Ukulungiswa kwe-Hydrogel Microspheres kusuka ku-Hydroxypropyl Methyl Cellulose

Lokhu kuhlola kusebenzisa indlela ye-reverse yesigaba sokumiswa kwe-polymerization, kusetshenziswa i-hydroxypropyl methylcellulose (HPMC) njengento eluhlaza, isisombululo se-sodium hydroxide njengesigaba samanzi, i-cyclohexane njengesigaba sikawoyela, kanye ne-divinyl sulfone (DVS) njengengxube exhumanisa i-Tween- 20 kanye ne-Span-60 njenge-dispersant, ivuselela ngesivinini se-400-900r / min ukulungisa i-hydrogel microspheres.

Amagama angukhiye: i-hydroxypropyl methylcellulose; i-hydrogel; ama-microspheres; hlakaza

1.Uhlolojikelele

1.1 Incazelo ye-hydrogel

IHydrogel (Hydrogel) iwuhlobo lwepolymer ephezulu yamangqamuzana equkethe amanzi amaningi esakhiweni senethiwekhi futhi ayincibiliki emanzini. Ingxenye yamaqembu e-hydrophobic kanye nezinsalela ze-hydrophilic zingeniswa ku-polymer encibilikayo emanzini enesakhiwo esixhumene nenethiwekhi, kanye ne-hydrophilic Izinsalela zibopha kuma-molecule wamanzi, zixhumanisa ama-molecule amanzi ngaphakathi kwenethiwekhi, kuyilapho izinsalela ze-hydrophobic zigcwala amanzi ukuze zenze isiphambano. - ama-polymers ahlanganisiwe. Amajeli namalensi okuxhumana empilweni yansuku zonke ayimikhiqizo ye-hydrogel. Ngokusho kobukhulu nokuma kwe-hydrogel, ingahlukaniswa ibe ijeli ye-macroscopic kanye nejeli encane (microsphere), kanti eyokuqala ingahlukaniswa ibe yikholomu, isiponji esinezimbotshana, i-fibrous, i-membranous, i-spherical, njll. I-microspheres elungiselelwe njengamanje kanye ne-nanoscale microspheres. abe nokuthamba okuhle, ukunwebeka, umthamo wokugcina uketshezi kanye ne-biocompatibility, futhi asetshenziswa ocwaningweni lwezidakamizwa eziboshiwe.

1.2 Ukubaluleka kokukhetha isihloko

Eminyakeni yamuva nje, ukuze kuhlangatshezwane nezidingo zokuvikelwa kwemvelo, izinto zokwakha ze-polymer hydrogel kancane kancane ziye zakhanga ukunaka okusabalele ngenxa yezakhiwo zazo ezinhle ze-hydrophilic kanye nokuvumelana kwe-biocompatibility. Ama-microspheres e-Hydrogel alungiswa kusuka ku-hydroxypropyl methylcellulose njengento eluhlaza kulokhu kuhlolwa. IHydroxypropyl methylcellulose iyi-ether ye-cellulose engeyona i-ionic, impushana emhlophe, ayinaphunga futhi ayinambitheki, futhi inezici ezingenakuthathelwa indawo zezinye izinto zokwenziwa ze-polymer, ngakho-ke inenani eliphakeme lokucwaninga emkhakheni we-polymer.

1.3 Isimo sokuthuthuka ekhaya naphesheya

IHydrogel iwuhlobo lwemithamo yemithi elidonse ukunaka okukhulu emphakathini wezokwelapha wamazwe omhlaba eminyakeni yamuva nje futhi ithuthuke ngokushesha. Kusukela u-Wichterle no-Lim bashicilela umsebenzi wabo wokuphayona kuma-HEMA axhumene kakhulu nama-hydrogel ngo-1960, ucwaningo nokuhlolwa kwama-hydrogel kuqhubekile nokujula. Maphakathi nawo-1970, uTanaka wathola ama-hydrogel azwela i-pH lapho ekala isilinganiso sokuvuvukala samajeli amadala e-acrylamide, okumaka isinyathelo esisha ocwaningweni lwama-hydrogel. izwe lami lisesigabeni sokuthuthukiswa kwe-hydrogel. Ngenxa yenqubo ebanzi yokulungiselela imithi yendabuko yamaShayina kanye nezingxenye eziyinkimbinkimbi, kunzima ukukhipha umkhiqizo owodwa ohlanzekile lapho izingxenye eziningi zisebenza ndawonye, ​​futhi umthamo mkhulu, ngakho ukuthuthukiswa komuthi waseShayina i-hydrogel kungase kuhambe kancane.

1.4 Izinto zokuhlola nezimiso

1.4.1 I-Hydroxypropyl methylcellulose

IHydroxypropyl methyl cellulose (HPMC), ephuma ku-methyl cellulose, iyi-ether ebalulekile exubile, eyingxenye yama-polymers angeyona i-ionic ancibilika emanzini, futhi ayinaphunga, ayinambitheki futhi ayinabuthi.

I-Industrial HPMC isesimweni sempushana emhlophe noma i-fibre emhlophe exekethile, futhi isisombululo sayo esinamanzi sinomsebenzi ongaphezulu, ukukhanya okuphezulu nokusebenza okuzinzile. Ngenxa yokuthi i-HPMC inendawo ye-gelation eshisayo, isixazululo se-aqueous somkhiqizo siyashiswa ukuze senze ijeli kanye ne-precipitates, bese siyancibilika ngemva kokupholisa, futhi izinga lokushisa le-gelation lokucaciswa okuhlukene komkhiqizo lihlukile. Izakhiwo zokucaciswa okuhlukile kwe-HPMC nazo zihlukile. Ukunyibilika kuyashintsha nge-viscosity futhi akuthintwa inani le-pH. I-viscosity ephansi, i-solubility enkulu. Njengoba okuqukethwe kweqembu le-methoxyl kuncipha, iphuzu lejeli le-HPMC liyakhula, ukuncibilika kwamanzi kuncipha, nomsebenzi ongaphezulu uyancipha. Embonini ye-biomedical, isetshenziswa kakhulu njengento elawula izinga le-polymer yezinto zokumboza, izinto zefilimu, namalungiselelo okukhishwa okuqhubekayo. Ingasetshenziswa futhi njenge-stabilizer, i-ejenti yokumisa okwesikhashana, i-adhesive tablet, kanye nesithuthukisi se-viscosity.

1.4.2 Umgomo

Usebenzisa indlela ye-reverse yesigaba sokumiswa kwe-polymerization, kusetshenziswa i-Tween-20, i-Span-60 compound dispersant kanye ne-Tween-20 njengama-dispersants ahlukene, thola inani le-HLB (i-surfactant iyi-amphiphile eneqembu le-hydrophilic kanye ne-lipophilic group Molecule, inani losayizi namandla ibhalansi phakathi kweqembu le-hydrophilic kanye neqembu le-lipophilic ku-molecule ye-surfactant ichazwa njengobubanzi obulinganiselwe be-hydrophilic-lipophilic balance value ye-surfactant i-Cyclohexane ingahlakaza kangcono isisombululo se-monomer futhi ihlakaze ukushisa okukhiqizwa ekuhlolweni ngokuqhubekayo Umthamo uphindwe izikhathi ezingu-1-5 kunesixazululo se-aqueous monomer Ngokuxutshwa kwe-divinyl sulfone engu-99% njenge-ejenti yokuxhumanisa, futhi inani le-ejenti yokuxhumanisa lilawulwa cishe ku-10% we inqwaba ye-cellulose eyomile, ukuze ama-molecule amaningi alayini ahlanganiswe elinye nelinye futhi axhumeke ekwakhiweni kwenethiwekhi Into ebophezela ngokuhlanganyela noma ehambisa noma ukwakheka kwebhondi ye-ionic phakathi kwamaketanga e-polymer molecular.

Ukushukumisa kubaluleke kakhulu kulokhu kuhlolwa, futhi isivinini ngokuvamile silawulwa egiyeni lesithathu noma lesine. Ngoba ubukhulu bejubane lokujikeleza buthinta ngokuqondile ubukhulu bama-microspheres. Uma isivinini sokujikeleza sikhulu kuno-980r/min, kuzoba khona into engathi sína yokunamathela odongeni, okuzonciphisa kakhulu isivuno somkhiqizo; I-agent yokuxhumanisa ijwayele ukukhiqiza ama-gel amaningi, futhi imikhiqizo eyindilinga ayikwazi ukutholwa.

2. Amathuluzi okuhlola nezindlela

2.1 Izinsimbi Zokuhlola

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

Ukulungiselela i-cellulose hydrogel microspheres, amakhemikhali ayinhloko asetshenziswa yi-cyclohexane, i-Tween-20, i-Span-60, i-hydroxypropyl methylcellulose, i-divinyl sulfone, i-sodium hydroxide, amanzi acwecwe, konke okuyi-Monomers kanye nezithasiselo ezisetshenziswa ngokuqondile ngaphandle kokwelashwa.

2.2 Ukulungiselela izinyathelo ze-cellulose hydrogel microspheres

2.2.1 Ukusebenzisa i-Tween 20 njenge-dispersant

Ukuqedwa kwe-hydroxypropylmethylcellulose. Kala ngokunembile u-2g we-sodium hydroxide bese ulungisa isisombululo se-sodium hydroxide esingu-2% ngeflask yevolumu ye-100ml. Thatha u-80ml wesisombululo se-sodium hydroxide esilungisiwe bese usishisa emanzini okugeza kuze kufike ku-50°C, linganisa u-0.2g we-cellulose bese uyifaka kwisisombululo se-alkaline, uyixube ngenduku yengilazi, uyibeke emanzini abandayo ukuze ugeze iqhwa, futhi uyisebenzise njengesigaba samanzi ngemva kokucaciswa kwesixazululo. Sebenzisa isilinda esiqediwe ukukala u-120ml we-cyclohexane (isigaba samafutha) ube yiflask enentamo emithathu, dweba u-5ml we-Tween-20 esigabeni samafutha ngesirinji, bese ugoqa ku-700r/min ihora elilodwa. Thatha uhhafu wesigaba se-aqueous esilungisiwe bese usifaka esitshalweni esinezintamo ezintathu bese ugoqa amahora amathathu. I-concentration ye-divinyl sulfone ingu-99%, ihlanjululwe ku-1% ngamanzi acwecwe. Sebenzisa i-pipette ukuthatha u-0.5ml we-DVS uyifake ku-50ml ye-volumetric flask ukuze ulungise i-1% DVS, i-1ml ye-DVS ilingana no-0.01g. Sebenzisa i-pipette ukuthatha u-1ml eflaskini enentamo emithathu. Govuza ekamelweni lokushisa amahora angu-22.

2.2.2 Ukusebenzisa i-span60 kanye ne-Tween-20 njengama-dispersants

Enye ingxenye yesigaba samanzi esisanda kulungiswa. Kala u-0.01gspan60 bese uyifaka eshubhuni yokuhlola, uyishise kubhavu wamanzi we-65-degree ize incibilike, bese uphonsa amaconsi ambalwa e-cyclohexane emanzini okugeza nge-dropper yerabha, futhi uyishise kuze kube yilapho isisombululo siphenduka sibe mhlophe njenge-milky. Yengeze ku-flask enezintamo ezintathu, bese ufaka u-120ml we-cyclohexane, ugeze ithubhu yokuhlola nge-cyclohexane izikhathi eziningana, ukushisa kwe-5min, uphole ekamelweni lokushisa, bese wengeza u-0.5ml we-Tween-20. Ngemuva kokugqugquzela amahora amathathu, i-1ml ye-DVS ehlanjululwe yengezwa. Govuza ekamelweni lokushisa amahora angu-22.

2.2.3 Imiphumela yokuhlola

Isampula elinyakazisiwe lacwiliswa endukwini yengilazi futhi yancibilika ku-50ml we-ethanol ephelele, futhi usayizi wezinhlayiyana walinganiswa ngaphansi kosayizi wezinhlayiyana ze-Malvern. Ukusebenzisa i-Tween-20 njenge-dispersant microemulsion kukhulu, futhi usayizi wezinhlayiyana olinganiselwe we-87.1% ngu-455.2d.nm, kanti usayizi wezinhlayiyana we-12.9% ngu-5026d.nm. I-microemulsion ye-Tween-20 kanye ne-Span-60 exutshwe dispersant ifana neyobisi, enosayizi wezinhlayiyana ezingu-81.7% we-5421d.nm kanye no-18.3% usayizi wezinhlayiyana we-180.1d.nm.

3. Ingxoxo yemiphumela yokuhlola

Nge-emulsifier yokulungiselela i-microemulsion ephambene, ngokuvamile kungcono ukusebenzisa inhlanganisela ye-hydrophilic surfactant kanye ne-lipophilic surfactant. Lokhu kungenxa yokuthi ukuncibilika kwe-surfactant eyodwa ohlelweni kuphansi. Ngemuva kokuthi lezi zibili zihlanganisiwe, amaqembu e-hydrophilic nomunye nomunye namaqembu e-lipophilic abambisana ukuze abe nomphumela wokuxazulula. Inani le-HLB futhi liyinkomba evame ukusetshenziswa lapho kukhethwa ama-emulsifiers. Ngokulungisa inani le-HLB, isilinganiso se-emulsifier yezingxenye ezimbili singathuthukiswa, futhi kungalungiselelwa ama-microspheres afanayo kakhulu. Kulesi sivivinyo, i-lipophilic ebuthakathaka i-Span-60 (HLB = 4.7) ne-hydrophilic Tween-20 (HLB = 16.7) isetshenziswe njenge-disperant, futhi i-Span-20 isetshenziswe iyodwa njenge-dispersant. Kusukela emiphumeleni yokuhlola, kungabonakala ukuthi i-compound Umphumela ungcono kune-dispersant eyodwa. I-microemulsion ye-compound dispersant ifana ngokufanayo futhi inokuvumelana okufana nobisi; i-microemulsion esebenzisa i-dispersant eyodwa ine-viscosity ephezulu kakhulu nezinhlayiya ezimhlophe. Ukuphakama okuncane kubonakala ngaphansi kwe-disperant ye-compound ye-Tween-20 ne-Span-60. Isizathu esingenzeka ukuthi ukungezwani kobuso besistimu ye-compound ye-Span-60 ne-Tween-20 kuphezulu, futhi i-disperant ngokwayo iphukile ngaphansi kokugqugquzela okunamandla ukuze kwakhiwe Izinhlayiya ezinhle zizothinta imiphumela yokuhlola. Ububi be-disperant Tween-20 ukuthi inenani elikhulu lamaketanga e-polyoxyethylene (n=20 noma ngaphezulu), okwenza isithiyo esibulalayo phakathi kwama-molecule atholakalayo sibe sikhulu futhi kube nzima ukuba minyene esibonakalayo. Uma sibheka inhlanganisela yemidwebo yosayizi wezinhlayiyana, izinhlayiya ezimhlophe ngaphakathi zingase zibe i-cellulose engahlakazeki. Ngakho-ke, imiphumela yalokhu kuhlolwa iphakamisa ukuthi umphumela wokusebenzisa i-compound dispersant ungcono, futhi ukuhlolwa kungaqhubeka nokunciphisa inani le-Tween-20 ukwenza ama-microspheres alungiselelwe afane kakhulu.

Ukwengeza, amanye amaphutha enqubweni yokusebenza kokuhlola kufanele ancishiswe, njengokulungiswa kwe-sodium hydroxide enqubweni yokuhlakazwa kwe-HPMC, ukuhlanjululwa kwe-DVS, njll., kufanele kulinganiswe ngangokunokwenzeka ukuze kuncishiswe amaphutha okuhlola. Okubaluleke kakhulu inani le-dispersant, isivinini kanye nokuqina kokunyakazisa, kanye nenani le-ejenti yokuxhumanisa. Kuphela lapho kulawulwa kahle lapho i-hydrogel microspheres enokusabalalisa okuhle kanye nosayizi wezinhlayiyana ezifanayo angalungiselelwa.