杩戞棩锛孅strong>娣卞湷鍗庡０寮哄寲鎶€鏈湁闄愬叕鍙伏/strong>涓嶞strong>澶╂触涓尰鑽ぇ瀛︽潕鏂囬緳鏁欐巿鍚堜綔锛屽湪璐ㄩ噺婧愪簬璁捐锛圏/span>Quality by Design, QbD锛夌悊蹇电殑鎸囧涓嬮噰鐢ㄥ０鍏辨尟鎶€鏈?/span>寮€鍙戜簡涓€绉嶈冻澶熷己澶х殑姹夐槻宸辩敳绱犵撼绫虫贩鎮墏绯荤粺锛岃绯荤粺鑳藉鏈夋晥鏀瑰杽姹夐槻宸辩敳绱犵殑婧惰В鎬ц兘锛屽悓鏃跺叿鏈夐珮绋冲畾鎬э紝楂樿浇鑽兘鍔涘拰涓€瀹氱殑瑙勬ā鍖栭€傚簲鎬?/strong>銆傜浉鍏虫垚鏋滃彂琛ㄤ簬銆夵/span>European Journal of Pharmaceutics and Biopharmaceutics銆婞/span>涓婏紝澶╂触涓尰鑽ぇ瀛﹀紶鏅撻槼鍚屽涓鸿鏂囩涓€浣滆€咃紝鎴戝叕鍙稿惔浼熷拰澶╂触涓尰鑽ぇ瀛︽潕鏂囬緳鏁欐巿涓鸿鏂囧叡鍚岄€氳浣滆€呫€侟/span>

璁烘枃棰樺綍锛欬/span>Xiaoyang Zhang, Xi Wang, Yao Zhang, Cunhao Li, Wei Wu^*, Wenlong Li^*. Acoustic resonance technology and quality by design approach facilitate the development of the robust tetrandrine nano-delivery system. European Journal of Pharmaceutics and Biopharmaceutics, DOI: 10.1016/j.ejpb.2024.114522.

鍥近/span>1姹夐槻宸辩敳绱犵殑缁撴瀯绀烘剰鍥近/span>

绮夐槻宸辩⒈(Tetrandrine, Tet)鏄竴绉岦strong>澶╃劧鐨勫弻鑻勫熀寮傚柟鍟夌敓鐗╃⒈锛圏/span>鍥近/span>1锛夛紝鍏锋湁闈炲父骞挎硾鐨勮嵂鐞嗘椿鎬э紝鍖呮嫭鎶楃檶銆佹姉鐐庛€佹姉绫婚婀挎€у叧鑺傜値銆佹姉鑴傝偑鐢熸垚銆侀檷鍘婞/strong>绛夈€傝繎骞存潵锛屽ぇ閲忕爺绌舵垚鍔熸彮绀轰簡Tet鐨勬姉鐧屼綔鐢紝鍖呮嫭鑲虹檶銆佽唨鑳辩檶銆佽倽鐧岀粏鑳炵郴銆佷钩鑵虹檶銆佷汉绫诲彛鑵旂檶銆佸棰堢檶銆佷汉鑴戣兌璐ㄦ瘝缁嗚優鐦｜/strong>绛夈€傛澶栵紝Tet宸茶幏寰楃編鍥键/span>FDA鎺堜簣鐨勫鍎胯嵂锛堝張绉扮綍瑙佺梾鑽級璧勬牸璁ゅ畾锛岄€傚簲鐥囦负鐧借鐥匋/strong>銆侟/span>2022骞寸編鍥键/span>FDA鎵瑰噯浜嗙敱缇庡浗Escend鍏徃鍙戣捣鐨凕/span>Tet鐢ㄤ簬娌荤枟澶嶅彂/闅炬不鎬х櫧琛€鐥呯殑涓村簥璇曢獙鐢宠銆侟/span>2021骞寸編鍥藉浗绔嬬檶鐥囩爺绌舵墍SEER鏁版嵁搴撴姤鍛婃樉绀猴紝缇庡浗姣忓勾鏂板鐧借鐥呮偅鑰匋/span>6涓囧浜猴紝鍚勭被鐧借鐥呮浜狘/span>2涓囧浜恒€傜櫧琛€鐥呮偅鑰呬簲骞寸敓瀛樼巼绾?/span>29%锛岄毦娌狐/span>/澶嶅彂鐨勭櫧琛€鐥呮偅鑰匋/span>3骞存€荤敓瀛樼巼涓嶈秴杩嘃/span>10%銆傜幇鏈夌敤浜庢不鐤楃櫧琛€鐥呯殑鑽墿渚嬪缁村濡ユ媺銆侀樋绯栬優鑻枫€佺淮濂堟墭鍏嬬瓑鑽墿鏈兘婊¤冻涓村簥闇€姹傦紝Tet琚涓烘渶鏈夋綔鍔涙敼鍙樿繖涓€鐜扮姸鐨勫€欓€夎嵂鐗╀箣涓€銆侟/span>

鍥近span style="line-height: 150%; font-family: " times="" new="">2铚傞笩澹板叡鎸妧鏈伐浣滃師鐞嗙ず鎰忓浘

铏界劧Tet鍏锋湁骞挎硾鐨勬不鐤楁綔鍔涳紝浣嗗畠鐨凕strong>浣庢按婧舵€у鑷村叾鍚告敹鍙楅檺鍜岀敓鐗╁埄鐢ㄥ害浣嶞/strong>锛岃繖涓ラ噸闄愬埗浜嗗畠鐨勪复搴婂簲鐢ㄣ€侟strong>绾崇背鍖栨槸涓€绉嶉€氳繃澧炲姞琛ㄩ潰绉€佸噺灏戞墿鏁ｅ眰鍘氬害鍜屾彁楂橀ケ鍜屾憾瑙ｅ害鏉ユ彁楂樿嵂鐗╃敓鐗╁埄鐢ㄥ害鐨勬湁鍓嶉€旂殑鏂规硶銆傜撼绫虫贩鎮墏鏄竴绉嶇敱绾嵂鐗╁拰灏戦噺绋冲畾鍓傜粍鎴愮殑浜氬井绫宠嵂鐗?strong>棰楃矑鍒嗘暎浣掽/strong>銆備笌鍏朵粬绾崇背灏哄鐨勮嵂鐗╀紶閫掔郴缁熺浉姣旓紝绾崇背娣锋偓鍓傚叿鏈夋垚鍒嗙畝鍗曪紝浣庢瘨鎬э紝楂樿浇鑽噺鍜岄€傜敤浜庡绉嶇粰鑽€斿緞鐨勪紭鍔军/span>銆傜撼绫虫贩鎮墏鍙噰鐢ㄨ嚜涓嬭€屼笂鍜岃嚜涓婅€屼笅涓ょ鏂规硶鍒跺銆侟strong>澹板叡鎸妧鏈?/span>锛圏/span>鍥近/span>2锛夋槸涓€绉岦strong>鏂板瀷鑷笂鑰屼笅鐨勬柟娉曪紝瀹冨叿鏈堻strong>姝ラ绠€鍗曪紝绮掑緞鍑忓皬鑳藉姏寮猴紝鍜屾墿灞曟€у己鐨勪紭鍔军/strong>銆傞鍏堬紝鍦ㄤ娇鐢ㄥ０鍏辨尟鎶€鏈埗澶囩撼绫虫贩鎮墏杩囩▼涓紝NS鍌ㄥ瓨鍦ㄥ埗澶囧鍣ㄤ腑锛孅strong>涓嶄笌浠櫒鐩存帴鎺ヨЕ锛岀爺绌朵汉鍛樺彲浠ラ€氳繃鏇存崲鍒跺瀹瑰櫒鏉ュ埗澶囦笉鍚屾壒娆＄殑澶勬柟銆傝繖鐪佸幓浜嗕华鍣ㄦ媶鍗搞€佹竻娲楀拰瀹夎绛夋楠わ紝澶уぇ鍑忓皯浜嗘壒娆＄敓浜т箣闂寸殑鍋滅暀闂撮殧鏃堕棿銆傜浜岋紝鍩轰簬涓嶅悓瑙勬牸鐨勫埗澶囧钩鍙帮紙鍥近/span>3锛堻/span>锛屽０鍏辨尟鎶€鏈彲浠ュ钩琛屽埗澶囧缁勫鏂癸紝杩欏ぇ澶ф彁楂樹簡閰嶆柟寮€鍙戞晥鐜囥€傜涓夛紝璇ユ妧鏈繕鍏锋湁闈炲父楂樼殑鐮旂（鏁堢巼锛岄€氬父鍙渶瑕?/span>2h宸﹀彸鏃㈠彲浠ュ埗澶囧嚭鍏锋湁鐞嗘兂鍏抽敭璐ㄩ噺灞炴€х殑绾崇背娣锋偓鍓傘€侟/span>

鍥近/span>3涓嶅悓瑙勬牸鍒跺骞冲彴鐨勭ず鎰忓浘

寮€鍙戜竴涓己澶х殑Tet-NS绯荤粺鏄竴涓鏉傜殑澶氬洜绱犺繃绋嬶紝闇€瑕佺爺绌朵汉鍛樺悎鐞嗗拰鏄庢櫤鍦伴€夋嫨宸ヨ壓鍜岄厤鏂瑰彉閲忋€侟/span>涓€娆′竴涓洜绱狅紙one factor at a time, OFAT锛夋柟娉曢€氬父琚敤鏉ヤ紭鍖栭厤鏂瑰拰宸ヨ壓鍙傛暟锛岀劧鑰岃鏂规硶鏄傝吹銆佽€楁椂骞朵笖涓嶈兘鏈夋晥鐮旂┒鍙橀噺涔嬮棿鐨勪氦浜掍綔鐢?/span>銆傚洜姝わ紝鎴戜滑閫夋嫨鍦?/span>QbD鐞嗗康鐨勬寚瀵间笅閲囩敤DoE鏉ュ紑鍙戣冻澶熷己澶х殑Tet-NS銆備竴鏂归潰锛孅/span>DoE鑳藉浠ユ渶鍚堢悊锛堣緝灏戯級鐨勫疄楠屾鏁拌瘑鍒奖鍝嶆渶缁堜骇鍝佽川閲忕殑鍏抽敭鍥犵礌鎴栬€呬紭鍖朁/span>Tet-NS鐨勫鏂瑰拰宸ヨ壓锛岃繖鍑忓皯浜嗘椂闂村拰璧勬簮鐨勬氮璐更/strong>銆傚彟涓€鏂归潰DoE鍙互璇勪及鍚屼竴瀹為獙涓嫭绔嬪彉閲忎箣闂寸殑澶氶噸鐩镐簰浣滅敤锛岃繖鏈夊姪浜庡鐢熶骇杩囩▼鐨勯€忓交鐞嗚В銆傚湪鏈爺绌朵腑锛孅/span>Plackett-Burman璁捐琚敤鏉ョ瓫閫夊奖鍝岦/span>Tet-NS鐨勫叧閿洜绱狅紝Box-Behnken璁捐琚敤鏉ョ爺绌跺拰浼樺寲鍏抽敭鍥犵礌浠ヨ幏寰楁渶浣崇撼绫虫贩鎮墏銆侟/span>

鏈爺绌堕娆℃弿杩颁簡鍦?/span>QbD鐞嗗康鐨勬寚瀵间笅浣跨敤澹板叡鎸妧鏈拰鍐峰喕骞茬嚗鎶€鏈紑鍙戣冻澶熷己澶х殑姹夐槻宸辩敳绱犵撼绫虫贩鎮墏绯荤粺銆傝绯荤粺鑳藉鏈夋晥鏀瑰杽Tet鐨勬憾瑙ｆ€ц兘锛屽悓鏃跺叿鏈夐珮绋冲畾鎬э紝楂樿浇鑽兘鍔涘拰瑙勬ā鍖栭€傚簲鎬с€傞鍏堬紝浠ラ珮閫氶噺鏂瑰紡鍏ㄩ潰鎺㈢储浜嗘眽闃插繁鐢茬礌绾崇背娣锋偓鍓傜殑鏈€浼樺鏂圭┖闂淬€傜浜岋紝Plackett-Burman璁捐琚敤鏉ョ瓫閫夊奖鍝岦/span>Tet-NS澶勬柟鐨勫叧閿洜绱狅紝Box-behnken璁捐琚敤鏉ョ爺绌跺拰浼樺寲鍏抽敭鍥犵礌浠ヨ幏寰楁渶浣崇撼绫虫贩鎮墏锛屻€傜涓夛紝鏈€浼樺鏂硅鎴愬姛鏀惧ぇ涓€鐧惧€嶃€傜鍥涳紝鑰冨療浜嗕笉鍚岀绫诲拰娴撳害鐨勫喎鍐讳繚鎶ゅ墏瀵瑰浐鍖栦骇鍝佸啀鍒嗘暎鎬х殑褰卞搷銆傜浜旓紝閫氳繃FT-IR, XRD, DSC, SEM瀵规渶浣充綋绯诲拰鍥哄寲浜у搧杩涜浜嗗叏闈㈣〃寰侊紝骞惰繘琛屼簡浣撳婧跺嚭搴﹀拰楗卞拰婧惰В搴︾爺绌躲€傛渶鍚庯紝鑰冨療浜咟/span>Tet-NS鐨勭煭鏈熺ǔ瀹氭€с€侟/span>

澹?/span>鍏辨尟鎶€鏈殑浣跨敤鏈夊姪浜庡叏闈㈡帰绱㈢撼绫虫贩鎮墏鐨勬渶浣冲鏂圭┖闂达紝骞跺彲浠ュぇ澶у姞閫熺撼绫虫贩鎮墏浠庡紑鍙戝埌宸ヤ笟瑙勬ā鐢熶骇鐨勭獊鐮淬€傜ǔ鍋ョ殑Tet 绾崇背缁欒嵂绯荤粺鐨勬垚鍔熷紑鍙戝彲浠ユ彁楂樺叾鍙ｆ湇鐢熺墿鍒╃敤搴︼紝淇冭繘 Tet 鐨勪复搴婂簲鐢ㄣ€傚悓鏃讹紝鏈爺绌剁殑鏂规硶鍜屾蹇靛苟涓嶅眬闄愪簬Tet锛屼篃閫傜敤浜庡叾浠栨按婧舵€у樊鐨勭墿璐ㄣ€侟/span>