Tài liệu Nghiên cứu bào chế và đánh giá sinh khả dụng viên nang aciclovir tác dụng kéo dài

        **********     VIÊN NANG ACICLOVIR      1         **********     CLOVIR           !"#$"% &' ()PGS. "#$%&$'()*$+, GS TS. Võ Xuân Minh  1 i LI C-M /N Tôi xin bày t lòng bi c: PGS. TS. Phm Th Minh Hu GS. TS. Võ Xuân Minh Nh  i thng dn và h   tôi trong thi gian làm lun án v!a qua. "#$% xin chân thành c&'()*+"*+, -/012 3()*+"*+ Nguy-40 563"*+, -n Trn Linh cùng toàn th7 các thy, cô giáo, k9 thut viên B; môn Bào ch, b; '#<=c l>c  , t?2@u kin thun l=i cho tôi hoàn thành lun án này. Trân trAng c&'  >  , t?2 @u kin cCa TS. Phùng ThD Vinh, ThS. Nguy-n ThD Thanh Th&o cùng các ki7m nghi' EF "G    ' "   Ac, Vin Ki7m nghim thuH$"G  I + Tôi xin chân thành c&'  J6 )M'   ,O Gng, PGS. TS. Nguy-n Thanh Bình, TS. Nguy-" /$R $M$$ FEF 4O2 t?26 ?i hA$U 6 'EO  tôi trong quá trình công tác, hAc tp và nghiên cWu. CuHi cùng, tôi xin c&'   G2  6EOY?n bè   # Z YF3  3 ;ng viên, t?o mA @u kin thun l= 7 tôi hoàn thành lun án. Hà N;3 O\]M ^_0'\_^_ /%"D Thu Giang ii L( 0 + ," )'- .&'" ./0 12 )+" 345"  " 6" )7u c9a riêng tôi. Các s; lit qu? nêu trong lu@n án là trung thA)B2) '3D".Ec ai công b; trong bFt kG công trình nào khác. HI J Thu Giang iii DANH M2C CÁC KÝ HI3U, CH÷ VIÕT T¾T ACV ACV-KDNM AUC BAK BP C-974 C max CMC [H DM DBP EBV EC EDTA FDA : : : : : : : : : : : : : : : GPDC GPKD HPCD HPLC : : : : HPMC HQC HSV HT KDNM Kl/kl Kl/tt KSGP KT KTT LLOQ LQC : : : : : : : : : : : : Aciclovir H)SUWH%>3#X" "6--Y) [<"3X) #!.")&" Benzalkonium clorid [E).^"W" (British Pharmacopoeia) Carbopol 974P NF {".|3 U;)3;.'34&" U0>33}" Carboxymethyl cellulose [E).^"H<3'Dung môi Dibutyl phtalat Virus Epstein-Barr Ethyl cellulose Acid ethylendiamintetraacetic }U'"U?"1‚3 U;)– 3 A)ƒ „-†‡Food and Drug Administration) ?ƒ ˆ"#E)) F3 ?ƒ ˆ"%‰&#2 2-hydroxypropyl E-cyclodextrin )%‚1Ž" 33}" ’>3#X" "6--Y) ’ ;1E"”% ;1E" ’ ;1E"”3 ^3X) ’^-•&–3?ƒ ˆ" H6""'"WH- —’[% +"3"3 F’ +"3"3 F ! Y".J" 1E"#!‡lower limit of quantification) $U%^-) 7""{".|3 Fƒ‡low quality control sample) iv MEC MQC MRT MTC NaDC NaGC NaLS NTN OCC PCC PEG PEPT P-gp PVA PVP RSD SCC SD SKD SMEDDS STT T 1/2 TBA TCCS  TEC TEER T max TT Tt/tt USP VA VKNTTW VZV WHO : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : {".|3;3 ^U)ˆ3–)#™"‡minimum effective concentration) $U%^-) 7""{".|34U"š5" ‡middle quality control sample)  '"1U34œ34U"š5" (mean retention time) {".|3;3 ^U/0.|)‡minimum toxic concentration) Natri deoxycholat Natri glycocholat Natri laurylsulfat 35" "U0<" DL-octanoylcarnitin clorid Palmitoyl-DL- carnitin clorid Polyoxyethylen glycol  F3B@" ) U0^"ƒžƒ3# P-glycoprotein Polyvinyl alcol Polyvinyl pyrolidon K30 |1<) ) U„"3}".;‡relative standard deviation) DL-stearoylcarnitin clorid |1<) ) U„" (standard deviation) " % ?#™" <3A" I ˆ' (self-microemulsifying drug delivery system) ;3 73A  '"š–"3 ? 4-thiobutylamidin 6U) U„")}•¢ }".}"•"  () Triethyl citrat <"34¢3 E"š5 (transepithelial electrical resistance)  '".Y3"{".|3 U;)3;.'34&" U0>33}" H6""'"WH- —’[) 7'£¤žž"¥  ^3X) ”3 ^3X) [E).^"† (United States Pharmacopeia) Viên nén Vacrax® 200 mg H<"%^-" <-3 U;)4U"§}" Virus Varicella- zoster ©) 7)3>3 >! (World Health Organization) v (22 56 7 ......................................................................................................... 1 CH/NG "8NG QUAN................................................................................... 3 1.1. ACICLOVIR.................................................................................................. 3 Y)}"B«aciclovir ............................................................................ 3 |3•;" 6")7U)?3 <" Fƒ3 Uaciclovir U'."36U ˆ' ........ 7  ¬­¬—¯ ’°[ ¬ .............................................................. 20 ’ –"<-B«3 U;)?ƒ ˆ"%‰&#2................................................. 20 |3•;#Y"3 U;)?ƒ ˆ" %‰&#2#±"3 ž&."U;" ............. 21 + 5" š2&) >3 U;)?ƒ ˆ"%‰&#2#Y"-2"š'&.................. 22 ²|3•; <?ƒ ˆ"%‰&#2) 7'aciclovir #±") &."U;" .... 24 ¬’­[³ H T§´ §´ ¬µ ............................ 28 ’ –"<-•" % ?#™"B23}".}"•"  ().............................. 28 1.3.2–" –•" % ?#™")9'3 U;)......................................................... 28 ·U0.J" B«.–" –•" % ?#™"B23}".}"•"  () ............ 31 ²|3•;" 6")7U•" % ?#™"."U;")9'aciclovir ............... 35 CH/ " :; 3<  = VÀ PH/NG PHÁP NGHIÊN > ....................................................................................................................... 39  ¹¬ºH —§´ ¬º ¬» ............................. 39 U06"13šJ................................................................................................... 40  U;) .;) >U ..................................................................................... 41 ²|"B@33 X" <- .............................................................................. 41 2.2. PH§´ —¼— ¬» ............................................................... 41 2.2.1. Ph}"ƒ –ƒ" 6")7U3X" 3 F-....................................................... 41 2.2.2. Ph}"ƒ –ƒš2&) > ............................................................................ 44 2.2.3. Ph}"ƒ –ƒ.–" –36U) U„") F31E" ....................................... 47 2.2.4. Ph}"ƒ –ƒ.–" –•" % ?#™"in vivo 346".|"B@33 X" <- ... 50 2.2.5. Ph}"ƒ –ƒ3 >3%>3 X" <-B23;U &–)+"3 7).................... 53 2.2.6. Ph}"ƒ –ƒ" 6")7U.|©".J" ..................................................... 54 CH/@"BE-;> ........................................................... 55 ­¬¬º¾¿ÀWW¬CLOVIR ............................................. 55 vi Á/0#A"-+ 5" -2"" /"3Y&.–" –3X" 3 F-)9'aciclovir.... 55  6")7U)?3 <"3X" 3 F-)9'WHU'-2"" /"3Y&.............. 60  6")7U)?3 <"3X" 3 F-)9'WHU'-2"•"  () .............. 62 ÁÂ[Ã Ä »  H¬W WH- —’[. 68  6")7Uš2&) > Y3aciclovir ?ƒ ˆ"%‰&#2 ........................... 68  6")7Uš2&) >B6""'"aciclovir 200 mg GPKD ...................... 87 ÁÂ[à ·¬ÅÆ  H¬W WH- —’[Ç·¬ IJH¬H ÈÁ¿¬É¿¹§Ê ........................... 89 ’ ?&•–3)–)3 +"•;)9'U–345" 3Y& Y3šË"g ph}"ƒ –ƒ3Y& Y3 !3B2#A%>"36U) U„" Y3WH ................................................................. 89 ’ ?&•–3)–)3 +"•;)9'U–345" š'&B2#A%>"36U) U„" Y3WH ?ƒ ˆ"%‰&#2 ........................................................................................... 94 «,UF3-|3•;) Ì36U) F31E") &B6""'"WH —’[......... 103 ²¼ ¬¼ÍÎÏ ....................................................................... 104 3.4.1. Theo dõi hàm lE" ............................................................................ 104 3.² ž&#Ð.| Ñ'3'" ............................................................................. 107 ¼ ¬¼¬’­[³ ............................................................... 110 3.5.1.  „-.J" ƒ }"ƒ –ƒ.J" 1E"WH34&" U0>33}ng............ 110 –" –•" % ?#™"B6""'"WH —’[................................. 121 CH/"= ............................................................................... 130 ²HÈNGHIÊN »­¬¬º¾¿ÀWW¬CLOVIR ....... 130 ²HÈ ¬»  H¬W W¬CLOVIR GPKD........ 134 ²HÈÁÂ[à ·¬ÅÆ  H ÈÁ¿¬É ¿¹§Ê H¬W WH- —’[....................................... 138 ²²Hȼ ¬¼ÍÎÏ ................................................................. 141 ²Hȼ ¬¼¬’­[³ ......................................................... 141 B 7O6................................................................................146 (2YZ [Y=\ ;E .147 3(B-0 .................................................................................148 #22 ............................................................................................................156 vii (2=-<=_ J& ^+^+ 4;6$C6aciclovir Z€ o‚G2 $M$'#G 5ƒM$6 4 J& ^+\+ 5H„'Y7 ƒ$C6aciclovir U 6'O YO2‚6$2-2 4 J& 1.3. ˆ;HY‰=$$W6aciclovir 7 J& ^+Š+ ˆ; H @  ƒ  F $W   ƒ& ‰‹  EO      A$   H $C6aciclovir 37 J& \+5. ‚M$ F ‰‹ G2  F$W 39 J& \+6. ‚M$# Hƒ9 Y62Y YD # 45 J& €+7. ‘Z $C6'O A$’“=‰'6 =$”1•3’–‚/ '?”5•EOH„'Y7 ƒ$C6–‚/”(app) 56 J& €+8. ‘Z $C6O6‰ H„'Y7 ƒ$C6–‚/ 57 J& €+™. ‘Z $C6š6‰ H„'Y7 ƒ$C6–‚/ 58 J& €+^_. ‘Z $C66‰ = –‚/„'U 6'O ›2 6 59 J& €+11. ‘Z $C6$M$$„0 „'Z$M$œ ;ƒM$6 =  EOH„'–‚/U 6'O  ?2 J& €+^\. ‘Z $C6$M$$„0 „'ƒ&0 „'–‚/U 6Y7 Y= 61 63 J& €+^€. ‘ Z  $C6 $M$ $„ 0  „'  ƒ& 0  „' –‚/ U 6 G  Y= 64 J& €+^Š. ‘Z $C6$M$$„0 „'ƒ&0 „'$C6–‚/U 6 'O H J& €+^. ˆW$;0 „'–‚/U 6$M$2?'O 66 67 J& €+^ž. 5  „?2?EO';HŸ$ $C6$M$' ?E$M$M‰=$ ;ƒM$6 J& €+^. "OM‰=$‰ $C6$M$' ? 69 70 J& €+^]. 5  „?2?EO';HŸ$ $C6$M$' ?$¡OM ‰=$‰ ƒM$6 J& €+^™. "O$C6$M$' ? 70 71 J& €+\_. 5  „?2?EO';HŸ$ $C6$M$' ?$W6$„0  „'ƒM$6 J& €+\^. ˆ;HŸ$ $C6?–‚/G$EO6 ƒY62'O (/– 72 73 viii J& €+\\. "Omàng bao GPKD ƒ&2M 74 J& €+\€. (G0'–‚/ &¡ EO'O Y62ƒ6$6 74 J& €+\Š. (G0'–‚/ &¡ !?Y62GPKD $W6$„0 „' khác nhau 75 J& 3.25. ‚M$'W$$C6Y;$ 77 J& €+\6. ‚M$Y‹ ;$ 77 J& €+\7. Tƒ  ' 78 J& €+\8. ¢H= GF Y7 ƒ3H$;$&EOO'= –‚/$C6? bao GPKD 79 J& €+29. (G0'–‚/ &¡ !?Y62 GPKD 80 J& 3.30. ‘Z $C6$M$Y;$$M$Y‹ ;$ 81 J& €+€1. ¢U &  $H GF'@'¥,¦2G'€+^ 86 J& €+€2. ˆ;HŸ$ $C6?–‚/)(¢<Y62›2›2$# W$H 86 J& €+€3. (G0'–‚/ &¡ !?Y62 ›2$# W$H 87 J& €+€4. ( G0' –‚/ & ¡  ›2  6 ! ? Y62 EO EF 6  GPKD J& 3.35. ¢U &M M;œ @ O'= ACV ƒG; Y;ƒ# 88 90 J& €+€6. ‘Z $C6H$;H=M‰=$‰   „$?2EO; Y@$A$$C6?–‚/ 91 J& €+€7. ‘Z $C6H$;¨M?  „?2?EO$„= ? YO2$ 92 J& €+€]+ ˆ;HŸ$ EO‰>ƒF $ ©?–‚/ 94 J& €+€™. (G0'–‚/ &¡ $C6$M$' ?ˆ5^3ˆ5\3ˆ5€3ˆ5Š 95 J& €+Š_. (G0'–‚/ &¡ !$M$' ?–‚/)(¢<Y62E; khí vào khác nhau 97 J& €+Š^. (G0'–‚/ &¡ !$M$' ?–‚/)(¢<Y62EM „ khí phun khác nhau 98 J& 3.42. ( G0' –‚/ & ¡  ! $M$ '  ? –‚/ )(¢< Y62 E ;  F $6# ƒ ƒM$6 99 J& €+Š€. (G0'–‚/ &¡ !$M$' ?–‚/)(¢<Y62EH$;  ‰D$Y62ƒM$6 100 ix J& €+ŠŠ+ ‚M$# Hƒ9 ƒY62'O )(¢<Y YD # 102 J& €+Š+ "F $ ©$C6?–‚/)(¢< 103 J& €+Š6. "F $ © $C6viên nang ACV 200 mg GPKD 104 J& €+Š7. (G0'–‚/$?$C6$M$' EF6 =$Y&2U &Z@  ƒ2¡6$„H$ 105 J& €+Š8. (G0'–‚/$?$C6$M$' EF6 Y&2U &Z@ ƒ>$ 105 J& €+Š9. 4; hoà tan $C6 viên nang ACV GP¢<›2‰ªZ@ ƒ2¡6 $„H$ 108 J& €+50. 4;2O6$C6EF6 –‚/)(¢< ›2‰ªZ@ ƒ>$ 109 J& €+51. ‘Z $C6 ' G ? 7'GR  6 $C6–‚/ 111 J& €+52. " U 6 6œ ;–‚/G2   EO‰ $$ 111 J& €+3. 4; $C6  $ © 112 J& €+4. «M$D ?D= ‰ 113 J& €+5. 4; 3;Ÿ?G2  O 114 J& €+6. 4; 3;Ÿ?ƒM$ O 115 J& €+7. (G0''? 116 J& €+8. 4;¬D$C6‰  ‰D$–‚/$ ©Z; 6 ž  117 J& €+9. 4;¬D$C6'   6 €$ ƒ­# – rã 118 J& €+60. 4;¬D$C6'   Z; 6 5  118 J& €+61. 4;¬D$C6'   Y&2U &Z- 40oC 119 J& €+ž2. 4;¬D$C6' 6 ¨¯G2 6 2- 6'›G6 \Š  120 J& €+63. 5O'= EOG0' –‚/ &¡ ›2 6$C6$M$ H$ 121  F$W *¢< J& 3.64. ,œ ;–‚/”μg/ml•G2   $¡6 ƒ H @ viên KT 122 J& €+ž5. ,œ ;–‚/”μg/ml) G2   $¡6 ƒ H @ EF/– 123 J& €+ž6. ‚M$# H‰=$; A$G  Y$C66EF/–EO¢" 124 J& €+ž7. J& –,±/–  $$M$# H‰=$; A$$C6EF¢"EO/– 124 J& €+ž8. ,œ ;–‚/”μg/ml•G2   $¡6 ƒ H @ viên TT 126 J& €+ž9. ,œ ;ACV (μg/ml•G2   $¡6 ƒ H @ viên KT 126 J& 3.70. ‚M$# H‰=$; A$G  Y$C6\EF""EO¢" 127 J& €+71. J& –,±/–  $$M$# H‰=$; A$$C6EF""EO¢" 128 x (2Z`< a Hình 1.1. 4œDœ ;‰=$$„G2 'M ›2 6$C6‰? GPKD so E‰? U $ 21 Hình 2.2. Jƒ $M‰A$'# Y¦G6³ 42 Hình 2.3. *œ$M$ 62?YO2$?–‚/Y  M¨M? 44 Hình 3.4. ‘Z $C6 O6‰ ƒ&0 „'$C6–‚/ 57 Hình 3.5. 4œDY7 ‰-ƒ&0 „'$C6–‚/U 6'O  ?2 60 H×nh 3.6. BiÓu ®å thÓ hiÖn møc ®é lμm t¨ng thÊm ACV cña c¸c chÊt t¨ng thÊm 62 Hình 3.7. ‘ Z  $C6 $M$ $„ 0  „'  ƒ& 0  „' –‚/ qua Y7 Y = Hình 3.8. Hình 3.9. 63 ‘ Z  $C6 $M$ $„ 0  „'  ƒ& 0  „' –‚/ qua trung bì = 65 ‘Z $C6$M$$„0 „'ƒ&0 „'–‚/U 6'O H 66 Hình3.10. 4œDY7 ‰-H$; &¡ –‚/!?Y62GPKD $W6$„ 0 „'ƒM$6 76 Hình 3.11. ˆŸM$C6´ž›2ƒH= ¶‚EO(/( 82 Hình 3.12. ˆŸM$C6´Š›2ƒH= ¶‚EO'6 ››6G6 83 Hình 3.13. ˆŸM$C6´]›2ƒH= ¶‚EO2?$„¡6‰·2 84 Hình 3.14. ˆŸM$C6´]›2ƒH= ¶‚EO"¶‚ 84 Hình 3.15. ˆŸM$C6´]›2ƒH= ¶‚EO2M’–‚/G2 EF 6 $C6#^$?2EY6 ƒY&2U &Z@ ƒ>$ 106 Hình 3.25. 4 œU  MGDG  YEO$7‰>2M’–‚/G2 EF 6 $C6#\$?2EY6 ƒY&2U &Z@ ƒ>$ 106 Hình 3.26. 4 œU  MGDG  YEO$7‰>2M’–‚/G2 EF 6 $C6#€$?2EY6 ƒY&2U &Z@ ƒ>$ 107 Hình 3.27. )%‚.{-$U U0>33}" 34" 110 Hình 3.28. *$ƒ¯œ'   G $¡6$ ©–‚/Zœ ;11±¸ 110 Hình 3.29. 4 $ ©–‚/G2   $¡ 112 Hình 3.30. 4œDY7 ‰- &¡ EG2$C6$M$ H$ F$W *¢< 121 Hình 3.31. 4 $2 œ ;-  6G  Y$C6\ H$¢"EO/– 123 Hình 3.32. 4 $2 œ ;-  6G  Y$C6\ H$""EO¢" 127 1 56 7 ž4ƒž• •-ƒ1ž, 12 1&Y B4U• -'" B@3 ) F3 # 34U0«" W[Ó 3 " %‚ •" 346")}3 ^% ԃ.«U%<"3 U@"1E•Õƒ –334^"3 2" š<" <" -™" 4|ƒ#&virus Hž4ƒž•12-|3š<" ƒ ©š>".E)35-3 F0¢ - 80 % dân châu ÂUÓ3Ì1<" ×-¢) /U¼)Ñ")'& }"" «U46" £34" Eƒ•?03 'B2 50 £34" Eƒ•" "&")ˆ16"U'.>"B4U•"20 ž&3©) 7)03>3 >! ‡ØÙÓ3Ì1<hž4ƒž••" #™) <".7" 2"3 734&"•;)–)š<" 1/0U' ." 35"  #™) "20 "'0 <"  B6- -2" "Ú& do virus ž4ƒž• ">U % +" .E).«U34J3 5 £š<" " /"36"ƒ –3B2¥ £š<" " /"3–ƒ –3•Õ3Û vong [52]. Aciclovir 12-|3#$") F33©" Eƒ)9'')d nucleosid - guanosin có tác #™" -Y"  B2 ) (" 1() 346" )–) B4U• /0 š<"  ¢ " š'& {- Herpes simplex 1&YB21&YÓ Varicella- zoster, Epstein-Barr và Cytomegalo. Ngoài ra #E)) F3"20 )Ñ")ˆ3–)#™"7)) >B4U•B6-'"ACV 7)) >) ("1() U–345" •" 3©" EƒW[)9'B4U•% ) œ",/-" @ƒB2&3>š2& [69], [3]. Tuy nhiên 3 U;) )ˆ3 '"š–"3 ?""‡-Ù"6"">U#±"#Y" 3 U;) U !) 3 5 ƒ ? U;" " «U 1S" 34&" "20 ‡²- 1S"ÙÓ /0 " «U ƒ «" ƒ 7)) &š<" " /"Ó )9'WH% +"3 ^#U0345 "{".|3 U;)-&"-U;"3Y"}3–)#™"#&3 U;) )ˆ.|3'"34&")?"!) 1$"#SU.«U Y") >Ó1Y)ˆ3X" 3 F-%‰-[13]. HFƒ3 U3 U;)U'."36U &–) @-B2% +" &2"3&2"‡’[."U;"3D.>"20%) [69]. ^% ) ƒ ™)" Þ" Y") >%^346"Ó34&" }") ™)"-U'.Ú)ˆ" «U" 6")7U )?3 <"3X" 3 F-B2š2&) >)–) <%^-•&–3?ƒ ˆ"WH" Ë-)?3 <" ’[ )9' #E) ) F3 "20 U0 " 6", 346" 3 > ! -! )ˆ -|3 Ú" Flamel Technology •?" ,UF3 B6" ACV GPKD ‡š<3 #E) ž"B4Ù –) )} •¢ 34&" "!) <" "'0 B$" ) Ì •?" ,UF3 )–) #Y" 3 U;) U !) ) 7' WH "  viên "‰"Ó 3 U;) -ß — S" 1!" )–) #Y" 3 U;) )9' WH 346" 3 J 34" 12 " @ƒ "&YÓ) ')ˆB6"GPKD U)SUB«•Û#™")–)#Y"3 U;) ) 7'ACV là 4F3 1!"Ó " F3 12 " Þ" .E3 )ˆ #J)  š<"  }" "Þ' 34&" " «U 34" Eƒ 2 aciclovir ƒ ? .E) #±" 3  '" #2Ó BX #™ .«U 34J .^ -×" #J)  % +" 3– ƒ –3ž4ƒž••-ƒ1ž,ƒ ?#±"3 U;)3 –" &Ô)#2 }"H5B@0B<)" 6" )7U35-4'#Y"3 U;)U;"GPKD có SKD ca&Ó)ˆ3 ^7"#™"B2&3 A)3×" •?",UF312BF".«)Fƒ3 >3Ó)ˆ‚" ã'34&"1ã" BA)" 6")7UB2•?",UF3 #E)ƒ „- ÁUF3ƒ –33D3 A)3>346"Ó) œ"3+3>" 2" bc$)d*ef+gjke$lvà mo*$c)op)*$q$rst*cviên nang aciclovir }oest*cq~ksj) B!các -™) tiêu sau: 1. BO2$ =$ viên nang aciclovir 200 mg GPKD ^\ . 2. 4M M*¢<$C6EF6 aciclovir GP¢<YO2$ GF; E   '. ^3 A) <"-™)36U.«4'Ó1U@"–"š'&{-)–)"|#U"•'U 1. ‚& „'$C6–‚/+ 2. « ‰> $# W$YO2$EF6 –‚/\__' )(¢<+ 3. « ‰> U GYO2$EF6 –‚/\__' )(¢<ZU '#Š___ EFEO@¨ „F $ ©$„= + 4. 4M M;¬D+ 5. 4M Mƒ&‰‹ viên nang ACV 200 mg GPKD trên chó. 3 CH/"8E 1.1. ACICLOVIR 1.1" " %)e‚ƒ*c„…aciclovir      +"3 7)ƒ /"3Û 18 H 11 N 5 0 3 ’ ;1E"ƒ /"3ÛÓ 6"% &' ()-amino-9[(2-hydroxy ethoxy)-methyl]-1,9-dihydro-6H-purin-6on [69], [1].     Aciclovir )ˆ)–)3X" ) F31‚ ˆ'•'U[1], [69], [13]: - DY"š|3%>33" -2U34", X33'"34&""!)Ó4F3ít tan trong alcol, tan 3A #& 34&" )–) #U" -+ #-ž3 01 •U1ä&,i#Ó 3'" .E) 34&" #U" #J)  %«-B2')#1&Ú"|3'")9'WH34&""!)3DÓ.>"1,6 mg/ml ¢ " <3 .|  - 25 o B2 Ó -”-1 ¢  o B2 ƒ ™ 3 U|) B2& ƒ -+ 34"‡š?"Ù - RFt b«n vÞ"Ó34&"-+34ng ki«m ©".J"  }"34&"-+34ng acid. -  <3.|"ˆ") ?0% &?" oÓ•'U.ˆšJƒ /" 90. - Aciclovir )ˆ Ë"•;ƒ /"10 pKa 1 = 2,41 ± 0,27 pKa 2 = 9,06 ± 0,88 -  ž&ƒ /"1&Y•" #E) ()ÓWH3 U|)" ˆ-[13] )ˆ3X" 3 F-%‰- 4   aciclovir !"# o$ % &$'( )*+  ,[13] STT pH ‡}ˆ*‰&cŠ&‹Œ 1 1,2 > 3,5 2 4,5 ~ 2,6 3 5,8 ~ 2,3 4 6,8 ~ 2,4 5 7,4 ~ 2,5  1.2. H-/ %0&4,+&5 aciclovir 6,%7 507-2 [13] STT pH ,p}$Ž&g)+q)l*‰# app , 10-6 cm/s) 1 7,4 0,12 2 7,4 0,25 3 7,4 0,43 4 - 1,08 5 6,8 1,26 6 6,5 và 7,4 2,00 "9':;   - SKD 3 ž&."U;"3 Fƒ B2% +"©".J" Ó% &?"20% 7)" % +"12-?"  ¢".>" Fƒ3 U3 U;) [3], [69]WH.E) Fƒ3 U) 90>U 3 ž&)}) >% U>) 3–"3 ™.|"Ó Fƒ3 U) @- và không hoàn toàn [13]. -  '".Y3 max •'U% U;"12Ó– [69]. - — /"š;aciclovir ƒ /"š;34&"#J) )}3 ^B2)–))}U'"" "Ú&Ó 3 @"Óƒ ©Ó4U|3Ó'"Ó1–) Ó)}Ó3Û)U"Ó"6--Y)Ó#J) /-.Y&Ó"!)-3Ó3 90 3" #J) Ó#J) "Ú&390{".|34&"#J) "Ú&390.Y33!i 50 £"{".| U0>3 3}"¹6"%>3ƒ4&3ž"3 FƒÓ% &?" % (9 - 33 £Ù U;)U'.E)nhau 3 'B2ƒ /"š;34&"•Þ'-ëFƒ3 UWHU'#'•'U% š+3 "4F3X3, 3U0" 6"% ?"" Fƒ3 U#E)) F3)ˆ3 ^3"16"% 3 '0.©3 2" ƒ S" )+"3 7)3 U;)[1], [3], [69]. 5 -  U0^" ˆ'B23 ?34D î— S"1!"3 U;).E).2&3 ?U'3 @"#!#Y"% +"š>".©9carboxy methoxy methyl guanin 12 ) F3 ) U0^" ˆ' .–" %^ )9' aciclovir, ) >-% &?"² £3©"1E"3 U;)3 F034&""!)3^U[69]. î '"š–"3 ?Çš<" " /")ˆ) 7)""3 @"š5" 3 "Ó3  '"š–"3 ?)9'WH% &?"2-Ó¢34ï•}•" 12²Ó)Ñ"¢š<" " /" •U03 @n mYn t 1/2 ðñÓ [3], [69]. <=> =': - Aciclovir 12-|3) F33}"3A"U)1ž&•#Ó)ˆ3–)#™") ("1()346"3> š2&" ×-B4U•ž4ƒž•WH)ˆ3–)#™"% –"1YH typ 1 và typ 2, VZV, EBV, Cytomegalo [3], [69]. - ^ )ˆ 3–) #™"Ó aciclovir ƒ ? .E) ƒ &•ƒ &401 ˆ'Ó 1S"  #& 3 0-#"%0"'•ž.Ô) š2&B@3) 9.^3Y&3 2" #$",UF3#ƒ &•ƒ '3B2 34ƒ &•ƒ '3¼1A))9'3 0-#"%0"'•ž¢H-Y" % &?" }"1S"•&B! ž"ò0-)9'3>š2&B@3) 9nên aciclovir .E) &Y3 ˆ' SU" ) ("1()34&" )–)3>š2&" ×-HAciclovir 34ƒ &•ƒ '37)) >3©" EƒW[B4U•B2•A " /" 16" )9' B4U• -2 % +" ?"  ¢" 5 .>" ) U0^" ˆ' )9' 3> š2& š5"  3 " [3], [69]. ? @; Aciclovir .E)) Ì.J" .«U34J34&")–)34" Eƒ•'U - «U34J% ¢.SUB2#Aƒ Ñ"" ×-H30ƒB230ƒ¢#'Ó"6- -Y)Ó3 S" %" B2•" #™)ÓB6-"Ú&#&H [3], [69]. - «U34J" ×-ž4ƒž•ò&•3ž4)Fƒ3X" ¢-3Óƒ ©, 3 S"%" [3], [69]. - «U34J% ¢.SUB23–ƒ –3 ž4ƒž••" #™) [3], [69]. - [A ƒ Ñ" B2 .«U 34J " ×- B4U• ¢ " •U0 ?- -×" #J) Ó )F0  ‰ƒ)}U'"Óš<" 3 90.@U [3], [69]. 6 A /  @; B C $  -  ;") Ì.J" ) &" Þ"š<" " /"-$")?-B!3 U;) [3], [69]. - Th@n tr(ng v!i bt t9a aciclovir trong th@n [3], [69]. #=> + % %,/ Aciclovir có th^ gây ra m|t s; tác d™ng ph™ sau: - Có th^ gÔp bu{n nôn, tiêu ch?0Ó"+"Ó.'Uš™ng, n©i ban, các ph?n 7ng v« thS"%" " ) ˆ"-Ôt, ?o giác, bu{n ng9 [3], [69]. - ng tiêm truy«"3ã" -Ych có th^ gÔp các ph?n 7"" B6-ÓB6- 3ã" -Ych ¢ vJ trí tiêm [3], [69]. - Kem bôi: Có khi gÔp c?m giác nóng bŽng hay nhói nhë ¢ vJ trí bôi kèm 3 ž&š'".Ž nhë [3], [69]. D'( =E  WH .E) #±" 34&" .«U 34J )–) 34" Eƒ š<"  #& H U' )–) ."% –)" 'U" 34'-3Óš+3Y) ÷ÓU;" &Ô)36-3ã" -Y) 34&")? ƒ Ñ" B2 .«U 34J š<"  ž4ƒž• [Y" 3 U;) 36- 3ã"  -Y)  .E) •Û #™" .^ .«U 34JB6- "Ú& #& H ¢ )? " š5"  3 " B2 " Þ" " •U0 ?- -×"#J) Ó)–)34" Eƒ" ×-H &Ô)HøH¢3 S"%" 34U"}"Ó"| 3Y" &Ô)š<"  ž4ƒž•"Ô"¢)–)"6--Y)[69]. Tuy nhiên, •Û#™"WH34&".«U34Jԃ-|3•; Y") >"  Fƒ3 U WH U' ." 36U ˆ' ) @-Ó ƒ ™ 3 U|) B2& 1«UÓ % +" ©" .J"  B2 hoàn 3&2"’ &?"¥£1«UU;"šJ3 ?34DU'ƒ /"[13]Ô)#±B@0 ."U;" B$".E)) Ì.J" " «U }"."36-#&"""D'.E)"U0)}/0viêm, B6-3ã" -Y) ¢BJ34X36-Ó36-3ã" -Y) " '" )ˆ3 ^/04'%>339'WH¢ 3 @"4" Eƒš+3Y) ÷Ó Fƒ3 U3 U;)4F3) @-|3•;" 6")7U) & 3 F0)–)3 U;) š+"&2#') 7'WH)S"%>3 Eƒ3 6-) F33"3 F-[48]. ’ +"."#±""2&¢346")ˆ ! SU >3B$"12)–)#Y"š2&) >U!)  1.3. I-/0&=': aciclovir STT =),}s‚•e %*cgjke$l 1 Herpevir 2 Vitrazolin LL Kem 3 Zovirax 4 Zoraxin 5 Aciclovir Stada Viên nén j&‹‚•*c $jpr*–+Ž} 200 mg Sanofi Synthelabo VN 5 %, tuýp 5g +"30[—ØU> Viên nén Viên phân tán ÷"#J) Kem ß34'-3 |3ƒ '36- Viên nén Kem 200, 400 và 800 mg 200, 400 và 800 mg 250 mg/5ml, chai 125 5 %, tuýp 2 g 3 %, tuýp 4,5 g 200 mg/5ml 200, 400 và 800 mg 5 %, tuýp 2g và 10g Viên nén Kem 200 và 800 mg 5 %, tuýp 2g, 5g Stada –VN Samchully Pharm 6 Vacrax Viên nén Kem 200 mg 5 %, tuýp 5g 7 Hutevir Viên nén 200 mg Glaxo SmithKline Valor Pharmaceuticals Hutecs Korea 8 Aciclovir Viên nén 200 mg Pharmaceutical Sinil Pharmaceuticals 9 Herpex Viên nén 200 mg Torrent Pharmaceuticals 10 Genvir Viên GPKD 600 mg Flamel Technologies 1.1""(‡}p*c$)d*ef+er)}$),*$Ž—}$+aciclovir ˜+ˆm‚™*c})d+$šˆ ACV )ˆ3X" 3 F-%‰-Ó3 /"#SUB2)ˆ% ;1E"ƒ /"3Û3 Fƒ‡ùÙ "6".E) Fƒ3 U) 90>UU'% ž ¢16"š2&[55], [66]Ó) Ì) >--|33û1< 4F3" Ž•&B!các ." Fƒ3 U% –), #&.ˆ’[."U;"3 FƒB2% +" ©".J" [69].  &.>""'0Ó)ˆ% –" «U" 6")7U.E)3 A) <"B!-™) .X) )?3 <"’[."U;")9'WHš'&{-3©" Eƒ)–)3«"#E)) F3 &Ô)áp #™"%†3 U@3)+"" < <".Y.