Transcription of (局)薬 - piis.pref.mie.lg.jp
1 22 6 28 . ( ) .. ( 1 ). 22 6 17 .. : lll . ( ). 14 9 . 47 17 2 . JO 0210001 .. ( ) .. ( ) . i . ( .. 1.. 1 . 2.. Bl . ` . r . 3.. 1. A.. 1: ( ) . i 1: : . ( ) ( ). : . (1) .. (2) ( ) .. 1 1. (3) . 18 H 24 . (Q&A) . 2 . Q&AC 5) .. 2. ( ). (1) ( ) ( ) . Ill . (2) .. 1 . 1 . 1 00 mg 1 00 .. 1 1.. XXx omg xXX.. omg .. ^ Omg . 2 2. 1 1 . ( ).. ' _12 . 1.. _ . ` . " . 1)1 1 1)1 1 . 2) ( ( ).. ) , ( ) .. , . ( . , , . ) . _ ] , SE .. : .. , . E l ral . : ( ) .. 3. 2: ( ) . ( ) ( ).. 1 .. (1) .. ( . ). (2) .. (3) ( ) .. 2 ( ) '. (1) ( ) . : (2) : . 2 . 1 . 1 00 mg OO mg .. : XXX O XXX 0 .. Ong . Omg Omg .. O .. Ong 1)1 1 1)1 1 . 2)( ) . ( ) , .. ( .. ( .. / ) . 1 . ( ) . ( ) . 5. 3: .. (1) .. (2) 12 2 8 39 . 1. (1) ) .. 21 ( ). (1) .. 3 1 : : . 1 lg . XXX , 100mg 1 XXX 100mg . /7 . omg Omg . " . ,g mg 2 5m .. F DEF 15m ( WW ).
2 ABC 3ma . DEF 15m .. innn . ) 1 . 1: WWW.. i :001 . l: .. 1: 1 .. 7 DEF3 . loO/. j T > FE > .. XXX 10 0 kg , ' . 7 . 80 0 kg , . 8,O k8 . XXX 100 kE , l ; . 5k (500L)" WW o5 (5 . , 5 D" , 5 .. : (411 ). cJn3h , DEF 015k , . F005kd .. 1 . 1.. 7.. BI .. B. 1 . 1.. 2.. I . (1) ( ) .. (2) . ( . ).. (3) . 1) ? 1. 2) . 3) ( ) .. (4) . 1 .. (5) . 1 . 2 . 711 ( ) ( . ) . 1: . 1 1: .. 1 .. (1) 17 2 10 0210001 .. (2) .. 1) .. (, ). ( ). = .. : 2) . 3) . 10.. 4) ( ) . ( ) . 2. ( ). (1) . _ . (2 .. , . (3) . ( . Fp5 . ) .. (4) . 11. 1-2: .. ( ) . 1.. (1) .. (2) t . , . 17 2 10 0210001 .. (1) .. (2) .. (3) .. 1) .. 2) .. ( ). ( ). (A B ) . 12. A . B B .. 2. ). ( . (1) .. (2) . 0 . (3) .. R UV ( ).. ( . o . ). (4) 1 . 13. 1 1-1 1-2 . l . Stcp l stcp l . [1] 016 , [ (6 9kg) , [1] (216k , E2] (6,k , (118 (11 8 k . (60L) F25 24 f60 Ll D5 7.
3 40 ,8 10 , l140 ,8 10 MF , . E3] E3] .. 40 E4], l140 , E4].. : . StCp 3 : l140 , l14 ) . [4] [4] . Step 4 Stcp 4 . [4] [4] .. =. StCp l [1 Step l [1] .. ( ( . ) ) . (lRl (HPLC . 4 (H 0 ) . 95% (HPLC) 4% (HPLC). 95 (HPLC). Step l ] Step l [2] .. ( ) ( ) IR . (IR ) ( ) . 97% ( ) 2% (HPLC) . 3% (KF) . % (IIPLC) /JF. ( ). Step l [3] stcp l [3] .. ( ( . ) ) . ). ( 1 . (TLC) (D . (IPLc ) 4 / (HPLC) . 10% . 10% . 14.. = . : . ) . ( . S"pl [l] . , IIPLё . : [2] . Step l . ,R .. lR : . 0 HPLC .. [2] .. '.. l [3] . ( ) . : c IR . I Step 2 [4] . ICP . 1 . Step 3 [4] .. 1 .. 16.. 2: . ( ,PII ) . ( ). [ ] Step l Step 2 1 Step 3 Ste,4. 11&12]( ) [31 [4] ( ) [5] . Step 5 : 16] 161. [ : ]. , s pl step 2 SteP 3 Step 4.. [1]&[2] ( ) . 31 14] ( )[5] . Step 5. 161 [61.. 1 , .. T .. : , ( ) .. 1 .. H .. ol . = . 2.. I B l .. (1) ( ) . 71/ '.))
4 (2) , (3) . 1) .. 2) . 3) ( ) .. (4) 7 . ( ) . (5) : . 1 3 ( ). (1) : . (2) . ( ) .. 1 . t .. (3) . 18. 2 . ) : [5] . 1 . Step l Stcp l . [1] (216 ) , E21 (69 [1] (216k . , : [21 (691 . , (118 (H . ( Ll F25 4 (60L) F" И . , . , .. r30 C ,8 10 , 30 ,8 10 , . [3] [3] . Step 2 Stcp 2 1. Stcp l [3] (aa kgl A (bb Stcp l [3] (aa tgl AFtbb kgl . A (cc L) (oc L) ..( . ) ( . 10 / " 10%' (2Ю. (21Xl . L) 10 /." 10%F Ll xx ' 100/0" pH . pH J pH t .. : .. , 00 , E4] .. l140t , [5] 0 , [5] .. 40 , [6] 40 , [6] . :11 1 .. Step 5 Stcp 5 . F40 , r40t , ( . 10 E63 10 ) [6] . Stcp 6 Ste,6 , [6] [6] . " . " . Stcp l [1] Stcp l [1] .. ( ( . ) ). (i (IR) . 4% (HPLC) 4 /0 (HPLC). 950/ KHPLC) 95% (HPLC). Stcp l [2] Step l [23 .. ( ) ( ) . 19. 1 . 8% (HPLC) 8% ( IPLC). ,0% (HPLC) 90 (HPLC). Stcp l [3] Stcp l [3] .. ( ( . ) ). (D (IRl 4 /. (HPLC) 4% (HPLC).)))))))))]
5 1000 ppm (GC). 1 O ppm (CC).. 93% (HPLC) ,3% (HPLCl Scp 3 [5] Stcp 3 [5] .. ( ( . ) ). (D (IR)..2 /O (HPLC) 2% ( C). 890 ppm (CC) 890 ppm (GC). 95 (HPLC) 95% (IIPLC). Stcp 5 [6] Stcp 5 [6] . '.. : . ( ) ( ). 04 HPLC) 04 /O (HPLC). 1 03 (HPLC) 1 03% (HPLC). 01% rHPLC) l% (HPLCD.. Stcp 6 [6] Stcp 6 [6] .. ( ) ( ). 040/ (HPLC) 04% (HPLC). 300 ppm (CC) 300 ppm (CC).. pH . PH : .. t . 20. 31 . ( . ( )14] . 1.. B l .. ( ) ( ) .. (2) . (3) . 1) . 1 2) . 3) . ) , .. (4) ( ep l) ( ). ( 131) . ( 141) .. (5) ( Step l) ( ).. ( . ( ) . (6) ( [31) ( . : [31) 1 situ .. 21. 2 ( ). (1) .. (2) . 1) .. 2) (A ) . A . A . (3) . 22. 3 . ) : [4] . 1 . Stcp l Stcp l . [1] 016 , [4 90 , [2] (690 . [1]r(216 . , , (1l o kgl . (i18 . (600 25 24 (60D 25t 24 . ' I: .. (50L) . 10 /." (30 (50L) (30 . 1) Ll [ 1]l t , lnslttl .. 00 ,8 10 . L) 1] . , E31 D J i.))]
6 XxO/. w% .. HPLC . Stcp 2 1 Step 2. Stcp l [3] ( 22k21 , lo . K200 stcp l , 1 . (2t10L) . L) . (4000 . 25 (400L) . F25 4 .. 4 , [4] , [43 .. l140 , [5] .. 40 [5] .. , C 0 , ( . lo . ) [5] 10,m ) [5] .. stcp S . [5] 1` .. " . Stcp l [i] Stcp l [11 .. ( ( . ) ) . (IRl (IR). 40/. (HPLC) 4% fHPLC). 95% (HPLC) 95% (HPLC). Stp: E2] Ste,1 E2] .. ( ) ( ). 8 fHPLC) 8% (HPLC). 9 tHPLC) 90 / KHPLC). J ) . ` . 23.. ( . ). (Rl (HttC). llxlo,pm (CC).. 93% (HPLC). Stop 2 [4] Step 2 E4] .. ( ( . ) ). (ID (IRl 2% (HPLC) 2% (HPLC). 3000 ppm (CC) 3000 ppm (CC) . 0 . 95% (HPLC) 1 O Dllln . 03) .. 95% (HPLC). Stcp 3 [5] Stcp 3 [5] .. : . ( ) ( ). 04% (HPLC) 04% (HH ). 1 03 (HPLC) 1 03% (HttC). 01% fHPLC) 01% ( 0.. Step 4 [5] Stcp 4 [5] .. ( ) ( ). 10 ppm (CC) 1000 ppm KCC).. 300 ppm (CC) 300 ppm (CC).. [3] . [3] i : : . 13] . O Sttp l hsitu.
7 141 Step 2 [31 .. 24. 4: . ( . ). [ ] Step l Step 2 Step 3. [1]&12]( ) ( ) [4] . Step 4. [5] [5]. [ i Step l Step 2 Step 3. [11&E2]( ) FHl ( )E43 . Step 4. [5] ]. 1 . B l .. (1) ( ) `. , . (2) . 1) . 2) . 3) ( ) . '. (3) ( [31) .. (4) ( [31) . ( ) . 2. ( ). (1) lA ) . A lll . A .. (2) 1 . 4 1 . ) : . [4] .. Stcp l . Stcp l [1] (21 6 kg) , [2] (69kD , [1] (21 6 kgl , E2] (6 9kg) , (118 ) 018 ) . (600 F25 24 (60L) 25 24 .. (50L) 10 /." (30 (50 Ll 10 (30. L) [3] PrE . L . xx% vv /. 5 3 . HPLC = , (10 . 40 ,8 10 . L) . [3] . Step2 Step 2. cp l , 1 (2000 31 ( 22 , lo /O" . Stcp l (2 CXl . (400L) L) 1400L) 25 . 25 4 .. 40 . , [4] 40 , [4] .. Step 3 .. 00 , [5] 40 , [5] .. Stcp 4 .. l140 , ( 40 , ( .. 10 m ) [5] 10 ) [5] . Stcp 5 Stcp S . [5] [5] . " " . Stcp l [1] stcP l [1] .. ( ( l . ) ). (IR) (ID. 4% (HPLC) 4% (HPLC). 95 oPLC) 95% rtIPLC).]
8 Stcp l [2] stcp l ] .. ( ) ( l ). 8% (HPLC) 8% ( C). 900/. (HPLC) 90 / (HPLC). s ol 3] .. 26.. p] . 13] ( . p] [31 .. 27. C.. 28. C.. 1 : . 2. : .. (1) ( ) .. (2) . ( t ). 1 . ( 3 .. ). (3) ( .. ). 29. 2.. 1: . 1 1: .. 1.. ( .. (1) : . (2) 17 2 10 0210001 .. 2 23 . ( .. ) . ' . (3) .. 2. ). ( . (1) . ( ) '. (2) . 30 . 1 1 1 . 1 . : : : . : : . ng mg , .. : , : : . , , , , , : , , .. > > . > . > > . > > . > , > . > . > > . > > . > > ;. > > . , PTPa , . " , " " .. , .. , ,PrP . 5 PTP I 5 . > > .. I 5 IF , 51 , . (X Y. o , o , kPD.. t .. 31.. 17 2 10 0210001 . 2 23 .. PTP .. 32. Fl1 12: . 1.. C l t .. (1) '. (2) 17 2 10 0210001 . J . 2 23 . ( . L/ . ) . (3) ( . ( ) ) ( . , ). 2 rtL( ). (1) . ( ( )1 ) .. 1 .. (2) rll . 1 . 33. 1 2 : . 1 . : : . : : . mg J mg J . : , , : , , , . , , , , , , .. > : > : . > > . > > . > > . >.)))
9 > > . > > . > > . > > . 10 1 IIC,1 . 111011 1 1 . ' l > > . , . P rP PrP , . * . , ". " ' . ild ;7: . t t . 230tl . ' 1900) . ,P rP ,PIP = . ittI ,, 11, m : 1 = , . 0"1'1 11 : 0211 1 1 = . 1 . ` .. > > . : . 1 I 1 . _111 ;=1 = = . ( . t . ` . 021o001 t,1. ` "11: . ,1 ..0 . ) .. 17 2 10 0210001 . 34.. 35. 2: . 2 1: . 1 . C l . rlI . (1) .. ). (2) ( ( ) . ) ( . ). (3) . (4) . : .. 2 ( ). (1) .. (2) ( 17 2 10 0210001 . ) .. 1 . (3) . lll .. (4) . 36.. 2 2-1 1 . 1 . : : . : : . mg f . : ,pH , : ,pH , . , , , , .. > > . > > . > > . X , X , . X , X , Xu, u, . X X . XL J X . : 1 o45 m 1 45 m X " X =" . i . ,pHa . >pHm : . 10 1moL" ,pH 60 0 1mo1/L" ,pH 60 . , OL . 1 , FOLJ . ,F2 2 ,F2 2 . > > . , : , : ( . , rn3 : , : , ` , : ) .. , . , (05mL. lmL 2mD 3 (05mL,llnLA( D 31. > k > . , , . > > . : . 1 1 .. 2 pH:55 65 21 pHiS5 15. 3 (X kP 3 , (X kPal.)))
10 ,XX= g ,XX g (05mL), yY g(1 L),Zz g (0 5mL),yY= g(10mL),ZZ g (2 0mLl ( [) fA6. 37.. ( ) : .. ( ) .. 38. 2-2: ( ) . 1 .. (1) ( . o ) . (2) ( ) . 2. ( ). (1) ? .. (2) . ' . (3) .. (4) . 39. 2 2-2 . 1 . : : . : : . mg r Ing .. : ,pH , ,pH , . , , , , .. > > . > > . > > . >pH >pH . : 21 1 11 : 1 1 .. " . > > . 50mL 511mL . (50mL) , (51hnL) , . , , .. 3 ', . '= 3 . > > . , , . > > .. 1 1 .. 2 pH:55-65 2 pH:55 .. 3 ,500. `5. 3 . ,500. 51 5mL 51 5mL .. ABS .. 40. 23: , . C l .. : (1) .. ( ) .. (2) '. (3) ( ) .. 2. th_( ). (1) (3) ..(2) .. ? ? .. (3) 1 . 71 . 41. 2 2-3 . 1 . : : . : : . mg r tng . : ,pH , : , , , . , , , , : .. > > . > . > > : . >pH >pH . , = 1 . l t 1 1 . _ " . = . > > . 5m 511mL .. 3 31. (50mL) . `50mLl . > : > . , , . > > .. 1 . 11 .. 2 pH:55 2 pH:53 65. `5. 3 ..500 : 3 ,500. 51 5mt 515mL .. ( ) . (3) .. 42.)]
