夏天无总生物碱-树脂复合物的制备

81Vol.8No.120101ChineseJournalofPharmaceuticsJan.2010p.17:20090527:(1982),(),,,[e-mail];(1959),(),,,,,Tel.[phone],[e-mail](2010)01001710110016(DSC)0.1mol·L-1HCl8g·L-15070µmH+R94Aionexchangeresin50[1][2]CorydalisDecumbensThunb.Pers.[3]2005[4]protopinetetrahydropalmatine1188FW100()DL180FA1104DF101SUV9100DSCPerkinElmerLC10ADSPD10AHW2000001×774.8%13.2%4.3%22.12.1.1100mL1.0mol·L-1HCl200~400nm288nm281nm285nm2.1.2C18200mm×4.6mm,5µm0.2%100:175:725pH3.43.51.0mL·min-12520µL2.1.35mg25mL0.1mol·L-1HCl0.1mol·L-1HCl0.040.10.20.5125102050mg·L-10.10.20.5125102050mg·L-120µLHPLCAρρ=0.110-3A−0.810-2r=0.99970.04~50mg·L-1ρ=0.110-3A−8.1310-2r=0.99970.1~50mg·L-12.20.1mol·L-1HCl254050024812h254050RSD2.0%1192.32.3.15095%8~101.0mol·L-1HCl1.0mol·L-1NaOHNa+H+[5]2.3.22.3.2.1HPLC(l)(2)(Q)(E)[6]Q=ρ0ρtV/mR(1)E=ρ0ρt/ρ0(2)Qt(g·g-1)ρ0g·L-1ρtt(g·L-1)V(mL)mR(mg)2.3.2.2H+Na+100mg0.1mol·L-1HCl8g⋅L-125mL50(Q)Q(t)12Na+Type;H+TypeFig.1Effectofdifferentanionformsontheexchangekineticcurvesofbatchmethodforprotopine208Na+Type;H+TypeFig.2EffectofdifferentanionformsontheexchangekineticcurvesofbatchmethodfortetrahydropalmatineH+Na+H+Na+2.3.2.3H+2100mg0.1mol·L-10.01mol·L-1HCl4g⋅L-125mL50(Q)Qt340.01mol•L-1HCl;0.1mol•L-1HClFig.3EffectofHClconcentrationontheexchangekineticcurvesofbatchmethodforprotopine0.01mol•L-1HCl;0.1mol•L-1HClFig.4EffectofHClconcentrationontheexchangekineticcurvesofbatchmethodfortetrahydropalmatine1210.01mol·L-1HCl2.3.2.470100140µm100mg0.1mol·L-1HCl8g⋅L-125mL50(Q)Q(t)5670µm;100µm;140µmFig.5Effectofparticlessizeoftheresinontheexchangekineticcurvesofbatchmethodforprotopine70µm;100µm;140µmFig.6Effectofparticlessizeofresinontheexchangekineticcurvesofbatchmethodfortetrahydropalmatine2.3.2.5100mg0.1mol·L-1HCl4.08.012.0g⋅L-150(Q)(E)QEρ078228QEFig.7RelationshipbetweeninitialprotopineconcentrationandprotopineavailabilityQEFig.8Relationshipbetweeninitialtetrahydropalmatineconcentrationandtetrahydropalmatineavailability2.3.2.6100mg0.1mol·L-1HCl8g⋅L-125mL254050(Q)Qt910254050Fig.9Effectoftemperatureontheexchangekineticcurvesofbatchmethodforprotopine1232540;50Fig.10Effectoftemperatureontheexchangekineticcurvesofbatchmethodfortetrahydropalmatine2.4differentialscanningcalorimetryDSC(001×7)(1:1)30~35010⋅min-12.0mg11240~295205149992231248ATotalalkaloids;BAnionexchangeresin;CPhysicalmixture;DTotalalkaloids-resincomplexesFig.11Differentialscanningcalorimetry(DSC)thermograms2.5[7]4012rTable1Thekineticsequationsofanionexchangeresinforprotopineat40ReactionorderRegressionequationrZeroorderreactionQ∞Qt=0.0134t+0.15880.8745Firstorderreactionln(Q∞Qt)=0.2383t1.48090.9306Secondorderreaction1/Q∞Qt=7.9856t14.2270.7059Table2Thekineticsequationsofanionexchangeresinfortetrahydropalmatineat40ReactionorderRegressionequationrZeroorderreactionQ∞Qt=4.810-3t+6.9910-20.8019Firstorderreactionln(Q∞Qt)=0.1401t2.49660.9465Secondorderreaction1/Q∞Qt=5.0337t+3.96770.82401253a.[8]b.3[9]H+Na+H+,,,,,H+8g·L-1,c.H+0.01mol·L-1HCl0.1mol·L-1HCl0.01mol·L-1HCl0.1mol·L-1HCl0.1mol·L-1HCl40.1mol·L-1HCl8g·L-150140µmH+[1],,.[J].,1997,13(6):613619.[2],.[J].,1995,26(2):9093.[3].[D].:2006:8.[4].:[M].:,2005:561.[5]GBT54761996[S].:1996.[6],.[J].,1999,15(4):289296.[7],,,.[J].,2001.17(1):3845.268[8].[M].4.:,2004:377.[9]CHANGRK.Formulationapproachesforsustained-releaseoralsuspension[J].PharmTechnol,1992,16(3):134141.PreparationoftotalalkaloidofRhizomaCorydalisdecumbentis-resincomplexesLIWei-nan,NIULei,SUNQi-shi,CHENDa-wei(SchoolofPharmacy,ShenyangPharmaceuticalUniversity,Shenyang110016,China)Abstract:ObjectiveTopreparetotalalkaloidofRhizomaCorydalisDecumbentis(traditionalChinesemedicine)-resincomplexeswitheffectiveingredientextractiveofRhizomaCorydalisDecumbentistotalalkaloids.MethodAnewtypeofexcipient-strongacidcationexchangeresinwasselectedasthedrugcarrierandRhizomaCorydalisDecumbentistotalalkaloidsasthemodeldrug.Usingprotopineandtetrahydropalmatineasrepresentativecomponents,thedrug-resincomplexeswerepreparedbybathexchangemethod.Thekeyfactorsinfluencingtheexchangereactionrateandequilibriumofprotopineandtetrahydropalmatinewithionexchangeresinwereinvestigated,includinganionformsofcationexchangeresin,ionconcentrationofthetotalalkaloidssolution,particlesizeoftheresin,initialdrugconcentration,andreactiontemperature.Thecombinationmechanismoftotalalkaloids-resinwasinvestigatedbydifferentialscanningcalorimetryaswell.ResultTheoptimaldrug-resincomplexespreparationconditionswithstaticexchangemethodwereasfollows:Afterdissolvingthetotalalkaloidsin0.1mol·L-1HCl,withtheinitialtotalalkaloidsconcentrationinsolution8g·L-1thedrug-resincomplexeswerepreparedwith140µmH+cationexchangeresinunder50.ConclusionThedifferentialscanningcalorimetryspectrogramshowedthatthecombinationforcebetweentotalalkaloidsandresinwasionicbondinteractioninsteadofphysicaladsorption,andthereactionofprotopineandtetrahydropalmatinewiththeionexchangeresinwereionexchangereaction.Keywords:pharmaceutics;complex;bathmethod;totalalkaloids;RhizomaCorydalisDecumbentis;drug-resin;protopine;tetrahydropalmatine()