剂的方法是本发明的主题。首先将青蒿琥酯粉末用环氧乙烷灭菌并置于无菌容器中。然后将含有的灭菌粉末溶解在无菌磷酸钠缓冲溶液中以产生可注射的静脉内或肌肉内制剂。磷酸钠溶解并稀释青蒿琥酯粉末，不结块或发泡，导致改良的药物。本发明还涉及治疗患有不复杂或严重和复杂的疟疾的患者的制剂和方法。

5. 发明申请

WO2006046949A1 SYNTHESIS AND ANTIMALARIAL ACTIVITY OF PYRROLO[3,2-f]QUINAZOLINE-1,3- DIAMINE DERIVATIVES 审中-公开
标题翻译：吡咯并[3,2-f]喹唑啉-1,3-二胺衍生物的合成和抗微生物活性
公开(公告)号：WO2006046949A1
公开(公告)日：2006-05-04
申请号：PCT/US2004/035254
申请日：2004-10-22
申请人： WALTER REED ARMY INSTITUTE OF RESEARCH (WRAIR) , AI, J., Lin , JIAN, Guan , QUAN, Zhang , SKILLMAN, Donald, R.
发明人： AI, J., Lin , JIAN, Guan , QUAN, Zhang , SKILLMAN, Donald, R.
IPC分类号： C07D487/04
CPC分类号： C07D487/04
摘要： The invention relates to derivatives of pyrroloquinazolinediamine, more specifically derivatives of 7-(substituted)-7H-pyrrolo[3,2-F] quinazoline-1,3-diamines that are non-toxic and are also effective in the treatment of malaria, including P. falciparum and P.vivax strains. The derivatives are certain carbamate derivatives, succinimide derivatives, alkylcarboxamides derivatives and acetamide derivative, phthalimides, alkylamines and all other amide and imide derivatives and their 1-hydroxy analogs,. The derivatives of the present invention are also soluble in common organic solvents to facilitate the purification in a large scale synthesis of the composition.
摘要翻译：本发明涉及吡咯并喹啉二胺的衍生物，更具体地说是7-（取代的）-7H-吡咯并[3,2-F]喹唑啉-1,3-二胺的衍生物，它们是无毒的并且也有效地用于治疗疟疾，包括恶性疟原虫和P.vivax菌株。衍生物是某些氨基甲酸酯衍生物，琥珀酰亚胺衍生物，烷基酰胺衍生物和乙酰胺衍生物，邻苯二甲酰亚胺，烷基胺和所有其它酰胺和酰亚胺衍生物及其1-羟基类似物。本发明的衍生物也可溶于普通的有机溶剂中以促进组合物的大规模合成中的纯化。

6. 发明申请

WO2003075904A3 CYCLODEXTRIN COMPLEXED ARTEMISININS 审中-公开
公开(公告)号：WO2003075904A3
公开(公告)日：2003-09-18
申请号：PCT/US2003/006283
申请日：2003-02-28
申请人： WRAIR , HARTELL, Mark, G. , BHATTACHARJEE, Apurba, K. , HICKS, Rickey, P. , VANHAMONT, John, E. , MILHOUS, Wilbur, K.
发明人： HARTELL, Mark, G. , BHATTACHARJEE, Apurba, K. , HICKS, Rickey, P. , VANHAMONT, John, E. , MILHOUS, Wilbur, K.
IPC分类号： A61K31/365
摘要： A stable form of artemisinin wherein an artelinic acid or artesunic acid is complexed with cyclodextrin analogs, preferably, β-cyclodextrin. The complexed cyclodextrin artemisinin formulation shields the peroxide portion of the artemisinin backbone from hydrolytic decomposition rendering it stable in solution. Artelinic acid and cyclodextrin are placed into contact with one another to yield a 2:1 molecular species. Artesunic acid and cyclodextrin yield a 1:1 molecular species. The complexed cyclodextrin artemisinin formulation is effective for the treatment of malaria and is stable in solution for long periods of time.

7. 发明申请

WO2008079127A1 ARTEMISININS IN THE CLINICAL AND VETERINARY MANAGEMENT OF KINETOPLASTID INFECTIONS 审中-公开
标题翻译：肠系膜感染的临床和兽医管理中的病例
公开(公告)号：WO2008079127A1
公开(公告)日：2008-07-03
申请号：PCT/US2006/049266
申请日：2006-12-22
申请人： WALTER REED ARMY INSTITUTE OF RESEARCH (WRAIR) , KUBATA, Bruno , MARTIN, Samuel , MILHOUS, Wilbur
发明人： KUBATA, Bruno , MARTIN, Samuel , MILHOUS, Wilbur
IPC分类号： A61K36/282 , A61P33/02
CPC分类号： A61K36/282
摘要： The invention relates to the treatment of kintoplastid infections by administering a pharmaceutical composition containing an extract from the plant Artemisia annua. The invention also relates to isolated, semi-synthetic and synthetic artemisinins that show improved efficacy in treating kinetoplastid infections. This invention also relates to a method of treating kintoplastid infections with artelinic acid and artemisinins and where Artelinic acid is administered orally.
摘要翻译：本发明涉及通过施用含有来自艾蒿植物的提取物的药物组合物来治疗激素质感染。本发明还涉及分离的，半合成的和合成的青蒿素，其在治疗动粒细胞感染中显示出改进的功效。本发明还涉及一种用阿魏酸和青蒿素治疗激素质感染的方法，其中口服阿片ic酸。

8. 发明申请

WO2007136617A2 ENDOTHELIAL MONOCYTE ACTIVATING POLYPEPTIDE II, A BIOMARKER FOR USE IN DIAGNOSIS AND TREATMENT OF BRAIN INJURY 审中-公开
标题翻译：内含单核细胞活化多肽II，用于诊断和治疗脑损伤的生物标记物
公开(公告)号：WO2007136617A2
公开(公告)日：2007-11-29
申请号：PCT/US2007/011613
申请日：2007-05-15
申请人： WALTER REED ARMY INSTITUTE OF RESEARCH (WRAIR) , DAVE, Jitendra, Ramantal , YAO, Changping , WILLIAMS, Anthony, Joseph , MAY, Xi-chun , TORTELLA, Frank, Casper , WANG, Ka-wang, Kevin , HAYES, Ronald, Lawrence
发明人： DAVE, Jitendra, Ramantal , YAO, Changping , WILLIAMS, Anthony, Joseph , MAY, Xi-chun , TORTELLA, Frank, Casper , WANG, Ka-wang, Kevin , HAYES, Ronald, Lawrence
CPC分类号： G01N33/6896 , G01N33/6863 , G01N33/6893 , G01N2333/52 , G01N2800/28 , G01N2800/2871
摘要： A diagnostic tool and method of diagnosing brain injury and brain injury type (traumatic vs. ischemic) by detecting the level of expression of endothelial monocyte- activating polypeptide II (EMAP-II) and comparing to a control. An increase of EMAP-II indicates the presence of traumatic brain injury and a decrease of EMAP-II indicates the presence of ischemic brain injury. Detection of EMAP-II can be done in brain tissue, biofluids such as cerebrospinal fluid or blood (including plasma and serum)
摘要翻译：通过检测内皮单核细胞激活多肽II（EMAP-II）的表达水平并与对照组比较，诊断脑损伤和脑损伤类型（创伤性与缺血性）的诊断工具和方法。 EMAP-II的增加表明存在创伤性脑损伤，EMAP-II的降低表明存在缺血性脑损伤。 EMAP-II的检测可以在脑组织，生物流体如脑脊液或血液（包括血浆和血清）中进行，

9. 发明申请

WO0128578A3 A PHARMACEUTICAL COMPOSITION CONTAINING pGLU-GLU-PRO-NH<2> AND METHOD FOR TREATING DISEASES AND INJURIES TO THE BRAIN, SPINAL CORD AND RETINA USING SAME 审中-公开
标题翻译：含有pGLU-GLU-PRO-NH2的药物组合物和用于治疗脑，脊髓和脊髓的疾病和损伤的方法
公开(公告)号：WO0128578A3
公开(公告)日：2001-11-22
申请号：PCT/US0029278
申请日：2000-10-20
申请人： WRAIR , MEYERHOFF JAMES L , KOENIG MICHAEL L , LONG JOSEPH B
发明人： MEYERHOFF JAMES L , KOENIG MICHAEL L , LONG JOSEPH B
IPC分类号： A61K38/06 , A61K45/06 , A61P25/00 , A61P27/02
CPC分类号： A61K45/06 , A61K38/06 , A61K2300/00
摘要： A neuroprotectant composition wherein the active ingredient is pGLU-GLU-PRO-NH or a combination of pGLU-GLU-PRO-NH (EEP) and N-tert-Butyl- alpha -(2-sulfophenyl)nitrone(SPBN) or other nitrone. A method of treating and preventing diseases and injuries of the brain, spinal cord and retina is also presented by administering the endogenous tripeptide EEP to a subject as a neuroprotectant or by administering EEP in combination with SPBN or other nitrone.
摘要翻译：一种神经保护剂组合物，其中活性成分是pGLU-GLU-PRO-NH 2或pGLU-GLU-PRO-NH 2（EEP）和N-叔丁基-α-（2-磺基苯基）硝酮的组合（SPBN）或其他硝酮。通过向作为神经保护剂的受试者施用内源性三肽EEP或通过与SPBN或其他硝酮组合施用EEP来提供治疗和预防脑，脊髓和视网膜的疾病和损伤的方法。

10. 发明申请

WO0018769A3 INDOLO[2,1-b]QUINAZOLE-6,12-DIONE ANTIMALARIAL COMPOUNDS AND METHODS OF TREATING MALARIA THEREWITH 审中-公开
标题翻译：吲哚并[2,1-b]喹唑-6,12-二酮类抗疟化合物及其治疗疟疾的方法
公开(公告)号：WO0018769A3
公开(公告)日：2000-09-08
申请号：PCT/US9922569
申请日：1999-09-28
申请人： WRAIR WALTER REID ARMY INST OF , PITZER KEVIN K , SCOVILL JOHN P , KYLE DENNIS E , GERENA LUCIA
发明人： PITZER KEVIN K , SCOVILL JOHN P , KYLE DENNIS E , GERENA LUCIA
IPC分类号： C07D471/14 , C07D487/04 , C07D487/14 , C07D498/04 , C07D513/04 , C07D487/22 , A61K31/38
CPC分类号： C07D471/14 , C07D487/04 , C07D487/14 , C07D513/04 , Y10S514/895
摘要： New use for compounds, compositions and methods are provided for treating malaria parasites in vitro and in vivo by administering indolo[2,1-b]quinazoline-6,12-dione compounds of Formula (I), wherein A, B, C, D, E, F, G and H are independently selected from carbon and nitrogen, or A and B or C and D can be taken together to be nitrogen or sulfur, with the proviso that not more than three of A, B, C, D, E, F, G and H are other than carbon; wherein R1 through R8 are independently selected from the group consisting of, but not limited to, the halogens (F, Cl, Br, and I), alkyl groups, trifluoromethyl groups, methoxyl groups, the carboxy methyl or carboxy ethyl group (COOCH3 or COOCH2CH3), nitro, aryl, heteroaryl, cyano, amino, dialkylaminoalkyl, 1-(4-alkylpiperazinyl), and the pharmaceutically acceptable salts thereof; and wherein X is independently selected from the group consisting of any atom especially oxygen, or any side chain necessary to make the indolo[2,1-b]quinazoline-6,12-dione compound a "prodrug" as the term is understood by one of ordinary skill in the art of medicinal chemistry. In other words, a side chain having a structure where a carbon-nitrogen double bond bears substituents that make the prodrug more water soluble and bioavailable.
摘要翻译：提供了通过施用式（I）的吲哚并[2,1-b]喹唑啉-6,12-二酮化合物在体外和体内治疗疟疾寄生虫的化合物，组合物和方法的新用途，其中A，B，C， D，E，F，G和H独立地选自碳和氮，或者A和B或C和D可以合在一起形成氮或硫，附带条件是A，B，C， D，E，F，G和H不是碳; 其中R 1至R 8独立地选自但不限于卤素（F，Cl，Br和I），烷基，三氟甲基，甲氧基，羧甲基或羧乙基（COOCH 3或硝基，芳基，杂芳基，氰基，氨基，二烷基氨基烷基，1-（4-烷基哌嗪基）及其药学上可接受的盐; 并且其中X独立地选自由任何原子特别是氧原子或任何制备吲哚并[2,1-b]喹唑啉-6,12-二酮化合物所必需的侧链，该术语可理解为“前药” 药物化学领域的普通技术人员之一。换句话说，具有碳 - 氮双键带有取代基的结构的侧链使得前药更易溶于水且具有生物利用度。

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