Mesoporous Silicon Dioxide 1. Um overview womkhiqizo (Um overview womkhiqizo) 1.1 Incazelo eziyisisekelo Zhongqi Mesoporous Silica, umkhiqizo osebenzayo wokwelapha okwenziwe ngenqubo ye-sol-gel, ubonakala njengothuli oluphaphathekile olumbala omhlophe. Izici zayo ezichazayo zifaka phakathi kwesakhiwo esijwayelekile se-mesoporous channel enezikhala eziphakathi kuka-2 no-50nm kanye nendawo ethile enkulu kakhulu. Lo msebenzi ubonisa amandla aphezulu okulayisha imithi, izinga lokukhululwa okulawulwayo, kanye nokuhambisana okuhle kwe-biocompatibility, ngenkathi uhlala ungasebenzi ngokwemvelo ezithako zokwelapha ezisebenzayo. Njengoba kunjalo, usebenza njengomkhiqizo oyinhloko wokuthwala ukuze kwakhiwe izinhlelo zokulethwa kwemithi ezinembile. 1.2 Izinzuzo eziyisisekelo Njengomkhiqizo ophakeme wokwelapha, Zhongqi Mesoporous Silica ixazulula kahle izinselelo zezimboni ezifana nokungafinyeleli kahle nokuphila kwesikhathi esifushane kwemithi ezakhiweni ezijwayelekile. Ngokuqondile ukulungiswa kwesakhiwo se-pore nezici ze-surface, ivumela ukulayisha imithi kahle nokukhululwa okuhlakaniphile, kuthuthukisa kakhulu ukutholakala kwe-bio ngenkathi kunciphisa imiphumela emibi. Umkhiqizo uhambisana nezindinganiso eziqinile zomhlaba wonke zokwelapha, uhlinzeka ngensiza eyinhloko yokwakha izinhlelo ezintsha zokwakha nokuthuthukiswa kwemithi ye-generic ephezulu. 2. Izici zomkhiqizo (Izici zomkhiqizo) 2.1 Izinzuzo zesakhiwo nezokusebenza •Isakhiwo se-mesoporous esiqondile: usayizi we-pore ungashintshwa ngokuqhubekayo ukusuka ku-5 kuya ku-30nm, ukusabalala kosayizi be-pore kuyi-uniform (ukuphambuka ≤2nm), indawo ethile ye-BET ingafinyelela ku-300-1000m²/g, futhi ivolumu ye-mesoporous ingafinyelela ku-2.0cm³/g, ihlinzeka ngendawo eyanele yokulayisha ama-molecule emithi. •Ukulawulwa kokukhululwa okuhlakaniphile: Ngokuqondile ukulungiswa kwesurface ye-pH esithintekayo, i-enzyme esithintekayo nezinye "izakhiwo ze-valve eziphendulayo", ukukhululwa okukhethekile kwemithi ezindaweni ezithile kungafezeka, futhi izinga lokukhululwa lingalawulwa ngokuqondile nge-±5% in vitro. •Ukuhambisana okuhle kwe-biocompatibility: I-SiO₂ purity ingaphezulu kuka-99.0%, okuqukethwe kwe-heavy metal kuphansi kuka-10ppm, okuqukethwe kwe-arsenic kuphansi kuka-3ppm, futhi akukho ukulimala okubonakalayo kwamaseli okuqinisekiswa ngovivinyo lwe-cytotoxicity, okuhambisana nezindinganiso zokuphepha kwezinto zokwelapha. •Ukushintshwa okuphezulu: ubuso bungaxhunywa ngokuqinile nezinsiza ezifana ne-folic acid, i-PEG ne-peptide ukuze kuqinisekiswe ukulethwa okuqondile, futhi ukusebenza kokuhlanganiswa okuqondile kuphakathi kuka-5-8 izikhathi phezulu kunezithwala ezijwayelekile. 2.2 Ukuqinisekiswa kwenqubo Inqubo yokwakha esekelwe kumasampula we-cationic surfactant ifinyelela izakhiwo ze-mesoporous ezihambisanayo kakhulu ngokulawula ngokunembile izinga lokuphendula, i-pH, kanye nokugxila kumasampula. Inqubo yokukhiqiza ihlale ihambisana nezindinganiso ze-GMP ngohlelo lokuhlola usayizi lwe-pore oluhlanganisiwe, kuqinisekisa ukulawulwa kwekhwalithi okuqinile ngokuhlolwa kweqoqo ngalinye ukuze kugcinwe izinga elizinzile nelilawulwayo phakathi nesikhathi sokukhiqiza. 2.3 Indima eyinhloko 1.Umsizi wokugeleza: thuthukisa ukugeleza kwe-API powder, ukuze umehluko wesisindo sokugcwalisa se-tablets ulawulwe ngaphakathi kuka-±3%, futhi ukusebenza kokucindezela i-tablet kwandiswe ngo-20%; 2.Ukuvimbela ukuhlanganiswa: ivimbela impahla ukuthi ingabambeki ku-punch, yehlisa umphumela wokuphuka nokubambeka, ikakhulukazi efanelekile ekulungiseleleni izithako ze-Chinese herbal ezinamafutha aphezulu; 3.Umhlali: thola umswakama omncane ku-tablet, delay ukwehla kwezithako ezisebenzayo, futhi wandise isikhathi sokuphila kwemithi sibe yizinyanga eziyi-12-24; 4.Umthwali wokukhululwa: Ngokulawula isakhiwo se-pore ukuze kulungiswe izinga lokukhululwa kwemithi, ukufaka u-0.2% ekwakhiweni kwe-tablet yokukhululwa okuqhubekayo kungafinyelela ukukhululwa kwemithi isikhathi eside. 3. Ipharamitha ezisemqoka (KTP) Ipharamitha izinto Ububanzi bezinkomba umthetho wokuhlola Okuqukethwe kwe-SiO₂ (ngemuva kokushiswa) ≥99.0% USP-NF <281> I-BET ethile ye-surface area (m²/g) 300-1000 Indlela yokumunca ye-BET I-Porosity (cm³g) 0.8-2.0 Umthetho we-BJH Usayizi ophakathi kwe-pore （nm） 5-30 Umthetho we-BJH Ukulahleka kwesisindo esomile (105℃,2h) ≤6.0% ukuhlaziywa kwe-gravimetric Okuqukethwe kwe-heavy metal (ppm) ≤10 I-atomic absorption spectrophotometry 4. Izinkambu zokusebenza (Izinkambu Zokusebenza) 1. Umthwali wemithi: Imithi ye-chemotherapy enezikhala eziphezulu (njenge-doxorubicin) ingakhululwa ngokunembile nge-pH/ukushisa ukuphendula ukuze kuncishiswe ukulimala kumaseli ajwayelekile; imithi engaxhunywanga (njenge-paclitaxel) ingafakwa ukuze kuthuthukiswe ukuxhunywa nokutholakala. 2. I-vector ye-genetic/vaccine: ivikela i-siRNA ne-plasmid DNA ekwehlisweni, ithuthukise ukutholwa kwamaseli ngokulungiswa ukuze kuqinisekiswe ukulethwa okuqondile; thola i-antigen ye-vaccine futhi wandise isikhathi sokugcina ukuze uqinise impendulo ye-immune. 3. Ukuhlola okuhlanganisiwe nokwelashwa: Layisha ama-dyes akhanyayo kanye nezithako ze-MRI/CT ukuze kwakhiwe ipulatifomu yokuhlola nokwelashwa yokubheka ngesikhathi sokulethwa kwemithi nezinguquko ze-lesion. 4. Ukulwa namagciwane nokulungiswa kwezicubu: layisha ama-ion e-silver nezidakamizwa zokulwa namagciwane ukuze uvimbele amagciwane isikhathi eside (ngokwelashwa kwezilonda); isakhiwo se-pore simela i-extracellular matrix, sithuthukisa ukukhula nokuhlukaniswa kwamaseli amancane, futhi siza ekulungiseni amathambo/nemisipha. 5. Izindinganiso nemithetho (Izindinganiso & Imithetho) •Uhambisana nezindinganiso eziningi zepharmacopoeia zomhlaba: USP-NF, European Pharmacopoeia (Ph. Eur.), Japanese Pharmacopoeia (JP), kanye neChina Pharmacopoeia (ChP 2025). •Thola ubufakazi obuhambisanayo: ukufakwa kwi-database ye-FDA ye-inactive ingredient, i-EU E551 yokwengeza ukudla. •Uhambisana nezikhombisi-ndlela zokuhambisana zomhlaba: ulandela izindinganiso zokukhiqiza ze-GMP kanye nezidingo ze-HACCP zokuphepha kokudla. 6. Iziphakamiso ezibalulekile zokuphatha nokugcina •Umsebenzi wokulayisha imithi: kunconywa ukuthi kwenziwe ekamelweni lokushisa (20-25℃) kanye nomswakama <50%. Indlela yokumunca yokuhlola isetshenziswa kumithi esolayo, futhi indlela yokuphuma kwesixazululo isetshenziswa kumithi esolayo. Isikhathi sokulayisha kufanele sibe okungenani amahora amabili. •Qaphela ukulungiswa kwesurface: amaqembu asebenzayo afana nama-amino nama-carboxyl kufanele alungiswe ku-pH phakathi kuka-5 no-8 ukuze kugwenywe ukulimala okukhulu kwe-asidi kanye ne-alkali kwesakhiwo se-mesoporous. •Izimo zokugcina: Vala ebhodleleni le-reagent elinsundu, ugcine endaweni epholile nepholile (15-25℃, umswakama ophakathi <50%), gwema ukugcina ukukhanya, kusebenze isikhathi esiyiminyaka emibili, uvule ukuze usebenzise phakathi kwezinyanga eziyi-1. 7. Izinzuzo zomkhiqizo (PA) •I-degree ephezulu yokwenza ngokwezifiso: usayizi we-pore kanye nendawo ethile ingalawulwa ngokunembile ngokuya ngosayizi wamamolekyuli e-API, ihlinzeka ngesisombululo sokuthwala esikhethekile. •Ukuhlanganiswa kwemisebenzi eminingi: inezisebenzi eziningi zokulayisha imithi, ukulethwa okuqondile nokukhululwa okuhlakaniphile, okwenza kube lula ukwakhiwa kwesakhiwo. •Ukuqinisekiswa kokuhambisana komhlaba: zonke izinkomba zihlangabezana nezidingo zepharmacopoeia zomhlaba, zisekela ukufaka izicelo zemithi ezintsha ezweni nasemhlabeni, zisheshise inqubo yokumaketha umkhiqizo. •Ukuthuthukiswa kwesevisi yezobuchwepheshe: hlinzeka ngentuthuko yenqubo yokulayisha imithi, ukuhlolwa kokukhululwa in vitro nezinye izinsizakalo ezingeziwe, ngokwesekwa kweqembu lezakhiwo zobuchwepheshe ngesikhathi sonke. 8. Ukuqinisekiswa kwesistimu yebhizinisi kanye nezindondo •FSSC22000 •ISO22000：2018 •ISO9001：2015 •SHC HALAL •OU KOSHER •Ubufakazi be-FDA •FAMI-QS •SEDEX •I-licence yokukhiqiza yokwengeza ukudla •I-licence yokukhiqiza yokwengeza ukudla •Ibhizinisi eliphakeme lezobuchwepheshe •Izinhlangano ezikhethekile, ezithuthukile nezintsha eGuangzhou •Amalungelo ayi-17 avela kwi-Office of State Intellectual Property