1. Qhov xwm txheej yooj yim ntawm HPMC
Hypromellose, lub npe lus Askiv hu ua hydroxypropyl methylcellulose, alias HPMC. Nws cov mis molecular yog C8H15O8-(C10Hl8O6)n-C8Hl5O8, thiab qhov hnyav molecular yog li 86,000. Cov khoom no yog cov khoom siv semi-synthetic, uas yog ib feem ntawm pawg methyl thiab ib feem ntawm polyhydroxypropyl ether ntawm cellulose. Nws tuaj yeem tsim los ntawm ob txoj kev: ib qho yog kho cov methyl cellulose ntawm qib tsim nyog nrog NaOH, thiab tom qab ntawd ua rau cov tshuaj tiv thaiv nrog propylene oxide hauv qhov kub thiab siab. Lub sijhawm ua tshuaj tiv thaiv yuav tsum tau ua kom cov methyl thiab hydroxypropyl pawg sib txuas nrog ether. Daim ntawv ntawm cov tshuaj tiv thaiv txuas nrog lub nplhaib anhydroglucose ntawm cellulose, thiab tuaj yeem ncav cuag qib xav tau; qhov thib ob yog kho cov paj rwb linter lossis ntoo pulp fiber nrog caustic soda, thiab tom qab ntawd tau txais los ntawm kev ua rau cov tshuaj tiv thaiv nrog chlorinated methane thiab propylene oxide ua ntu zus, thiab tom qab ntawd ua kom huv si, sib tsoo, ua rau cov hmoov zoo thiab sib xws lossis granule. HPMC yog ntau yam cellulose ntuj tsim los ntawm cov nroj tsuag, thiab nws kuj yog ib qho tshuaj zoo heev, uas muaj ntau qhov chaw. Tam sim no, nws siv dav hauv tsev thiab txawv teb chaws, thiab nws yog ib qho ntawm cov tshuaj siv tshuaj uas muaj kev siv ntau tshaj plaws ntawm cov tshuaj noj.
Cov khoom no xim yog dawb mus rau dawb mis nyuj, tsis muaj tshuaj lom thiab tsis muaj saj, thiab nws yog cov hmoov granular lossis fibrous, yooj yim ntws. Nws ruaj khov nyob rau hauv lub teeb thiab av noo. Nws swells hauv dej txias los ua cov kua nplaum dawb mis nyuj nrog qee qib ntawm viscosity. Qhov xwm txheej sol-gel interconversion tuaj yeem tshwm sim vim qhov kub hloov pauv ntawm qee qhov concentration ntawm cov kua. Nws yooj yim heev rau yaj hauv 70% cawv lossis dimethyl ketone, thiab yuav tsis yaj hauv cawv anhydrous, chloroform lossis ethoxyethane.
Hypromellose muaj kev ruaj khov zoo thaum pH nyob nruab nrab ntawm 4.0 thiab 8.0, thiab nws tuaj yeem nyob ruaj khov ntawm 3.0 thiab 11.0. Tom qab khaws cia rau 10 hnub ntawm qhov kub ntawm 20 ° C thiab qhov av noo ntawm 80%, Cov coefficient nqus dej ntawm HPMC yog 6.2%.
Vim muaj qhov sib txawv ntawm cov ntsiab lus ntawm ob qho kev hloov pauv hauv cov qauv ntawm hypromellose, methoxy thiab hydroxypropyl, ntau hom khoom tau tshwm sim. Hauv qhov kev sib xyaw tshwj xeeb, ntau hom khoom muaj qhov tshwj xeeb viscosity thiab Thermal gelation kub, yog li ntawd, muaj cov khoom sib txawv thiab tuaj yeem siv rau ntau lub hom phiaj. Cov tshuaj pharmacopoeias ntawm ntau lub tebchaws muaj cov lus qhia sib txawv thiab kev qhia rau tus qauv: European Pharmacopoeia yog raws li ntau qib ntawm cov viscosities sib txawv thiab ntau qib ntawm kev hloov pauv ntawm cov khoom lag luam hauv khw. Nws yog qhia los ntawm qib ntxiv rau tus lej. Lub chav tsev yog mPa • s. Tom qab ntxiv 4 tus lej los qhia cov ntsiab lus thiab hom ntawm txhua tus neeg hloov pauv ntawm hypromellose, piv txwv li, hypromellose 2208, ob tus lej thawj zaug sawv cev rau feem pua ntawm methoxy pawg, ob tus lej kawg sawv cev rau hydroxypropyl Kwv yees li feem pua ntawm cov rooj plaub.
2. Txoj kev ntawm kev yaj HPMC hauv dej
2.1 Txoj kev siv dej kub
Vim tias hypromellose tsis yaj hauv dej kub, nws tuaj yeem sib xyaw ua ke hauv dej kub thaum pib, thiab tom qab ntawd thaum nws txias, ob txoj hauv kev ib txwm muaj raws li hauv qab no:
(1) Muab cov dej kub uas xav tau rau hauv lub thawv thiab ua kom sov txog li 70 ℃. Maj mam ntxiv cov khoom hauv qab kev sib xyaw qeeb qeeb. Thaum pib, cov khoom ntab rau ntawm qhov chaw ntawm dej, thiab tom qab ntawd maj mam ua cov slurry. Txias cov slurry.
(2) Ntxiv 1/3 lossis 2/3 ntawm cov dej uas xav tau rau hauv lub thawv thiab ua kom sov txog 70 ° C kom cov khoom tawg los npaj cov dej kub slurry, thiab tom qab ntawd ntxiv cov dej txias lossis dej khov seem rau hauv cov dej kub slurry. Hauv cov slurry, txias cov khoom sib tov tom qab do.
2.2 Txoj kev sib tov hmoov
Cov hmoov me me thiab lwm yam khoom xyaw hmoov uas muaj sib npaug lossis ntau dua raug sib xyaw kom tag los ntawm kev sib tov qhuav, thiab tom qab ntawd ntxiv dej kom yaj. Lub sijhawm no, cov hypromellose tuaj yeem yaj yam tsis muaj kev sib sau ua ke.
3. Cov txiaj ntsig ntawm HPMC
3.1 Kev yaj hauv dej txias
Nws yaj tau hauv dej txias hauv qab 40 ° C lossis 70% ethanol. Nws yeej tsis yaj hauv dej kub saum 60 ° C, tab sis nws tuaj yeem gelled.
3.2 Kev tsis muaj tshuaj lom neeg
Hypromellose (HPMC) yog ib hom cellulose ether uas tsis yog ionic. Nws cov kua tsis muaj ionic thiab tsis cuam tshuam nrog cov ntsev hlau lossis cov organic ionic. Yog li ntawd, lwm cov khoom siv tsis cuam tshuam nrog nws thaum lub sijhawm npaj.
3.3 Kev Ruaj Ntseg
Nws ruaj khov rau ob qho tib si kua qaub thiab alkali, thiab tuaj yeem khaws cia ntev ntawm pH 3 txog 1l, thiab nws cov viscosity tsis muaj kev hloov pauv pom tseeb. Cov kua dej ntawm hypromellose (HPMC) muaj cov nyhuv tiv thaiv pwm thiab tuaj yeem tswj tau qhov ruaj khov viscosity zoo thaum lub sijhawm khaws cia ntev. Cov tshuaj siv tshuaj HPMC muaj qhov ruaj khov zoo dua li cov uas siv cov tshuaj ib txwm muaj (xws li dextrin, hmoov txhuv nplej siab, thiab lwm yam).
3.4 Kev kho qhov viscosity
Cov viscosity sib txawv ntawm HPMC tuaj yeem sib xyaw ua ke hauv cov feem sib txawv, thiab nws cov viscosity tuaj yeem hloov pauv raws li qee txoj cai, thiab muaj kev sib raug zoo linear, yog li nws tuaj yeem xaiv raws li qhov yuav tsum tau ua.
3.5 Kev ua haujlwm ntawm lub cev tsis muaj zog
HPMC tsis nqus lossis metabolized hauv lub cev, thiab tsis muab calories, yog li nws yog ib qho khoom siv zoo rau kev npaj tshuaj.
3.6 Kev Ruaj Ntseg
Feem ntau ntseeg tias HPMC yog cov khoom tsis muaj tshuaj lom thiab tsis ua rau khaus. Qhov nruab nrab ntawm cov tshuaj tua neeg rau nas yog 5g / kg, thiab qhov nruab nrab ntawm cov tshuaj tua neeg rau nas yog 5.2g / kg. Cov tshuaj txhua hnub tsis muaj teeb meem rau tib neeg lub cev.
4. Daim ntawv thov ntawm HPMC hauv kev npaj
4.1 Siv ua cov khoom siv txheej zaj duab xis thiab cov khoom siv tsim zaj duab xis
Hypromellose (HPMC) yog siv ua cov khoom siv ntsiav tshuaj txheej. Piv nrog cov ntsiav tshuaj txheej ib txwm muaj xws li cov ntsiav tshuaj txheej qab zib, cov ntsiav tshuaj txheej tsis muaj qhov zoo pom tseeb hauv kev zais qhov saj thiab tsos, tab sis lawv qhov nyuaj thiab friability, nqus dej noo, tawg, nce qhov hnyav txheej thiab lwm yam ntsuas zoo dua. Qib qis-viscosity ntawm cov khoom no yog siv ua cov khoom siv txheej zaj duab xis yaj hauv dej rau cov ntsiav tshuaj thiab cov ntsiav tshuaj, thiab qib siab-viscosity yog siv ua cov khoom siv txheej zaj duab xis rau cov txheej txheem organic solvent. Qhov concentration siv feem ntau yog 2.0% -20%.
4.2 ua ib qho binder thiab disintegrant
Cov khoom no qib qis viscosity siv tau ua ib qho binder thiab disintegrant rau cov ntsiav tshuaj, tshuaj ntsiav, thiab granules, thiab qib siab viscosity tsuas yog siv tau ua ib qho binder. Qhov ntau npaum li cas sib txawv nrog ntau tus qauv thiab cov kev xav tau. Feem ntau, qhov ntau ntawm cov binder siv rau cov ntsiav tshuaj granulation qhuav yog 5%, thiab qhov ntau ntawm cov binder siv rau cov ntsiav tshuaj granulation ntub yog 2%.
4.3 Ua ib tus neeg sawv cev ncua
Tus neeg sawv cev rau kev ncua yog ib yam khoom siv gel uas muaj viscosity hydrophilicity. Kev siv tus neeg sawv cev rau kev ncua hauv tus neeg sawv cev rau kev ncua tuaj yeem ua rau qeeb qeeb ntawm cov khoom me me, thiab nws tuaj yeem txuas rau ntawm qhov chaw ntawm cov khoom me me kom tiv thaiv cov khoom me me los ntawm kev polymerizing thiab condensing rau hauv ib pawg. Cov neeg sawv cev rau kev ncua ua lub luag haujlwm tseem ceeb hauv kev tsim cov khoom ncua. HPMC yog ntau yam khoom zoo heev. Cov kua colloidal yaj rau hauv nws tuaj yeem txo qhov nro ntawm cov kua-khoom sib txuas thiab lub zog dawb ntawm cov khoom me me, yog li ua kom muaj kev ruaj khov ntawm cov kab ke sib txawv. Cov khoom no yog cov kua dej ncua siab viscosity siab npaj ua tus neeg sawv cev rau kev ncua. Nws muaj cov nyhuv zoo rau kev ncua, yooj yim rau redisperse, tsis nplaum, thiab cov khoom me me flocculated. Tus nqi ib txwm yog 0.5% txog 1.5%.
4.4 Siv ua ib qho blocker, qeeb thiab tswj tau tso tawm tus neeg sawv cev thiab tus neeg sawv cev tsim cov qhov hws
Cov khoom no qib siab viscosity yog siv los npaj cov ntsiav tshuaj hydrophilic gel matrix sustained-release, retarders thiab cov neeg sawv cev tswj-tso rau cov ntsiav tshuaj sib xyaw matrix sustained-release. Nws muaj cov nyhuv ntawm kev ncua kev tso tshuaj. Nws qhov kev siv concentration yog 10% ~ 80% (W /W). Qib qis viscosity yog siv los ua tus neeg sawv cev rau cov qauv tso tawm ruaj khov lossis tswj. Cov koob tshuaj pib xav tau rau cov txiaj ntsig kho mob ntawm hom ntsiav tshuaj no tuaj yeem ncav cuag sai, thiab tom qab ntawd cov txiaj ntsig tso tawm ruaj khov lossis tswj tau raug siv, thiab cov tshuaj ntshav zoo concentration tau khaws cia hauv lub cev. Hypromellose hydrates los tsim ib txheej gel thaum nws ntsib dej. Lub tshuab ntawm cov tshuaj tso tawm los ntawm cov ntsiav tshuaj matrix yog qhov feem ntau yog kev sib kis ntawm cov txheej gel thiab kev puas tsuaj ntawm cov txheej gel.
4.5 Cov kua nplaum tiv thaiv siv ua cov khoom ua kom tuab thiab colloid
Thaum cov khoom no siv ua cov khoom ua kom tuab, qhov concentration ib txwm yog 0.45% ~ 1.0%. Cov khoom no kuj tseem tuaj yeem ua rau kom cov kua nplaum hydrophobic ruaj khov, tsim cov colloid tiv thaiv, tiv thaiv cov khoom me me sib sau ua ke thiab sib sau ua ke, yog li ntawd txwv tsis pub cov av noo tsim. Nws qhov concentration ib txwm yog 0.5% ~ 1.5%.
4.6 Siv ua cov khoom siv capsule
Feem ntau, cov khoom siv ntawm lub plhaub capsule yog gelatin feem ntau. Cov txheej txheem tsim khoom ntawm Ming capsule plhaub yog yooj yim, tab sis muaj qee qhov teeb meem thiab cov xwm txheej xws li kev tiv thaiv tsis zoo ntawm cov dej noo thiab cov tshuaj oxygen rhiab heev, txo cov tshuaj yaj, thiab qeeb ntawm kev tawg ntawm lub plhaub capsule thaum khaws cia. Yog li ntawd, hypromellose yog siv los ua tus hloov pauv rau cov khoom siv capsule hauv kev npaj cov capsules, uas txhim kho qhov moldability thiab siv cov nyhuv ntawm lub capsule, thiab tau txais kev txhawb nqa dav hauv tsev thiab txawv teb chaws.
4.7 Ua ib qho bioadhesive
Kev siv tshuab bioadhesive, kev siv cov khoom siv nrog cov polymers bioadhesive, los ntawm kev lo rau ntawm cov mucosa hauv lub cev, txhim kho kev sib txuas thiab kev nruj ntawm kev sib cuag ntawm kev npaj thiab mucosa, yog li cov tshuaj maj mam tso tawm thiab nqus los ntawm mucosa kom ua tiav lub hom phiaj ntawm kev kho mob. Nws tau siv dav tam sim no Nws yog siv los kho cov kab mob ntawm lub qhov ntswg thiab qhov ncauj mucosa. Kev siv tshuab bioadhesion hauv plab yog ib hom kev xa tshuaj tshiab uas tau tsim nyob rau xyoo tas los no. Nws tsis tsuas yog ua kom lub sijhawm nyob ntev ntawm cov tshuaj npaj hauv txoj hnyuv plab, tab sis kuj txhim kho kev ua tau zoo ntawm cov tshuaj nrog lub cell membrane ntawm qhov chaw nqus thiab hloov pauv qhov fluidity ntawm lub cell membrane. Lub zog nkag mus ntawm cov tshuaj mus rau cov hlwb epithelial ntawm txoj hnyuv me me tau txhim kho, yog li txhim kho bioavailability ntawm cov tshuaj.
4.8 Ua ib qho gel sab nraud
Ua ib qho kev npaj nplaum rau daim tawv nqaij, gel muaj ntau yam zoo xws li kev nyab xeeb, kev zoo nkauj, kev ntxuav yooj yim, tus nqi qis, cov txheej txheem npaj yooj yim, thiab kev sib raug zoo nrog cov tshuaj. Nyob rau hauv xyoo tas los no, nws tau txais kev saib xyuas dav dav thiab tau dhau los ua kev txhim kho ntawm kev npaj sab nraud ntawm daim tawv nqaij.
4.9 Ua ib qho tshuaj tiv thaiv nag lossis daus hauv lub kaw lus emulsification
Lub sijhawm tshaj tawm: Lub Kaum Ob Hlis-16-2021