中国生物药的骄傲，共鉴全球独家生物药——rhTPO
<div style="max-width:100%;overflow:hidden;"><section data-role="outer" label="edit by 135editor"><section data-tools="135编辑器" data-id="106509"><section style="text-align: center;margin: 10px auto;transform-style: preserve-3d;"><section style="width: 40px;margin-bottom: -15px;margin-left: 15px;transform: translateZ(10px);"><br></section><section style="width: 40px;margin-bottom: -15px;margin-left: 15px;transform: translateZ(10px);"><br></section><section style="width: 40px;margin-bottom: -15px;margin-left: 15px;transform: translateZ(10px);"><br></section><section style="width: 40px;margin-bottom: -15px;margin-left: 15px;transform: translateZ(10px);"></section><section style="width: 40px;height: 3px;background-color: rgb(255, 255, 255);margin-bottom: -2px;margin-left: 15px;transform: translateZ(9px);overflow: hidden;"><br></section><section style="border-width: 1px;border-style: solid;border-color: rgb(15, 36, 62);padding-top: 5px;padding-right: 5px;transform: translateZ(8px);"><section style="background-color: rgb(255, 255, 255);padding: 35px 20px;"><section data-autoskip="1" style="text-align: justify;line-height: 1.75em;background: transparent;"><p style="letter-spacing: 1.5px;vertical-align: inherit;"><span style="color:#0f243e;font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;"><span style="font-size: 16px;color: #002060;"><strong>全球独家上市的一类新药——rhTPO</strong></span></span></p><section style="outline: 0px;letter-spacing: 0.544px;line-height: 1.75em;"><p style="text-indent: 2em;font-family: system-ui, -apple-system, BlinkMacSystemFont, Arial, sans-serif;"><span style="font-size: 14px;font-family: Helvetica, Arial, sans-serif;">沈阳三生自主研发并在全球独家上市的国家一类新药-重组人血小板生成素(rhTPO)，商品名——特比澳于2005年在我国上市，<span style="outline-style: initial;color: rgb(67, 67, 67);">目前已成为原发免疫性血小板减少症（ITP）</span><span style="letter-spacing: 0.544px;caret-color: red;outline-style: initial;color: rgb(67, 67, 67);">（以往称为特发性血小板减少性紫癜）和肿瘤化疗所致的血小板减少（CIT）的治疗药物。</span><span style="color: rgb(67, 67, 67);letter-spacing: 0.544px;caret-color: red;">2017 年，特比澳被国家医保目录正式纳入乙类目录范畴，用于 CIT 和 ITP 的治疗药物。</span></span></p><p style="text-align:center;text-indent: 0em;font-family: system-ui, -apple-system, BlinkMacSystemFont, Arial, sans-serif;"><span style="font-size: 14px;font-family: Helvetica, Arial, sans-serif;"><span style="color: rgb(67, 67, 67);letter-spacing: 0.544px;caret-color: red;"></span></span></p><p style="text-align:center;text-indent: 0em;"><span style="color:#434343;font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;"><span style="font-size: 14px;">图1：三生制药rhTPO分子结构（来源网络）</span></span></p><p style="text-align:center;text-indent: 0em;"><br></p><p style="text-indent: 2em;font-family: system-ui, -apple-system, BlinkMacSystemFont, Arial, sans-serif;"><span style="font-size: 14px;font-family: Helvetica, Arial, sans-serif;"><span style="color: rgb(67, 67, 67);letter-spacing: 0.544px;caret-color: red;">rhTPO 是在中国仓鼠卵巢细胞（CHO)中表达的全长重组、332个氨基酸高度糖基化的人 TPO ，研究人员在血小板减少症的患者中进行了一项试验，结果显示，在给予单剂量 rhTPO 后，患者的血小板数量在第 4-5 天时就出现了升高趋势，并在第 10-14 天时，血小板数量达到了中位峰值，并且试验过程中没有出现严重不良反应。</span></span></p></section></section></section></section></section></section><section data-tools="135编辑器" data-id="106509"><section style="text-align: center;margin: 10px auto;transform-style: preserve-3d;"><section style="width: 40px;margin-bottom: -15px;margin-left: 15px;transform: translateZ(10px);"></section><section style="width: 40px;height: 3px;background-color: rgb(255, 255, 255);margin-bottom: -2px;margin-left: 15px;overflow: hidden;transform: translateZ(9px);"><br></section><section style="border-width: 1px;border-style: solid;border-color: rgb(15, 36, 62);padding-top: 5px;padding-right: 5px;transform: translateZ(8px);"><section style="background-color: rgb(255, 255, 255);padding: 35px 20px;"><section data-autoskip="1" style="text-align: justify;line-height: 1.75em;letter-spacing: 1.5px;background: transparent;"><p style="vertical-align: inherit;"><span style="font-size: 16px;color: rgb(0, 32, 96);font-family: Helvetica, Arial, sans-serif;"><strong>rhTPO下游纯化工艺解决方案</strong></span></p><section><p style="margin-bottom: 15px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;"><span style="font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;">rhTPO下游纯化工艺主要是去除细胞培养过程CHO-HCP,CHO-HC-DNA,CHO-HC-RNA，内毒素，培养基组分及未糖基化的rhTPO等。</span></p><p style="margin-bottom: 5px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;"><span style="color:#002060;"><strong><span style="font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;">rhTPO制备工艺流程：</span></strong></span></p><p style="margin-bottom: 5px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;"><span style="font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;">细胞培养(CHO)——固液分离（离心）——收集上清夜——澄清（MF等）——UF/DF（2-8℃，10KDa ,TFF，30-50倍）——AEX初步纯化（DEAE Seplife FF)——中度纯化HIC（Butyl Seplife FF)——精细纯化SEC（Seplife S-200)——UF/DF（2-8℃，10KDa ,TFF,调整浓度置换缓冲液）——除菌过滤（0.22um直压过滤）——制剂化</span></p><p style="margin-bottom: 5px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;"><span style="font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;">注：高度糖基化的rhTPO在CIT 和 ITP质粒中有良好的效果，若制备工艺中，糖基化rhTPO中混有非糖基化的rhTPO，可以运用亲和层析Boricacid Seplife 4FF(软胶）及Boricacid Seplife LXPM 5504（硬胶）进行糖基化rhTPO的特异性吸附纯化。</span></p><p style="margin-bottom: 5px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;"><br></p><p style="margin-bottom: 5px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;"><strong><span style="font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;"><span style="color:#002060;">rhTPO纯化常用填料</span></span></strong></p><p style="margin-bottom: 5px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;"><span style="font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;">AEX:<strong><span style="color:#002060;">DEAE Seplife FF</span></strong>用于rhTPO的初步纯化，从培养液中快速分离出目标物质，减少体积，去除大部分的杂质及可能存在的蛋白酶。</span></p><p style="margin-bottom: 5px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;"><span style="font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;">HIC：<strong><span style="color:#002060;">Butyl Seplife FF</span></strong>去除离子交换层析后原液中残留的HCP等杂质。</span></p><p style="margin-bottom: 5px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;"><span style="font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;">SEC：<strong><span style="color:#002060;">Seplife S-200</span></strong>去除rhTPO制备过程降解片段及聚集体，未糖基化组分等痕量杂质。</span></p><p style="margin-bottom: 5px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;"><span style="font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;">AC：<strong><span style="color:#002060;">Boricacid Seplife 4F</span></strong><strong><span style="color:#002060;">F</span></strong>，特异性的结合糖基化rhTPO,分离高度糖基化rhTPO中未糖基化的组分。</span></p><p style="margin-bottom: 5px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;"><br></p><p style="margin-bottom: 15px;text-indent: 2em;color: rgb(51, 51, 51);font-size: 14px;line-height: 1.75em;font-family: arial, stheiti, simsun, sans-serif;"><span style="font-family: Helvetica, Arial, sans-serif;">以上仅供参考。更多关于rhTPO下游工艺解决方案或纯化层析填料，请联系蓝晓科技：0512-65160522</span></p></section></section></section></section></section></section><section data-role="outer" label="edit by 135editor"><section data-tools="135编辑器" data-id="106509"><section style="text-align: center;margin: 10px auto;transform-style: preserve-3d;"><section style="width: 40px;margin-bottom: -15px;margin-left: 15px;transform: translateZ(10px);"></section><section style="width: 40px;height: 3px;background-color: rgb(255, 255, 255);margin-bottom: -2px;margin-left: 15px;overflow: hidden;transform: translateZ(9px);"><br></section><section style="border-width: 1px;border-style: solid;border-color: rgb(15, 36, 62);padding-top: 5px;padding-right: 5px;transform: translateZ(8px);"><section style="background-color: rgb(255, 255, 255);padding: 35px 20px;"><section data-autoskip="1" style="text-align: justify;line-height: 1.75em;letter-spacing: 1.5px;background: transparent;"><p style="vertical-align: inherit;"><span style="color:#0f243e;font-family:Helvetica Neue, Helvetica, Hiragino Sans GB, Apple Color Emoji, Emoji Symbols Font, Segoe UI Symbol, Arial, sans-serif;"><span style="font-size: 16px;color: #002060;"><strong>rhTPO发展大记事</strong></span></span></p><section><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><span style="color:#002060;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;">1882年</span></span></strong></span><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;">：意大利医生Bizzozero 用显微镜在血液中观察血液，发现微小粒子（2-4um)，并将其命名为platelet(血小板）。</span></span></p><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><span style="color:#002060;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;">1906年</span></span></strong></span><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;"></span><span style="font-size: 14px;">：美国马塞诸萨州综合医院的病理学家James Homer Wright 显微镜下观察到血小板与骨髓里巨核细胞有着相同的着色性质，还用实验证明了血小板减少与出血有关。</span></span></p><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;">1919年</span></span></strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;"></span><span style="font-size: 14px;">：医生George Minot （ 1934 年因发现维生素 B12 而获得诺贝尔奖）在进行了大量紫癜性出血的研究后，提出了血小板减少的两种假设：一是体内存在特定的毒物，一旦血小板形成，毒物就会以最快的速度将血小板破坏掉；二是巨核细胞在形成血小板的过程中由于受到毒性反应而造成血小板发育不良。</span></span></p><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;">1958年</span></span></strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;"></span><span style="font-size: 14px;">：匈牙利血液学家Endre Kelemen信誓旦旦地宣布了血液中一定存在一种调节血小板生成的促血小板生成素（TPO）。</span></span></p><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><span style="color:#002060;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;">1992年</span></span></strong></span><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;"></span><span style="font-size: 14px;">：科学家在一只患有骨髓增生性白血病的小鼠身上发现了原癌基因 c-mpl 后，TPO 的研究才取得了巨大的进展。研究人员发现这个原癌基因编码的 c-Mpl 蛋白具有与 TPO 受体相同的所有特征。研究人员将 c-Mpl 配体加入到剔除了巨核细胞集落刺激因子（MEG-CSF）的血小板减少的血浆中，结果发现血小板的数量确实升高了——证实c-Mpl 配体就是 TPO ,TPO提取取得巨大成功。</span></span></p><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><span style="color:#002060;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;">1994年</span></span></strong></span><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;"></span><span style="font-size: 14px;">：学家开始对两种重组血小板生成素进行临床研究，一个是美国Amgen领导的聚乙二醇化人巨核细胞生长发育因子( PEG-rhMGDF )，一个是由三生制药领导的重组人血小板生成素( rhTPO）。</span></span></p><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><span style="color:#002060;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;">1996年</span></span></strong></span><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;"></span><span style="font-size: 14px;">：3月三生制药的rhTPO完成工艺开发进入中试。同年12月开展动物试验。</span></span></p><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><span style="color:#002060;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;">1998年</span></span></strong></span><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;"></span><span style="font-size: 14px;">：10月获得临床试验批件。</span></span></p><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><span style="color:#002060;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;">1999年：</span></span></strong></span><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;"></span><span style="font-size: 14px;">8月开始一期临床试验。</span></span></p><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><span style="color:#002060;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;">2000年</span></span></strong></span><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;"></span><span style="font-size: 14px;">：6月一期临床试验结束。</span></span></p><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><span style="color:#002060;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;">2003年</span></span></strong></span><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;"></span><span style="font-size: 14px;">：6月完成三期临床试验。</span></span></p><p style="text-align:justify;outline: 0px;letter-spacing: 1.5px;text-indent: 2em;"><span style="color:#002060;"><strong><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;">2005年</span></span></strong></span><span style="font-family:Helvetica, Arial, sans-serif;"><span style="font-size: 14px;color: #002060;"></span><span style="font-size: 14px;">：获一类新药证书。</span></span></p></section></section></section></section></section></section><section data-tools="135编辑器" data-id="106509"><section style="text-align: center;margin: 10px auto;transform-style: preserve-3d;"><section style="width: 40px;margin-bottom: -15px;margin-left: 15px;transform: translateZ(10px);"></section><section style="width: 40px;height: 3px;background-color: rgb(255, 255, 255);margin-bottom: -2px;margin-left: 15px;overflow: hidden;transform: translateZ(9px);"><br></section><section style="border-width: 1px;border-style: solid;border-color: rgb(15, 36, 62);padding-top: 5px;padding-right: 5px;transform: translateZ(8px);"><section style="background-color: rgb(255, 255, 255);padding: 35px 20px;"><section data-autoskip="1" style="text-align: justify;line-height: 1.75em;letter-spacing: 1.5px;background: transparent;"><p style="vertical-align: inherit;"><span style="font-size: 16px;color: rgb(0, 32, 96);font-family: Helvetica, Arial, sans-serif;"><strong>参考资料</strong></span></p><section><p style="text-align:justify;margin-bottom: 5px;outline: 0px;letter-spacing: 0.544px;line-height: 1em;font-family: system-ui, -apple-system, BlinkMacSystemFont, Arial, sans-serif;"><span style="outline: 0px;text-indent: 32px;text-align: left;font-size: 12px;font-family: Helvetica, Arial, sans-serif;">1.一种重组血小板生成素及其制剂的生产方法，专利公开号：CN1186119A</span></p><p style="text-align: left;border-width: 0px;border-style: initial;border-color: initial;font-size: 16px;margin-top: 0.63em;margin-bottom: 5px;counter-reset: list-1 0 list-2 0 list-3 0 list-4 0 list-5 0 list-6 0 list-7 0 list-8 0 list-9 0;color: rgb(25, 25, 25);line-height: 1em;font-family: Arial, 微软雅黑, 宋体, simsun, sans-serif;"><span style="border-width: 0px;border-style: initial;border-color: initial;font-size: 12px;font-family: Helvetica, Arial, sans-serif;">2.Kelemen E, Cserhati I, Tanos B. Demonstration and some properties of human thrombopoietin in thrombocythaemic sera. Acta haematologica, 1958, 20(6): 350-355.</span></p><p style="text-align: left;border-width: 0px;border-style: initial;border-color: initial;font-size: 16px;margin-top: 0.63em;margin-bottom: 5px;counter-reset: list-1 0 list-2 0 list-3 0 list-4 0 list-5 0 list-6 0 list-7 0 list-8 0 list-9 0;color: rgb(25, 25, 25);line-height: 1em;font-family: Arial, 微软雅黑, 宋体, simsun, sans-serif;"><span style="border-width: 0px;border-style: initial;border-color: initial;font-size: 12px;font-family: Helvetica, Arial, sans-serif;">3.Kuter D J. Milestones in understanding platelet production: a historical overview. British journal of haematology, 2014, 165(2): 248-258.</span></p><p style="text-align: left;border-width: 0px;border-style: initial;border-color: initial;font-size: 16px;margin-top: 0.63em;margin-bottom: 5px;counter-reset: list-1 0 list-2 0 list-3 0 list-4 0 list-5 0 list-6 0 list-7 0 list-8 0 list-9 0;color: rgb(25, 25, 25);line-height: 1em;font-family: Arial, 微软雅黑, 宋体, simsun, sans-serif;"><span style="border-width: 0px;border-style: initial;border-color: initial;font-size: 12px;font-family: Helvetica, Arial, sans-serif;">4.Makar R S, Zhukov O S, Sahud M A, et al. Thrombopoietin levels in patients with disorders of platelet production: diagnostic potential and utility in predicting response to TPO receptor agonists. American journal of hematology, 2013, 88(12): 1041-1044.</span></p></section></section></section></section></section></section><section data-role="paragraph"><section data-role="paragraph" style="margin-bottom: 0px;outline: 0px;letter-spacing: 0.544px;white-space: normal;text-align: center;color: rgb(34, 34, 34);font-family: -apple-system, BlinkMacSystemFont, Helvetica Neue, PingFang SC, Hiragino Sans GB, Microsoft YaHei UI, Microsoft YaHei, Arial, sans-serif;background-color: rgb(255, 255, 255);"><section data-tools="135编辑器" data-id="106509" style="outline: 0px;letter-spacing: 0.544px;"><section style="margin: 10px auto;outline: 0px;transform-style: preserve-3d;"><section style="margin-bottom: -2px;margin-left: 15px;outline: 0px;width: 40px;height: 3px;overflow: hidden;transform: translateZ(9px);"><br></section></section></section></section></section></section></section><p style="display: none;"><mp-style-type data-value="3"></mp-style-type></p></div>
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