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1. 发明授权

US5589516A Liquid preparation of antithrombin-III and stabilizing method therefor 失效
标题翻译：抗凝血酶III的液体制剂及其稳定方法
公开(公告)号：US5589516A
公开(公告)日：1996-12-31
申请号：US351268
申请日：1994-12-05
申请人： Katsuhiro Uriyu , Akimasa Ohmizu , Hajime Fukuyama , Kazuo Takechi , Kazumasa Yokoyama
发明人： Katsuhiro Uriyu , Akimasa Ohmizu , Hajime Fukuyama , Kazuo Takechi , Kazumasa Yokoyama
IPC分类号： A61K38/57 , A61K47/10 , A61K47/12 , A61K47/18 , A61K47/26 , A61K47/36 , A61K35/16 , A61K39/395 , A61K37/18 , A61K37/64
CPC分类号： A61K47/36 , A61K38/57 , A61K47/10 , A61K47/12 , A61K47/183 , A61K47/26 , A61K9/0019 , Y10S514/802
摘要： A liquid preparation of antithrombin-III (AT-III), comprising an AT-III and an organic acid, a salt thereof, a sugar sulfate or a surfactant as a stabilizer, and a liquid preparation of AT-III, having a pH of 9-10. The preparation of the present invention is stable after long-term preservation and poses no clinical problems in terms of pharmacological effects and safety. The preparation is more advantageous than lyophilized preparations in that it does not require dissolution in injectable distilled water and can be used easily. Accordingly, the preparation is clinically very useful.
摘要翻译： PCT No.PCT / JP94 / 00563 Sec。 371日期1994年12月5日第 102（e）1994年12月5日PCT PCT 1994年4月5日PCT公布。第WO94 / 22471号公报日期：1994年10月13日含有AT-III和有机酸，其盐，糖硫酸盐或表面活性剂作为稳定剂的抗凝血酶III（AT-III）的液体制剂和AT-III的液体制剂，pH为9-10。本发明的制剂在长期保存后是稳定的，在药理作用和安全性方面没有临床问题。该制剂比冻干制剂更有利，因为其不需要在可注射的蒸馏水中溶解并且可以容易地使用。因此，该制剂在临床上非常有用。

2. 发明授权

US4740462A Non-phosphorylated peptides from casein-based material 失效
标题翻译：来自酪蛋白的材料的非磷酸化肽
公开(公告)号：US4740462A
公开(公告)日：1988-04-26
申请号：US821460
申请日：1986-01-22
申请人： Gerard Brule , Roger Loic , Jacques Fauquant , Michel Piot
发明人： Gerard Brule , Roger Loic , Jacques Fauquant , Michel Piot
IPC分类号： A23J3/00 , A23J3/10 , A23J3/34 , A23L1/305 , A61K38/00 , A61K38/01 , A61K38/17 , C07K1/14 , C12P21/06 , A61K37/18 , C07K1/00
CPC分类号： A61K38/018 , A23J3/34 , A23J3/344 , A23L33/19
摘要： Nonphosphorylated peptides and phosphopeptides useful as alimentary products or medicaments are produced by proteolytic enzyme hydrolysis of a casein-based material. Ultrafiltration is used to separate phosphopeptides and nonphosphorylated peptides after hydrolysis. A bivalent cation is added to form aggregates of the phosphopeptides, and the aggregated phosphopeptides are separated from the nonphosphorylated peptides by ultrafiltration. The phosphopeptides form salts, which have dietefic uses, with macroelements such as calcium and/or magnesium and/or oligoelements such as iron and zinc.
摘要翻译：用作消化产物或药物的非磷酸化肽和磷酸肽通过酪蛋白基材料的蛋白水解酶水解产生。超滤用于在水解后分离磷酸肽和非磷酸化肽。加入二价阳离子以形成磷酸肽的聚集体，并且聚集的磷酸肽通过超滤从非磷酸化肽分离。磷酸肽形成具有日粮消费用途的盐，具有诸如钙和/或镁和/或稀土元素如铁和锌的大量元素。

3. 发明授权

US4094973A Medical protein hydrolysate and process of using the same 失效
标题翻译：医药蛋白水解物及其使用方法
公开(公告)号：US4094973A
公开(公告)日：1978-06-13
申请号：US685050
申请日：1976-05-10
申请人： Harry J. Robertson
发明人： Harry J. Robertson
IPC分类号： A61K35/12 , A61K35/57 , A61K38/01 , A61L26/00 , A61K37/18 , A61K37/02
CPC分类号： A61L26/0057 , A61K35/57 , A61K38/012 , A61L26/0047 , Y10S514/801
摘要： Medical protein hydrolysate is produced from the feet of young freshly killed poultry. The protein, thus produced, is an extract of polypeptides and amino acids. It is in the form of a powder or a gel, each of which is suitable for topical application to living cells of animals and humans for aiding in healing. The process of production of the protein hydrolysate includes treating the washed and comminuted poultry feet or other source of protein with a dilute acid, preferably acetic acid, and drying under low heat conditions the resulting solution to a powder or to a gel. The process of using the protein hydrolysate including periodic topical application to a traumatized (wound) area. In the event that treatment is to be below the surface, an aqueous solution of the protein can be injected into the area to be treated.
摘要翻译：用于药用的蛋白质水解产物是从新鲜杀死的小禽的脚上产生的。如此产生的蛋白质是多肽和氨基酸的提取物。它是粉末或凝胶的形式，其中每一种适用于局部施用于动物和人的活细胞以辅助愈合。生产蛋白质水解产物的方法包括用稀酸（优选乙酸）处理家禽或其他蛋白质源的脚，洗涤并分成颗粒，并在低热条件下干燥所得溶液直到粉末或凝胶获得。蛋白质水解物可以周期性局部施用于创伤区域（伤口）。在表面施用处理的情况下，蛋白质的水溶液可以注入待处理区域。

4. 发明授权

US07776834B2 Immunostimulatory properties of oligonucleotide-based compounds comprising modified immunostimulatory dinucleotides 失效
标题翻译：包含修饰的免疫刺激二核苷酸的基于寡核苷酸的化合物的免疫刺激性质
公开(公告)号：US07776834B2
公开(公告)日：2010-08-17
申请号：US11268714
申请日：2005-11-07
申请人： Sudhir Agrawal , Dong Yu , Ekambar Kandimalla
发明人： Sudhir Agrawal , Dong Yu , Ekambar Kandimalla
IPC分类号： A61K31/70 , A61K38/00 , A61K37/18 , A61K39/00 , A61K39/35 , A61K39/36 , A01N43/04 , C07H21/02 , C07H21/04
CPC分类号： A61K31/70
摘要： The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides an immunostimulatory oligonucleotides for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunostimulatory oligonucleotides of the invention preferably comprise novel purines. The immunostimulatory oligonucleotides according to the invention further comprise at least two oligonucleotides linked at their 3′ ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunostimulatory oligonucleotide and having an accessible 5′ end.
摘要翻译：本发明涉及在免疫治疗应用中寡核苷酸作为免疫刺激剂的治疗用途。更具体地，本发明提供了用于产生免疫应答的方法或用于治疗需要免疫刺激的患者的免疫刺激性寡核苷酸。本发明的免疫刺激性寡核苷酸优选包含新的嘌呤。根据本发明的免疫刺激性寡核苷酸还包含至少两个在其3'末端连接的寡核苷酸，核苷间键或官能化核碱基或糖与非核酸连接体，至少一个寡核苷酸是免疫刺激性寡核苷酸并具有可接近的5' 结束。

5. 发明授权

US06989366B2 Exendins, exendin agonists, and methods for their use 失效
公开(公告)号：US06989366B2
公开(公告)日：2006-01-24
申请号：US10187051
申请日：2002-06-28
申请人： Nigel Robert Arnold Beeley , Kathryn S. Prickett , Sunil Bhavsar
发明人： Nigel Robert Arnold Beeley , Kathryn S. Prickett , Sunil Bhavsar
IPC分类号： A61K38/00 , A61K37/18
CPC分类号： A61K9/0019 , A61K38/00 , A61K38/22 , A61K38/2207 , A61K38/2264 , A61K38/23 , A61K47/02 , A61K47/10 , A61K47/12 , A61K47/26 , A61K47/44 , C07K14/57563 , Y10S514/866 , A61K2300/00
摘要： Methods for treating conditions or disorders which can be alleviated by reducing food intake are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist, alone or in conjunction with other compounds or compositions that affect satiety. The methods are useful for treating conditions or disorders, including obesity, Type II diabetes, eating disorders, and insulin-resistance syndrome. The methods are also useful for lowering the plasma glucose level, lowering the plasma lipid level, reducing the cardiac risk, reducing the appetite, and reducing the weight of subjects. Pharmaceutical compositions for use in the methods of the invention are also disclosed.

6. 发明授权

US06956026B2 Use of exendins for the reduction of food intake 失效
标题翻译：使用exendins来减少食物摄取量
公开(公告)号：US06956026B2
公开(公告)日：2005-10-18
申请号：US09003869
申请日：1998-01-07
申请人： Nigel Robert Arnold Beeley , Sunil Bhavsar
发明人： Nigel Robert Arnold Beeley , Sunil Bhavsar
IPC分类号： A61K45/00 , A61K35/56 , A61K38/00 , A61K38/17 , A61K38/22 , A61K38/23 , A61P3/04 , A61P3/06 , A61P3/10 , A61P9/00 , C07K14/575 , A61K37/18
CPC分类号： A61K9/0019 , A61K38/00 , A61K38/22 , A61K38/2207 , A61K38/2264 , A61K38/23 , A61K47/02 , A61K47/10 , A61K47/12 , A61K47/26 , A61K47/44 , C07K14/57563 , Y10S514/866 , A61K2300/00
摘要： Methods for treating conditions or disorders which can be alleviated by reducing food intake are disclosed which comprise administration of an effective amount of an exendin or an exendin agonist, alone or in conjunction with other compounds or compositions that affect satiety. The methods are useful for treating conditions or disorders, including obesity, Type II diabetes, eating disorders, and insulin-resistance syndrome. The methods are also useful for lowering the plasma glucose level, lowering the plasma lipid level, reducing the cardiac risk, reducing the appetite, and reducing the weight of subjects. Pharmaceutical compositions for use in the methods of the invention are also disclosed.
摘要翻译：公开了通过减少食物摄入可以缓解的病症或病症的方法，其包括单独施用有效量的毒蜥外泌肽或毒蜥外泌肽激素，或与影响饱腹感的其它化合物或组合物联合施用。该方法可用于治疗条件或障碍，包括肥胖，II型糖尿病，进食障碍和胰岛素抵抗综合征。该方法对于降低血浆葡萄糖水平，降低血浆脂质水平，降低心脏风险，降低食欲和降低受试者的体重也是有用的。还公开了用于本发明方法的药物组合物。

7. 发明授权

US5334380A Anti-endotoxin, interleukin-1 receptor antagonist and anti-tumor necrosis factor antibody with arginine-free formulations for the treatment of hypotension 失效
标题翻译：抗内毒素，白细胞介素-1受体拮抗剂和抗肿瘤坏死因子抗体与无精氨酸制剂治疗低血压
公开(公告)号：US5334380A
公开(公告)日：1994-08-02
申请号：US910868
申请日：1992-06-30
申请人： Robert G. Kilbourn , Owen W. Griffith , Steven S. Gross
发明人： Robert G. Kilbourn , Owen W. Griffith , Steven S. Gross
IPC分类号： A61K31/415 , A61K31/715 , A61K38/04 , A61K38/19 , A61K37/02 , A61K37/04 , A61K37/18
CPC分类号： A61K31/415 , A61K31/715 , A61K38/20 , A61K39/395
摘要： Methods and compositions for treating and inhibiting hypotension related to both endotoxin and cytokine-induced shock are provided. A therapeutic regimen useful in the present invention includes an arginine-free parenteral formulation administered with or followed by the administration of an anti-endotoxin antibody, an interleukin-1 or interleukin-2 receptor antagonist, an anti-tumor necrosis factor antibody or a combination thereof. Most preferably, the administration of an arginine-free parenteral formulation augments the anti-hypotensive effect of the various antibodies and antagonist described so as to provide an effective treatment for various forms of hypotension. The therapeutic regimens of the invention are proposed to provide for a decrease in nitric oxide synthase, and thereby an increase in blood pressure in vivo, particularly in animals with cytokine- and/or endotoxin-induced hypotension. The parenteral formulation of the therapeutic regimen and methods of the invention are arginine-free and provide a decrease in plasma arginine levels. Reduced plasma, serum, or tissue levels of arginine in the animal function to augment the hypertensive action of the various antibodies and antagonist to be administered concurrently or subsequent to the administration of the parenteral formulation. Limiting and/or eliminating substrate arginine for nitric oxide synthesis, coupled with limiting and/or eliminating induction of nitric oxide synthase activity with the antibodies and antagonists of the present invention, provides a regimen for treating and/or inhibiting hypotension attendant a variety of conditions and treatments, including chemotherapeutic agent therapy (IFN, TNF, IL-1, IL-2), septic shock, trauma, exposure to endotoxins or cytokines, or other conditions in which hypotension is attendant.
摘要翻译：提供了治疗和抑制与内毒素和细胞因子诱导的休克有关的低血压的方法和组合物。用于本发明的治疗方案包括给予或随后施用抗内毒素抗体，白细胞介素-1或白细胞介素-2受体拮抗剂，抗肿瘤坏死因子抗体或组合的无精氨酸胃肠外制剂其中。最优选地，施用不含精氨酸的肠胃外制剂增加了所描述的各种抗体和拮抗剂的抗低血压作用，以便为各种形式的低血压提供有效的治疗。本发明的治疗方案被提出用于减少一氧化氮合酶，从而提高体内血压，特别是在具有细胞因子和/或内毒素诱导的低血压的动物中。本发明的治疗方案和方法的肠胃外制剂是无精氨酸的并且提供血浆精氨酸水平的降低。在动物功能中降低精氨酸的血浆，血清或组织水平，以增加在肠胃外制剂的同时或之后施用的各种抗体和拮抗剂的高血压作用。限制和/或消除用于一氧化氮合成的底物精氨酸，加上限制和/或消除与本发明的抗体和拮抗剂的一氧化氮合成酶活性的诱导，提供了治疗和/或抑制伴有多种病症的低血压的方案和治疗方法，包括化疗药物治疗（IFN，TNF，IL-1，IL-2），脓毒性休克，创伤，暴露于内毒素或细胞因子，或其他伴有低血压的病症。

8. 发明授权

US07119120B2 Phosphate transport inhibitors 有权
标题翻译：磷酸盐转运抑制剂
公开(公告)号：US07119120B2
公开(公告)日：2006-10-10
申请号：US10327627
申请日：2002-12-20
申请人： Thomas H. Jozefiak , Cecilia M. Bastos , Andrew T. Papoulis , Stephen Randall Holmes-Farley
发明人： Thomas H. Jozefiak , Cecilia M. Bastos , Andrew T. Papoulis , Stephen Randall Holmes-Farley
IPC分类号： A61K31/18 , A61K31/16 , A61K37/18
CPC分类号： A61K45/06 , A61K31/166 , A61K31/17 , A61K31/18 , A61K31/415 , A61K31/63 , A61K33/38 , A61K2300/00
摘要： Disclosed are compounds which have been identified as inhibitors of phosphate transport. Many of the compounds are represented by Structural Formula (I): Ar1—W—X—Y—Ar2; or a pharmaceutically acceptable salt thereof. Ar1 and Ar2 are independently a substituted or unsubstituted aryl group or an optionally substituted five membered or six membered non-aromatic heterocylic group fused to an optionally substituted monocylic aryl group. W and Y are independently a covalent bond or a C1–C3 substituted or unsubstituted alkylene group. X is a heteroatom-containing functional group, an aromatic heterocyclic group, substituted aromatic heterocyclic group, non-aromatic heterocyclic group, substituted non-aromatic heterocyclic group, an olefin group or a substituted olefin group. Also disclosed are methods of treating a subject with a disease associated with hyperphosphatemia, as well as a disease mediated by phosphate-transport function. The methods comprise the step of administering an effective amount of the one of the compounds described above.
摘要翻译：公开了已被鉴定为磷酸盐转运抑制剂的化合物。许多化合物由结构式（I）表示：<？in-line-formula description =“In-line Formulas”end =“lead”？> Ar -WXY-Ar _{2 <？in-line-formula description =“In-line Formulas”end =“tail”？>或其药学上可接受的盐。 Ar 1和Ar 2独立地是与任选取代的单环芳基稠合的取代或未取代的芳基或任选取代的五元或六元非芳族杂环基。 W和Y独立地是共价键或C1-C3取代或未取代的亚烷基。 X为含杂原子的官能团，芳香族杂环基，取代芳香族杂环基，非芳香族杂环基，取代非芳香族杂环基，烯基或取代烯基。还公开了治疗患有与高磷酸盐血症相关的疾病的受试者以及由磷酸盐转运功能介导的疾病的方法。所述方法包括施用有效量的上述一种化合物的步骤。}

9. 发明授权

US06878514B1 Methods for identifying agents that inhibit serum aging factors and uses and compositions thereof 失效
公开(公告)号：US06878514B1
公开(公告)日：2005-04-12
申请号：US09536551
申请日：2000-03-28
申请人： Dorothy M. Morré , D. James Morré
发明人： Dorothy M. Morré , D. James Morré
IPC分类号： A61K31/122 , C12Q1/00 , A61K49/00 , A61K37/18 , A01N37/18
CPC分类号： A61K31/122 , Y02A50/411
摘要： The invention described herein encompasses methods of preventing or treating disorders caused by oxidative damage by an aging-specific isoform of NADH oxidase (AR-NOX). The invention encompasses methods of assaying, screening, and identifying agents that inhibit AR-NOX, as well as methods using ubiquinone to inhibit the ability of AR-NOX to generate reactive oxygen species. These agents may be formulated into pharmaceutical compositions in the prevention and treatment of disorders caused by oxidative damage.

10. 发明授权

US5334408A Nutrient composition containing non-phosphorylated peptides from casin-based material 失效
标题翻译：含有酪蛋白基材料的非磷酸化肽的营养成分
公开(公告)号：US5334408A
公开(公告)日：1994-08-02
申请号：US888370
申请日：1992-05-26
申请人： Gerard Brule , Loic Roger , Jacques Fauquant , Michel Piot
发明人： Gerard Brule , Loic Roger , Jacques Fauquant , Michel Piot
IPC分类号： A23J3/34 , A23J3/00 , A61K37/18 , C07K1/00 , C12P21/06
CPC分类号： A23J3/344 , A23J3/34
摘要： Non-phosphorylated peptides and phosphopeptides useful as alimentary products or medicaments are produced. A hydrolyzate containing non-phosphorylated peptides and phosphopeptides is prepared by proteolytic enzyme hydrolysis of a casein-based material. The hydrolyzate is subjected to ultrafiltration with a membrane which allows peptides to pass through to produce a permeate containing the non-phosphorylated peptides and phosphopeptides. A bivalent cation-containing salt capable of aggregating the phosphopeptides is added to the permeate to produce a mixture containing phosphopeptide aggregates and non-phosphorylated peptides. The mixture is subjected to ultrafiltration with a membrane that retains the phosphopeptide aggregates and separates them from the non-phosphorylated peptides. The non-phosphorylated peptides have nutritive value and can be used to form compositions for providing nutrition. The phosphopeptides form salts, which have dietetic uses, with macroelements such as calcium and/or magnesium and/or oligoelements such as iron and zinc.
摘要翻译：产生用作消化产物或药物的非磷酸化肽和磷酸肽。通过酪蛋白基材料的蛋白水解酶水解制备含有非磷酸化肽和磷酸肽的水解产物。将水解产物用膜进行超滤，该膜允许肽通过以产生含有非磷酸化肽和磷酸肽的渗透物。将能聚集磷酸肽的含二价阳离子的盐加入到渗透物中以产生含有磷酸肽聚集体和非磷酸化肽的混合物。将混合物用保留磷酸肽聚集体的膜进行超滤，并将其与非磷酸化肽分离。非磷酸化肽具有营养价值，可用于形成用于提供营养的组合物。磷酸肽形成具有饮食用途的盐，其具有诸如钙和/或镁和/或稀土元素如铁和锌的大量元素。

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