Ukulungiswa kwe-Hydrogel Microspheres evela kwi-Hydroxypropyl Methyl Cellulose

Olu vavanyo lwamkela indlela ye-reverse ukumiswa kwepolymerization, kusetyenziswa i-hydroxypropyl methylcellulose (HPMC) njengento ekrwada, isisombululo se-sodium hydroxide njengesigaba samanzi, i-cyclohexane njengesigaba se-oyile, kunye ne-divinyl sulfone (DVS) njengoMxube odibanisa i-Tween- I-20 kunye ne-Span-60 njenge-dispersant, ivuselela ngesantya se-400-900r / min ukulungiselela i-hydrogel microspheres.

Amagama angundoqo: i-hydroxypropyl methylcellulose; ihydrogel; ii-microspheres; abasasaza

1.Isishwankathelo

1.1 Inkcazo ye-hydrogel

IHydrogel (Hydrogel) luhlobo lwepolymer ephezulu yemolekyuli equlethe ubuninzi bamanzi kwisakhiwo sothungelwano kwaye ayinyibiliki emanzini. Inxalenye yamaqela e-hydrophobic kunye neentsalela ze-hydrophilic zingeniswa kwi-polymer e-soluble yamanzi kunye ne-network crosslinked structure, kunye ne-hydrophilic Iintsalela zibophelela kwiimolekyuli zamanzi, zidibanisa iimolekyuli zamanzi ngaphakathi kwenethiwekhi, ngelixa i-hydrophobic residues idumba ngamanzi ukwenza umnqamlezo. iipolima ezidityanisiweyo. Iijeli kunye neelensi zoqhagamshelwano kubomi bemihla ngemihla zizo zonke iimveliso ze-hydrogel. Ngokobungakanani kunye nokumila kwe-hydrogel, inokohlulwa ibe yijeli ye-macroscopic kunye nejeli encinci ye-microsphere (i-microsphere), kunye neyokuqala inokwahlulwa ibe yi-columnar, i-porous sponge, i-fibrous, i-membranous, i-spherical, njl njl. babe nokuthamba okulungileyo, ukunwebeka, umthamo wokugcina ulwelo kunye ne-biocompatibility, kwaye zisetyenziswa kuphando lwamachiza abanjisiweyo.

1.2 Ukubaluleka kokukhethwa kwesihloko

Kwiminyaka yakutshanje, ukuze kuhlangatyezwane neemfuno zokukhuselwa kwendalo, izixhobo ze-polymer hydrogel ziye zatsala ingqalelo ebanzi ngokuthe ngcembe ngenxa yeepropathi zazo ezilungileyo ze-hydrophilic kunye ne-biocompatibility. I-Hydrogel microspheres yalungiswa ukusuka kwi-hydroxypropyl methylcellulose njengesixhobo ekrwada kolu vavanyo. I-Hydroxypropyl methylcellulose yi-ether ye-cellulose engekho i-ionic, i-powder emhlophe, ivumba kunye nencasa, kwaye ineempawu ezingenakubuyiselwa zezinye izinto zokwenziwa kwe-polymer, ngoko inexabiso eliphezulu lophando kwintsimi ye-polymer.

1.3 Ubume bophuhliso ekhaya naphesheya

IHydrogel luhlobo lwedosi yamayeza ethe yatsala ingqalelo enkulu kuluntu lwezonyango lwamazwe aphesheya kwiminyaka yakutshanje kwaye ikhule ngokukhawuleza. Ukususela ekubeni u-Wichterle no-Lim bapapasha umsebenzi wabo wobuvulindlela kwi-HEMA edibanisa i-hydrogels edibeneyo kwi-1960, uphando kunye nokuhlolwa kwee-hydrogels kuye kwaqhubeka kunzulu. Phakathi kwiminyaka yoo-1970, uTanaka wafumanisa iihydrogels ezingeva nge-pH xa wayelinganisa umlinganiselo wokudumba weejeli ze-acrylamide ezindala, ephawula inyathelo elitsha kuphononongo lwee-hydrogels. ilizwe lam likwinqanaba lophuhliso lwe-hydrogel. Ngenxa yenkqubo ebanzi yokulungiselela amayeza emveli aseTshayina kunye namalungu antsonkothileyo, kunzima ukukhupha imveliso enye esulungekileyo xa amacandelo amaninzi esebenza kunye, kwaye umthamo mkhulu, ngoko ke uphuhliso lwamayeza aseTshayina ihydrogel lunokucotha.

1.4 Izixhobo zovavanyo kunye nemigaqo

1.4.1 I-Hydroxypropyl methylcellulose

I-Hydroxypropyl methyl cellulose (HPMC), i-derivative ye-methyl cellulose, i-ether ebalulekileyo exutywe, eye-non-ionic water-soluble polymers, kwaye ayinavumba, ayinancasa kwaye ayinayo ityhefu.

I-Industrial HPMC ikwimo yomgubo omhlophe okanye ifayibha emhlophe ekhululekile, kwaye isisombululo sayo samanzi sinomsebenzi womphezulu, ukukhanya okuphezulu kunye nokusebenza okuzinzileyo. Ngenxa yokuba i-HPMC inepropati ye-thermal gelation, isisombululo se-aqueous imveliso sifudunyezwa ukwenza i-gel kunye ne-precipitates, kwaye emva koko iyayinyibilika emva kokupholisa, kunye nobushushu be-gelation yenkcazo eyahlukeneyo yemveliso yahlukile. Iipropati zeenkcazo ezahlukeneyo ze-HPMC nazo zahlukile. Utshintsho lwe-solubility kunye ne-viscosity kwaye aluchaphazeli ixabiso le-pH. I-viscosity ephantsi, i-solubility enkulu. Njengoko umxholo weqela le-methoxyl uyancipha, i-gel point ye-HPMC iyanda, i-solubility yamanzi iyancipha, kwaye umsebenzi womphezulu uyancipha. Kwishishini le-biomedical, isetyenziswa ikakhulu njengesixhobo sokulawula i-polymer kwizinto zokugquma, izixhobo zefilimu, kunye namalungiselelo okukhutshwa okuzinzileyo. Isenokusetyenziswa njenge-stabilizer, i-arhente yokumisa, i-tablet encamathelayo, kunye ne-viscosity enhancer.

1.4.2 Umgaqo

Ukusebenzisa i-reverse yesigaba sokunqunyanyiswa kwe-polymerization indlela, usebenzisa i-Tween-20, i-Span-60 i-dispersant edibeneyo kunye ne-Tween-20 njenge-dispersants eyahlukileyo, misela ixabiso le-HLB (i-surfactant yi-amphiphile eneqela le-hydrophilic kunye neqela le-lipophilic Molecule, ubungakanani bobungakanani kunye namandla. ibhalansi phakathi kweqela le-hydrophilic kunye neqela le-lipophilic kwi-molecule ye-surfactant ichazwa njengoluhlu olusondeleyo lwexabiso le-hydrophilic-lipophilic balance of the surfactant i-Cyclohexane inokusasaza kangcono isisombululo se-monomer kunye nokuchitha ukushisa okwenziwa kuvavanyo ngokuqhubekayo Idosi yi-1-5 yamaxesha esisombululo se-aqueous monoma kunye ne-concentration ye-99% ye-divinyl sulfone njenge-agent edibanisayo, kwaye inani le-agent edibanisayo ilawulwa malunga ne-10% ye Ubunzima beselulosi eyomileyo, ukuze iimolekyuli ezininzi ezilandelelanayo zidityaniswe enye kwenye kwaye ziqhagamshelwe kwisakhiwo sothungelwano.

Ukuvuselela kubaluleke kakhulu kolu vavanyo, kwaye isantya silawulwa ngokubanzi kwigiya lesithathu okanye lesine. Ngenxa yokuba ubungakanani besantya sokujikeleza buchaphazela ngokuthe ngqo ubukhulu be-microspheres. Xa isantya sokujikeleza sikhulu kune-980r / min, kuya kuba yinto enzulu yokubambelela eludongeni, eya kunciphisa kakhulu imveliso yemveliso; I-agent edibanisa i-cross-link ivame ukuvelisa ii-gels ezininzi, kwaye iimveliso ezijikelezayo azikwazi ukufunyanwa.

2. Izixhobo zovavanyo kunye neendlela

2.1 Izixhobo zoMfuniselo

Ibhalansi ye-elektroniki, i-multifunctional electric stirrer, i-polarizing microscope, i-Malvern particle size analyzer.

Ukulungiselela i-cellulose hydrogel microspheres, iikhemikhali eziphambili ezisetyenzisiweyo yi-cyclohexane, i-Tween-20, i-Span-60, i-hydroxypropyl methylcellulose, i-divinyl sulfone, i-sodium hydroxide, amanzi adibeneyo, zonke ezo i-Monomers kunye ne-additives zisetyenziswa ngokuthe ngqo ngaphandle kwonyango.

2.2 Amanyathelo okulungiselela i-cellulose hydrogel microspheres

2.2.1 Ukusebenzisa i-Tween 20 njenge-dispersant

Ukuchithwa kwe-hydroxypropylmethylcellulose. Ukulinganisa ngokuchanekileyo i-2g ye-sodium hydroxide kwaye ulungiselele isisombululo se-2% ye-sodium hydroxide kunye ne-flask ye-volumetric 100ml. Thatha i-80ml yesisombululo esilungisiweyo se-sodium hydroxide kwaye uyitshise kwindawo yokuhlambela amanzi malunga ne-50°C, ulinganise i-0.2g ye-cellulose kwaye uyifake kwisisombululo se-alkaline, ugxobhoze ngentonga yeglasi, uyibeke emanzini abandayo ukuhlamba i-ice, kwaye uyisebenzise njengesigaba samanzi emva kokuba isisombululo sicaciswe. Sebenzisa i-cylinder ephumelele ukulinganisa i-120ml ye-cyclohexane (isigaba seoli) kwi-flask enentamo ezintathu, udwebe i-5ml ye-Tween-20 kwisigaba seoli kunye nesirinji, kwaye ugxobhoze kwi-700r / min ngeyure enye. Thatha isiqingatha sesigaba se-aqueous esilungiselelwe kwaye udibanise kwi-flask enentamo ezintathu kwaye ugxobhoze iiyure ezintathu. I-concentration ye-divinyl sulfone yi-99%, ihlanjululwe kwi-1% ngamanzi adibeneyo. Sebenzisa i-pipette ukuthatha i-0.5ml ye-DVS kwi-flask ye-volumetric ye-50ml ukulungiselela i-1% ye-DVS, i-1ml ye-DVS ilingana ne-0.01g. Sebenzisa i-pipette ukuthatha i-1ml kwi-flask yentamo emithathu. Gxuma kwiqondo lokushisa kweeyure ze-22.

2.2.2 Ukusebenzisa i-span60 kunye ne-Tween-20 njengabasasazi

Esinye isiqingatha sesigaba samanzi esisanda kulungiswa. Ubunzima be-0.01gspan60 kwaye udibanise kwi-tube yokuvavanya, ushushu kwindawo yokuhlambela amanzi angama-65-degree de inyibilike, uze ulahle amaconsi ambalwa e-cyclohexane kwindawo yokuhlambela ngamanzi kunye ne-dropper ye-rubber, kwaye uyifudumeze de isisombululo sijike sibe mhlophe. Yongeza kwi-flask yentamo emithathu, uze ungeze i-120ml ye-cyclohexane, uhlambulule ityhubhu yokuvavanya nge-cyclohexane ngamaxesha amaninzi, ukushisa kwe-5min, ukupholisa phantsi kweqondo lokushisa, kwaye ungeze i-0.5ml ye-Tween-20. Emva kokuvuselela iiyure ezintathu, i-1ml ye-DVS ehlanjululweyo yongezwa. Gxuma kwiqondo lokushisa kweeyure ze-22.

2.2.3 Iziphumo zovavanyo

Isampulu evuselelweyo yacwiliswa kwintonga yeglasi kwaye yachithwa kwi-50ml ye-ethanol epheleleyo, kwaye ubungakanani be-particle bulinganiswe phantsi kwe-Malvern particle sizer. Ukusebenzisa i-Tween-20 njenge-dispersant microemulsion iyancipha, kwaye umlinganiselo we-particle olinganisiweyo we-87.1% ngu-455.2d.nm, kunye nobukhulu be-particle ye-12.9% yi-5026d.nm. I-microemulsion ye-Tween-20 kunye ne-Span-60 i-dispersant edibeneyo ifana neyobisi, kunye ne-81.7% ye-particle ye-5421d.nm kunye ne-18.3% ye-particle ye-180.1d.nm.

3. Ingxoxo ngeziphumo zovavanyo

Kwi-emulsifier yokulungiselela i-inverse microemulsion, kudla ngokuba ngcono ukusebenzisa ikhompawundi ye-hydrophilic surfactant kunye ne-lipophilic surfactant. Oku kungenxa yokuba ukunyibilika kwe-surfactant enye kwinkqubo kuphantsi. Emva kokuba ezi zimbini zidityanisiwe, amaqela e-hydrophilic enye kunye namaqela e-lipophilic asebenzisana kunye ukuze abe nefuthe le-solubilizing. Ixabiso le-HLB likwasisalathiso esisetyenziswa ngokuqhelekileyo xa ukhetha i-emulsifiers. Ngokulungelelanisa ixabiso le-HLB, umlinganiselo we-emulsifier ye-component component-component inokulungiswa, kwaye i-microspheres efanayo iyakwazi ukulungiswa. Kulo vavanyo, i-lipophilic ebuthakathaka i-Span-60 (HLB = 4.7) kunye ne-hydrophilic Tween-20 (HLB = 16.7) isetyenziswe njenge-dispersant, kwaye i-Span-20 isetyenziswe yodwa njenge-dispersant. Ukususela kwiziphumo zovavanyo, kunokubonwa ukuba i-compound Isiphumo singcono kune-dispersant eyodwa. I-microemulsion ye-compound dispersant ifana ngokufanayo kwaye inobisi olufana nobisi; i-microemulsion esebenzisa i-dispersant enye ine-viscosity ephezulu kakhulu kunye namasuntswana amhlophe. Incopho encinci ibonakala phantsi kwe-compound dispersant ye-Tween-20 kunye ne-Span-60. Isizathu esinokwenzeka kukuba i-interfacial tension ye-compound system ye-Span-60 kunye ne-Tween-20 iphezulu, kwaye i-disperant ngokwayo iyaphulwa phantsi koxinzelelo oluphezulu olushukumisayo ukwenza iinqununu ezintle ziya kuchaphazela iziphumo zovavanyo. Ukungalungi kwe-dispersant Tween-20 kukuba inenani elikhulu lamatyathanga e-polyoxyethylene (n = 20 okanye kunjalo), eyenza isithintelo se-steric phakathi kwee-molecule ze-surfactant ibe nkulu kwaye kunzima ukuba lukhuni kwi-interface. Ukujonga kwindibaniselwano yesayizi ye-particle size diagrams, amasuntswana amhlophe ngaphakathi anokuba yi-cellulose engaxutywanga. Ke ngoko, iziphumo zolu vavanyo zibonisa ukuba isiphumo sokusebenzisa i-compound dispersant singcono, kwaye uvavanyo lunokunciphisa ngakumbi inani le-Tween-20 ukwenza i-microspheres elungisiweyo ifane ngakumbi.

Ukongezelela, ezinye iimpazamo kwinkqubo yokusebenza yovavanyo kufuneka zincitshiswe, ezifana nokulungiswa kwe-sodium hydroxide kwinkqubo yokuchithwa kwe-HPMC, i-dilution ye-DVS, njl., kufuneka ibekwe emgangathweni kangangoko kunokwenzeka ukunciphisa iimpazamo zovavanyo. Into ebaluleke kakhulu yimali ye-dispersant, isantya kunye nokuqina kokuvuselela, kunye nenani le-agent edibanisayo. Kuphela xa kulawulwa ngokufanelekileyo i-hydrogel microspheres ene-dispersion elungileyo kunye nobukhulu be-particle size ilungiswe.