Izinto ezincedisayo kwiyeza zizinto ezincedisayo kunye nezinto ezincedisayo ezisetyenziswa ekuvelisweni kwamayeza nasekuqulunqweni kwemiyalelo, kwaye ziyinxalenye ebalulekileyo yokulungiselela amayeza. Njengezinto zendalo ezithathwe kwi-polymer, i-cellulose ether ineempawu zokubola kwezinto eziphilayo, ukungabi natyhefu, kunye nexabiso eliphantsi, njenge-sodium carboxymethyl cellulose, i-methyl cellulose, i-hydroxypropyl methyl cellulose, i-hydroxypropyl cellulose,Ii-ether ze-celluloseEzifana ne-hydroxyethyl cellulose kunye ne-ethyl cellulose zibaluleke kakhulu kwizixhobo zokuncedisa amayeza. Okwangoku, iimveliso zamashishini amaninzi e-cellulose ether asekhaya zisetyenziswa kakhulu kwiindawo eziphakathi nezisezantsi zoshishino, kwaye ixabiso elongezelelweyo aliphezulu. Eli shishini lifuna ngokungxamisekileyo ukuguqula nokuphucula kunye nokuphucula usetyenziso lweemveliso oluphezulu.
Izinto ezincedisayo kwiyeza zidlala indima ebalulekileyo ekuphuhlisweni nasekuvelisweni kweefomyula. Umzekelo, kumalungiselelo okukhululwa okuqhubekayo, izinto zepolymer ezifana nee-cellulose ethers zisetyenziswa njengezinto ezincedayo kwiyeza kwiipellets ezikhutshwayo rhoqo, iintlobo ngeentlobo ze-matrix sustained-release formulations, ii-coated sustained-release formulations, ii-sustained-release capsules, iifilimu zamayeza ezikhutshwayo rhoqo, kunye namayeza e-resin akhutshwayo rhoqo. Amalungiselelo kunye namalungiselelo okukhululwa kolwelo asetyenziswa kakhulu. Kule nkqubo, iipolymers ezifana nee-cellulose ethers zihlala zisetyenziswa njengabathwali bamayeza ukulawula izinga lokukhululwa kwamayeza emzimbeni womntu, oko kukuthi, kufuneka zikhutshwe kancinci emzimbeni ngesantya esimiselweyo ngaphakathi kwexesha elithile ukuze kufezekiswe injongo yonyango olusebenzayo.
Ngokwezibalo zeSebe leeNgcebiso noPhando, kukho malunga neentlobo ezingama-500 zezinto ezincedayo kwimarike kwilizwe lam, kodwa xa kuthelekiswa ne-United States (ngaphezu kweentlobo ezili-1500) kunye ne-European Union (ngaphezu kweentlobo ezingama-3000), kukho umahluko omkhulu, kwaye iintlobo zisencinci. Izinto ezincedayo kwiyeza zelizwe lam Amandla ophuhliso lwemarike makhulu kakhulu. Kuyaqondakala ukuba izinto ezilishumi eziphezulu kwiyeza kwimarike yelizwe lam zii-capsules ze-gelatin zonyango, i-sucrose, i-starch, i-powder coating yefilimu, i-1,2-propylene glycol, i-PVP, i-hydroxypropyl methylcellulose (HPMC), kunye nee-microcrystalline fibers. I-Vegetarian, i-HPC, i-lactose.
"I-ether ye-cellulose yendalo ligama eliqhelekileyo loluhlu lwezinto eziphuma kwi-cellulose eziveliswa yi-reaction ye-alkali cellulose kunye ne-etherifying agent phantsi kweemeko ezithile, kwaye yimveliso apho amaqela e-hydroxyl kwi-cellulose macromolecule athathelwa indawo ngokuyinxenye okanye ngokupheleleyo ngamaqela e-ether. Ii-ether ze-Cellulose zisetyenziswa kakhulu kwiindawo ze-petroleum, izixhobo zokwakha, izinto zokugquma, ukutya, amayeza kunye neekhemikhali zemihla ngemihla. Kuzo zonke iindawo, iimveliso ze-pharmaceutical-grade zikwindawo ephakathi nephezulu kwishishini kwaye zinexabiso elongezelelweyo eliphezulu. Ngenxa yeemfuno ezingqongqo zomgangatho, ukuveliswa kwee-ether ze-pharmaceutical-grade cellulose nako kunzima. Kunokuthiwa umgangatho weemveliso ze-pharmaceutical-grade unokumela amandla obuchwephesha eenkampani ze-cellulose ether. I-ether ye-Cellulose idla ngokufakwa njenge-retarder, i-matrix material kunye ne-thickener ukwenza iipilisi ze-matrix ezikhutshwayo rhoqo, izinto zokugquma ezinyibilikayo esiswini, izinto zokupakishwa ze-microcapsule ezikhutshwayo rhoqo, izixhobo zefilimu yeziyobisi ezikhutshwayo rhoqo, njl.
I-Sodium carboxymethyl cellulose (CMC-Na) yi-cellulose ether enemveliso enkulu kwaye isetyenziswa kakhulu ekhaya nakwamanye amazwe. Yi-ionic cellulose ether eyenziwe ngekotoni kunye nomthi ngokusebenzisa i-alkalization kunye ne-etherification nge-chloroacetic acid. I-CMC-Na sisithako samayeza esisetyenziswa rhoqo. Ihlala isetyenziswa njengesihlanganisi sokulungiselela okuqinileyo kunye ne-arhente yokwandisa, ukuqina kunye nokuxhoma kumalungiselelo olwelo. Ingasetyenziswa kwakhona njenge-matrix enyibilikayo emanzini kunye nezinto zokwenza ifilimu. Ihlala isetyenziswa njengesixhobo sefilimu yeziyobisi esikhutshwayo rhoqo kunye nethebhulethi ye-matrix esikhutshwayo rhoqo kwi-sustained (controlled) release formulations.
Ukongeza kwi-sodium carboxymethyl cellulose njengezinto ezincedisayo kwiyeza, i-croscarmellose sodium ingasetyenziswa njengezinto ezincedayo kwiyeza. I-Crosscarmellose sodium (CCMC-Na) yinto enganyibilikiyo emanzini apho i-carboxymethyl cellulose isabela khona ne-cross-linking agent kubushushu obuthile (40-80°C) phantsi kwesenzo se-inorganic acid catalyst kwaye icocwe. I-crosslinking agent ingaba yi-propylene glycol, i-succinic anhydride, i-maleic anhydride, i-adipic anhydride, nezinye izinto ezinjalo. I-Crosscarmellose sodium isetyenziswa njenge-disintegrant kwiipilisi, ii-capsules kunye nee-granules kumalungiselelo omlomo. Ixhomekeke kwimiphumo ye-capillary kunye nokudumba ukuze ifikelele kwi-disintegration. Inoxinzelelo oluhle kunye ne-disintegration enamandla. Izifundo zibonise ukuba izinga lokudumba kwe-croscarmellose sodium emanzini likhulu kunelo le-disintegrants eziqhelekileyo ezifana ne-low-substituted sodium carboxymethyl cellulose kunye ne-hydrated microcrystalline cellulose.
I-Methyl cellulose (MC) yi-non-ionic cellulose monoether eyenziwe ngekotoni nangomthi ngokusebenzisa i-alkalization kunye ne-methyl chloride etherification. I-Methyl cellulose inokunyibilika kwamanzi kakuhle kwaye izinzile kuluhlu lwe-pH oluphakathi kwe-2.0 ukuya kwi-13.0. Isetyenziswa kakhulu kwizakhi zamayeza, kwaye isetyenziswa kwiipilisi ezingaphantsi kolwimi, i-intramuscular injections, i-ophthalmic preparations, i-oral suspensions, i-oral tablets kunye ne-topical preparations. Ukongeza, kwi-suspensions-release formulations, i-MC ingasetyenziswa njenge-hydrophilic gel matrix sustainable-release formulation, i-gastric-soluble coating material, i-sustainable-release microcapsule packaging material, i-sustainable-release drug film material, njl.
I-Hydroxypropyl methylcellulose (HPMC) yi-non-ionic cellulose mixed ether eyenziwe ngekotoni kunye nomthi ngokusebenzisa i-alkalization kunye ne-etherification ye-propylene oxide kunye ne-methyl chloride. Ayinavumba, ayinancasa, ayinatyhefu, iyanyibilika emanzini abandayo, kwaye i-gels emanzini ashushu. I-Hydroxypropyl methylcellulose luhlobo lwe-cellulose mixed ether oluye lwanda ngokukhawuleza kwimveliso, ukusetyenziswa kunye nomgangatho kwiminyaka eli-15 edlulileyo. Ikwayenye yezona zinto zinkulu ezisetyenziswayo ekhaya nakwamanye amazwe. Isetyenziswe njengesithako samayeza kangangeminyaka ephantse ibe ngama-50. Iminyaka yembali. Okwangoku, ukusetyenziswa kwe-HPMC kubonakala kakhulu kwezi zinto zintlanu zilandelayo:
Enye ifana ne-binder kunye ne-disintegrant. I-HPMC njenge-binder ingenza iyeza libe lula ukulimanzisa, kwaye linokwanda izihlandlo ezininzi emva kokufunxa amanzi, ngoko ke inokuphucula kakhulu ukunyibilika okanye ukukhululwa kwethebhulethi. I-HPMC ine-viscosity enamandla, kwaye inokuphucula i-particle viscosity kwaye iphucule ukucinezeleka kwezinto ezikrwada ezine-texture ecacileyo okanye eqinileyo. I-HPMC ene-viscosity ephantsi ingasetyenziswa njenge-binder kunye ne-disintegrant, kwaye i-HPMC ene-viscosity ephezulu ingasetyenziswa kuphela njenge-binder.
Okwesibini, isetyenziswa njengesixhobo sokukhulula esihlala ixesha elide nesilawulwayo xa kulungiselelwa ukutya ngomlomo. I-HPMC sisixhobo se-hydrogel matrix esisetyenziswa rhoqo kumalungiselelo okukhululwa okuqhubekayo. I-HPMC yodidi oluphantsi lwe-viscosity (5 ~ 50mPa·s) ingasetyenziswa njenge-binder, i-viscosity increasing agent kunye ne-suspending agent, kwaye i-HPMC yodidi oluphezulu lwe-viscosity (4000 ~ 100000mPa·s) ingasetyenziswa ukulungiselela iipilisi ze-mixed matrix sustainable-release kunye ne-sustained-release Blocker yee-capsules kunye neepilisi ze-hydrophilic gel matrix sustainable-release. I-HPMC iyanyibilika kulwelo lwesisu, ineengenelo zokucinezeleka okuhle, ukunyibilika okuhle, amandla okulayisha amayeza aqinileyo kunye neempawu zokukhululwa kwamayeza ezingachaphazeleki yi-pH. Sisixhobo esibaluleke kakhulu se-hydrophilic carrier kwiinkqubo zokulungiselela ukukhululwa okuqhubekayo kwaye sihlala sisetyenziswa njenge-hydrophilic gel matrix kunye nezinto zokugquma zamalungiselelo okukhululwa okuqhubekayo, kwaye isetyenziswa kumalungiselelo okudada esiswini kunye nezinto ezincedisayo ze-membrane yeziyobisi ezikhutshwa rhoqo.
Okwesithathu kukusetyenziswa njengearhente yokwenza ifilimu yokugquma.I-HPMCineempawu ezilungileyo zokwenza ifilimu. Ifilimu eyenziwe yiyo iyafana, icacile, kwaye iqinile, kwaye akulula ukunamathela ngexesha lokuveliswa. Ingakumbi kumayeza okulula ukufunxa umswakama kwaye angazinzanga, ukuyisebenzisa njengomaleko wokuzahlula kunokuphucula kakhulu uzinzo lweyeza kwaye kuthintele. Ifilimu itshintsha umbala. I-HPMC ineenkcazo ezahlukeneyo ze-viscosity. Ukuba ikhethwe ngokufanelekileyo, umgangatho kunye nembonakalo yeepilisi ezigqunyiweyo zingcono kunezinye izinto, kwaye uxinzelelo lwayo oluqhelekileyo yi-2% ukuya kwi-10%.
I-Four isetyenziswa njengesixhobo sekhaphu. Kwiminyaka yakutshanje, ngenxa yokuqhambuka rhoqo kwezifo zezilwanyana kwihlabathi liphela, xa kuthelekiswa neekhaphu zegelatin, iikhaphu zezityalo ziye zaba yinto entsha ethandwayo kumashishini amayeza nokutya. I-Pfizer ikhuphe ngempumelelo i-HPMC kwizityalo zendalo kwaye yalungisa iikhaphu zemifuno ze-VcapTM. Xa kuthelekiswa neekhaphu zemveli ze-gelatin ezingenamikhono, iikhaphu zemifuno zinezibonelelo zokuzivumelanisa ngokubanzi, akukho mngcipheko wokusabela okunqamlezileyo, kunye nokuzinza okuphezulu. Izinga lokukhululwa kwamayeza lizinzile, kwaye umahluko ngamnye umncinci. Emva kokuqhekeka emzimbeni womntu, awufunxwa kwaye unokukhutshwa. Ukhutshwa emzimbeni. Ngokweemeko zokugcina, emva kovavanyo oluninzi, phantse awukhuli phantsi kweemeko zokufuma eziphantsi, kwaye iipropati zeqokobhe lekhaphu zisazinzile phantsi kokufuma okuphezulu, kwaye ii-indexes ezahlukeneyo zeekhaphu zezityalo phantsi kweemeko zokugcina ezigqithisileyo azichaphazeleki. Ngokuqonda kwabantu iikhaphu zezityalo kunye nokuguqulwa kweengcamango zonyango loluntu ekhaya nakwamanye amazwe, imfuno yemarike yeekhaphu zezityalo iya kukhula ngokukhawuleza.
Eyesihlanu injenge-agent yokumisa. Ukulungiswa kolwelo lohlobo lokumisa luluhlobo olusetyenziswa rhoqo kwikliniki, oluyinkqubo yokumisa eyahlukileyo apho amayeza aqinileyo anganyibilikiyo asasazwa kwindawo yokumisa ulwelo. Uzinzo lwenkqubo lumisela umgangatho wokulungiswa kolwelo lokumisa. Isisombululo se-HPMC colloidal sinokunciphisa uxinzelelo lwe-solid-liquid interfacial, sinciphise amandla angenamphezulu wamasuntswana aqinileyo, kwaye sizinzise inkqubo yokumisa eyahlukileyo. Yiarhente yokumisa egqwesileyo. I-HPMC isetyenziswa njengesithambisi samaconsi eliso, esinomxholo we-0.45% ukuya kwi-1.0%.
IHydroxypropyl cellulose (HPC) yi-non-ionic cellulose monoether eyenziwe ngekotoni nangomthi ngokusebenzisa i-alkalization kunye ne-propylene oxide etherification. I-HPC idla ngokunyibilika emanzini angaphantsi kwama-40°C kunye nesixa esikhulu se-polar solvents, kwaye ukusebenza kwayo kunxulumene nomxholo we-hydroxypropyl kunye nomgangatho we-polymerization. I-HPC ingahambelana namayeza ahlukeneyo kwaye ayinayo i-inertness entle.
I-hydroxypropyl cellulose ethathelwe indawo kancinci(L-HPC)Isetyenziswa kakhulu njengesixhobo sokuqhawula iipilisi kunye nesokubopha. Iimpawu zayo zezi: kulula ukucinezela nokuyila, ukusebenza kwayo okuqinileyo, kunzima ngakumbi ukuyila, iipilisi zeplastiki neziqhekekileyo, ukongeza i-L -HPC inokuphucula ubulukhuni bethebhulethi kunye nokukhanya kwembonakalo, kwaye inokwenza ithebhulethi iqhekeke ngokukhawuleza, iphucule umgangatho wangaphakathi wethebhulethi, kwaye iphucule isiphumo sokunyanga.
I-hydroxypropyl cellulose (H-HPC) efakwe endaweni ephezulu ingasetyenziswa njenge-arhente yokubopha kwiipilisi, iigranules kunye neegranules ezincinci kwicandelo lezemithi. I-H-HPC ineempawu ezintle zokwenza ifilimu, kwaye ifilimu ephumayo iqinile kwaye iyanwebeka, enokuthelekiswa nee-plasticizers. Ngokuxutywa nezinye ii-arhente zokugquma ezichasene nokumanzi, ukusebenza kwefilimu kunokuphuculwa ngakumbi, kwaye idla ngokusetyenziswa njengezinto zokugquma ifilimu kwiipilisi. I-H-HPC ingasetyenziswa njengezinto ze-matrix ukulungiselela iipilisi ezikhutshwayo ezisisigxina, ii-pellets ezikhutshwayo ezisisigxina kunye neepilisi ezikhutshwayo ezisisigxina eziphindwe kabini.
I-Hydroxyethyl cellulose (HEC) yi-non-ionic cellulose monoether eyenziwe ngekotoni nangomthi ngokusebenzisa i-alkalization kunye ne-ethylene oxide etherification. I-HEC isetyenziswa kakhulu njenge-thickener, i-colloidal protective agent, i-adhesive, i-dispersant, i-stabilizer, i-suspending agent, i-film-forming agent kunye nezinto ezikhupha kancinci kwicandelo lezonyango. Ingafakwa kwi-emulsions, kwi-ointments, nakwii-eye drops kumayeza asetyenziswa kwi-topical. Ulwelo oluselwayo, iipilisi eziqinileyo, ii-capsules kunye nezinye iindlela zokulinganisa. I-Hydroxyethyl cellulose ifakiwe kwi-US Pharmacopoeia/US National Formulary kunye ne-European Pharmacopoeia.
I-Ethyl cellulose (EC) yenye yezona zinto zisetyenziswa kakhulu kwi-cellulose derivatives ezinganyibilikiyo emanzini. I-EC ayisiyotyhefu, izinzile, ayinyibiliki emanzini, kwizisombululo ze-asidi okanye ze-alkaline, kwaye iyanyibilika kwi-organic solvents ezifana ne-ethanol kunye ne-methanol. I-solvent esetyenziswa rhoqo sisinyibilikisi esixutyiweyo se-toluene/ethanol 4/1 (ubunzima). I-EC ineendlela ezininzi zokusetyenziswa kwi-drug-release release, kwaye isetyenziswa kakhulu njenge-carrier kunye ne-microcapsules, izinto zokugquma ifilimu, njl.njl. kwi-sustainable release, njenge-tablet retarders, i-adhesives, izinto zokugquma ifilimu, njl.njl. Isetyenziswa njenge-matrix material film ukulungiselela iintlobo ezahlukeneyo zee-matrix-release tablets, njengezinto ezixutyiweyo ukulungiselela amalungiselelo okugquma agqumayo kunye nee-pellets ezikhutshwayo, njenge-encapsulation assistant material ukulungiselela ii-microcapsules ezikhutshwayo; ingasetyenziswa kakhulu njenge-carrier material. Isetyenziselwa ukulungiselela i-solid dispersions; ingasetyenziswa kakhulu kwi-pharmaceutical material njengento yokwenza ifilimu kunye ne-protective coating, kwaye ingasetyenziswa njenge-binder kunye ne-filler. Njengesigqubuthelo sokukhusela iipilisi, inokunciphisa ubuthathaka beepilisi kumswakama kwaye ithintele ukuba amayeza angatshintshi umbala kwaye onakaliswe kukufuma; inokwenza umaleko weglue okhupha kancinci kwaye ifake i-polymer encinci ukuze ikhulule isiphumo seziyobisi rhoqo.
Ngamafutshane, i-sodium carboxymethyl cellulose enyibilikayo emanzini, i-methyl cellulose, i-hydroxypropyl methyl cellulose, i-hydroxyethyl cellulose kunye ne-oil-soluble ethyl cellulose zonke zisekelwe kwiimpawu zazo. Iimpawu zemveliso zisetyenziswa kwizixhobo zamayeza njengezinto zokuncamathisela, izinto ezinyibilikayo, izinto zokukhulula ezihlala ixesha elide nezilawulwayo zokulungiselela ngomlomo, ii-arhente zokwenza ifilimu, izinto ze-capsule kunye nee-agents zokumisa. Ukujonga ihlabathi, iinkampani ezininzi zamazwe ngamazwe zangaphandle (iShin-Etsu Japan, iDow Wolff kunye neAshland) zifumene imakethi enkulu ye-pharmaceutical cellulose eTshayina kwixesha elizayo, kwaye nokuba imveliso inyukile okanye idibene, zinyuse ubukho bazo kweli candelo. Utyalo-mali ngaphakathi kwesicelo. IDow Wolff ibhengeze ukuba iya kwandisa ingqalelo yayo kwifomyula, izithako kunye neemfuno zemarike yokulungiselela amayeza yaseTshayina, kwaye uphando lwayo lwesicelo luya kuzama ukusondela kwimarike. ICandelo le-Wolff Cellulose leDow Chemical kunye neColorcon Corporation yase-United States liseke umanyano oluzinzileyo nolulawulwayo lokulungiselela ukukhululwa kwihlabathi liphela. Inabasebenzi abangaphezu kwe-1,200 kwizixeko ezili-9, amaziko ezinto ezili-15 kunye neenkampani ezi-6 ze-GMP. Iingcali zophando ezisetyenzisiweyo zibonelela ngeenkonzo kubathengi kumazwe amalunga ne-160. I-Ashland ineziseko zemveliso eBeijing, eTianjin, eShanghai, eNanjing, eChangzhou, eKunshan naseJiangmen, kwaye ityale imali kumaziko ophando lwetekhnoloji amathathu eShanghai naseNanjing.
Ngokwezibalo ezivela kwiwebhusayithi ye-China Cellulose Association, ngo-2017, imveliso yasekhaya ye-cellulose ether yayiyi-373,000 tons kwaye umthamo wentengiso wawuyi-360 lamawaka eetoni. Ngo-2017, umthamo wentengiso ye-ionicI-CMCyayiziitoni ezingama-234,000, ukonyuka kwe-18.61% unyaka nonyaka, kwaye umthamo wokuthengiswa kwe-non-ionic CMC yayiziitoni ezili-126,000, ukonyuka kwe-8.2% unyaka nonyaka. Ukongeza kwi-HPMC (udidi lwezinto zokwakha) iimveliso ezingezizo ze-ionic,I-HPMC(udidi lweyeza), i-HPMC (udidi lokutya), i-HEC, i-HPC, i-MC, i-HEMC, njl. zonke zinyuke ngokuchaseneyo nomkhwa, kwaye imveliso kunye nokuthengiswa kuqhubekile nokwanda. Ii-ether ze-cellulose zasekhaya bezikhula ngokukhawuleza kangangeminyaka engaphezu kweshumi, kwaye imveliso ibe yeyokuqala kwihlabathi. Nangona kunjalo, uninzi lweemveliso zeenkampani ze-cellulose ether zisetyenziswa kakhulu kushishino oluphakathi nolusezantsi, kwaye ixabiso elongezelelweyo aliphezulu.
Okwangoku, uninzi lwamashishini e-cellulose ether asekhaya akwixesha elibalulekileyo lotshintsho nophuculo. Afanele aqhubeke nokwandisa uphando lwemveliso kunye nemizamo yophuhliso, aqhubeke nokuphucula iintlobo zemveliso, asebenzise ngokupheleleyo iTshayina, eyona marike inkulu kwihlabathi, kwaye andise imizamo yokuphuhlisa iimarike zangaphandle ukuze amashishini akwazi ukwanda ngokukhawuleza. Gqibezela utshintsho kunye nophuculo, ungene kwinqanaba eliphakathi ukuya kweliphezulu loshishino, kwaye ufezekise uphuhliso olungenabungozi noluluhlaza.
Ixesha leposi: Epreli-25-2024