???? ???? Target-oriented Preparations

1
???? ???? Target-oriented Preparations
????? ??
2
????

• ????????????????
• ?????????
• ???????????????????????,?????????????
• ??????????????????????????????????????????????,???
  ???????????
• ????????????,????????

3
Main Contents

• ??? Introduction
• ??? ????????????
• ??? Liposomes
• ??? Nanoparticles
• ??? Emulsion and microemulsion
• ??? Microspheres
• ??? Active target-oriented preparations
• ??? physi-chemical target-oriented
• preparations

4
Introduction

• ?????? (target-oriented drug delivery
  system,??TODDS)??????
• ??????????????????????????????????????????????
  ??????????????

5
target-oriented drug delivery system

• ??????????????????
• ?????????????????
• ????????????,??????????

6

• TODDS???20??70??,??TODDS????????????,
• ????????, TODDS???????????,????????????????

TODDS
7

• 1995??????????????????
• ??????????????
• 1984????????TODDS??,?????

TODDS
8
???20??80????TODDS???

• ??????????????????????,?????????????????????

TODDS
??TODDS?????
9

• ??-????????
• ??-?????

????? ???? ???????
?????? ???????
10

• ??TODDS???
• 1. ?????????, TDDS?????
• ? ??????????????
• ? ??????????????????(??????
  ??????,??????Kupffer??)
• ? ?????????????????(?????)?

11

• 2. ?????????,TDDS???????
• ???????
• ???????
• ??????????

TODDS
12
???????

• 1 ????
• ?????,????????????(microparticles drug delivery
  systems)

• ??????????
• ??????????

13
???????

• 2 ????
• ?????????????????,??????????

PEG?
14
???????

• 2 ????
• ?????????????????,
• ??????????,
• ?????????????

15
Cell
Micro- particles
???????????????
16
???????????????
17
???????

• 3 ??????
• ??????????
• ??????????
• ?????

? ?? pH
18
???????

• ??????(macromolecular conjugates)

liposomes
polymeric nanoparticle
Microparticles systems
block copolymer micelle
dendrimer(???)
19
??????

• ??????(macromolecular conjugates)???????????????
• ?????????????????????????????????
• ??????????????????????

20
Macromolecular conjugates
21
Microparticles drug delievey systems

• ????????????,??????????,????????
• ?????????,?????????????????,???????????
• ????????,??????????????????,?????????????????

22
(No Transcript)
23

• ???
• ???(liposomes)
• ???????
• ????????
• ????????

24

• ??????
• ??????(polymeric nanoparticle)
• ???????????(biocompatible polymers)??,
• ???10-1000 nm?
• ???????????????,
• ????????????????

25

• ???????
• ???????
• (block copolymer micelle)
• ???????????
• ??????????,
• ??10-100 nm?
• ???????????,
• ????????????????

26

• ???
• ???(Dendrimer)????????????,????????????????
• ??????????????
• ????,?????
• ?????,???????
• ??????????????

27
???

• ??????????????????????????,??,????????????????

28
????

• ???????
• ???????
• ??????????

TODDS
29
TODDS ????
(?)??????

• ???????????????????
• ??????,??????????
• ????????
• ??????(?????)??????
• ??????????

30
TODDS ????

• (?)??????
• ??,??????????????

Liposomes
Micro- emulsions
Microspheres
Nanoparticles
31
(No Transcript)
32
(No Transcript)
33
(No Transcript)
34
(No Transcript)
35

• ?1 ??????????????????????
• ? ? ? ?
  ? ? ?
• ??? ???
  ???????????
• 
  ?????????
• ???? ?????
  
• ?????????? ????
• ???? W/O?? ?????????
• ???
  ???????
• ? ? ????? ???
• ???? EC?? ???????????
• ???? ??
• ???? ???? ??????
• ????? ??
• EC??
  ???,???,?????
• 
  

36
TODDS ????
????????????

• ??????????????,???????????????????
• ????50nm???????????????
• ??7µm???????????????
• ??7µm?????????????????????????,??????????????????

37

• ????????????
• ????,???????
• ? ???
• ???
• ?????
• ????????????????
• ????,???????????????
• ???????????????

TODDS ????
38
TODDS ????

• (?)??????
• ?????????????,?????????????????????
• ????????

Modified liposomes Modified micropaticles Modified
nanoparticles
????????? ??????
39
TODDS ????

• ?????????
• ?????

????? ????? ?????(?????????)
40
TODDS ????

• ????4µm?
• ??????????
• ???????
• ??????
• ?????????,
• ???????????????????

41
(No Transcript)
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???? (Prodrugs)
TODDS ????

• ??????????,
• ???????????
• ????????

43
TODDS ????

• (?)????????
• ?????????????????????????????
• ??????????

?????? ??????
??????
pH???????
44

• ??TODDS?????
• TODDS??????

?????
???
???
???
45

• ??TODDS?????
• TODDS????????????????????
• ???????????????
• ???????????????????(??pH??)
• ???????????????????????
• ?????????????????????????

46
??TODDS?????
?????? ???????
47
????
??TODDS?????

• ??????????????,?????????????,????????,????????????
  ??????????????????????

48
????
??TODDS?????

• ??????????????,???????????????????????????????????
  ?????????????,??????????ß-?????????????????,??????
  ????????????????

49
????
??TODDS?????

• ????????????????????????????,????????,????????????
  ???????????,??????????????????????

50
????
??TODDS?????

• ??????????????????????????,???????????????????????
  ?????????,??????????????????,???????,?????????

51
????
??TODDS?????

• ??,?????TODDS,?
• ?????????
• ????
• ??????

52
TODDS ??

• ??????????????????
• ?????,
• ??????????
• ??????????????,
• ?????????

53
TODDS ??

• ??,????????????
• ???????,
• ???????????????????,
• ????????????

54
TODDS ??

• TODDS????????????????????????????????????????????,
  ?????????????????,?????????????????????????

55

• ???TODDS???

????
????
????
??????????
????
????
56
???????????

• ????????????????????
• 1. ?????(re )
• 2. ???? (te )
• 3. ???? (Ce )

57

• 1.?????(re)
• re(AUCi)p/(AUCi)s
• ??AUCi????-????????i??????????????,??p?s?????
  ?????????
• re??1?????????????????,re????????,?????1??????
  ?

58

• 2.????(te)
• te (AUC)?/(AUC)??
• ??te?????????????????????
• te???1????????????????????te???,?????
• ????te???????te???,???????????????

59

• 3.????(Ce)
• Ce(Cmax)p/(Cmax)s
• ??Cmax????,?????????Ce????????????????
• Ce???,???????????????

60

• ???????????
• TDDS??????????????????????
• ?????????????
• ?????????????????,?????????????
• ???TDDS????????

TODDS
61

• ???????????
• ????(gene therapy)??????????????????????????????,
• ??????????????????????????????????????
• ????????????????DNA??,??????????,???????????????21
  ???????????????????

TODDS
62

• ??
• TDDS???????????????????
• ????????????????
• ?TDDS????????????????????????
• ??????????????????????

TODDS
63

• ??
• ??????????????????????????????????????????????????
  ?????????????????????????
• ??????,????????????????????????????????

TODDS
64
??? ??????? ?????

• 1? ???????
• ????
• ??????
• ??
• ????
• 2? ?????????

65
Introduction

• TODDS????EhrlichP?1906??????100??,???????????????
  ????????????????????,??TODDS?????????????,
• ??????????????????????????,??TODDS??????????

66

• ?20??80?????,???????????TODDS,????????????????????
  ???????
• 1993?FlorenceAT???Jorunal of Drug
  Targeting,????TODDS?????,???????TODDS?????????

67
?????????

• ???????????????
• ? ????????(??????)???????????????(??????)
• ? ????????????????,?????????,??????????????????
  ?(????)
• ? ???????????????,???????????????????????(?????
  ?)?

68

• ????????,TODDS?????????
• ?????????
• ???????
• ????????

????????????????
69
???????????????

• ??????? ??????
  ????
• ??-???????????
• ????????????
• ???? ???????
• ????
• 
  ?????
• ??????,??
  ???????
• ?????

70
??????? ?????????
??????(??) ????? ?????
???(??????) ??????

• ??

????(???/???) ?????(???/???)
71
????????
??????
????
?????
?????? ??????
????
????
72
??????
?????????
????
????
Microparticles
????
?? ??
?? ????
??
????
73
???????
??????
????????????
???????????
??????
??? (??????)
??????
74
???????
??????
??????????
???(??????)
??????
??????
????
????
????
??
75
??????
??????
????
????
??????
Microparticles
????
????????
????????
?? ????
?? ??
??????
????
??
76
??????
???????
????????????
???????????
??????
????? (???/???)
???? (???/???)
77
?????? (???/???)
??????
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????
??????
????
????
78
?????? (???/???)
??????
??????
????
????
Microparticles
??
????
?? ??
?? ????
79
??
??????

• ????????????????????????????????
• ??????????????????????????????????????????
• ?????????-??????????????

80
TODDS?????

• ??????????????????????? ??????????????????????????
  ??,?????????????,??????????????????,??????????????
  ??????????

?????
81
???????????????????

• ????

???? ?????? ?? ????
82
? ????
????? ?????

• ??????????????????????TODDS???????????,???????????
  ?,?????????????
• ???????????????
• ????????????,??????????????

83
?????????????
84
????
????? ?????

• ?????????????(MPS)?????????
• ??????????????????(??????IgG???C3b,??????????)????
  ??????????

85
????
????? ?????

• ?????????????????????????????????
• ???????????????????????????????????
• ??,?N-??????????????????C3b????,??????????????????
  ??

86
????
????? ?????

• ?????????????????????????????????
• ??????????????????????????,????????????

PEG?
87
????
????? ?????

• ???????,???????,??????????(??????)?
• ??,???????????,?????????????
• ?????????????????????????

88
????
????? ?????

• ???????????????????????,?????????????
• ????????????????????,?????????????

89
????
????? ?????

• ??????????????????????(??????)????????
• ??????????????????????????????????
• ????????????????????????????????????????????????

90
????
????? ?????

• ?????????????????????????????
• ??????????????????????(???????????)??

91
??????
????? ?????

• ????????????????????????????????????????????
• ??,?????????????????????(??????)?
• ??????????(?????????),????????,????????????,??????
  ?

?????
92
??
????? ?????

• ???????????????(????),
• ???????????????

?????
93
????
????? ?????

• ???????????,????????????
• ????????????????????,??????(?????????????)
• ?????????????,????????????

94
?????????????
95
????
????? ?????

• ??????????????????????????????????pH??????????
• ??30nm???????????????,???50nm????????????????????,
  ????????????????????????????????

96
? ?????????
????? ?????

• ???????????????
• ?TODDS???????
• ?TODDS????????
• ???????????TODDS????
• ?TODDS???????????
• ?TODOS??????????????????????
• ???????????????

97
??????????????
98
Levy??

• ????????????????????????
• ??????????????????????????????,????????????,??????
  ???????????
• ???????????????????????????,????TODDS????????????

99
?????

• ???????,?????????????????????
• ??TODDS,??????????????????????????,????????
• ????????????????????????(????????????????????????)
  ?????????????

100
TODDS????(T)????(???????,NT)????????T???
AUQ??????????? ????t??????Q???QCV(?W)?? C?t??????
V?W??????????
101

• ??Levy????TODDS????????,???????????,?????????
• ??,??????????????????,?????????????
• ??,???????????,????????????????????????????????

102
???

• 1.  ?????????
• 2. ???????
• 3. ???????????
• 4. ????????????

103
? ?