| 序号 | 专利名 | 申请号 | 申请日 | 公开（公告）号 | 公开（公告）日 | 发明人 |
|---|---|---|---|---|---|---|
| 1 | 一种用金属离子沉淀剂制备胰激肽释放酶的方法 | CN201610989190.3 | 2016-11-10 | CN106480001A | 2017-03-08 | 余蓉; 许小枫; 蔡应婷 |
| 本发明属于生物制药领域，具体涉及的是用金属离子沉淀剂制备胰激肽释放酶的方法。以猪胰脏或生产胰岛素后所剩的胰渣作为原料，水性溶液提取，金属离子沉淀剂进行沉淀，制备胰激肽释放酶。本发明成功建立了一种新型制备胰激肽释放酶的方法，舍弃制备过程中有机溶剂的大量运用、降低生产成本、简化操作步骤、减少环境污染及安全隐患，在提高胰脏原料的利用度方面具有重要意义。 | ||||||
| 2 | 一种氯化钠-氨水、丙酮协同纯化胰激肽酶原的方法及含有胰激肽酶原的药物组合物 | CN201410807820.1 | 2014-12-23 | CN104531647A | 2015-04-22 | 刘冠男; 林晓磊; 孙延年 |
| 本发明公开了一种氯化钠-氨水、丙酮协同纯化胰激肽酶原的方法及含有胰激肽酶原的药物组合物。本发明的技术方案是以猪胰为原料提取、沉淀猪胰制成丙酮粉后，灵活运用醋酸提取、丙酮沉淀，乙醚脱脂脱水，氯化钠-氨水、丙酮协同除杂等传统蛋白纯化技术，制备胰激肽酶原。本发明具有生产周期短，操作简单，对化学和热稳定性好、成本低廉的特点，非常适用于规模化大生产。 | ||||||
| 3 | 一种二次亲和层析法提取激肽释放酶原的方法及含激肽释放酶原的药物组合物 | CN201410807948.8 | 2014-12-23 | CN104498462A | 2015-04-08 | 刘乃山; 林晓磊; 刘翠珍 |
| 本发明公开了一种二次亲和层析法提取激肽释放酶原的方法及含有激肽释放酶原的药物组合物，其特点在于优化原有亲和层析提取糜蛋白酶原和胰蛋白酶原的洗脱条件，从中提取激肽释放酶原的收率为0.2%～0.4%。 | ||||||
| 4 | 一种胰激肽原酶纯化工艺 | CN201510467037.X | 2015-08-03 | CN105176953A | 2015-12-23 | 王轲; 周翔; 潘伟忠 |
| 本发明公开了一种胰激肽原酶纯化工艺，该工艺包括提取、超滤、盐析、层析、超滤浓缩、及除菌冻干过程。与现有技术相比，本发明具有以下优点：（1）本发明所述胰激肽原酶纯化工艺能够适应工业化大规模的生产的需求，重现性好、保证不同生产批次的产品质量；（2）本发明所述胰激肽原酶纯化工艺缩短了整个生产工序的时间，自动化程度高；（3）本发明所述胰激肽原酶纯化工艺每批次可获得3.5亿单位的胰激肽原酶产品，且产品纯度达到90%以上，比活大于800 U/mg·pro，整个层析工艺花费的时间缩短至4小时以内。 | ||||||
| 5 | 一种疏水色谱纯化激肽释放酶的方法 | CN201410807827.3 | 2014-12-23 | CN104498460A | 2015-04-08 | 刘冠男; 林晓磊; 孙延年 |
| 本发明公开一种疏水色谱纯化激肽释放酶的方法，该方法通过以下工艺步骤：（1）离子交换层析;（2）盐析；（3）超滤；（4）热原处理；（5）透析；（6）疏水色谱；（7）冻干，制备激肽释放酶。本发明对激肽释放酶的生产工艺进行不断改进，特别是对各工艺参数进行反复的实验研究，不断优化，最终确立了一套更为科学的规模化生产工艺，经疏水色谱纯化所得的激肽释放酶的效价高达1500～1800iu/mg,并且各项指标均符合中国药典规定。 | ||||||
| 6 | 一种高度纯化胰激肽酶原的方法及含有胰激肽酶原的药物组合物 | CN201410807821.6 | 2014-12-23 | CN104480091A | 2015-04-01 | 刘冠男; 林晓磊; 孙延年 |
| 本发明公开了一种高度纯化胰激肽酶原的方法及含有胰激肽酶原的药物组合物。本发明的技术方案是以猪胰为原料提取、沉淀猪胰制成丙酮粉后，灵活运用醋酸提取、丙酮沉淀，乙醚脱脂脱水，氯化钠-氨水、丙酮协同除杂，离子交换树脂DEAE-琼脂糖快胶分步洗脱等传统与现代相结合的蛋白纯化技术，高度纯化胰激肽酶原。本发明具有生产周期短，对化学和热稳定性好、成本低的特点，非常适用于规模化大生产。 | ||||||
| 7 | 一种用醋酸提取胰激肽酶原的方法及含有胰激肽酶原的药物组合物 | CN201410807746.3 | 2014-12-23 | CN104513816A | 2015-04-15 | 刘乃山; 林晓磊; 孙延年 |
| 本发明公开了一种用醋酸提取胰激肽酶原的方法及含有胰激肽酶原的药物组合物。本发明的技术方案是以猪胰为原料提取、沉淀猪胰制成丙酮粉后，灵活运用醋酸提取、丙酮沉淀，乙醚脱脂脱水等传统蛋白纯化技术，制备胰激肽酶原。本发明操作简单，生产周期短，成本低廉，非常适用于规模化大生产。 | ||||||
| 8 | 聚乙二醇化的组织激肽释放酶及其制备方法和应用 | CN201310745409.1 | 2013-12-30 | CN104073482A | 2014-10-01 | 马永; 王俊; 邱晶; 吴鼎龙; 徐春林; 陈晨; 王耀方 |
| 聚乙二醇化的组织激肽释放酶及其制备方法和应用，涉及聚乙二醇修饰的蛋白类药物，所述组织激肽释放酶具有SEQ ID No.1或SEQ ID No.2所示的序列，所述组织激肽释放酶可以是天然或重组的，其中聚乙二醇为分子量为20-40kDa的聚乙二醇，其中所述聚乙二醇在组织激肽释放酶的N端伯氨基上偶联。本发明提供的聚乙二醇化的KLK1，在具有半衰期明显延长、免疫原性显著降低、结构稳定均一的等优点的基础上，更大程度的提高了其生物活性，尤其在治疗脑卒中及糖尿病肾病方面更加显著。 | ||||||
| 9 | 用于增加胰岛素敏感性和治疗糖尿病的方法 | CN201280040043.1 | 2012-06-15 | CN103889435A | 2014-06-25 | J.D.鲍威尔; B.肖; P.F.沃尔利; G.M.德尔戈夫; A.维克曼 |
| 本文描述了用于增加胰岛素敏感性和用于治疗糖尿病(I型和II型)的方法。本文还描述了用于增加受试者中褐色脂肪的量和用于治疗代谢性病症包括肥胖的方法。 | ||||||
| 10 | Human tissue kallikrein 1 glycosylation isoforms | US15153126 | 2016-05-12 | US09839678B2 | 2017-12-12 | Matthew Charles; Tadeusz Kolodka; Mark Williams |
| Provided are preparations of tissue kallikrein-1 (KLK1) glycoforms having a defined number of oligosaccharide units per KLK1 molecule. Also provided are mixtures of such glycoforms, pharmaceutical compositions containing such glycoforms or mixtures thereof, methods of obtaining the rhKLK1 glycoforms, and therapeutic uses thereof. | ||||||
| 11 | PEGYLATED TISSUE KALLIKREIN, AND PREPARATION METHOD THEREFOR AND USES THEREOF | US15109364 | 2014-01-09 | US20170049864A1 | 2017-02-23 | Bruce Yong MA; Jun WANG; Jing QIU; Dinglong WU; Chunlin XU; Chen CHEN; Yaofang WANG |
| The present invention relates to polyethylene glycol (PEG) modified protein drugs, and a PEGylated tissue kallikrein, a preparation method and use thereof are disclosed. The tissue kallikrein has a sequence as shown in SEQ ID No. 1 or SEQ ID No. 2, and the tissue kallikrein may be natural or recombinant. The PEG has a molecular weight of 20 to 40 kDa, and is conjugated to the N-terminal primary amino of the tissue kallikrein. In addition to the advantages of significantly extended half-life, significantly reduced immunogenicity and stable and uniform structure, the biological activity of the PEGylated KLK1 provided in the present invention is improved to a higher extent, which is more significant in the treatment of cerebral apoplexy and diabetic nephropathy in particular. | ||||||
| 12 | Human tissue kallikrein 1 glycosylation isoforms | US14677122 | 2015-04-02 | US09364521B2 | 2016-06-14 | Matthew Charles; Tadeusz Kolodka; Mark Williams |
| Provided are preparations of tissue kallikrein-1 (KLK1) glycoforms having a defined number of oligosaccharide units per KLK1 molecule. Also provided are mixtures of such glycoforms, pharmaceutical compositions containing such glycoforms or mixtures thereof, methods of obtaining the rhKLK1 glycoforms, and therapeutic uses thereof. | ||||||
| 13 | HUMAN TISSUE KALLIKREIN 1 GLYCOSYLATION ISOFORMS | US14677122 | 2015-04-02 | US20150196624A1 | 2015-07-16 | Matthew Charles; Tadeusz Kolodka; Mark Williams |
| Provided are preparations of tissue kallikrein-1 (KLK1) glycoforms having a defined number of oligosaccharide units per KLK1 molecule. Also provided are mixtures of such glycoforms, pharmaceutical compositions containing such glycoforms or mixtures thereof, methods of obtaining the rhKLK1 glycoforms, and therapeutic uses thereof. | ||||||
| 14 | Pegylated tissue kallikrein, and preparation method therefor and uses thereof | US15109364 | 2014-01-09 | US10052368B2 | 2018-08-21 | Bruce Yong Ma; Jun Wang; Jing Qiu; Dinglong Wu; Chunlin Xu; Chen Chen; Yaofang Wang |
| The present invention relates to polyethylene glycol (PEG) modified protein drugs, and a PEGylated tissue kallikrein, a preparation method and use thereof are disclosed. The tissue kallikrein has a sequence as shown in SEQ ID No. 1 or SEQ ID No. 2, and the tissue kallikrein may be natural or recombinant. The PEG has a molecular weight of 20 to 40 kDa, and is conjugated to the N-terminal primary amino of the tissue kallikrein. In addition to the advantages of significantly extended half-life, significantly reduced immunogenicity and stable and uniform structure, the biological activity of the PEGylated KLK1 provided in the present invention is improved to a higher extent, which is more significant in the treatment of cerebral apoplexy and diabetic nephropathy in particular. | ||||||
| 15 | HUMAN TISSUE KALLIKREIN 1 GLYCOSYLATION ISOFORMS | US15153126 | 2016-05-12 | US20170119862A1 | 2017-05-04 | Matthew Charles; Tadeusz Kolodka; Mark Williams |
| Provided are preparations of tissue kallikrein-1 (KLK1) glycoforms having a defined number of oligosaccharide units per KLK1 molecule. Also provided are mixtures of such glycoforms, pharmaceutical compositions containing such glycoforms or mixtures thereof, methods of obtaining the rhKLK1 glycoforms, and therapeutic uses thereof. | ||||||
| 16 | METHODS FOR INCREASING INSULIN SENSITIVITY AND TREATING DIABETES | US14126994 | 2012-06-15 | US20140205578A1 | 2014-07-24 | Jonathan D. Powell; Bo Xiao; Paul Worley; Gregg M. Delgoffe; Adam Waickman |
| Described herein are methods for increasing insulin sensitivity and for treating Diabetes (Type I and Type II). Also described herein are methods for increasing the amount of brown fat in a subject and for treating metabolic disorders, including obesity. | ||||||
| 17 | Diagnosis and therapeutic method of metabolic disruption | JP2013058106 | 2013-03-21 | JP2013129672A | 2013-07-04 | WILLIAMS MARK |
| PROBLEM TO BE SOLVED: To provide a compound for treatment of insulin resistance and diabetes.SOLUTION: The disease can be treated by using tissue kallikrein-1. | ||||||
| 18 | A method for treating a method and diabetes increase insulin sensitivity | JP2014516023 | 2012-06-15 | JP2014520119A | 2014-08-21 | ジョナサン デイビッド パウエル，; ボウ シャオ，; ポール エフ． ウォーリー，; グレッグ マイケル デルゴフィー，; アダム ウィックマン， |
| インスリン感受性を増加させるための方法、および糖尿病（Ｉ型およびＩＩ型）を処置するための方法が本明細書において記載される。 被験体における褐色脂肪量を増加させるための方法、および肥満症をはじめとする代謝障害を処置するための方法もまた、本明細書において記載される。 例えば、被験体における糖尿病を予防または処置するための方法であって、カリクレインファミリーペプチダーゼまたはその生物学的に活性な断片を該被験体に投与することを含む、方法が記載される。 | ||||||
| 19 | Diagnostic and therapeutic methods of metabolic disorders | JP2009521075 | 2007-07-26 | JP2009544630A | 2009-12-17 | ウイリアムズ，マーク |
| The invention relates to pharmaceutical compositions comprising tissue kallikrem (TK), and optionally a diabetes drug, a method of screening for a metabolic disorder by determining the concentration of TK and insulin in a biological sample from a test subject, a method of screening for a therapeutic agent for the treatment or prevention of a metabolic disorder, and a method for treating or preventing a metabolic disorder using a pharmaceutical composition comprising TK. | ||||||
| 20 | HUMAN TISSUE KALLIKREIN 1 GLYCOSYLATION ISOFORMS | US13909220 | 2013-06-04 | US20130323222A1 | 2013-12-05 | Matthew Charles; Tadeusz Kolodka; Mark Williams |
| Provided are preparations of tissue kallikrein-1 (KLK1) glycoforms having a defined number of oligosaccharide units per KLK1 molecule. Also provided are mixtures of such glycoforms, pharmaceutical compositions containing such glycoforms or mixtures thereof, methods of obtaining the rhKLK1 glycoforms, and therapeutic uses thereof | ||||||
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