CHINA BIOTECHNOLOGY ,720 PEG PEG. 20kDa ; [2 ] PEG. (methoxypoly ethylene glycol,mpeg), [4 ] PEG [1 ] PEG. (1 50kDa),, mpeg. 3,

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1 23 10 CHINA BIOTECHNOLOGY , ( ),,,, 40,720 FDA, 200 ( FDA ) 20kDa ;,, 1, (methoxypoly ethylene glycol,mpeg), ; ; [1 ] PEG, (1 50kDa),, (mpeg) FDA mpeg : : , com, mpeg 40 (BSA) ( G2CSF) 22 ( IL22) PEG ( 1),, PEG,, [2 ] 2, 30 % Motoo Yamasaki [3 ] PEG (rhg2csf) ( 1 rhg2csf PEG ), ;, PEG PEG [4 ] PEG,,,, PEG [5 ],, PEG ( 2)

2 PEG (PEG) (PEG) 5min 412h 5128min 6918h 115h 12h 110h 12h 2a 3 8h 65h min 206min 22 44min 256min 4min 20min, ; [6 ],2SOD 5min 6h ; 2GH 5min 2 3h,Aimme Guider Paige rhg2csf, G2CSF 6 [7 ],, 2 PEG Π Amgen SDΠ01 2b Schering Plough PEG2Intron g 2a Hoffman2La Roche Pegasys g Pharmacia Pharmacia Pharmacia Pharmacia 22 Pharmacia Diosynth RTP Inc Enzon ONCASPAR Enzon ADAGEN 140, HSA [9 ] HGS HSA 2 IL2 2, (HSA), 50 [10 ] 73 ( 40gΠL), Barbourin,, Barbourin [11 ],,,,, ( 66kDa), [12 ] (), Fc Green Cross HSA (C 2 C 4),, IL210, IL210Π HSA HSA IgG [8 ] 2 Fc IL210 [13 ] 1990 delta Chamow [14 ] CD4ΠIgG, CD4 V1,V2,, Ig Fc, 1997 HSA ( HGS) Fv (scfv) Fc Yeh CD4 HSA, ( IgG1 ) HSA2CD4, CD4,scFv 25kDa 106kDa,

3 10 : h 93 h [15 ] scfv, L2L2 2 h 9 h [16 ] IL22, GM2CSF, TNF, CD4, TNFR, TNFR IgG1 (C 1) (Tpo) C, [17 ] ( Epo)2Tpo, Epo 8h 12h Π,,,,,, 3 PCR ,Cys2125, Cys2125 Ser Ala 1, 112h [18 ] (rtpa), tpa ( K22tPA TNK2tPA) K22tPA tpa , K1 E F,, 4 5 ; TNK2tPA tpa 103 Thr Asn ;117 Asn Gln ; Lys2962His2972 Arg2982Arg299 4 Ala, 4, FDA, AI (apoai) (AIM), apoai Arg 173 Cys 173, AIM Cys 173, 4, 411,,,,, 2 (PLGA),,,, Zenica Zoladex, (goserelin) PLGA, 1mm,, 316mg, ( POE) 60,, FDA,,,, [19 ],, ( ),,

4 , [21 ] (LHRH),,,,,, 412,,,,, 5,,,,,, Goodson [20 ] Thr 3 Cys 3 2IL2 2, PEG,, TGF 2PE38,, PEG,, [ 1 ],,..,1998,19 (5) : [ 2 ],,,. 22b.,2001,31 (1) :74 77 [ 3 ] Motoo Yamasaki,Makoto Asano,Masami Okabe,et al. Modification of recombinant human granulocyte colony2stimulating factor and its derivative ND28 with polyethylene glycol. J Biochem, 1994,115 : [ 4 ] Gombotz,et al. Prolonged release of GM2CSF,2001,US [ 5 ] Breton J,Gurevich V. Characterization of a natural disulfide2linked conjugate of pro2utopians ( pro2utopians ) with albumin. Fibrinolysis,1990,3 (4) :160 [ 6 ] Chuang VT, Kragh2Hansen U, Otagiri M, et al. Pharmaceutial strategies utilizing recombinant human serum albumin. Pharmaceutical Research,2002,19 (5) : [ 7 ] Stephen D, Gillies, Kin2Ming Lo,et al. Improved circulating half2 life and efficacy of an antibody2interleukin 2 immunoncytokin based on reduced intracellular proteolysis, Clinical Cancer Research, 2002,8 : [ 8 ] Kobayashi K, Nakamura N, Sumi A, et al. The development of recombinant human serum albumin. Ther Apher,1998,2 (4) : [ 9 ]Patrice Yeh,Didier Landais,Marc Lemaitre,et al. Design of yeast2 secreted albumin derivatives for human therapy : Biological and antiviral properties of a serum albumin2cd4 genetic conjugate. Proc Natl Acad Sci. USA,1992,89 : [ 10 ] Balance D J ,CN [ 11 ] Marques J A, George J K, Smith IJ, et al. A barbourin2albumin fusion protein that is slowly cleared in vivo retains the ability to inhibit platelet aggregation in vitro. Thromb Haemost, 2001, 86 (3) : [ 12 ] Sheffield W P, Smith I J, Syed S, et al. Prolonged in vivo anticoagulant activity of a hirudin2albumin fusion protein secreted from Pichia pastoris. Blood Coagul Fibrinolysis,2001,12 (6) : [ 13 ],. Ig.,2000,7 (3) : [ 14 ] Chamow SM,Duliege AM,Ammann A,et al. CD4 immunoadhesins in anti2hiv therapy :New developments,int J Cancer,1992,7 :69 [ 15 ] Powers D B,Amersdorfer P, Poul M, et al. Expression of single2 chain Fv2Fc fusions in Pichia pastoris. J Immunol Methods,2001, 251 (122) : [ 16 ] Guo L,Wang J,Qian S,et al. Construction and structural modeling of a single2chain Fv2asparaginase fusion protein resistant to

5 10 : 27 proteolysis. Biotechnol Bioeng,2000,70 (4) : [ 17 ],,,. Epo2Tpo (c).,2001,15 (1) :5 8 [ 18 ].. :, [ 19 ] Heller J. Chemically self2regulated drug delivery system. J Controlled Release,1988,8 :11 [ 20 ] Goodson R T, Katre N V. Site2directed PEGylation of recombinant interleukin22 at its glycosylation site. Biol Technology,1990,8 : [ 21 ] Phillips PC, Catterall M, Colvin OM, et al. Transforming growth factor2alpha2pseudomonas exotoxin fusion protein ( TGF2alpha2 PE38) treatment of subcutaneous and intracranial human glioma and medulloblastoma xenografts in athymic mice,cancer Reaserch, 1994,54 (4) : The Advance of Reserch of Long Effect Peptides Medine Wang Xiuzhen 1 Wu Jun 2 Meng Xianjun 1 (1 Food Science Department of Shenyang Agriculture University Shengyang ) (2 Institute of Biotechnology Academy of Military Medical Science Beijing ) Abstract The time of recombinant peptides medine remain in vivo effect the dosage and therapeutic effect extremely. So, it become one of important tasks that to reconstitute these drugs for prevention of rapid degradation and short half2life. After many years unremitting efforts,a lot of long effect peptides medicine have been on the market or on clinical trial. To reach this goal, the following ways such as chemical modification, gene fusion,point mutaion and delivery systems revolution are reviewed. Key words Peptides medicine Half2life , 15,,, Her22 B,,Class VCH3,,,,,, (),,,,, ()