Izinto ezisiza ekwenziweni kwemithi ziyizinto ezisizayo nezisetshenziswayo ekukhiqizeni imithi nasekubhaleni imiyalelo, futhi ziyingxenye ebalulekile yamalungiselelo emithi. Njengento etholwe kwi-polymer yemvelo, i-cellulose ether inezici zokubola kwe-biodegradability, ukungabi nobuthi, kanye nenani eliphansi, njenge-sodium carboxymethyl cellulose, i-methyl cellulose, i-hydroxypropyl methyl cellulose, i-hydroxypropyl cellulose,Ama-cellulose ethersnjenge-hydroxyethyl cellulose ne-ethyl cellulose zinenani elibalulekile lokusetshenziswa kwezisiza zemithi. Njengamanje, imikhiqizo yamabhizinisi amaningi e-cellulose ether asekhaya isetshenziswa ikakhulukazi emasimini aphakathi nendawo aphansi embonini, futhi inani elingeziwe aliphezulu. Imboni idinga ukuguqula ngokuphuthumayo futhi ithuthukise futhi ithuthukise ukusetshenziswa kwemikhiqizo esezingeni eliphezulu.
Izinto ezisizayo zemithi zidlala indima ebalulekile ekuthuthukisweni nasekukhiqizweni kokwakheka. Isibonelo, emalungiselelweni okukhishwa okuqhubekayo, izinto ze-polymer ezifana ne-cellulose ethers zisetshenziswa njengezihlanganisi zemithi kuma-pellets akhishwa okuqhubekayo, ukwakheka okuhlukahlukene kokukhishwa okuqhubekayo kwe-matrix, ukubunjwa kokukhishwa okuqhubekayo okuhlanganisiwe, ama-capsules akhishwa okuqhubekayo, amafilimu ezidakamizwa ezikhishwa okuqhubekayo, kanye nokukhululwa okuqhubekayo kwezidakamizwa. Amalungiselelo kanye namalungiselelo okukhishwa okuqhubekayo okuwuketshezi asetshenziswe kabanzi. Kulolu hlelo, ama-polymers afana ne-cellulose ethers ngokuvamile asetshenziswa njengabathwali bezidakamizwa ukulawula izinga lokukhululwa kwezidakamizwa emzimbeni womuntu, okungukuthi, kudingeka ukuthi akhishwe kancane kancane emzimbeni ngenani elimisiwe phakathi kwebanga lesikhathi esithile ukuze kuzuzwe inhloso yokwelashwa okuphumelelayo.
Ngokwezibalo zoMnyango Wokubonisana Nokucwaninga, kunezinhlobo ezingaba ngu-500 zezinto ezisizayo emakethe ezweni lami, kodwa uma kuqhathaniswa ne-United States (izinhlobo ezingaphezu kuka-1500) kanye ne-European Union (izinhlobo ezingaphezu kuka-3000), kukhona umehluko omkhulu, futhi izinhlobo zisencane. izinto ezisiza ezweni lami kwezemithi Amandla okuthuthuka emakethe makhulu. Kuyaqondakala ukuthi izingxenye eziyishumi ezihamba phambili zemithi esikalini semakethe yezwe lami amaphilisi e-gelatin okwelapha, i-sucrose, isitashi, impushana yokugcoba ifilimu, i-1,2-propylene glycol, i-PVP, i-hydroxypropyl methylcellulose (HPMC), kanye nemicu ye-microcrystalline. Imifino, i-HPC, i-lactose.
I-ether yemvelo ye-cellulose yigama elijwayelekile lochungechunge lwe-cellulose derivatives ekhiqizwa ukusabela kwe-alkali cellulose kanye ne-etherifying agent ngaphansi kwezimo ezithile, futhi iwumkhiqizo lapho amaqembu e-hydroxyl ku-cellulose macromolecule ashintshwa ingxenye noma ngokuphelele ngamaqembu e-ether. emasimini, imikhiqizo ye-pharmacy-grade ngokuyisisekelo iphakathi nendawo ephezulu embonini futhi inenani eliphakeme elingeziwe Ngenxa yezidingo eziqinile zekhwalithi, ukukhiqizwa kwe-cellulose ethers yezinga lemithi nakho kunzima kakhulu amaphilisi e-matrix akhishwa njalo, izinto zokumboza ezincibilika esiswini, izinto zokupakisha ezikhishwa njalo ze-microcapsule, izinto zefilimu ezikhishwa njalo zezidakamizwa, njll.
I-sodium carboxymethyl cellulose (CMC-Na) iyi-ether ye-cellulose ephumayo futhi isetshenziswa kakhulu ekhaya naphesheya. I-ionic cellulose ether eyenziwe ngekotini nokhuni ngokusebenzisa i-alkalization kanye ne-etherification nge-chloroacetic acid. I-CMC-Na iyisakhi semithi esetshenziswa kakhulu. Ivamise ukusetjenziswa njenge-binder yamalungiselelo aqinileko nanjenge-ejenti ejiyako, eqinako neyimisako yokulungiselela uketshezi. Ingasetshenziswa futhi njenge-matrix encibilikayo emanzini kanye nezinto zokwakha ifilimu. Ivamise ukusetshenziswa njengefilimu yesidakamizwa ekhishwa njalo kanye nethebulethi ye-matrix ekhishwa okuqhubekayo ekwakhiweni kokukhishwa okuqhubekayo (okulawulwayo).
Ngaphezu kwe-sodium carboxymethyl cellulose njengezihlanganisi zemithi, i-croscarmellose sodium ingasetshenziswa futhi njengezihlanganisi zemithi. I-carboxymethyl cellulose sodium (CCMC-Na) i-cross-linked carboxymethyl cellulose iwuketshezi olungancibiliki emanzini lapho i-carboxymethyl cellulose isabela khona ne-agent exhumanisa endaweni ethile ezingeni lokushisa elithile (40-80°C) ngaphansi kwesenzo se-inorganic acid catalyst futhi iyahlanzwa. I-agent ehlanganisayo ingaba i-propylene glycol, i-succinic anhydride, i-anhydride ye-maleic, i-anhydride ye-adipic, nokunye okunjalo. I-Croscarmellose sodium isetshenziswa njenge-disintegrant yamaphilisi, amaphilisi kanye nama-granules ekulungiseleleni ngomlomo. Incike emiphumeleni ye-capillary kanye nokuvuvukala ukuze kuzuzwe ukuhlakazeka. Inokucindezela okuhle nokuhlakazeka okuqinile. Ucwaningo luye lwabonisa ukuthi izinga lokuvuvukala le-croscarmellose sodium emanzini likhulu kunalelo lama-disintegrants avamile njenge-low-substituted sodium carboxymethyl cellulose kanye ne-hydrated microcrystalline cellulose.
I-Methyl cellulose (MC) iyi-non-ionic cellulose monoether eyenziwe ngokotini nokhuni ngokusebenzisa i-alkalization kanye ne-methyl chloride etherification. I-Methyl cellulose inokunyibilika okuhle kakhulu kwamanzi futhi izinzile ebangeni le-pH lika-2.0 kuya ku-13.0. Isetshenziswa kabanzi kuma-excipients emithi, futhi isetshenziswa kumathebulethi angaphansi kwezilimi, imijovo ye-intramuscular, amalungiselelo e-ophthalmic, amaphilisi omlomo, ukumiswa komlomo, amaphilisi omlomo kanye namalungiselelo ama-topical. Ukwengeza, ekwakhekeni kokukhishwa okuqhubekayo, i-MC ingasetshenziswa njenge-hydrophilic gel matrix ukwakheka kokukhishwa okuqhubekayo, izinto zokunamathela ezincibilika esiswini, izinto zokupakisha ezikhishwa njalo ze-microcapsule, impahla yefilimu yezidakamizwa ekhishwa okuqhubekayo, njll.
IHydroxypropyl methylcellulose (HPMC) iyi-ether engeyona ionic cellulose eyenziwe ngokotini nokhuni ngokusebenzisa i-alkalization kanye ne-etherification ye-propylene oxide ne-methyl chloride. Ayinaphunga, ayinambitheki, ayinabuthi, iyancibilika emanzini abandayo, namajeli emanzini ashisayo. IHydroxypropyl methylcellulose iwuhlobo lwe-cellulose exubile ye-ether ebilokhu ikhula ngokushesha ekukhiqizeni, ekusetshenzisweni nakwikhwalithi kule minyaka eyi-15 edlule. Futhi ingesinye sezisiza ezinkulu zemithi ezisetshenziswa ekhaya naphesheya. Isetshenziswe njenge-excipient yezemithi cishe iminyaka engama-50. Iminyaka yomlando. Njengamanje, ukusetshenziswa kwe-HPMC kubonakala kakhulu kulezi zici ezinhlanu ezilandelayo:
Enye injenge-binder ne-disintegrant. I-HPMC njengesibophezelo ingenza umuthi ube lula ukumanzisa, futhi inganwebeka izikhathi ezingamakhulu ngemva kokumunca amanzi, ngakho ingathuthukisa kakhulu ukuhlakazeka noma ukukhululwa kwethebhulethi. I-HPMC ine-viscosity eqinile, futhi ingathuthukisa i-viscosity yezinhlayiyana futhi ithuthukise ukuminyana kwezinto ezingavuthiwe ngokuthungwa okuhlanzekile noma okuqinile. I-HPMC ene-viscosity ephansi ingasetshenziswa njenge-binder kanye ne-disintegrant, futhi i-HPMC ene-viscosity ephezulu ingasetshenziswa kuphela njenge-binder.
Okwesibili, isetshenziswa njengento eqhubekayo futhi elawulwayo yokukhululwa yamalungiselelo omlomo. I-HPMC yinto evame ukusetshenziswa ye-hydrogel matrix kumalungiselelo okukhishwa okuqhubekayo. I-HPMC yebanga eliphansi le-viscosity (5～50mPa·s) ingasetshenziswa njengesibophezelo, i-ejenti ekhulisa i-viscosity kanye ne-ejenti elengayo, kanye ne-HPMC yebanga le-viscosity grade (4000～100000mPa·s) ingasetshenziswa ukulungisa i-matrix yezinto ezixubile ezikhipha amaphilisi kanye namaphilisi e-hydrophilic e-hydrophilic akhululayo amaphilisi akhishwa njalo. I-HPMC iyancibilika oketshezini lwamathumbu, inezinzuzo zokucindezelwa okuhle, uketshezi oluhle, umthamo oqinile wokulayisha izidakamizwa nezici zokukhishwa kwezidakamizwa ezingathintwa i-pH. Kuyinto ebaluleke kakhulu ethwala i-hydrophilic ezinhlelweni zokulungiselela ukukhishwa okuqhubekayo futhi ivame ukusetshenziswa njenge-hydrophilic gel matrix kanye nezinto ezinamathelayo zamalungiselelo okukhishwa okuqhubekayo, futhi isetshenziswa ekulungiseleleni okuntantayo kwesisu kanye nezinto ezisizayo zolwelwesi lwezidakamizwa.
Okwesithathu kufana ne-ejenti yokuhlanganisa ifilimu.I-HPMCinezinto ezinhle zokwenza ifilimu. Ifilimu eyakhiwe yiyo ifana, isobala, futhi iqinile, futhi akulula ukunamathela ngesikhathi sokukhiqiza. Ikakhulukazi izidakamizwa ezilula ukumunca umswakama futhi azinzile, ukuyisebenzisa njengesendlalelo sokuzihlukanisa kungathuthukisa kakhulu ukuzinza kwesidakamizwa futhi kuvimbele Ifilimu ishintsha umbala. I-HPMC inezinhlobonhlobo zokucaciswa kwe-viscosity. Uma kukhethwe kahle, ikhwalithi nokubukeka kwamaphilisi aboshwe kungcono kunezinye izinto, futhi ukugxila kwawo okuvamile ku-2% kuya ku-10%.
Okune kusetshenziswe njengempahla ye-capsule. Eminyakeni yamuva nje, njengoba kuqubuke njalo izifo eziwumshayabhuqe zezilwane emhlabeni wonke, uma kuqhathaniswa namaphilisi e-gelatin, amaphilisi ezitshalo asephenduke isithandwa esisha embonini yemithi nokudla. I-Pfizer ikhiphe ngempumelelo i-HPMC ezitshalweni zemvelo futhi yalungiselela amaphilisi emifino e-VcapTM. Uma kuqhathaniswa namaphilisi e-gelatin angenalutho, amaphilisi emifino anezinzuzo zokuguquguquka okubanzi, akukho bungozi bokusabela okuxhumanisa, kanye nokuzinza okuphezulu. Izinga lokukhishwa kwezidakamizwa lizinzile, futhi umehluko ngamunye mncane. Ngemva kokuhlakazeka emzimbeni womuntu, awumuncwa futhi ungakhishwa. Ikhishwe emzimbeni. Ngokuya kwezimo zokugcina, ngemva kokuhlolwa okuningi, cishe akubiki ngaphansi kwezimo eziphansi zomswakama, futhi izakhiwo zegobolondo le-capsule zisazinzile ngaphansi komswakama ophezulu, futhi izinkomba ezihlukahlukene zama-capsules ezitshalo ngaphansi kwezimo zokugcina ezimbi azithinteki. Ngokuqonda kwabantu ngamaphilisi ezitshalo kanye nokuguqulwa kwemiqondo yemithi yomphakathi ekhaya naphesheya, isidingo semakethe samaphilisi ezitshalo sizokhula ngokushesha.
Eyesihlanu injenge-ejenti elengayo. Ukulungiswa koketshezi lohlobo olumisiwe kuyifomu elivame ukusetshenziswa lemithamo yomtholampilo, okuwuhlelo lokusabalalisa oluhlukahlukene lapho izidakamizwa eziqinile ezingenakuncibilika zihlakazwa endaweni yokusabalalisa uketshezi. Ukuzinza kwesistimu kunquma izinga lamalungiselelo oketshezi lokumiswa. Isixazululo se-HPMC se-colloidal singanciphisa ukungezwani kwe-solid-liquid interfacial, sinciphise amandla angaphandle ezinhlayiya eziqinile, futhi sizinzise uhlelo lokuhlakazeka oluhlukahlukene. Kuyi-ejenti enhle kakhulu yokumisa okwesikhashana. I-HPMC isetshenziswa njenge-thiener yamaconsi esweni, enokuqukethwe okungu-0.45% kuya ku-1.0%.
IHydroxypropyl cellulose (HPC) iyi-non-ionic cellulose monoether eyenziwe ngokotini nokhuni ngokusebenzisa i-alkalization kanye ne-propylene oxide etherification. I-HPC ivamise ukuncibilika emanzini angaphansi kuka-40 ° C kanye nenani elikhulu lezincibilikizeli ezimhlophe, futhi ukusebenza kwayo kuhlobene nokuqukethwe kwe-hydroxypropyl kanye nezinga le-polymerization. I-HPC ingahambisana nemithi ehlukahlukene futhi ibe nokungangeni kahle.
I-hydroxypropyl cellulose efakwe endaweni ephansi(L-HPC)isetshenziswa kakhulu njenge-disintegrant yethebhulethi kanye ne-binder. Izici zayo yilezi: ukucindezelwa kulula futhi kwakhiwe, ukusebenza okuqinile, ikakhulukazi okunzima ukuwenza, amaphilisi epulasitiki namaphilisi aphukayo, engeza i-L －HPC ingathuthukisa ubulukhuni bethebhulethi kanye nokukhanya kokubukeka, futhi ingenza ithebhulethi ihlakazeke ngokushesha, ithuthukise ikhwalithi yangaphakathi yethebhulethi, futhi ithuthukise umphumela wokwelapha.
I-high substituted hydroxypropyl cellulose (H-HPC) ingasetshenziswa njenge-ejenti ebophayo yamaphilisi, ama-granules nama-granules amahle emkhakheni wezokwelapha. I-H-HPC inezinto ezinhle kakhulu zokwenza ifilimu, futhi ifilimu ewumphumela iqinile futhi iyanwebeka, engafaniswa ne-plasticizers. Ngokuxuba namanye ama-anti-wet coating agents, ukusebenza kwefilimu kungathuthukiswa ngokuqhubekayo, futhi kuvame ukusetshenziswa njengento yokugqoka ifilimu yamaphilisi. I-H-HPC ingasetshenziswa futhi njengezinto ze-matrix ukuze kulungiswe amaphilisi akhishwa ngokuqhubekayo e-matrix, amaphilisi akhishwa isikhathi eside kanye namaphilisi akhishwa ngokugcwele anezendlalelo ezimbili.
IHydroxyethyl cellulose (HEC) iyi-non-ionic cellulose monoether eyenziwe ngekotini nokhuni ngokusebenzisa i-alkalization kanye ne-ethylene oxide etherification. I-HEC isetshenziswa kakhulu njenge-thickener, i-colloidal protective agent, i-adhesive, dispersant, stabilizer, i-ejenti yokumisa, i-ejenti eyenza ifilimu kanye nezinto ezikhishwa kancane emkhakheni wezokwelapha. Ingasetshenziswa kuma-emulsions, amafutha okugcoba, namaconsi iso ukuze uthole imithi ye-topical. Uketshezi lomlomo, amaphilisi aqinile, amaphilisi kanye namanye amafomu omthamo. I-Hydroxyethyl cellulose ifakiwe ku-US Pharmacopoeia/US National Formulary kanye ne-European Pharmacopoeia.
I-Ethyl cellulose (EC) ingenye yezinto eziphuma ku-cellulose ezingancibiliki emanzini ezisetshenziswa kakhulu. I-EC ayinabo ubuthi, izinzile, ayincibiliki emanzini, e-asidi noma ezixazululweni ze-alkaline, futhi incibilika kuzincibilikisi zemvelo njenge-ethanol ne-methanol. I-solvent evame ukusetshenziswa iyi-solvent exubile ye-toluene/ethanol 4/1 (isisindo). I-EC inokusetshenziswa okuningi emalungiselelweni okukhishwa okuqhubekayo kwezidakamizwa, futhi isetshenziswa kabanzi njengesithwali nama-microcapsules, okokuhlanganisa izinto zokwakha ifilimu, njll. amalungiselelo okukhululwa okuqhubekayo, njengamaphilisi okubukisa amaphilisi, izinto zokunamathisela, izinto zokumboza ifilimu, njll. Isetshenziswa njengefilimu ye-matrix ukuze kulungiswe izinhlobo ezahlukene ze-matrix yokulungiselela ukukhishwa okuzinzile ukuze kukhululwe amaphilisi ezinto ezihlanganisiwe ahlanganisiwe, ama-pellets akhishwa ngokuqhubekayo, njengento eyisizayo ye-encapsulation yokulungiselela ukukhishwa okuqhubekayo kwama-microcapsules; ingasetshenziswa futhi kabanzi njengempahla yenethiwekhi Isetshenziselwa ukulungisa ama-dispersions aqinile; ingasetshenziswa kabanzi kubuchwepheshe bezemithi njengento eyenza ifilimu kanye nengubo evikelayo, futhi ingasetshenziswa njenge-binder ne-filler. Njengesivikelo sokuvikela amaphilisi, kunganciphisa ukuzwela kwamaphilisi kumswakama futhi kuvimbele izidakamizwa ukuba zingaguquki futhi zonakaliswe umswakama; ingase futhi yakhe isendlalelo seglue ekhishwa kancane futhi i-microencapsulate i-polymer ukuze ikhulule ngokuqhubekayo umphumela womuthi.
Kafushane, i-sodium carboxymethyl cellulose encibilikayo emanzini, i-methyl cellulose, i-hydroxypropyl methyl cellulose, i-hydroxypropyl cellulose, i-hydroxyethyl cellulose kanye ne-oil-soluble ethyl cellulose konke kusekelwe kokuhlukana kwazo. amalungiselelo, ama-ejenti ahlanganisa amafilimu, izinto ze-capsule kanye nama-agent amisayo. Uma sibheka umhlaba, izinkampani eziningana zakwamanye amazwe zakwamanye amazwe (Shin-Etsu Japan, Dow Wolff kanye ne-Ashland) zaqaphela imakethe enkulu ye-cellulose yezemithi e-China esikhathini esizayo, futhi noma ukwanda kokukhiqiza noma ukuhlanganiswa, ziye zandisa ubukhona bazo kulo mkhakha. Ukutshala imali ngaphakathi kwesicelo. U-Dow Wolff umemezele ukuthi izokwandisa ukunaka kwayo ekwakhiweni, izithako kanye nezidingo zemakethe yaseShayina yokulungiselela imithi, futhi ucwaningo lwayo lwesicelo luzophinde luzame ukusondela emakethe. I-Wolff Cellulose Division ye-Dow Chemical and Colorcon Corporation yase-United States isungule umfelandawonye oqhubekayo wokulungiselela ukukhishwa emhlabeni jikelele. Inabasebenzi abangaphezu kwe-1,200 emadolobheni ayi-9, izikhungo zempahla eziyi-15 kanye nezinkampani ezi-6 ze-GMP. Ochwepheshe bocwaningo abasetshenziswayo bahlinzeka ngamasevisi kumakhasimende cishe emazweni ayi-160. I-Ashland inezisekelo zokukhiqiza e-Beijing, e-Tianjin, e-Shanghai, e-Nanjing, e-Changzhou, e-Kunshan nase-Jiangmen, futhi itshale imali ezikhungweni zocwaningo lwezobuchwepheshe ezintathu e-Shanghai nase-Nanjing.
Ngokwezibalo ezivela kuwebhusayithi ye-China Cellulose Association, ngo-2017, ukukhiqizwa kwasekhaya kwe-cellulose ether kwakungamathani angu-373,000 futhi umthamo wokuthengisa wawungamathani ayizinkulungwane ezingu-360. Ngo-2017, umthamo wangempela wokuthengisa we-ionicI-CMCkwaba amathani angu-234,000, ukwanda ngo-18.61% unyaka nonyaka, futhi umthamo wokuthengisa we-CMC engeyona i-ionic wawungamathani angu-126,000, okuwukunyuka ngo-8.2% unyaka nonyaka. Ngaphezu kwe-HPMC (ibanga lezinto zokwakha) imikhiqizo engeyona eye-ionic,I-HPMC(ibanga lemithi), i-HPMC (ibanga lokudla), i-HEC, i-HPC, i-MC, i-HEMC, njll. Bonke bavuke ngokumelene nomkhuba, futhi ukukhiqizwa nokuthengisa kuye kwaqhubeka kwanda. Ama-ether e-cellulose asekhaya abelokhu ekhula ngokushesha ngaphezu kweminyaka eyishumi, futhi ukukhishwa kwawo sekungowokuqala emhlabeni. Kodwa-ke, iningi lemikhiqizo yezinkampani ze-cellulose ether isetshenziswa ikakhulukazi phakathi nendawo ephansi yemboni, futhi inani elingeziwe aliphezulu.
Njengamanje, amabhizinisi amaningi asekhaya e-cellulose ether asesikhathini esibucayi soshintsho nokuthuthukiswa. Kufanele baqhubeke nokwandisa imizamo yocwaningo nokuthuthukiswa kwemikhiqizo, ngokuqhubekayo bacebise izinhlobo zemikhiqizo, basebenzise ngokugcwele iShayina, imakethe enkulu kunazo zonke emhlabeni, futhi bakhulise imizamo yokuthuthukisa izimakethe zangaphandle ukuze amabhizinisi akwazi ukwanda ngokushesha ngangokunokwenzeka. Qedela uguquko nokuthuthukisa, faka imboni emaphakathi ukuya phezulu, futhi uzuze intuthuko enempilo neluhlaza.
Isikhathi sokuthumela: Apr-25-2024