ͼƬ dz̸ҩÎï´«ÊäϵͳÑо¿µÄ¼¸¸öÈȵã_Ó¢ÐÛÁªÃ˱ÈÈüѺעapp_¹Ù·½ÍøÕ¾ÏÂÔØ~

Ó¢ÐÛÁªÃ˱ÈÈüѺעapp_¹Ù·½ÍøÕ¾ÏÂÔØ~

µ±Ç°Î»ÖãºÖ÷Ò³ > ±ÏÒµÂÛÎÄ > ҽҩѧ > ҩѧ > >

dz̸ҩÎï´«ÊäϵͳÑо¿µÄ¼¸¸öÈȵã

À´Ô´::δ֪ | ×÷Õß:Ó¢ÐÛÁªÃ˱ÈÈüѺעapp_¹Ù·½ÍøÕ¾ÏÂÔØ~ | ±¾ÎÄÒÑÓ°Ïì ÈË

Õª¡¡Òª¡¡Í¨¹ý²éÔĽüÄê¹úÍâÎÄÏ×£¬Öصã½éÉÜÁËÒ©Îï´«Êäϵͳ½ÏеĽøÕ¹£¬ÓÐÂö³åʽ¸øҩϵͳ£¬½á³¦¶¨Î»¸øҩϵͳ¼°ÊÜÌåÐÍÓëÃâÒßÐÍ°ÐÏòÖƼÁµÈÄÚÈÝ¡£

¡¡¡¡¹Ø¼ü´Ê£ºÒ©Îï´«Êäϵͳ¡¡Âö³åʽ¸øҩϵͳ¡¡½á³¦¶¨Î»¸øҩϵͳ¡¡ÊÜÌåÐÍÓëÃâÒßÐÍ°ÐÏòÖƼÁ

¡¡¡¡Ò©Îï´«Êäϵͳ(Drug Delivery Systems,DDS)ϵָÈËÃÇÔÚ·ÀÖμ²²¡µÄ¹ý³ÌÖÐËù²ÉÓõĸ÷ÖÖÖÎÁÆÒ©ÎïµÄ²»Í¬¸øÒ©ÐÎʽ£¬ÔÚ60Äê´úÒÔÇ°µÄÒ©¼ÁѧÖгÆΪ¼ÁÐÍ¡£Èç×¢Éä¼Á¡¢Æ¬¼Á¡¢½ºÄÒ¼Á¡¢ÌùƬ¡¢ÆøÎí¼ÁµÈ¡£Ëæ×Å¿ÆѧµÄ½ø²½£¬¼ÁÐ͵ķ¢Õ¹ÒÑÔ¶Ô¶³¬Ô½ÆäÔ­ÓеÄÄÚº­£¬ÐèÒªÓÃÒ©Îï´«Êäϵͳ»ò¸øÒ©Æ÷(Device)ÕâÀàÊõÓï¼ÓÒÔ±íÊö£¬¼´Ô­ÓÉÒ©ÎïÓ븨ÁÏÖƳɵĸ÷ÖÖ¼ÁÐÍÒÑÂú×ã²»ÁËÁÙ´²ÖÎÁƵÄÐèÒª£¬ÓеĽ«Ò©ÎïÖƳÉÊäעϵͳ¹©Óã¬ÓеÄÔò²ÉÓÃîѺϽðÖƳɸøÒ©Æ÷Ö²ÈëÌåÄÚÓ¦Óã¬Ê¹ÁÙ´²ÓÃÒ©¸üÀíÏ뻯¡£Îª¿Ë·þÆÕͨÖƼÁµÄÓÐЧѪŨά³Öʱ¼ä¶ÌµÄȱÏÝ£¬³öÏÖÁ˳¤Ð§×¢Éä¼Á£¬¿Ú·þ³¤Ð§¸øҩϵͳ»ò»º/¿ØÊÍÖƼÁ¡¢¾­Æ¤¸øҩϵͳµÈһϵÁÐеÄÖƼÁ¡£ÓÉÓÚ»º/¿ØÊÍÖƼÁµÄÌص㣬ËüµÄÊг¡Ç°¾°¿´ºÃ¡£»ºÊÍÖƼÁͨ³£ÊÇÖ¸¿Ú·þ¸øÒ©ºóÄÜÔÚ»úÌåÄÚ»ºÂýÊÍ·ÅÒ©Îʹ´ïÓÐЧѪŨ£¬²¢ÄÜά³ÖÏ൱³¤Ê±¼äµÄÖƼÁ¡£¿ØÊÍÖƼÁϵָÊÍÒ©ËٶȽöÊܸøҩϵͳ±¾ÉíµÄ¿ØÖÆ£¬¶ø²»ÊÜÍâ½çÌõ¼þ£¬ÈçpH¡¢Ã¸¡¢Àë×Ó¡¢Î¸³¦È䶯µÈÒòËصÄÓ°Ïì£Û1£Ý£¬ÊÇ°´Éè¼ÆºÃµÄ³ÌÐò¿ØÖÆÊÍÒ©µÄÖƼÁ£¬ÈçÁ㼶ÊÍÒ©µÄÉø͸±Ã£¬Âö³åÊÍÒ©µÄ΢Í裬½á³¦¶¨Î»ÊÍÒ©µÄƬ¼Á»ò½ºÄÒÒÔ¼°×Ô¶¯µ÷½ÚÊÍÒ©µÄÒȵºËظøÒ©Æ÷µÈµÈ¡£ÒàÓÐЩÎÄÏ׶ԻºÊÍ¡¢¿ØÊÍÖƼÁ²»¼ÓÑϸñÇø·Ö£¬Í³³ÆΪ»º/¿ØÊÍÖƼÁ¡£

¡¡¡¡¹úÍâÏÖÓйæ¸ñ²»Í¬µÄ»º/¿ØÊÍÖƼÁÉÌÆ·´ïÊý°ÙÖÖÒÔÉÏ£¬Æä¼ÁÐÍÒàÓÐƬ¼Á¡¢½ºÄÒ¡¢Ë¨¼Á¡¢Éø͸±Ã¡¢Í¸Æ¤ÌùƬ¡¢Ò©Ìõ¡¢Ö²Èë¼Á¡¢Õ³Ä¤Õ³¸½¼Á¼°×¢Éä¼ÁµÈ¶àÖÖÐÎʽ£¬ÆäÖÐÒÔ¿Ú·þ»º/¿ØÊÍÖƼÁ·¢Õ¹×î¿ì¡£»ºÊÍ΢Í轺ÄÒ¼ÁÓ뻺ÊÍƬÏà±È£¬¾ßÓа²È«ÏµÊý¸ßµÄÌص㣬һ¸ö½ºÄÒÊÇÓÉÉÏ°ÙÁ£»ºÊÍ΢Íè×é³É£¬ÈôÓиö±ðСÍè½øÈë賦µÀºó·¢ÉúѸËÙ±À½âÊÍÒ©µÄÏÖÏó£¬ÆäÓ°ÏìÊÇ΢СµÄ£¬¶ø»ºÊÍƬÈôÓбÀÊÍÏÖÏó£¬ÒòÆäµ¥´Î¼ÁÁ¿±ÈÆÕͨÖƼÁ´ó£¬Æäºó¹ûÊDz»ÑÔ¶øÓ÷µÄÁË£»¶øÇÒ»ºÊÍ΢Í轺ÄÒ²»Ò׶Ôθ¿ÕËÙÂÊÂýµÄ»¼Õß·¢Éúµþ¼ÓÊͷŵÄÏÖÏó£¬ÒÔ¼°²»Ò×ÊÜθҺpHÖµ±ä»¯µÄ¸öÌå²îÒìµÄÓ°Ïì¡£Òò´Ë£¬»ºÊÍ΢Í轺ÄұȻºÊÍƬ¸ü¾ßÓз¢Õ¹Ç°¾°¡£

¡¡¡¡ÎÒ¹úÔçÔÚ1977Äê°æµÄÖйúÒ©µä¾ÍÊÕÔØÁË·ÀÖÎѪÎü³æ²¡µÄûʳ×ÓËáÌàÄÆ»ºÊÍƬ£¬µ«ÔÚÕâ·½ÃæµÄÑо¿Ö±µ½80Äê´ú²Å±»¹ã·ºÖØÊÓ¡£1995ÄêÎÒ¹úÅú×¼µÄ»º/¿ØÊÍÖƼÁ¾ÍÓÐ7¸ö£¬Ö¬ÖÊÌ塢΢Çò¡¢ºÁ΢Á£µÈÑÇ΢Á£·ÖÉ¢¸øҩϵͳÒÔ¼°½á³¦¶¨Î»¸øҩϵͳÕâÀà¿Ú·þ°ÐÏò¸øÒ©ÖƼÁ¹úÄÚÑо¿Ò²ºÜ»îÔ¾(Ä¿Ç°Ö¬ÖÊÌåÒÑÓÐÅú×¼Éú²úµÄÆ·ÖÖ)¡£½ñ¾ÍÒÔϼ¸¸ö²àÃæ½øÐиÅÊö¡£

1¡¡ÐÂÐÍ»º/¿ØÊÍÖƼÁÑо¿¸Å¿ö

1.1¡¡Î¸ÄÚÖÍÁôÐÍ¿ØÊ͸øҩϵͳ£Û2£¬3£Ý¡¡¿É²ÎÔÄÓйØÎÄÏס£

1.2¡¡Âö³åʽ¸øҩϵͳ¡¡¸ù¾Ýʱ³½Ò©ÀíѧÑо¿£¬Ò©ÎïµÄÖÎÁÆ×÷Óᢲ»Á¼·´Ó¦ºÍÌåÄÚ¹ý³Ì¾ùÓÐʱ¼ä½ÚÂÉ£¬ÕâÒѳÉΪÉè¼Æ¶¨Ê±ÊÍÒ©ÕâÀà¿ØÊÍÖƼÁµÄÖØÒªÒÀ¾Ý¡£ÊÍÒ©·½Ê½·ûºÏÈËÌåÖçÒ¹½ÚÂɱ仯µÄ¹æÂÉ£¬ÕâÊǽü´úÒ©¼ÁѧÑо¿µÄÒ»ÖÖÐÂÐÍÊÍҩģʽ¡£¹úÍâÓжà¼ÒÖÆÒ©ÆóÒµÕýÔÚÑо¿¿ª·¢ÕâÀàÂö³åʽ¸øҩϵͳ£¬¹úÄÚÒàÒÑ¿ªÊ¼Ñо¿¡£

¡¡¡¡Âö³åÊÍҩϵͳ(pulsatile release system)¿Ú·þʱ½«ÒÔʱ¿ØµÄ·½Ê½ÔÚ賦µÀÄÚÌض¨²¿Î»ÊÍ·ÅÒ©Îï¡£ÕâÀà¸øҩϵͳÌرðÊÊÓÃÓÚÒ¹¼ä»òÐѺóÂíÉÏÐèÒªÓÐÒ»¸öѪŨ·åÖµµÄ¼²²¡(ÈçʧÃß¡¢Ïø´­¡¢¹Ø½ÚÑס¢¾Ö²¿È±ÑªÐÔÐÄÔಡµÈ)£¬Ò²ÊÊÓÃÓÚÔÚ³¦µÀ½Ïϲ¿Î»´¦ÊÍÒ©ºÍÎüÊÕµÄÄÇЩ¼²²¡(Èç½á³¦°©¡¢À£ÑñÐԽ᳦Ñס¢¿Ú·þëÄÀàµÈ)¡£Ä¿Ç°¹úÍâͶÈëÕâÀàÑо¿µÄÖ÷ÒªÓÐƽ´­Ò©¡¢ÐÄѪ¹ÜÒ©ºÍH2ÊÜÌå×è¶Ï¼Á¼°ÒȵºËصȡ£ÒýÈëעĿµÄÊÇALZA¹«Ë¾ºÍSearle¹«Ë¾¹²Í¬¿ª·¢µÄάÀ­ÅÁÃ×ÖçÒ¹½ÚÂÉÂö³åÊÍҩϵͳÉÌÆ·ÃûΪCalan- OROS¡£ÖÎÁÆʵ¼ùÖ¤Ã÷£º¸ßѪѹ»¼Õß×î¼Ñ¸øҩʱ¼äΪÇ峿3µã×óÓÒ£¬´Ëʱ»¼ÕßÌåÄÚ¶ù²è·Ó°·Ë®Æ½Ôö¸ß£¬ÐÄÔࡢѪ¹ÜÊÕËõ¼ÓÇ¿£¬Òò¶ø×î¿ÉÄܳöÎÊÌ⣬¸Ã¸øҩϵͳÍíÉÏÁÙ˯ǰ·þÓ㬴ÎÈÕÇ峿¿ÉÊÍ·ÅÂö³å¼ÁÁ¿µÄÒ©Îʮ·Ö·ûºÏ¸Ã²¡½ÚÂɱ仯µÄÐèÒª£¬Ô¤¼Æ¸Ã¼ÁÐͺܿ켴¿ÉÉÏÊС£

1.2.1¡¡Âö³åÊÍҩƬ¡¡°´Ê±¿Ø±À½â»úÖÆ(time-controlled disintegration mechanism)Éè¼ÆµÄÒ»ÖÖ¸Éѹ°üÒÂƬ¿É´ïÂö³åÊÍҩ֮ĿµÄ¡£ÆäƬоÓÉÒ©ÎïÓë±À½â¼Á×é³É£¬ÆäÍâ¿ÇÊÇÓÉË®Éø͸ÐÔСµÄ¸´ºÏ²ÄÁÏ×é³É¡£µ÷½ÚÍâ¿Çºñ¶ÈÓëË®Éø͸ÐÔ¼´¿É¿ØÖÆÆäÂö³åÊÍҩʱ¼ä¡£ÀýÈ磺ÒÔÑÎËáÁòµª?NFDA1?ͪΪģÐÍÒ©Îï(ÔڽϿíµÄ賦µÀÄڿɱ»ÎüÊÕ)£¬Ñ¡ÓÃôȼ׻ùÏËάËظÆ(ECG-505)×÷±À½â¼Á£¬Ó²Ö¬ËáþΪÈ󻬼ÁѹÖƳÉƬо¡£Íâ¿ÇÓÉÇ⻯±ÍÂéÓÍ(HCO)¡¢¾ÛÂÈÒÒÏ©(PVC)ºÍ¾ÛÒÒ¶þ´¼(PEG6000)»ìºÏ×é³É£¬²ÉÓÃ90¡«94¡æÈÛÈÚ·¨ÖÆÁ££¬È¡20Ä¿¿ÅÁ££¬ÒÔ¸Éѹ°üÒ·¨ÖÆƬ£¬µ÷½ÚPEGÓÃÁ¿¼°Íâ¿Çºñ¶È¼´¿É¿ØÖÆË®µÄÉø͸ËÙÂÊ¡£ÕâÖÖϵͳµÄƽ¾ùʱÖÍΪ(7±1)h£¬´ËʱҩÎïÔÚ15 minÄÚÊÍ·ÅÍê±Ï¡£

1.2.2¡¡Âö³åÊÍҩ΢Íè£Û4£Ý¡¡Òà³Æʱ¿Ø±¬ÁÑϵͳ(time-controlled explosion system£¬TES)¡£ÕâÖÖÇòÐÎ΢ÍèµÄ½á¹¹¿É·Ö4²ã£¬´ÓÀïµ½Íâ·ÖÍèо¡¢Ò©Îï²ã¡¢ÅòÕͼÁ²ã¼°Ë®²»ÈÜÐÔ¾ÛºÏÎïÍâ²ãÒÂĤ£¬¼ûͼ1¡£µ±Ë®·Ýͨ¹ýÍâ²ãÒÂĤÏòϵͳÄÚÉø͸£¬½Ó´¥ÅòÕͼÁ£¬Ò»µ©Ë®»¯ÅòÕͼÁµÄÅòÕÍÁ¦³¬¹ýÍâ²ãÒÂĤµÄ¿¹ÕÅÇ¿¶Èʱ£¬Ä¤¿ªÊ¼ÆÆÁÑ£¬´¥·¢Ò©ÎïÊÍ·Å¡£¿Éͨ¹ý¸Ä±äÍâ²ãÒÂĤµÄºñ¶ÈÀ´¿ØÖÆÊÍ·ÅÒ©ÎïµÄʱ¼ä¡£ÀýÈ磬ÍèоÓÃÌÇÍè(nonpareil)£¬ÆäÍâ²ãÒÀ´Î°üÉÏÒ©Îï²ã¡¢ÅòÕͲã(L-HPC)¼°Íâ²ãECĤ£¬µ±ÅòÕͲãºñ¶È(180 μm)¹Ì¶¨Ê±£¬ECĤ²ãµÄºñ¶È¿ÉÓ°ÏìÊÍÒ©µÄʱÖÍ(tL)£¬Èçθ¸´°²TES£¬ECĤºñΪ20 μmʱ£¬tLΪ1 h£»ECĤºñΪ25 μmʱ£¬tLΪ2 h£»ECĤºñΪ30 μmʱ£¬tLΪ3h¡£ÈôECĤ(25 μm)ºñ¹Ì¶¨£¬Ôòµ÷½ÚL-HPC²ãµÄºñ¶ÈÒà¿Éµ÷½ÚÊÍҩʱ¼ä£¬Èçtiap ride hydrochloride TES,ÔÚL-HPCΪ120 μmºñʱ£¬¾­Àú1hµÄʱÖͺóÊÍÒ©£¬µ«ÒÂĤ6hҲδÆÆ£»ÈôL-HPCΪ180 μmʱ£¬2hºóÒÂĤ¿ªÊ¼ÆÆÁÑ£¬6hÄÚÈ«ÆÆ£¬Ò©ÎïÊÍ·Åͬ²½½øÐС£¡¡¡¡TES¿ÉÊÊÓÃÓÚ¸÷ÖÖÀí»¯ÐÔÖʲ»Í¬µÄÒ©Îï¡£ÕâÀà¸øҩϵͳ¹úÄÚÒàÒÑ¿ªÊ¼Ñо¿¡£

1.3¡¡½á³¦¶¨Î»¸øҩϵͳ£Û5¡«11£Ý¡¡½á³¦²¿Î»¼²²¡ÈçÀ£ÑñÐԽ᳦Ñס¢½á³¦°©µÈÒªÇóÄÜÔڽ᳦²¿Î»ÊÍÒ©£»´ËÍ⣬Ëæ×ÅÉúÎ﹤³ÌµÄ·¢Õ¹£¬¶àëÄÀà¡¢µ°°×ÀàÒ©ÎïÔö¶à£¬ÕâÀàÒ©Îïͨ³£Òª×¢Éä¸øÒ©£¬ÒòËüÃÇÔÚ賦µÀÉ϶ÎÎȶ¨ÐÔ¼°ÎüÊÕÀûÓò¹Ê²»ÒË¿Ú·þ£¬¿ÉÊÇÔڽ᳦¶Î½µ½âµ°°×µÄøÀà½ÏÉÙ£¬ÍùÍùÎüÊÕÀûÓýϺã¬ÈôÄÜÖƳɽ᳦¶¨Î»¸øҩϵͳ£¬Ôò¶àëÄÀà¡¢µ°°×ÀàÒ©Îï¿Ú·þ¸øÒ©¾ÍÓÐÏ£Íû£¬Òò¶ø¹úÄÚÍâ¾ùÖÂÁ¦ÓÚÑÐÖÆ¿ª·¢ÕâÀàÐÂÐ͸øҩϵͳ¡£ÕâÀà¸øҩϵͳͨ³£¿ÉÓÉÏÂÁм¸ÖÖ²ÄÁÏÖƳɡ£

1.3.1¡¡pHÃô¸ÐµÄ³¦ÈܲÄÁÏ¡¡²ÉÓÃË«²ãÒÂĤ¿ØÖÆÒ©ÎïÔڽ᳦²¿Î»ÊÍ·Å¡£È磺½«ÏûÑ×Í´(25%W/W)¡¢ÈéÌÇ(62%W/W)¡¢µí·Û(10%W /W)»ìÔÈ£¬ÒÔ10%(W/V)PVPË®ÈÜҺʪÈóÖÆÁ££¬55¡æ¸ÉÔÕûÁ£ºó¼Ó1%M.S£¬ÒÔΦ 4.5 mm°¼³åѹƬºó°üHPMC»ºÊÍÒ²ã(ÔöÖØ35.7%£¬Å䷽Ϊ£ºMethocel K15 5.0,PEG400 1.0,Talc 2.0,PVP 2.5£¬ÒÒ´¼84.0£¬Ë®5.5)£¬ÔÙ°ü³¦Ò²ã(ÔöÖØ5%£¬Å䷽Ϊ£º8%(W/V)Eudragitl,2%DEP)¡£ÕâÀà²ÄÁÏÒ×Êܳ¦µÀpHÖµ±ä»¯µÄÓ°Ïì¡£

1.3.2¡¡Ê±¿ØÐͲÄÁÏ¡¡Í¨³£Ê³ÎïÔÚθ¼°Ð¡³¦·Ö±ðÖÍÁôÔ¼3h×óÓÒ£¬ËùÒÔʳÎïÔËÐÐÖÁ½á³¦Ô¼Ðè5¡«7h¡£ÈôÄÜ¿ØÖÆÔÚ5¡«7hÊÍÒ©Õß¼´¿É´ï½á³¦¸øҩ֮Ч¡£Ç°Êöʱ¿ØÐÍÂö³åÊÍҩϵͳ¼´Êô´ËÀ࣬ÕâÀà¸øҩϵͳÒò¸÷ÈËθÅÅ¿ÕËÙÂʲ»Í¬£¬ËùÒÔ¸öÌå²îÒì½Ï´ó¡£

1.3.3¡¡Ã¸Ïû»¯ÐͲÄÁÏ¡¡ÀûÓý᳦²¿Î»ÌØÓеÄ΢ÉúÎïËù²úÉúµÄø£¬ÒÔ½µ½â¸ß·Ö×Ó²ÄÁ϶øÊÍÒ©£¬ÀýÈ磬żµª¾ÛºÏÎï¡¢¹û½ºµÈ¿É±»½á³¦ÖÐÌØÓеÄ΢ÉúÎïø½µ½â¶øÊÍÒ©¡£ÕâÀà²ÄÁϽ᳦¶¨Î»µÄרÊôÐÔ½ÏÇ°Á½ÀàÇ¿¡£

1.3.4¡¡ÆäËû¡¡²ÉÓøßƵ½ºÄÒ£¬ÔÚ½º¿ÇÉÏ×°Ò»¸ö΢ÐÍÏßȦ£¬ÔÚ¸ßƵ´Å³¡×÷ÓÃÏÂÏßȦ²úÉúµçÁ÷£¬Òý·¢½º¿ÇÆÆÁѶøÊÍÒ©¡£

1.4¡¡×Ô¶¯µ÷½Ú¸øҩϵͳ£Û12£¬13£Ý¡¡¿É²ÎÔÄÓйØÎÄÏס£

2¡¡°ÐÏò¸øҩϵͳÑо¿ÏÖ×´

¡¡¡¡ÔÚÁÙ´²ÖÎÁƼ²²¡µÄ¹ý³ÌÖÐÍùÍùÐèÒªÌá¸ßÒ©ÎïµÄ°ÐÏòÐÔ£¬ÒÔÆÚ×î´óÏ޶ȵØÔöÇ¿Ò©ÎïµÄÁÆЧ£¬Í¬Ê±Ê¹Ò©ÎïµÄ²»Á¼·´Ó¦½µÖÁ×îµÍ£¬Òò´Ë°ÐÏò¸øҩϵͳ(TDDS)ÒѳÉΪÏÖ´úÒ©¼ÁѧµÄÖØÒªÄÚÈÝ¡£Í¨³£¿É½«¿ØÊÍÖƼÁ·Ö³ÉÁ½´óÀࣺһÀàרÃÅÑо¿ÈçºÎ¿ØÖÆÖƼÁÖÐÒ©ÎïÊͷŵÄËٶȣ¬¼´Á㼶¡¢Ò»¼¶»¹ÊÇÂö³åʽÊÍÒ©£¬ÒÖ»ò×Ôµ÷ʽÊÍÒ©µÈµÈ(ÒÑÔÚÇ°ÊöÄÚÈÝÖÐÌÖÂÛ)£»ÁíÒ»ÀàרÃÅÑо¿ÈçºÎ¿ØÖÆÖƼÁÖÐÒ©ÎïÊͷŵÄÈ¥Ïò£¬ÕâÊÇÒ»ÀàÒªÇó¸ü¸ß¡¢ÄѶȸü´óµÄÐÂÖƼÁ£¬Òò¶ø½«Æä¹éÊôÓÚ°ÐÏòÖƼÁ½øÐе¥ÁÐÌÖÂÛ¡£

2.1¡¡°ÐÏò¸øÒ©ÖƼÁµÄ·ÖÀà

2.1.1¡¡°´¸øҩ;¾¶·Ö¡¡È«Éí×÷ÓðÐÏò¸øÒ©ÖƼÁ£¬¼´Í¨¹ý¿Ú·þ»ò×¢ÉäµÈ·½Ê½¸øÒ©ºó£¬ÄÜʹҩÎïµ¼ÏòËùÐè·¢»Ó×÷ÓõIJ¿Î»£»·ÇÈ«Éí×÷ÓõİÐÏò¸øÒ©ÖƼÁ£¬¼´¾Ö²¿ÓÃÒ©ºó£¬Ò©Îï¾ÍÔڸò¿Î»·¢»ÓÖÎÁÆ×÷Óá£

2.1.2¡¡°´×÷Ó÷½Ê½·Ö¡¡Ö÷¶¯°ÐÏò(active targeting)¸øÒ©ÖƼÁ¾ßÓÐʶ±ð°Ð×éÖ¯»ò°Ðϸ°ûµÄ´ó·Ö×Ó£¬ÒÔÆäΪÔØÌåµÄÄÜÁ¦£»±»¶¯°ÐÏò(passive targeting)¸øÒ©ÖƼÁ£¬ÏñÖ¬ÖÊÌ塢΢Çò¡¢ºÁ΢Á£¡¢Èé¼Á»ò¸´ÈéµÈ΢Á£ÔØÌåÖƼÁ£¬¶Ô°Ðϸ°û²¢ÎÞʶ±ðÄÜÁ¦£¬µ«¿É¾­ÑªÑ­»·µ½´ïËüÃDz»ÄÜͨ¹ýµÄëϸѪ¹Ü´²£¬²¢Ôڸò¿Î»ÊÍÒ©¡£

2.1.3¡¡°´Ò©Îï×÷ÓÃˮƽ·Ö¡¡Ò»¼¶°ÐÏò£¬Èç΢Á£ÔØÌåÖƼÁÖ»Äܽ«Ò©ÎïÊäËÍÖÁÌض¨µÄÆ÷¹Ù£»¶þ¼¶°ÐÏò£¬ÏµÖ¸Äܽ«Ò©ÎïÊäËÍÖÁijÆ÷¹ÙµÄÌض¨²¿Î»£»Èý¼¶°ÐÏò£¬ÏµÖ¸Äܽ«Ò©ÎïÊäËÍÖÁÌض¨²¿Î»µÄ²¡±äϸ°ûÄÚ¡£ÈçÈôÄܽ«Ò©ÎïÖƳÉÈý¼¶°ÐÏòÖƼÁ£¬Ôò¿ÉʹҩÎïÔÚϸ°ûˮƽÉÏ·¢»Ó×÷Óã¬Ò©Îï¿ÉרÃŹ¥»÷²¡±äϸ°û£¬¶ÔÕý³£Ï¸°ûûÓлò¼¸ºõûÓв»Á¼µÄÓ°Ï죬¿ÉʹҩÎïµÄÁÆЧ´ïµ½×îÀíÏëµÄ³Ì¶È¡£

2.1.4¡¡°´ÎïÀíÐÎ̬·Ö¡¡Ë®²»ÈÜÐÔÖƼÁÖ¸Ö¬ÖÊÌ塢΢Çò¡¢ºÁ΢Á£¡¢Èé¼Á»ò¸´ÈéµÈË®²»ÈÜÐÔ΢Á£ÔØÌåÖƼÁ£»ÁíÒ»ÀàÊÇË®ÈÜÐÔµÄÌØÒì»ò·ÇÌØÒìÐÔ´ó·Ö×ÓÔØÌåÖƼÁ£¬°üÀ¨ºÏ³É´ó·Ö×ÓÓëÌìÈ»µÄÉúÎï´ó·Ö×Ó(Èç¾Û¶àÌÇ¡¢¿¹Ìå¡¢ºËÌÇ¡¢ºËËáµÈ)ÔØÌåÖƼÁ£¬Ò©ÎïµÄ°ÐÏòÖ÷Ҫƾ½èÔØÌåϵͳÀ´ÊµÏÖ£¬¹ÊÓֿɳÆΪҩÎïÔØÌåϵͳ (drug-carrier systems)¡£

ÎÄÏ××ÊÁϾ­³£²ÉÓÃÖ÷¶¯°ÐÏòÓë±»¶¯°ÐÏò¸øÒ©ÖƼÁµÄ·ÖÀà·¨¡£

¡¡¡¡ÔÚÒÔÍùÑо¿ÖУ¬±»¶¯°ÐÏò¸øÒ©Ñо¿½Ï¶à£¬ÈçÖ¬ÖÊÌåµÈ΢Á£ÔØÌåÖƼÁ£¬½øÈë»úÌåºó£¬¿É°´ÆäÁ£¾¶´óС·Ö²¼ÓÚ²»Í¬µÄÔàÆ÷£º¾²Âö×¢Éä7¡«12 μmµÄ΢Á££¬¿É±»·Î²¿»úеÐÔ½ØÂ˶øÉãÈ¡£»¶¯Âö×¢Éä´óÓÚ12 μmµÄ΢Á££¬¿É×èÖÍÓÚëϸѪ¹Ü´²¶øµ½´ï¸Î¡¢ÉöºÉÁöÆ÷¹ÙÖУ»¾²Âö¡¢¶¯Âö»ò¸¹Ç»×¢Éä0.1¡«0.2 μmµÄ΢Á££¬ºÜ¿ì±»Íø×´ÄÚƤϵͳ(RES)µÄ¾ÞÊÉϸ°ûÍÌÊÉ×îÖÕµ½´ï¸ÎÔà¿Ý·ñÊÏϸ°ûµÄÈÜøÌåÖС£

2.2¡¡°ÐÏò¸øҩϵͳ·¢Õ¹Ç÷ÊÆ¡¡Îª½øÒ»²½Ìá¸ßÒ©ÎïµÄ°ÐÏòÐÔ£Û14£¬15£Ý£¬¿Æѧ¼ÒÃÇÓÖ½«ÄÜʶ±ð°Ðϸ°ûµÄ´ó·Ö×ÓÁ¬½ÓÓÚÒ©ÎïÔØÌåµÄ±íÃæ(»òÓëÒ©Îï·Ö×ÓÖ±½ÓÏàÁª)£¬È磺½«µ¥¿Ë¡¿¹ÌåÁ¬½ÓÓÚº¬Ò©Ö¬ÖÊÌå(»òºÁ΢Á£)µÄ±íÃ棬¿ÉÌá¸ßÒ©Îï¶ÔÖ×Áöϸ°ûµÄ°ÐÏòÐÔ£¬µ«ÒòʵÌåÁöÄÚѪ¹©²î£¬ËüÏòÁöÌåÄÚ²¿°ÐÏòµÄЧ¹ûÒà²î£»½ø¶øÑÐÖÆÈËÊóǶºÏ¿¹Ö×Áöϸ°ûºËµ¥¿Ë¡¿¹Ìå(chTNT)Ö¬ÖÊÌ壬ʹÆä°ÐÏòʵÌåÁöÄÚµÄЧ¹û±Èµ¥¿¹Ö¬ÖÊÌå´óΪÌá¸ß£¬ÕâÖÖÃâÒßÐÍÖ¬ÖÊÌå×÷ΪҩÎï´«ÊäϵͳµÄÑо¿±¨µÀËäΪÊý²»¶à£¬µ«Ä¿Ç°ÒÑÊܹúÄÚÍâѧÕßµÄÆÕ±é¹Ø×¢¡£

¡¡¡¡Ñо¿±íÃ÷¶àÊýÖ×Áöϸ°û±íÃæÉϵÄÒ¶ËáÊÜÌ壬ÔÚÊýÁ¿ºÍ»îÐÔÉϾù±ÈÕý³£Ï¸°û´óµÃ¶à£¬Òò¶ø¿ÉÖƱ¸Ò¶ËáÖ¬ÖÊÌ壬ËüÒÔÒ¶ËáÊÜÌåΪ½éµ¼£¬Ìá¸ßÁËÖ¬ÖÊÌå¶ÔÖ×Áöϸ°ûµÄ°ÐÏòÐÔ¡£

¡¡¡¡Ò¶ËáÖ¬ÖÊÌåÒ×µ¼Ïò“½¡¿µ”Ö×Áöϸ°ûĤ£¬¹ÊΪ·ÇÍíÆÚÖ×ÁöÖÎÁÆÒ©ÎïµÄÓÅÁ¼´«Êäϵͳ£»chTNT-Ö¬ÖÊÌåÒ×´©Í¸“²»½¡¿µ”Ö×Áöϸ°ûĤ¶ø°ÐÏòϸ°ûºË£¬¹ÊΪÍíÆÚÖ×ÁöÖÎÁÆÒ©ÎïµÄÓÅÁ¼´«Êäϵͳ£¬ÕâÑùÁ½ÖÖ²»Í¬µÄ°ÐÏòÖ¬ÖÊÌå¿ÉÓÃÓÚÖÎÁƲ»Í¬Éú³¤ÆڵĹãÆ×Ö×Áö¡£

¡¡¡¡1966ÄêMorellµÈ·¢ÏÖ²¸È鶯ÎïµÄ¸ÎʵÖÊϸ°ûĤ±íÃæ´æÔÚÈ¥ÍÙÒºËáÌǵ°°×ÊÜÌå(Asialoglycoprotein receptor,ASGPr)£¬¸ÃÊÜÌåÄÜרһÐÔµØʶ±ðÒÔ°ëÈéÌÇΪ¶Ë»ùµÄÌǵ°°×£¬Òò¶øÒÔÕâÑùµÄÌǵ°°×ΪÔØÌ壬¿É½«Ò©Îïµ¼Ïò¸ÎʵÖÊϸ°û(¸Î·ÇʵÖÊϸ°û(¿Ý·ñÊÏϸ°ûºÍÄÚƤϸ°û)µÄ±íÃæÓиʶÌÇÊÜÌå)£¬²¢Ö÷¶¯Ïò¸Îϸ°ûµÄÈÜøÌåתÔË£¬¶øÊÜÌå±¾ÉíÓÖÄÜÖØлص½Ï¸°ûĤ¡£

¡¡¡¡Ä¿Ç°¹úÄÚÍâ¶ÔÊÜÌåÐÍÓëÃâÒßÐÍ°ÐÏòÖƼÁÑо¿±¨µÀ½Ï¶à£¬Í¨¹ýÕâÁ½Öֽ鵼·½Ê½ÒÔÌá¸ßÒ©ÎïµÄ°ÐÏòÐÔ£¬Ê¹Ò©Ð§·¢»ÓµÃ×îºÃ£¬²»Á¼·´Ó¦½µÖÁ×îС¡£

¡¡¡¡»¹¿É½«Ò©ÎïÖƳɴÅÐÔÖƼÁ£¬ÒÔÌá¸ßÒ©ÎïµÄ°ÐÏòÐÔ£¬È纬³¬Î¢´ÅÁ£µÄÑÎËᰢùËص°°×΢Çò£¬¶¯Âö×¢Éäºó£¬ÔÚ°ÐÇøÌåÍâ´Å³¡µÄÒýµ¼Ï£¬Æä°ÐÇøÒ©ÎïŨ¶È±È¾²Âö×¢Éäͬ¼ÁÁ¿µÄÓÎÀ밢ùËظ߳ö100±¶¡£ÁÙ´²ÊÔÑé±íÃ÷£¬´ÅÐÔÖƼÁÖеĴÅÐÔ³¬Î¢Á£×Ó¿ÉÒÔ¶¨ÆÚ°²È«µØ±»ÅųöÌåÍâ¡£µ«ÉдæÔڴų¡µÄÇ¿¶È¡¢ÌݶÈÓ듾۽¹”ÎÊÌ⣬´Å³¡ÊÇ·ñ»á¸Ä±äºìϸ°ûµÄ»úÄܺ͸ıäѪÁ÷µÄ·½Ê½µÈÎÊÌ⣬¾ùÓдý½øÒ»²½Ñо¿¡£

¡¡¡¡µÍÃܶÈÖ¬µ°°×(LDL)£Û16£ÝÊÇ´æÔÚÓÚ²¸È鶯ÎïѪ½¬ÖеÄÖ¬µ°°×¡£ÈËѪ½¬ÖÐLDL¿ÉЯ´øѪ½¬µ¨¹Ì´¼×ÜÁ¿µÄ2/3£¬ÊÇϸ°ûÍâÔ´ÐÔµ¨¹Ì´¼µÄÖ÷ÒªÀ´Ô´¡£LDLÌåÄÚ´úлÖ÷Òª¾­ÓÉϸ°ûĤ±íÃæµÄÌØÒìÐÔLDLÊÜÌåʶ±ð£¬´Ó¶ø½øÈëϸ°ûÄÚ±»ÀûÓã¬ÔÚϸ°ûÄÚµÄÄÚÔ´ÐÔµ¨¹Ì´¼²»ÄÜÂú×ãÐèҪʱ£¬Í¨¹ýµ÷½Úϸ°ûĤÉÏLDLÊÜÌåµÄÊýÄ¿ºÍ»îÐÔ£¬ÒÔÔö¼Ó¶ÔLDLµÄÎüÊÕ¶øÔö¼Ó¶ÔÍâÔ´ÐÔµ¨¹Ì´¼µÄÀûÓá£LDLÖ÷Òª¾­¸ÎÄÚÌض¨µÄLDLÊÜÌåÇå³ý¡£°©Ï¸°û³£¾ßÓÐÄÚÔ´ÐÔµ¨¹Ì´¼ºÏ³ÉÕÏ°­£¬ÇÒÓÉÓÚÆä´óÁ¿ÔöÖ³¸´ÖÆ£¬Ï¸°ûĤ¶Ôµ¨¹Ì´¼µÄ´óÁ¿ÐèÇó£¬Ï¸°û±íÃæLDLÊÜÌåµÄ»îÐÔ¼°ÊýÁ¿ÔÚijЩ°©Ï¸°ûÖи߳öÕý³£Ï¸°û20±¶ÒÔÉÏ£¬Òò´Ë£¬²ÉÓÃLDLºÉÔØ¿¹°©Ò©Î¿É´ó´óÌá¸ß¶ÔijЩ°©Ï¸°ûµÄ°ÐÏòÐÔ¡£LDLÊÇÄÚÔ´ÐÔÖ¬µ°°×£¬½«Ëü×÷ΪҩÎïÔØÌ壬¼´¿É±ÜÃâÖ¬ÖÊÌå¡¢µ¥¿Ë¡¿¹ÌåµÈÔÚÌåÑ­»·Öб»Íø×´ÄÚƤϵͳѸËÙÇå³ýµÄÎÊÌ⣬ÓÖ¿ÉÃÖ²¹Ò»°ãÔØÌå´æÔڵİÐÏòÐÔ²îµÄ²»×㣬Õâ¶Ô½â¾öµ±Ç°¿¹°©Ò©ÎﻯÁÆÖдæÔڵİÐÏòÐԲ²»Á¼·´Ó¦´óµÄÎÊÌâ¾ßÓÐÖØÒªÒâÒå¡£

¡¡¡¡ÔÚϸСµÄÒ©ÎïÔØÌå΢Á£½øÈëÌåÑ­»·Ê±Ò×±»RESµÄ¾ÞÊÉϸ°ûÍÌÊÉ£¬´Ó¶øÓ°ÏìÒ©Îïµ½´ïËùÐèÖÎÁƵİÐÇø£¬¹Ê´Ë£¬»Ø±ÜRESµÄÍÌÊÉ×÷ÓÃÒѳÉΪҩÎïÔØÌå°ÐÏòÐÔµÄÖصã¿ÎÌâÖ®Ò»£Û17£¬18£Ý¡£Èô½«¿Õ°×ÔØÌåÏÈÓÃRES±¥ºÍ£¬È»ºóÔÙ¸øº¬Ò©ÔØÌ壬¼´¿ÉÖ±´ï°ÐÇø£¬µ«´Ë¾Ù»áʹ»úÌåÃâÒß¹¦ÄÜÊÜË𣬲¢°é·¢ÆäËû¼²²¡£¬¹Ê´Ë·¨²»¿ÉÈ¡£»ÈôÒÔ»úÌåÄÚÔ´ÐÔÎïÖÊÈçLDLΪÔØÌ壬Ôò¿É»Ø±ÜRESµÄÍÌÊÉ¡£½üÄêÀ´Ñо¿½Ï¶àµÄÊǻرÜRESµÄÃâÒßÖ¬ÖÊÌå(RES-avoiding immunoliposomes)£¬¼´ÔÚº¬Ò©Ö¬ÖÊÌåµÄ±íÃæ¼ÈÓÐIgGÃâÒß¿¹Ì壬ÓÖ¹üÒÔPEG£¬¼ûͼ2¡£ÕâÑù¼È»Ø±ÜÁ˾ÞÊÉϸ°ûµÄÍÌÊÉ£¬Óֿɽ«Ò©Îïµ¼Ïò°Ðϸ°û¡£PEG¿É»Ø±ÜRESÍÌÊɵĻúÖÆËäδÍêÈ«¸ãÇ壬µ«ÕâÓëPEG·Ö×Ӿ߶ÀÌؽṹÓйأ¬¼´ÓëÆäÇ¿Ç×Ë®ÐÔºÍÓÐÒ»¶¨µÄ÷·¸ï¡¡ÈÐÐÔÓйأ¬ÍƲâPGE¾ßÓÐÄ£·Â°×ϸ°û¡¢ºìϸ°û±íÃæ´æÔڵĶàÌÇ»ùÒòµÄ¹¦ÄÜ¡£ÓÖÈç»Ø±ÜRESµÄ·ÇÀë×Ó±íÃæ»îÐÔ¼ÁÄÒÅÝ(nonionic surfactant vesicles,NsVs¼´Niosomes)£¬ÓÉPEG2000-µ¨¹Ì´¼ÑÜÉúÎï(PEG-ch)ÖƳɵij¤Ñ­»·°¢Ã¹ËØ·ÇÀë×Ó±íÃæ»îÐÔ¼ÁÄÒÅÝ(long circulation adriamycin NsVs,L-ADM-NsVs)£¬Æä±íÃæÉϵÄPEG²ãÔöÇ¿Á˸ÃÄÒÅݵÄÇ×Ë®ÐÔ£¬´Ó¶ø¼õÉÙRESµÄÍÌÊÉ£¬ÑÓ³¤ÑªÖÐÑ­»·Ê±¼ä£¬Ìá¸ß°ÐÏòÐÔºÍÒÖÁö»îÐÔ¡£

²Î¿¼ÎÄÏ×

¡¡1¡¡Ansel HC,Popovich NG,Allen LV.Pharmaceutical dosage forms and drug delivery systems.Williams & Wilkins Baltimore.6th ed.New York:Marcel Dekker Inc,1995.218¡«220

¡¡2¡¡Deshpande AA,Shah NH,Rhodes CT,et al.Development of a novel controlled-release system for gastric retention.Pharm Res,1997,14(6)¡Ã815

¡¡3¡¡Shalaby WSW,Blevins WE,Park K.In vitro and in vivo studies of enzyme-digesbible hydrogels for oral drug delivery.J Controlled Release,1992,19(1¡«3)¡Ã131

¡¡4¡¡Ueda S,Yamagulchi H,Kotani M,et al.Development of a novel drug release system,time-controlled explosion system(TES)¢ò.Chem Pharm Bull,1994,42(4)¡Ã246

¡¡5¡¡Bieck PR.Colonic drug absorption and metabolism.New York:Marcel Dekker Inc,1993.169¡«172

¡¡6¡¡Gazzanig A,Sangalli ME,Giordano F.Oral chronotopic drug delivery systems:achievement of time and/or sit specifity.Eur J Pharm Biopharm,1994,40(4)¡Ã246

¡¡7¡¡Rubinstein A,Radai R,Ezra M,et al.In vitro evaluation of calcium pectinate:a potential colon-specific drug delivery carrier.Pharm Res,1993,10(2)¡Ã258

¡¡8¡¡Ashford M,Fell J,Attwood D,et al.Studies on pectin formulations for colonic drug delivery.J Controlled Release,1994,30(3)¡Ã225

¡¡9¡¡Leopold CS,Friend DR.A dexamethasone-poly (L-aspartic acid) conjugate as potential prodrug for colon-specific drug delivery.Eur J Pharm Biopharm,1996,42(Suppl 1)¡ÃS485

10¡¡Bieck PR.Colonic drug absorption and metabolism.New York:Marcel Dekker Inc,1993.145¡«148

11¡¡Sako K,Nakashima H,Sawada T,et al.Relationship between gelation rate of controlled-release acetaminophen tablets containing ployethylene oxide and colonic drug release in dogs.Pharm Res,1996,13(4)¡Ã549

12¡¡Anderson JM,Kim SW,Kope¨¯ch J,et al.Advances in drug delivery systems 5.London£¬New York,Tokyo:Elsevier Amsterdam,1992.145¡«159

13¡¡Kitano S,Koyamay ,Kataoka K,et al.A novel drug delivery system utilizing a glucose responsive polymer complex between poly(vinyl alcohol)and poly(N-vinl-2-pyrrolidone)with a phenylboronic acid moiety.J Controlled Release,1992,19(1¡«3)¡Ã161

14¡¡Gottschalk S,Cristiano RJ,Smith LC,et al.Folate receptor mediated DNA delivery into tumor cells:potosomal disruption results in enhanced gene expression.Gene Ther,1994,1(1)¡Ã185

15¡¡Rojansakuly.Antisense oligonucleotide therapeutics:drug delivery and targeting.Adv Drug Delivery Rev,1996,18(2)¡Ã115

16¡¡Bijsterbosch MK,Berkel TJCV.Native and modified lipoproteins as drug delivery systems.Adv Drug Delivery Rev,1990,5(3)¡Ã231

17¡¡Herron JN,Gentry CA,Davies SS,et al.Antibodies as targeting moiesties:affinity measurements conjugation chemistry and applications in immanoliposomes.J Controlled Release,1994,28(1¡«3)¡Ã155

18¡¡Kuke I,Hayashi T,Tabata Y,et al.Synthesis of poly (ethylene glycol)derivatives with different branchings and their use for protein modification.J Controlled Release,1994,30(1)¡Ã27


Ó¢ÐÛÁªÃ˱ÈÈüѺעapp_¹Ù·½ÍøÕ¾ÏÂÔØ~

ÈÈ°ñÔĶÁTOP

±¾ÖÜTOP10

2050ÀýӲĤÍâ×èÖÍÒ©ÎïÀ©É¢ÔÙÈÏʶ

2050ÀýӲĤÍâ×èÖÍÒ©ÎïÀ©É¢ÔÙÈÏʶ

£ÛÕªÒª£Ý Ä¿µÄ ̽ÌÖӲĤÍâ×èÖͳõÁ¿ÔÚ²»Í¬´©´ÌµãµÄÀ©É¢Çé¿ö¡£×ÊÁÏÓë·½·¨ 2050ÀýӲĤÍâ×èÖͲ¡Àý£¬Ïêϸ¼Ç¼...