{"id":121205,"date":"2019-11-21T01:31:44","date_gmt":"2020-04-21T00:49:53","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/121205\/"},"modified":"2020-04-21T08:49:54","modified_gmt":"2020-04-21T00:49:54","slug":"31a26d0aad","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/121205\/","title":{"rendered":"\u4eff\u5236\u836f\u4e00\u81f4\u6027\u8bc4\u4ef7\u4e2d\u4eba\u4f53\u751f\u7269\u7b49\u6548\u6027\u8bd5\u9a8c\u8c41\u514d\u7533\u8bf7\u7684\u8fdb\u5c55\u53ca\u8f85\u6599\u5f71\u54cd\u8003\u91cf\u70b9"},"content":{"rendered":"
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2 \u57fa\u4e8eBCS\u5206\u7c7b\u7684 <\/p>\n<\/section>\n<\/section>\n<\/section>\n


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\u836f\u7528\u8f85\u6599\u662f\u751f\u4ea7\u836f\u54c1\u548c\u8c03\u914d\u5904\u65b9\u65f6\u7684\u8d4b\u5f62\u5242\u548c\u9644\u52a0\u5242\uff0c\u662f\u836f\u7269\u5236\u5242\u7684\u57fa\u7840\u6750\u6599\u548c\u91cd\u8981\u7ec4\u6210\u90e8\u5206\uff0c\u662f\u53ef\u80fd\u5f71\u54cd\u836f\u54c1\u8d28\u91cf\u3001\u5b89\u5168\u6027\u548c\u6709\u6548\u6027\u7684\u91cd\u8981\u6210\u5206\u3002<\/span><\/p>\n

<\/span>\u8f85\u6599\u7684\u7269\u6599\u6027\u8d28\u3001\u529f\u80fd\u6027\u8d28\u3001\u6765\u6e90\u3001\u751f\u4ea7\u5de5\u827a\u3001\u751f\u7269\u836f\u5242\u5b66\u6027\u8d28\u90fd\u53ef\u80fd\u5f71\u54cd\u5236\u5242\u6027\u8d28\uff0c\u89c1\u56fe2\u3002<\/span><\/p>\n

\"\u4eff\u5236\u836f\u4e00\u81f4\u6027\u8bc4\u4ef7\u4e2d\u4eba\u4f53\u751f\u7269\u7b49\u6548\u6027\u8bd5\u9a8c\u8c41\u514d\u7533\u8bf7\u7684\u8fdb\u5c55\u53ca\u8f85\u6599\u5f71\u54cd\u8003\u91cf\u70b9\"<\/p>\n

<\/span>\u901a\u5e38\uff0c\u836f\u7269\u4e3b\u8981\u5438\u6536\u90e8\u4f4d\u662f\u5c0f\u80a0\u3002<\/span>\u6b63\u5e38\u6210\u4eba\u5c0f\u80a0\u5168\u957f5\uff5e7m\uff0c\u904d\u5e03\u7ed2\u6bdb\u819c\uff0c\u5177\u6709\u5de8\u5927\u7684\u6bd4\u8868\u9762\u79ef\uff0c\u9762\u79ef\u7ea6200m2\uff0c\u4e00\u822c\u836f\u7269\u6eb6\u6db2\u5728\u5c0f\u80a0\u505c\u75592\uff5e4h\u3002<\/span>\u5c0f\u80a0\u4e0a\u76ae\u7ec6\u80de\u9876\u819c\u8868\u8fbe\u6709\u591a\u79cd\u5185\u5411\u8f6c\u8fd0\u4f53( \u5982\u5be1\u80bd\u8f6c\u8fd0\u4f53PepTide \u7b49) \uff0c\u8fd9\u4e9b\u8f6c\u8fd0\u4f53\u53c2\u4e0e\u6c28\u57fa\u9178\u3001\u80bd\u7c7b\u4ee5\u53ca\u591a\u79cd \u8425\u517b\u7269\u8d28\u7684\u5438\u6536\u3002<\/span><\/p>\n

<\/span>\u6b64\u5916\uff0c\u4eba\u7c7b\u548c\u556e\u9f7f\u7c7b\u52a8\u7269\u5c0f\u80a0\u4e0a\u76ae\u7ec6\u80de\u9876\u819c\u8fd8\u8868\u8fbe\u80fd\u91cf\u4f9d\u8d56\u7684\u5916\u5411\u8f6c\u8fd0\u4f53\uff0c\u5982P-\u7cd6\u86cb\u767d (P-glycoprotein\uff0cP-gp) \u3001\u591a\u836f\u8010\u836f\u76f8\u5173\u86cb\u767d2( multidrug resistance-associated protein 2\uff0cMRP2) \u3001\u4e73\u817a\u764c\u8010\u836f\u86cb\u767d( breast cancer resistance protein\uff0cBCRP) \u3002<\/span>\u8fd9\u4e9b\u8f6c\u8fd0\u4f53\u5bf9\u836f\u7269\u5438\u6536\u6709\u663e\u8457\u5f71\u54cd\u3002<\/span><\/p>\n

<\/span>P-gp\u86cb\u767d\u5916\u6392\u836f\u7269\u7684\u4f5c\u7528\u673a\u5236\u662f: \u5f53\u836f\u7269\u4e0e\u5e95\u7269\u7ed3\u5408\u533a\u63a5\u89e6\u65f6\uff0cATP\u9176\u63a5\u89e6\u5230\u6838\u82f7\u9178\u7ed3\u5408\u673a\u6784\u533a ( nucleotide binding domain\uff0cNBD) \u4e0a\uff0cATP\u6c34\u89e3\u63d0\u4f9b\u80fd\u91cf\uff0cP-gp\u7ed3\u6784\u6784\u578b\u6539\u53d8\uff0c\u5c06\u836f\u7269\u4ece\u9ad8\u4eb2\u548c\u7684\u4f4d\u70b9\u8f6c\u79fb\u81f3\u4f4e\u4eb2\u548c\u7684\u4f4d\u70b9\u5e76\u88ab\u6392\u51fa\u5230\u7ec6\u80de\u5916\u3002<\/span><\/p>\n

<\/span>\u5176\u5916\u6392\u836f\u7269\u65f6\u5177\u6709\u5e95\u7269\u4f5c\u7528\u5e7f\u6cdb\u30012\u79cd\u5e95\u7269\u53ef\u4e0eP-gp\u7ade\u4e89\u6027\u7ed3\u5408\u3001ATP\u4f9d\u8d56\u6027\u548c\u5916\u6392\u9971\u548c\u6027\u7b49\u7279\u5f81\u3002<\/span><\/p>\n

<\/span>\u5f88\u591a\u975e\u79bb\u5b50\u578b\u8868\u9762\u6d3b\u6027\u5242\u90fd\u5177\u6709\u6291\u5236P-gp\u4f5c\u7528\uff0c\u800c\u79bb\u5b50\u578b\u8868\u660e\u6d3b\u6027\u5242( \u9633\u79bb\u5b50\u8868\u9762\u6d3b\u6027\u5242\u3001\u9634\u79bb\u5b50\u8868\u9762\u6d3b\u6027\u5242\u548c\u4e24\u6027\u79bb\u5b50\u8868\u9762\u6d3b\u6027\u5242) \u65e0\u6b64\u4f5c\u7528\uff0c\u8fd9\u53ef\u80fd\u4e0e\u5b83\u4eec\u6240\u5e26\u7684\u7535\u8377\u6709\u5173\uff3b2\uff3d\u3002<\/span><\/p>\n

<\/span>\u7ec6\u80de\u8272\u7d20P450(CYP) \u662f\u4eba\u5c0f\u80a0\u6700\u4e3b\u8981\u7684\u2160\u76f8\u4ee3\u8c22\u9176\uff0c\u662f\u7531\u591a\u79cd\u540c\u5de5\u9176\u7ec4\u6210\u7684\u57fa\u56e0\u8d85\u5bb6\u65cf\u3002<\/span>CYP3A4\u662fCYP\u6700\u91cd\u8981\u4e9a\u578b\u4e4b\u4e00\uff0c\u53c2\u4e0e\u80a0\u9053\u7ea690%\u836f\u7269\u4ee3\u8c22\u3002<\/span>\u4ee5\u8868\u9762\u6d3b\u6027\u5242\u548c\u805a\u5408\u7269\u4e3a\u4e3b\u7684\u836f\u7528\u8f85\u6599\u80fd\u6291\u5236CYP3A4\u6d3b\u6027\uff0c\u63d0\u9ad8AUC\uff0c\u964d\u4f4eCL\/F\uff0c\u63d0\u9ad8\u836f\u7269\u53e3\u670d\u751f\u7269\u5229\u7528 \u5ea6\u3002<\/span><\/p>\n

<\/span>P-gp\u4e0e\u836f\u7269\u4ee3\u8c22\u9176CYP3A4\u5448\u73b0\u534f\u540c\u4f5c\u7528\u3002<\/span>\u56e0\u57fa\u4e8eBCS\u5206\u7c7b\u7684BE\u8c41\u514d\u7533\u8bf7\u5df2\u8981\u6c42\u63d0\u4f9b\u6eb6\u51fa\u5ea6\u4fe1\u606f\uff0c\u5e76\u5bf9\u6eb6\u51fa\u5ea6\u6709\u5feb\u901f\u6eb6\u51fa\u6216\u975e\u5e38\u5feb\u901f\u6eb6\u51fa\u8981\u6c42\uff0c\u72ed\u4e49\u4e0a\u8f85\u6599\u5bf9\u836f\u7269\u4f53\u5185\u5438\u6536\u7684\u5f71\u54cd\u5373\u4e3a\u8f85\u6599\u79cd\u7c7b\u4e0e\u7528\u91cf\u5bf9\u53e3\u670d\u56fa\u4f53\u5236\u5242\u5728\u4f53\u5185\u5d29\u89e3\u540e\u5c0f\u80a0\u5438\u6536\u6027\u8d28\u7684\u5f71\u54cd\u3002<\/span><\/p>\n

<\/span>\u5f71\u54cd\u65b9\u5f0f\u5305\u62ec\u5f71\u54cd\u836f\u7269\u6e17\u900f\u6027\u3001\u5f71\u54cd\u836f\u7269\u6eb6\u89e3\u6027\u3001\u5f71\u54cd\u5c0f\u80a0\u52a8\u529b\u4ece\u800c\u5f71\u54cd\u5c0f\u80a0\u901a\u8fc7\u65f6\u95f4\u3001\u5f71\u54cd\u9ecf\u6db2\u5b8c\u6574\u6027\u3001\u5f71\u54cd\u751f\u7406pH\u503c\u3001\u5f71\u54cd\u836f\u7269\u4ee3\u8c22\u3001\u5f71\u54cd\u8f6c\u8fd0\u86cb\u767d\u529f\u80fd\u3001\u6539\u53d8\u5c0f\u80a0\u819c\u8868\u9762\u5fae\u89c2\u73af\u5883\u7b49\uff3b3-8\uff3d\u3002<\/span><\/p>\n

<\/span>\u4ee5\u4e0b\u5bf9\u5e38\u89c1\u7684\u53ef\u80fd\u5f71\u54cd\u5438\u6536\u7684\u8f85\u6599\u79cd\u7c7b\u3001\u7528\u91cf\u53ca\u5f71\u54cd\u65b9\u5f0f\u8fdb\u884c\u5206\u6790\u3002<\/span><\/p>\n

\n
\n
\n
\n
\n
\n
3.1
<\/section>\n<\/section>\n

<\/p>\n

\u7cd6\u9187\u7c7b<\/section>\n

<\/span><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

<\/span><\/p>\n

\u7cd6\u9187\u901a\u5e38\u7528\u4f5c\u53e3\u670d\u56fa\u4f53\u5236\u5242\u4e2d\u7684\u7a00\u91ca\u5242\u6216\u751c\u5473\u5242\uff0c\u5305\u62ec\u7518\u9732\u9187\u3001\u5c71\u68a8\u9187\u3001\u9ea6\u82bd\u7cd6\u9187\u3001\u6728\u7cd6\u9187\u548c\u4e73\u7cd6\u9187\u7b49\u3002<\/span><\/p>\n

<\/span>\u5927\u591a\u6570\u7cd6\u9187\u96be\u4ee5\u5438\u6536\uff0c\u5728\u80a0\u9053\u4e2d\u5b58\u5728\u6e17\u900f\u4f5c\u7528\uff0c\u53ef\u4ee5\u901a\u8fc7\u5728\u5c0f\u80a0\u4e2d\u7684\u6e17\u900f\u52bf\u6765\u5f71\u54cd\u4f4e\u6e17\u900f\u6027\u836f\u7269\u7684\u5438\u6536\uff0c\u79f0\u4e3a\u201c\u6e17\u900f\u6d3b\u6027\u8f85\u6599\u201d\u3002<\/span><\/p>\n

<\/span>\u4e0e\u9ad8\u6e17\u900f\u6027\u5316\u5408\u7269\u76f8\u6bd4\uff0c\u6b64\u7c7b\u8f85\u6599\u5bf9\u4f4e\u6e17\u900f\u6027\u836f\u7269\u7684\u5438\u6536\u548c\u751f\u7269\u5229\u7528\u5ea6\u7684\u5f71\u54cd\u66f4\u663e\u8457\u3002<\/span>\u6709\u7814\u7a76\u8868\u660e\uff0c\u5f53\u5c71\u68a8\u9187\u7528\u91cf\u4ece1.25g\u589e\u52a0\u52302.5\u548c5g\u65f6\uff0cBCS \u2162\u7c7b\u836f\u7269\u96f7\u5c3c\u66ff\u4e01\u751f\u7269\u5229\u7528\u5ea6\u964d\u4f4e\u4e867.2%\u300125%\u548c45.5%\u3002<\/span><\/p>\n

<\/span>\u76f8\u6bd4\u4e4b\u4e0b\uff0c\u5728\u7f8e\u6258\u6d1b\u5c14\u6eb6\u6db2\u6216\u8336\u78b1\u7247\u4e2d\u52a0\u5165\u5c71\u68a8\u9187\u6ca1\u6709\u53d1\u73b0\u8be5\u4e0d\u826f\u4f5c\u7528\uff0c\u8868\u660e\u5c71\u68a8\u9187 \u6e17\u900f\u4f5c\u7528\u5bf9BCS I\u7c7b\u836f\u7269\u7684\u751f\u7269\u5229\u7528\u5ea6\u6216\u751f\u7269\u7b49\u6548\u6027\u51e0\u4e4e\u65e0\u5f71\u54cd\uff0c\u800c\u5bf9BCS \u2162\u7c7b\u836f\u7269\u5f71\u54cd\u660e\u663e\u3002<\/span><\/p>\n

<\/span>\u5728\u7518\u9732\u9187\u4e2d\u4e5f\u89c2\u5bdf\u5230\u7c7b\u4f3c\u5f71\u54cd\u4f5c\u7528\uff0c\u4f7f\u7528\u7518\u9732\u9187 2.264g\u53ef\u5bfc\u81f4\u897f\u54aa\u66ff\u4e01\u751f\u7269\u5229\u7528\u5ea6\u964d\u4f4e\u7ea630%\uff3b2\uff3d\u3002<\/span><\/p>\n

<\/span>\u9664\u4e86\u6e17\u900f\u4f5c\u7528\u5916\uff0c\u7cd6\u9187\u7c7b\u8f85\u6599\u5bf9\u836f\u7269\u4f53\u5185\u5438\u6536\u7684\u5f71\u54cd\u8fd8\u53ef\u80fd\u7531\u4e8e\u6c34\u901a\u91cf\u53d8\u5316\u800c\u5bfc\u81f4\u8de8\u819c\u62d6\u66f3\u6548\u5e94\uff0c\u4ee5\u53ca\u6539\u53d8\u80c3\u80a0\u9053\u795e\u7ecf\u514d\u75ab\u6fc0\u7d20\u63a7\u5236\u7b49\u3002<\/span>\u7cd6\u9187\u7c7b\u8f85\u6599\u5bf9\u5316\u5408\u7269\u7684\u80a0\u5438\u6536\u5f71\u54cd\u8fd8\u4f9d\u8d56\u4e8e\u5316\u5408\u7269\u7684\u5438\u6536\u7279\u5f81(\u5982\u5438\u6536\u673a\u5236\u548c\u5438\u6536\u4f4d\u70b9)\u3002<\/span><\/p>\n

\n
\n
\n
\n
\n
\n
3.2
<\/section>\n<\/section>\n

<\/p>\n

\u805a\u4e59\u4e8c\u9187<\/section>\n

<\/span><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

<\/span><\/p>\n

\u8868\u9762\u6d3b\u6027\u5242\u805a\u4e59\u4e8c\u9187( polyethylene glycol\uff0cPEG)\u76f8\u5bf9\u5206\u5b50\u8d28\u91cf\u8303\u56f4\u5e7f(200\uff5e35000) \uff0c\u4f4e\u76f8\u5bf9\u5206\u5b50\u8d28\u91cf(\uff1c600) PEG\u672c\u8d28\u4e0a\u662f\u6db2\u4f53\uff0c\u901a\u5e38\u7528\u4e8e\u589e\u52a0\u6c34\u6eb6\u6027\u5dee\u836f\u7269\u7684\u6eb6\u89e3\u5ea6\u548c\u751f\u7269\u5229\u7528\u5ea6\uff0c\u8fd8\u53ef\u4f5c\u4e3a\u589e\u5851\u5242\u3001\u6eb6\u5242\u3001\u8f6f\u818f\u53ca\u6813\u5242\u7684\u57fa\u8d28\u3001\u7247\u5242\u53ca\u80f6\u56ca\u5242\u7684\u6da6\u6ed1\u5242 \u7b49\u3002<\/span>PEG\u7ed3\u6784\u5f0f\u89c1\u56fe3\uff0c\u4e0d\u540c\u7ea7\u522bPEG\u76f8\u5bf9\u5e73\u5747\u5206\u5b50\u91cf\u89c1\u88681\u3002<\/span>
<\/p>\n

\"\u4eff\u5236\u836f\u4e00\u81f4\u6027\u8bc4\u4ef7\u4e2d\u4eba\u4f53\u751f\u7269\u7b49\u6548\u6027\u8bd5\u9a8c\u8c41\u514d\u7533\u8bf7\u7684\u8fdb\u5c55\u53ca\u8f85\u6599\u5f71\u54cd\u8003\u91cf\u70b9\"<\/p>\n

PEG\u4e0d\u80fd\u5728\u80a0\u5185\u88ab\u5438\u6536\uff0c\u800c\u901a\u8fc7\u6e17\u900f\u4f5c\u7528\u4fdd\u7559\u6d41\u4f53\u3002<\/span><\/p>\n

<\/span>PEG\u5f71\u54cd\u836f\u7269\u5438\u6536\u7684\u673a\u5236\u8f83\u590d\u6742\uff0c\u5305\u62ec\u7a00\u91ca\u3001\u6eb6\u89e3\u5ea6\u6539\u53d8\u3001\u5bf9\u80a0\u9ecf\u819c\u76f4\u63a5\u4f5c\u7528\u3001\u52a0\u901f\u80a0\u9053\u8f6c\u8fd0\u65f6\u95f4\u4ee5\u53ca\u4e0e\u5916\u6392\u8f6c\u8fd0\u86cb\u767dP-gp\u5177\u6709\u76f8\u4e92\u4f5c\u7528\u4ece\u800c\u5bfc\u81f4\u80a0\u6e17\u900f\u6027\u4e0e\u8fd0\u52a8\u6027\u53d1\u751f\u53d8\u5316\u7b49\u3002<\/span><\/p>\n

<\/span>\u7814\u7a76\u8868\u660e\uff0c\u4e0d\u540c\u6d53\u5ea6<\/span>PEG-400\u5bf9\u96f7\u5c3c\u66ff\u4e01\u7684\u5c0f\u80a0\u5438\u6536\u5177\u6709\u4e0d\u540c\u5f71\u54cd\u4f5c\u7528\uff0c\u4e14\u5448\u73b0\u6027\u522b\u5dee\u5f02\u3002<\/span><\/p>\n

<\/span>\u5bf9\u4e8e\u7537\u6027\u53d7\u8bd5\u8005\uff0c\u968f\u7740PEG-400\u5728 0.5\uff5e1.5 g\u8303\u56f4\u5185\u589e\u52a0\uff0c\u5cf0\u503c\u8fbe\u52300.75g\uff0c\u7136\u540e\u9010\u6e10\u4e0b\u964d\u81f31.5g\u7684\u57fa\u7ebf\u3002<\/span>\u5bf9\u4e8e<\/span>\u66f4\u5927<\/span>\u5242<\/span>\u91cf\u7684PE<\/span>G-400\uff0c2.<\/span>5\uff0c5\uff0c10g <\/span><\/span>PEG-400\u5206\u522b\u4f7f<\/span>\u96f7<\/span>\u5c3c\u66ff\u4e01<\/span>\u6eb6\u6db2\u7684\u751f\u7269\u5229\u7528\u5ea6\u7ea6\u964d\u4f4e38<\/span>%<\/span>\uff0c38%\u548c 31%\u3002<\/span><\/p>\n

<\/span>\u5bf9\u4e8e\u5973\u6027\u53d7\u8bd5\u8005\uff0c0.5\uff5e1.5 g\u7684PEG-400\u964d\u4f4e\u96f7\u5c3c\u66ff\u4e01\u751f\u7269\u5229\u7528\u5ea6\u3002<\/span>\u96f7\u5c3c\u66ff\u4e01\u751f\u7269\u5229\u7528\u5ea6\u7684\u6027\u522b\u5dee\u5f02\u90e8\u5206\u5f52\u56e0\u4e8ePEG-400\u5bf9\u5c0f\u80a0\u8f6c\u8fd0\u7684\u6e17\u900f\u4f5c\u7528\u53ca\u5176\u901a\u8fc7\u6291\u5236P-gp\u5916\u6392\u8f6c\u8fd0\u548c(\u6216) \u6539\u53d8\u819c\u6d41\u52a8\u6027\u800c\u8c03\u8282\u80a0\u901a\u900f\u6027\u4e4b\u95f4\u7684\u6f5c\u5728\u7efc\u5408\u76f8\u4e92\u4f5c\u7528\u3002<\/span><\/p>\n

<\/span>\u5c0f<\/span>\u5242\u91cf( 0.5\uff5e1.5g) \u4e0b\uff0c\u5728\u7537\u6027\u53d7\u8bd5\u8005\u4e2d\uff0cPEG-400\u5bf9\u96f7\u5c3c\u66ff\u4e01\u751f\u7269\u5229\u7528\u5ea6\u7684\u63d0\u9ad8\u662f\u7531\u4e8e\u8be5\u8f85\u6599\u5177\u6709\u8c03\u8282\u80a0\u901a\u900f\u6027\u80fd\u529b\u3002<\/span>\u800c\u5728\u5c0f\u80a0\u8f6c\u8fd0\u65f6\u95f4\u663e\u8457\u52a0\u5feb\uff0c\u906e\u853d\u4e86\u8f83\u5927\u5242\u91cf(\u22652.5g) PEG-400 \u7684\u5438\u6536\u589e\u5f3a\u673a\u5236\u3002<\/span>\u53e6\u4e00\u65b9\u9762\uff0c\u5973\u6027\u53d7\u8bd5\u8005\u53ef\u80fd\u5177\u6709\u8f83\u9ad8\u6bd4\u4f8b\u7684\u80a0\u5916\u6392\u51fa\u8f6c\u8fd0\u86cb\u767d\u5982\u4e73\u817a\u764c\u6297\u6027\u86cb\u767d ( breast cancer resistance protein\uff0cBCRP) \uff0c\u53ef\u80fd\u9020\u6210\u751f\u7269\u5229\u7528\u5ea6\u6027\u522b\u5dee\u5f02\uff3b2\uff3d\u3002<\/span><\/p>\n

<\/span>\u95eb\u65b9\uff3b7\uff3d\u91c7\u7528\u5916\u7ffb\u80a0\u56ca\u6cd5\u4f5c\u4e3a\u4f53\u5916\u6a21\u578b\uff0c\u7814\u7a76\u6392\u9664\u795e\u7ecf\u548c\u8840\u6d41\u60c5\u51b5\u4e0b PEG-400 \u5bf9\u73af\u5b62\u7d20\u80a0\u9053\u5438\u6536\u7684\u4f5c\u7528\u3002<\/span>\u7ed3\u679c\u663e\u793a\uff0c5mg\u00b7mL\uff0d1 PEG-400 ( 23.16%) \u548c10mg\u00b7mL\uff0d1 PEG-400( 42.08%) \u572890min\u65f6\u80fd\u663e\u8457\u589e\u52a0\u73af\u5b62\u7d20\u900f\u819c\u5438\u6536\u91cf\u3002<\/span>\u6574\u4f53\u52a8\u7269\u6a21\u578b\u5b9e\u9a8c\u4e5f\u663e\u793a\uff0c\u4e0d\u540c\u6d53\u5ea6PEG-400\u80fd\u4e0d\u540c\u7a0b\u5ea6\u63d0\u9ad8\u73af\u5b62\u7d20\u6700\u5927\u8840\u836f\u6d53\u5ea6\u53ca\u836f\u7269\u6d53\u5ea6-\u65f6\u95f4\u66f2\u7ebf\u4e0b\u9762\u79ef(AUC) \u3002<\/span>PEG-4000\u548cPEG-400\u5177\u6709\u76f8\u4f3c\u6e17\u900f\u4f5c\u7528\u6027\u8d28\u5e76\u5f71\u54cd\u80a0\u9053\u4e2d\u7684\u836f\u7269\u5438\u6536\u3002<\/span><\/p>\n

<\/span>\u963f\u83ab\u897f\u6797\u4e3aBCS \u2162\u7c7b\u836f\u7269\uff0c\u5176\u80a0\u9053\u8f6c\u8fd0\u7531\u88ab\u52a8\u6269\u6563\u548c\u901a\u8fc7\u4e8c\u80bd\u8f7d\u4f53\u4ecb\u5bfc\u7684\u4e3b\u52a8\u8f6c\u8fd0\u6240\u8fdb\u884c\u3002<\/span>\u6709\u7814\u7a76\u8868\u660e\uff0c\u5c0f\u5242\u91cf(2.95 g)PEG-4000\u5c06\u963f\u83ab\u897f\u6797AUC\u964d\u4f4e\u4e868.4%\uff0c\u5242\u91cf\u8303\u56f4\u4e3a 2.95\uff5e10g \u7684 PEG-4000 \u6e17\u900f\u52bf\u548c\u836f\u7269\u751f\u7269\u5229\u7528\u5ea6\u964d\u4f4e\u4e4b\u95f4\u5b58\u5728\u7ebf\u6027\u5173\u7cfb\u3002<\/span>\u5f53\u5728 Caco-2\u7ec6\u80de\u7cfb\u4e2d\u4e0e PEG-400\u3001PEG-2000 \u548c PEG-20000 \u5b75\u80b2\u65f6\uff0c\u53d1\u73b0\u7f57\u4e39\u660e123 ( P-gp \u5e95\u7269) \u7684\u5916\u6392\u8f6c\u8fd0\u663e\u8457\u964d\u4f4e\u3002<\/span><\/p>\n

<\/span>\u8fd9\u4e9bPEG\u5bf9\u80a0 P-gp \u529f\u80fd\u7684\u6291\u5236\u4f5c\u7528\u5728 0.1%\uff5e20% (V\/V \u6216W\/V) \u7684\u8303\u56f4\u5185\u5448\u6d53\u5ea6\u4f9d\u8d56 \u6027\u3002<\/span>\u8fd8\u53d1\u73b0\u5176\u4ed6PEG\u884d\u751f\u7269\uff0c\u4f8b\u5982 PEG-32 \u6708\u6842\u9178\u7518\u6cb9\u916f\u3001PEG-35 \u84d6\u9ebb\u6cb9\u3001PEG-20 \u786c\u8102\u9178\u916f\u3001PEG-50\u786c\u8102\u9178\u916f\u3001PEG-12\u786c\u8102\u9178\u916f\u548c PEG-660 12-\u7f9f\u57fa\u786c\u8102\u9178\u916f\u5bf9P-gp \u529f\u80fd\u7684\u6291\u5236\u4f5c\u7528\u4e0e\u8f85\u6599\u6d53\u5ea6\u7684\u5bf9\u6570\u76f8\u5173\uff3b2\uff3d\u3002<\/span><\/p>\n

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3.3
<\/section>\n<\/section>\n

<\/p>\n

\u5341\u4e8c\u70f7\u57fa\u786b\u9178<\/section>\n

<\/span><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u5341\u4e8c\u70f7\u57fa\u786b\u9178\u94a0 (sodium dodecyl dulfate\uff0cSDS) \u5bf9\u4f4e\u6e17\u900f\u6027\u836f\u7269\u7684\u6e17\u900f\u6027\u663e\u793a\u6d53\u5ea6\u4f9d\u8d56\u4f5c\u7528\uff0cSDS\u5728\u4f4e\u6d53\u5ea6( 0.139 mmol\u00b7L\uff0d1 ) \u65f6\u589e\u52a0\u836f\u7269\u8868\u89c2\u6e17\u900f\u6027(Papp)\uff0cSDS\u6d53\u5ea6\u589e\u52a0\u65f6\uff0c\u7531\u4e8e\u8d4b\u5f62\u5242\u4ecb\u5bfc\u7684\u5bf9\u5355\u5c42\u7ec6\u80de\u819c\u7684\u7834\u574f\u4f5c\u7528\uff0c\u836f\u7269\u6e17\u900f\u6027\u751a\u81f3\u66f4\u5927\u3002<\/span><\/p>\n

<\/span>\u7814\u7a76\u8868\u660e\uff0c\u5c11\u91cfSDS(3.64 mg) \u5373\u5f71\u54cd\u5229\u57f9\u916e\u7247\u751f\u7269\u5229\u7528\u5ea6\u3002<\/span>\u4eff\u5236\u836f\u963f\u4ed1\u81a6\u9178\u901f\u91ca\u7247\u4e2d(BCS \u2162\u7c7b\u836f\u7269) \u6dfb\u52a0SDS\u800c\u539f\u7814\u836f\u54c1\u4e2d\u672a\u6dfb\u52a0\uff0c\u5bfc\u81f4\u963f\u4ed1\u81a6\u9178\u751f\u7269\u5229\u7528\u5ea6\u589e\u52a05\uff5e6 \u500d\uff0c\u8fdb\u800c\u5bfc\u81f4\u751f\u7269\u4e0d\u7b49\u6548\u3002<\/span>\u963f\u53f8\u5339\u6797\u7247(BCS\u2162\u836f\u7269) \uff0cSDS4mg \u589e\u52a0\u5176\u751f\u7269\u5229\u7528\u5ea6\u8d85\u8fc7 5\u500d\u3002<\/span><\/p>\n

\n
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3.4<\/section>\n<\/section>\n

<\/p>\n

\u805a\u5c71\u68a8\u916f\u7c7b
<\/section>\n

<\/span> <\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u805a\u5c71\u68a8\u916f\u7c7b\u975e\u79bb\u5b50\u8868\u9762\u6d3b\u6027\u5242\u5e38\u4f5c\u4e3a\u96be\u6eb6\u6027\u836f\u7269\u589e\u6eb6\u5242\u4e0e\u4e73\u5316\u5242\u3002<\/span>\u6709\u7814\u7a76\u8868\u660e\uff0c\u805a\u5c71 \u68a8\u916f<\/span>80\u53ef\u589e\u52a0\u7f57\u4e39\u660e123\u5728\u5355\u5c42Caco-2\u7ec6\u80de\u6a21\u578b\u4e2d\u9876\u819c-\u57fa\u5e95\u819c(apical side-basolateral side\uff0cAP-BL) \u65b9\u5411\u7684\u8f6c\u8fd0\u5e76\u51cf\u5c11\u57fa\u5e95\u819c-\u9876\u819c( BL-AP) \u65b9\u5411\u7684\u8f6c\u8fd0\u3002<\/span><\/p>\n

<\/span>\u7531\u4e8e\u805a\u5c71\u68a8\u916f80\u5bf9 P-gp \u7684\u6291\u5236\u4f5c\u7528\uff0c\u805a\u5c71\u68a8\u916f80\u53ef\u589e\u52a0 P-gp \u5e95\u7269\uff0c\u5982\u897f\u54aa\u66ff\u4e01\u3001\u73af\u5b62\u7d20\u7b49\u836f\u7269\u7684\u8868\u89c2\u6e17\u900f\u7cfb\u6570\u3002<\/span><\/p>\n

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3.5<\/section>\n<\/section>\n

<\/p>\n

\u6cca\u6d1b\u6c99\u59c6\uff08poloxamer\uff09<\/section>\n

<\/span><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u6cca\u6d1b\u6c99\u59c6\u4e3a\u805a\u6c27\u4e59\u70ef\u805a\u6c27\u4e19\u70ef\u919a\u5d4c\u6bb5\u5171\u805a\u7269\uff0c\u5206\u5b50\u91cf1000\uff5e7000\uff0c\u7531\u9002\u91cf\u7684\u805a\u6c27\u4e19\u70ef\u4e0e\u805a\u6c27\u4e59\u70ef\u5171\u805a\u6210\u4eb2\u6cb9\u6c34\u5e73\u8861\u503c\u4e0d\u540c\u7684\u5316\u5408\u7269\uff0c\u4e3a\u4e00\u7c7b\u65b0\u578b\u7684\u9ad8\u5206\u5b50\u975e\u79bb\u5b50\u578b\u8868\u9762\u6d3b\u6027\u5242\uff0c\u53ef\u7528\u4f5c\u5236\u5242\u7684\u4e73\u5316\u5242\u3001\u7a33\u5b9a\u5242\u3001\u589e\u6eb6\u5242\u3001\u5438\u6536\u4fc3\u8fdb\u5242\u3001\u56fa\u4f53\u5206\u6563\u5242\u3001\u7f13\u91ca\u6750\u6599\u3002<\/span><\/p>\n

<\/span>\u6cca\u6d1b\u6c99\u59c6\u4fc3\u8fdb\u836f\u7269\u5438\u6536\uff0c\u4e00\u65b9\u9762\u7531\u4e8e\u672c\u54c1\u4f7f\u80a0\u8815\u52a8\u53d8\u6162\uff0c\u836f\u7269\u5728\u80c3\u80a0\u9053\u4e2d\u6ede\u7559\u65f6\u95f4\u589e\u957f\uff0c\u5438\u6536\u589e\u52a0\uff0c\u4ece\u800c\u80fd\u63d0\u9ad8\u53e3\u670d\u5236\u5242\u751f\u7269\u5229\u7528\u5ea6\uff0c\u53e6\u4e00\u65b9\u9762\u4e3a\u589e\u52a0\u80a0\u58c1\u901a\u900f\u6027\uff0c\u4fc3\u8fdb\u836f\u7269\u5438\u6536\u3002<\/span><\/p>\n

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3.6
<\/section>\n<\/section>\n

<\/p>\n

\u5361\u6ce2\u59c6<\/section>\n

<\/span><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

<\/span>\u5361\u6ce2\u59c6\u662f\u4ee5\u975e\u82ef\u6eb6\u5242\u4e3a\u805a\u5408\u6eb6\u5242\u7684\u4e19\u70ef\u9178\u952e\u5408\u70ef\u4e19\u57fa\u8517\u7cd6\u6216\u5b63\u620a\u56db\u9187\u70ef\u4e19\u919a\u7684\u9ad8\u5206\u5b50\u805a\u5408\u7269\uff0c\u53ef\u4ee5\u7528\u4e8e\u53e3\u670d\u56fa\u4f53\u5236\u5242\u7684\u6da6\u6e7f\u5242\u3001\u7c98\u5408\u5242\u7b49\u3002<\/span><\/p>\n

<\/span>\u798f\u8f9b\u666e\u5229\u662fPept1\u8f6c\u8fd0\u4f53\u9ad8\u4eb2\u548c\u529b\u7684\u5e95\u7269\uff0c\u5b59<\/span>\u7b71\uff3b6\uff3d\u4ee5\u5176\u4e3a\u63a2\u9488\u5e95\u7269\uff0c\u53d1\u73b00.1%\u548c 0.2%\u5361\u6ce2\u59c6934P\u5bf9\u798f\u8f9b\u666e\u5229\u7a7a\u80a0\u7684\u5438\u6536\u6709\u663e\u8457\u4fc3\u8fdb\u4f5c\u7528(P\uff1c0.05) \uff0c0.5%\u5361\u6ce2\u59c6 934P \u5bf9\u798f\u8f9b\u666e\u5229\u5728\u5341\u4e8c\u6307\u80a0\u3001\u7a7a\u80a0\u548c\u56de \u80a0\u4e09\u6bb5\u80a0\u7684\u5438\u6536\u90fd\u6709\u663e\u8457\u4fc3\u8fdb\u4f5c\u7528(P\uff1c0.05)\u3002<\/span><\/p>\n

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3.7
<\/section>\n<\/section>\n

<\/p>\n

\u7126\u78f7\u9178\u94a0<\/section>\n

<\/span><\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

\u7126\u78f7\u9178\u94a0(sodium pyrophosphate)\u53ef\u7528\u4f5c\u6ce1\u817e\u5242\u8f85\u6599\uff0c\u5bfc\u81f4\u836f\u7269\u4ea7\u54c1\u5feb\u901f\u5d29\u89e3\u3002<\/span><\/p>\n

<\/span>\u5728\u96f7\u5c3c\u66ff\u4e01\u76f8\u5bf9\u751f\u7269\u5229\u7528\u5ea6\u7814\u7a76\u4e2d\uff0c\u53d1\u73b0\u540c\u65f6\u7ed9\u4e881.132 mg(5.1mmol) \u7126\u78f7\u9178\u94a0\u53ef\u663e\u8457\u964d\u4f4e\u96f7\u5c3c\u66ff\u4e01\u5438\u6536(AUC\u51cf\u5c1154%) \uff0c\u8fd9\u4e0e\u4f7f\u7528\u95ea\u70c1\u6444\u5f71\u6210\u50cf\u6280\u672f\u5f97\u5230\u7684\u5c0f\u80a0\u8f6c\u8fd0\u65f6\u95f4\u51cf\u5c1156%\u7684\u7ed3\u679c\u5e73\u884c\uff3b2\uff3d\u3002<\/span><\/p>\n

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4 \u7ed3\u675f\u8bed<\/p>\n<\/section>\n<\/section>\n<\/section>\n


<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n
BE\u8c41\u514d\u53ef\u7b80\u5316\u4eff\u5236\u836f\u4e00\u81f4\u6027\u8bc4\u4ef7\u6d41\u7a0b\uff0c\u51cf\u5c11\u4e0d\u5fc5\u8981\u7684\u5065\u5eb7\u4eba\u4f53\u836f\u7269\u66b4\u9732\uff0c\u964d\u4f4e\u8bc4\u4ef7\u8d39\u7528\uff0c\u52a0\u5feb\u8bc4\u4ef7\u8fdb\u7a0b\uff0c\u4f46\u4e5f\u9762\u4e34\u7740\u7814\u7a76\u96be\u5ea6\u5927\u3001\u6280\u672f\u8981\u6c42\u9ad8\u3001\u5177\u4f53\u6807\u51c6\u89c4\u8303\u8fd8\u4e0d\u591f\u660e\u786e\u7684\u95ee\u9898\uff0c\u9700\u8981\u4f01\u4e1a\u5145\u5206\u628a\u63e1\u653f\u7b56\u8981\u6c42\uff0c\u79d1\u5b66\u5206\u6790BE\u8c41\u514d\u98ce\u9669\uff0c\u5e76\u4e0e\u836f\u76d1\u90e8\u95e8\u4fdd\u6301\u901a\u7545\u7684\u6c9f\u901a\u4ea4\u6d41\u3002<\/span><\/section>\n

\u53c2\u8003\u6587\u732e <\/span><\/em><\/span><\/p>\n

\uff3b1\uff3dICH\uff0eM9 Biopharmaceutics classification system based biowa\uff0divers\uff3bEB\/OL\uff3d\uff0e\uff3b2018-07-07\uff3d\uff0ehttps:\/\/www\uff0eich\uff0eorg\/fileadmin\/Public_Web_Site\/ICH_Products\/Guidelines\/ Multidisciplinary\/M9\/M9EWG_DraftGuideline_Step2_2018_ 0606\uff0epdf <\/span><\/em><\/span><\/p>\n

\uff3b2\uff3dCHENML\uff0cSADRIEHN\uff0cYUL\uff0eImpact of osmotically active excipients on bioavailability and bioequivalence of BCS class III drugs\uff3bJ\uff3d\uff0eAaps J\uff0c2013\uff0c15( 4) : 1043\uff0d1050\uff0e <\/span><\/em><\/span><\/p>\n

\uff3b3\uff3dZARMPIP\uff0cFLANAGAN T\uff0cMEEHAN E\uff0cet al\uff0eBiophar\uff0d maceutical aspects and implications of excipient variability in drug product performance\uff3bJ\uff3d\uff0eEur J Pharm Biopharm\uff0c2016\uff0c111: 1\uff0d15\uff0e <\/span><\/em><\/span><\/p>\n

\uff3b4\uff3d ALF\uff32EDO G A\uff0eInteractions between active pharmaceutical ingredients and excipients affecting bioavailability: impact on bioequivalence\uff3bJ\uff3d\uff0eEU\uff32 J PHA\uff32M SCI\uff0c2014\uff0c65: 89\uff0d97\uff0e <\/span><\/em><\/span><\/p>\n

\uff3b5\uff3d BHA\uff32ATE S S\uff0cBHA\uff32ATE S B\uff0cBAJAJ A N\uff0e Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review\uff0e\uff3bJ\uff3d\uff0e J Excipients Food\uff0c2010\uff0c1( 3) : 3\uff0d26\uff0e <\/span><\/em><\/span><\/p>\n

\uff3b6\uff3d \u5b59\u7b71\uff0e\u836f\u7528\u8f85\u6599\u5bf9\u798f\u8f9b\u666e\u5229\u94a0\u80a0\u9053\u5438\u6536\u5f71\u54cd\u7684\u7814\u7a76\uff3bD\uff3d\uff0e \u6b66\u6c49: \u534e\u4e2d\u79d1\u6280\u5927\u5b66\uff0c2013: 34\uff0d36\uff0e <\/span><\/em><\/span><\/p>\n

\uff3b7\uff3d \u95eb\u65b9\uff0e\u8f85\u6599\u6291\u5236 P-\u7cd6\u86cb\u767d\u836f\u6cf5\u4f5c\u7528\u4e0e\u73af\u5b62\u7d20 A \u80a0\u9053\u5438\u6536 \u5173\u7cfb\u7684\u7814\u7a76\uff3bD\uff3d\uff0e\u6b66\u6c49: \u534e\u4e2d\u79d1\u6280\u5927\u5b66\uff0c2009: 18\uff0d22\uff0e <\/span><\/em><\/span><\/p>\n

\uff3b8\uff3d \u5468\u6676\uff0e\u8c03\u63a7\u80a0\u9053\u4ee3\u8c22\u63d0\u9ad8\u836f\u7269\u53e3\u670d\u751f\u7269\u5229\u7528\u5ea6\u7684\u5236\u5242\u6280 \u672f\u7814\u7a76\uff3bD\uff3d\uff0e\u5317\u4eac: \u5317\u4eac\u534f\u548c\u533b\u5b66\u9662\uff0c2015: 50\uff0d54\uff0e<\/span><\/em><\/span><\/p>\n

\u58f0\u660e\uff1a<\/span><\/em><\/span>\u8fdb\u5316\u8bba\u5bf9\u672c\u6587\u89c2\u70b9\u4fdd\u6301\u4e2d\u7acb\u3002<\/span><\/em><\/span>\u6587\u7ae0\u4ec5\u4f9b\u4ea4\u6d41\u5b66\u4e60\u4f7f\u7528\uff0c\u7248\u6743\u5f52\u539f\u4f5c\u8005\u6240\u6709\uff0c\u5982\u9047\u7248\u6743\u95ee\u9898\u8bf7\u4e0e\u6211\u4eec\u8054\u7cfb\u3002<\/span><\/em><\/span><\/span><\/em><\/span><\/p>\n


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