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A61K9/22
(2006.01)
A61K9/24
(2006.01)
A61K31/16
(2006.01)
A61K31/485
(2006.01)
2477995
"3$#'/$*$7"2!*4*/$(&3'4*/40
(21)(22)
7=DKL=
2010106202/15, 20.07.2007
+=E=[email protected]=AEG;E=G8AL=J;MGEK9DH=-8.3;8.5;-14;.5=-;ȴ.;G8.;堒.7A0;.5L-;.3;=-23;.4J;-20.;8.;M-2;.5G; .7;-14;.5K2;.79;-24.;]-2;Y.6;H=9.;^0;E;E=
20.07.2007
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+=E=HAJ=9I=DKL9
20.07.2007
[email protected]=O99I=DKL9
27.08.2011
"[email protected]=A
27.03.2013
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US 2003/0092724 A1, 15.05.2003. US
2005/158382 A1, 21.07.2005. US 2005/0112195
A1, 26.05.2005. RU 2230556 C2, 20.06.2004.
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RU2477995C2
RUSSIAN FEDERATION
FEDERAL SERVICE
FOR INTELLECTUAL PROPERTY
(51)Int. Cl.
A61K9/22
(2006.01)
A61K9/24
(2006.01)
A61K31/16
(2006.01)
A61K31/485
(2006.01)
2477995
ABSTRACT OF INVENTION
(21)(22)Application:
2010106202/15, 20.07.2007
(24)Effective date
20.07.2007
Priority:
(22)Date of filing:
20.07.2007
(43)Application published:
27.08.2011
Bull.24
(45)Date of publication:
27.03.2013Bull.9
(85)Commencement of
national phase:
24.02.2010
(86)PCT application:
US 2007/073957(20.07.2007)
(87)PCT publication:
WO 2009/014534(29.01.2009)
Mail address:
129090, Moskva, ul.B.Spasskaja, 25, str.3, OOO
"Juridicheskaja firma Gorodisskij i Partnery",
pat.pov. A.V.Mitsu, reg.
364
(72)Inventor(s):
LJu Vehj (US)
ROZENBERG Jorg (DE)
VERLE Gerd (DE)
KESSLER Tomas I. (DE)
BRAJTENBAKh Jorg (DE)
DURAK Salikh (DE)
RIKhTER Fridrikh V. (US)
DUTTA Sandip (US)
FORMULATIONS OF NON-OPIOID AND LIMITED OPIOID ANALGESICS
(57)Abstract:
FIELD: medicine, pharmaceutics.
SUBSTANCE: present
invention refers to
medicine and de
cal compositions
having central and non-cen
tral layers for drug
delivery, particularly a
ddictive drugs, substantially
enclosed in a core porti
on, and a non-addictive drug
in a non-core portion. The given compositions having
a reduced addiction potentia
l. In the composition, a
preferentially addictive
drug represents opioid,
while a non-addictive drug
RU2477995C2
RU2477995C2
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5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
H8;JHAE9E;@T-7.5;ພ-;.5;11.;[email protected];.5T-;.9;[email protected];EGD
H8;[email protected];NM9F;C=8:=LAL9;E9;[email protected]
LABJ=AJAL8=E=DJAI=
GAJ;[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
[email protected];@TA
500
:B=O;E=:9AC;=
H89KK;J;99H=O9;EP=EA[=L
389KK;J;99
H=O9;EP
;@AK;LPJAI98AK= .4;;[email protected];.4A1;K-1;.4;;.4;LP-2;f.5;JA10;I7.6;.4;K=;退 .4;;[email protected];.4A1;K-1;.4;;.4;LP-2;f.5;JA10;I7.6;.4;K=;退=DCA8:=A?;GH;9K=;E
AUC
[email protected]JA=AE
[email protected];@TA
9,1
:[email protected];@TA
19,9
:B9
AUC
=O;E=:9AC;[email protected];@TA
28,6
:[email protected];@TA
59,1
5J8PBA:K=89=E;AGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
AUC
B9J8ALAJ[email protected];@TA
7,0
:[email protected];@TA
26,2
AUC
[email protected]=O;E=:9AC;[email protected];@TA
18,4
:[email protected];@TA
79,9
5J8PBA:K=89=E;AGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
AUC
[email protected][email protected];@TA
11,3
:[email protected];@TA
18,7
:B9
AUC
[email protected]=O;E=:9AC;[email protected];@TA
28,7
:BJA
[email protected];@TA
53,5
38;JHAE9E;@T-9.2;ພ-;.2;@-1;.2T;-8.4;AK\EA:K=89-9.2;ພ-;.2;@-1;.2T;-8.4;=E;AGP[;[email protected];-9.2;ພ-;.2;@-1;.2T;-8.4;9D
GLA8AGETKNGKA?AFJ;9DC=8:=O;KE9;GLAMLA:HAI9O99
in vitro
9:;;EJKPSC=INM
[email protected]?AFJ;9D
9BJ;[email protected]=FJAMC=INGLA8AGETKNGKA?AFJ;9D
in vitro
9:;;E[email protected];[email protected];[email protected]=O;E=:9AC;=9[email protected];KAMHA8DJAL
[email protected];[email protected]A=?9E=8E8=E=H;E=B;:9B9J8=E=
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
H8;JHAE9E;@T-7.5;ພ-;.5;11.;[email protected];.5T-;.9;[email protected];EGD
H8;[email protected];NM9F;C=8:=LAL9;E9;[email protected]
LABJ=AJAL8=E=DJAI=
GAJ;[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
[email protected];@TA
500
:B=O;E=:9AC;=
H89KK;J;99H=O9;EP=EA[=L
+AI98AK==DCA8:=A?;GH;9K=;EL-0.7;क.;K-1;.1=-;.3;18.;^-2;Y.8;L-6.;稀-0.7;क.;K-1;.1=-;.3;18.;^-2;Y.8;L-6.;稀AO;[email protected]=I:;;8;I
(C1)
B9J8ALAJ[email protected];@TA
0,18
:[email protected];@TA
1,51
:B9
LAO;[email protected]=I:;
;8;I
[email protected]=O;E=:9=G-2;v.3;J0.4;[email protected];W.9;=-10;.2O-;.2;E-1;.8=;:-7.;Y-1;.80;AC;=G-2;v.3;J0.4;[email protected];W.9;=-10;.2O-;.2;E-1;.8=;:-7.;Y-1;.80;[email protected];@T=G-2;v.3;J0.4;[email protected];W.9;=-10;.2O-;.2;E-1;.8=;:-7.;Y-1;.80;A
2,34
:[email protected];@TA
7,24
5H8;JHAE9E;@T-22;.99E;@T-;(.3;NSK=89=-22;.99E;@T-;(.3;E=S
AGP[;[email protected];9D
E=L9SL=LGAGE=K
15,
JAI98AK==DCA8:=A?;GH;9K=;E
[email protected]
B9J8ALAJ[email protected];@TA
0,32
:[email protected];@TA
1,51
:B9
[email protected]=O;E=:9AC;[email protected];@TA
2,34
:[email protected];@TA
5,50
.: 6
RU2477995C2
5;LAEA8NSJ8PB9SK=89=E=SAGP[;[email protected];9D
H8;JHAE9E;@T.5E;-6.7;@;.5T;-22.;У[email protected];EGD
H8;[email protected];NM9F;C=8:=LAL9;E9;[email protected]
LABJ=AJAL8=E=DJAI=
GAJ;[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
[email protected];@TA
500
:B=O;E=:9AC;=
H89KK;J;99H=O9;EP=EA[=L
+AI98AK==DCA8:=A?;GH;9K=;EL-0.7;क.;K-1;.1=-;.3;18.;^-2;Y.8;L-6.;稀-0.7;क.;K-1;.1=-;.3;18.;^-2;Y.8;L-6.;稀AO;[email protected]=I:;;8;I
(C1)
B9J8ALAJ[email protected];@TA
0,30
:[email protected];@TA
1,06
:B9
[email protected]=O;E=:9AC;[email protected];@TA
2,75
:[email protected];@TA
5,57
5H8;JHAE9E;@T.3;ຖ.;>-1;.1;;.3;[email protected];T-19;.500;NSK=8.3;ຖ.;>-1;.1;;.3;[email protected];T-19;.500;9=E=SAGP[;[email protected].3;ຖ.;>-1;.1;;.3;[email protected];T-19;.500;;9D
JAI98AK==DCA8:=A?;GH;9K=;E
[email protected][email protected];@TA
0,45
:[email protected];@TA
1,06
[email protected]=O;E=:9AC;[email protected];@TA
2,75
:[email protected];@TA
4,43
5J8PB9SK=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;[email protected];@TA
1,18
:LB
:@[email protected];@TA
3,63
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=
?9E=8E8=E=H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;==EA[=L
5H8;JHAE9E;@T.8E;࢞;[email protected];-7.6;NS
K=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;ELA:-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;?998A-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;K=-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;PQ
[email protected]=9=O;E=:9AC;[email protected];@TA
1,18
:LB
:@JA
[email protected];@TA
2,76
:LB
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;[email protected];@TA
1,38
:LB
:@[email protected];@TA
2,79
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=
?9E=8E8=E=H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5H8;JHAE9E;@T.4;.4;1;[email protected];.4;T-7.; NS
K=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;ELA:-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;?998A-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;K=-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;PQ
[email protected]=9=O;E=:9AC;[email protected];@TA
1,38
:LB
:@JA
[email protected];@TA
2,23
:LB
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5H8;JHAE9E;@T.1;ç.1;9;[email protected];.1T;-8.5;NSK=89=.1;ç.1;9;[email protected];.1T;-8.5;E=SAGP[;[email protected];.1;ç.1;9;[email protected];.1T;-8.5;9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;=
1,80
0,42
:LB
:@G
95%
JAK;89E;@TN:9E;[email protected]:[email protected];J;BAI=.2;;;[email protected];@T.2;;A
1,61
:@JA
[email protected];@TA
2,00
:LB
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
. 95%
JAK;89E;@TNM9E;[email protected]@D
LA:?998AK=AM
[email protected]=9=O;E=:9AC;[email protected]=;H8;JHAE9E;@T-12;.69E;-12.;@T;-180;NS
K=89=EAKAGP[;[email protected];9D9LA[email protected];8;L8NK=;EGD
. 95%
JAK;89E;@TNM9E;[email protected]
[email protected];J;BAI=;.8;16.;«9DLA:?9.8;16.;«98AK=.8;16.;«.8;16.;«AM
[email protected]A=9=O;E=:9AC;[email protected]
[email protected]=SAJ9EGDKJ9=H=IA;[email protected];@TAAE
1,46
1,96
:LB
[email protected];
KK;J;9DKL=;GEK;AJ.6;16.;G16;.4E1;.6K;-23;.7A;.2;J7.4;AL8=E.6;16.;G16;.4E1;.6K;-23;.7A;.2;J7.4;AMJAIN
:BB9J8ALAJA=9
500
:B=O;E=:9AC;=
H=O9;EP
;@AK;LP
[email protected]?;GH;9K=;EJAGE=EA .70;N;P8AK .70;[email protected]=I:;AH9A9J .70;ABA
9;AH9A9JABA=[email protected];[email protected]?;GH;-8.5;000;;9D-8.5;000;G9F;-8.5;000;9D9-8.5;000;E;-8.5;000;G9K-8.5;000;[email protected];J;@=S
[email protected];@TA
[email protected];KK;=-20;.2G9;.6=-;ɵ.;H-2;.6A;.2G;[email protected];.6;-;ɕ.;K-1;K-1;-0;.6J;;J;9D
389KK;J;[email protected];K;8NS
=:;89L=O;[email protected]=H=JNS;K8AH;MO;K
K=GEɵ.; =26;.3G;ɴ.;縦.70;AGE9
LABJ=GAGE=K=J=HE98AK=
EA?N
A[email protected]J;[email protected];J=I=;-9.6;9.6;[email protected];-9.6;9.6;J;9D;@AK;LPL=FJN;
=GAKH89
;A?SAJ9:AGE9
[email protected];@TA
20-45%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
C=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;[email protected];@T000;A
[email protected];@T=G-9;.9=-;ɤ.;)-2;g.8;H-15;.58-;.19;-2.5;[email protected];.79I;-1;.7;;[email protected];.10;A
20-
45%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MK
E;;120;9;[email protected];@T120;A
=G=K
0,01
. HCl
H89
:9H89
5J8PBA:
K=89=E;AGP[;[email protected];9D
[email protected];@TA
25-35%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.9;;-7.5;9;[email protected];@T.9;;-7.5;A
=G=9
.: 7
RU2477995C2
[email protected];@TA
25-35%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-6;1;.20;9;[email protected];@T-6;1;.20;A
=G=K
0,01
. HCl
H89
:9H89
&8A:;EABA
KJ8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=
KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.7;; .70;9;[email protected];@T.7;; .70;A
[email protected];@T=-9G; -8K;-264;.1J1;.6A-;ɳ.;H-5;.28-;.2; -2.;[email protected]; .69;I9E;;-9.8;[email protected];∞A
=GAK
9HA:;TU;M:;8;AE
60%
[email protected];@TA
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
8,5
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.4;9.2;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7;1;.20;9;:;-7;1;.20;;;;:[email protected];@T.2;;.2;:-27;H-1;.88;-6.4; ?-6;[email protected];-0;.8I9;@T;-26.;«A
=GAK
9HA
:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-5.7;13.;у9;:;-5.7;13.;у;;;:[email protected];@T-5.7;13.;:-2;h.7;H-12;.58-;.19;?-5.;[email protected]; .7I;.9; -9.;~-;[email protected];.7;T-15;.100;A
=GAK
"J=LA
LABJ=K=89=EGI=:;[email protected];N:KNGKA?AFJ;9;:GAGE=K==J=HE98AK=
EA?NA-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];J-13;.8A?;-9.2;N-26;.6A;-19.;л-13;.8A?;-9.2;N-26;.6A;-19.;л=I=;-9.8;9.4;[email protected];J;-9.8;9.4;9D;@AK;LPJK=8=I=KGPEL9
;A?SAJ9:AGE9
EABJ=HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=G=JA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=G=JA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D\EABAK=89=E=
AGP[;[email protected];9DGI=:;[email protected];N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
B9J8ALAJA=
KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.7;; .70;9;[email protected];@T.7;; .70;A
.: 8
RU2477995C2
[email protected];@T=-9G; -8K;-264;.1J1;.6A-;ɳ.;H-5;.28-;.2; -2.;[email protected]; .69;I9E;;-9.8;[email protected];∞A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.1;;.1;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;:;.5;9.3;;;;:
[email protected];@TA
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
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:[email protected];@TA
5,57
H8;JHAE9E;@T-8.7;ພ-;.7;@-9;.7T-;.90;NSK=89=-8.7;ພ-;.7;@-9;.7T-;.90;E=SAGP[;[email protected];-8.7;ພ-;.7;@-9;.7T-;.90;9D
JAI98AK==DCA8:=A?;GH;9K=;E
[email protected][email protected]9I9E;@TA
0,45
:[email protected];@TA
1,06
[email protected]=O;E=:9AC;[email protected];@TA
2,75
:[email protected];@TA
4,43
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
.: 12
RU2477995C2
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;[email protected];@TA
1,18
:LB
:@[email protected];@TA
3,63
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=
?9E=8E8=E=H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5H8;JHAE9E;@T.4;.4;1;[email protected];.4;T-7.; NS
K=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;ELA:-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;?998A-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;K=-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;PQ
[email protected]=9=O;E=:9AC;[email protected];@TA
1,18
:LB
:@JA
[email protected];@TA
2,76
:LB
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;[email protected];@TA
1,38
:LB
:@[email protected];@TA
2,79
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=
?9E=8E8=E=H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5H8;JHAE9E;@T.4;.4;1;[email protected];.4;T-7.; NS
K=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;ELA:-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;?998A-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;K=-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;PQ
[email protected]=9=O;E=:9AC;[email protected];@TA
1,38
:LB
:@JA
[email protected];@TA
2,23
:LB
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5H8;JHAE9E;@T.1;ç.1;9;[email protected];.1T;-8.5;NSK=89=.1;ç.1;9;[email protected];.1T;-8.5;E=SAGP[;[email protected];.1;ç.1;9;[email protected];.1T;-8.5;9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;=
1,80
0,42
:LB
:@G
95%
JAK;89E;@TN:9E;[email protected]:[email protected];J;BAI=.2;;;[email protected];@T.2;;A
1,61
:@JA
[email protected];@TA
2,00
:LB
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
. 95%
JAK;89E;@TNM9E;[email protected]@D
LA:?998AK=AM
[email protected]=9=O;E=:9AC;[email protected]=;H8;JHAE9E;@T-12;.69E;-12.;@T;-180;NS
K=89=EAKAGP[;[email protected];9D9LA[email protected];8;L8NK=;EGD
. 95%
JAK;89E;@TNM9E;[email protected]
[email protected];J;BAI=;.8;16.;«9DLA:?9.8;16.;«98AK=.8;16.;«.8;16.;«AM
[email protected]A=9=O;E=:9AC;[email protected]
[email protected]=SAJ9EGDKJ9=H=IA;[email protected];@TAAE
1,46
1,96
:LB
[email protected];
KK;J;9DKL=;GEK;AJ.6;16.;G16;.4E1;.6K;-23;.7A;.2;J7.4;AL8=E.6;16.;G16;.4E1;.6K;-23;.7A;.2;J7.4;AMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=H=O9;EP
;@AK;LP
&A[email protected]?;GH;9K=;E
JAGE=EA .50;N;P .50;[email protected]=I:;AH9A9J .50;ABA9 .50;;AH9A9J .50;ABA= .50;[email protected];[email protected]
A?;GH000;;;9D000;G9F000;;9D9000;E;000;G000;[email protected];J;@[email protected];@T000;A
[email protected];
KK;J;9D
389KK;J;[email protected];K;8NS=:;89L=O;[email protected]=H=JNS
;K8AH;MO;K
K=G.8=;G11.;踀EAGE9
LABJ=GAGE=K=J=HE98AK=
EA?NA-14;.3A?;N-27;.3A;-9.7;[email protected];-14;.3A?;N-27;.3A;-9.7;[email protected]
H8;J=I=;.6;26.;«[email protected];J;.6;26.;«9D;@AK;LPL=FJN;
=GAKH89-9.8;=-10;.2G9;.4A-; .2K;-275;.5H-;.6;-2;h.9;;A?SAJ9:AGE9
[email protected];@TA
20-45%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-6;1;.20;9;[email protected];@T-6;1;.20;A
[email protected];@T-9=-; .4G;=-27;.79;-268;.1H-;.8;-1;[email protected];-13I; .69;-23;.2;1;[email protected];-10T;-18.;лA
20-45%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.7;;.7;9;[email protected];@T.7;;.7;A
=G=K
0,01
. HCl
H89
:9H89
5J8PBA:K=89=E;AGP[;[email protected];9D
[email protected];@TA
25-35%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-6;1;.20;9;[email protected];@T-6;1;.20;A
[email protected];@T-9=-; .4G;=-27;.79;-268;.1H-;.8;-1;[email protected];-13I; .69;-23;.2;1;[email protected];-10T;-18.;лA
25-35%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.7;;.7;9;[email protected];@T.7;;.7;A
=G=K
0,01
. HCl
H89
:9H89
&8A:;EABA
KJ8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;AE
60%
[email protected];@TA
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
8,5
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
.: 13
RU2477995C2
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7;1;.20;9;:;-7;1;.20;;;;:[email protected];@T.2;;.2;:-27;H-1;.88;-6.4; ?-6;[email protected];-0;.8I9;@T;-26.;«A
=GAK
9HA
:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-5.7;13.;у9;:;-5.7;13.;у;;;:[email protected];@T-5.7;13.;:-2;h.7;H-12;.58-;.19;?-5.;[email protected]; .7I;.9; -9.;~-;[email protected];.7;T-15;.100;A
=GAK
"J=LA
LABJ=K=89=EGI=:;[email protected];N:KNGKA?AFJ;9;:GAGE=K==J=HE98AK=
EA?NA-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];J-13;.8A?;-9.2;N-26;.6A;-19.;л-13;.8A?;-9.2;N-26;.6A;-19.;л=I=;-9.8;9.4;[email protected];J;-9.8;9.4;9D;@AK;LPJK=8=I=KGPEL9
;A?SAJ9:AGE9
EABJ=HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=G=JA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=G=JA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D\EABAK=89=E=
AGP[;[email protected];9DGI=:;[email protected];N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
B9J8ALAJA=
KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.7;; .70;9;[email protected];@T.7;; .70;A
[email protected];@T=-9G; -8K;-264;.1J1;.6A-;ɳ.;H-5;.28-;.2; -2.;[email protected]; .69;I9E;;-9.8;[email protected];∞A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.1;;.1;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9DGAGE=K=GI=:;J@;N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;:;.5;9.3;;;;:
[email protected];@TA
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.5;12.;Δ9;:-6.5;12.;Δ;;;;:[email protected];@T-6.5;12.;:-2;i.5;H-13;.38-;.99;-0.3;?-5.;[email protected];.59I;.1; -10;.5E-;.3;;[email protected];.90;A
=GAK
5H8;JHAE9E;@T-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;A:K=89=-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;E;AGP[;[email protected]-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;;9D
=GEAD[;;9IA?8;E;9;AEAG9EGDL
LA:HAI9O99
BJ;O;[email protected][email protected];8F9E\LGO9H9;E
GHAGA?NMLA[email protected]=ET
KNGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
9;O;[email protected][email protected];8F9E\LGO9H9;E
.: 14
RU2477995C2
RU2477995C2
38;JHAE9E;@T-12;.89E;-12.;@1;.6T;-28.;лAH89KK;J-12;.89E;-12.;@1;.6T;-28.;л;99H=O9;-12;.89E;-12.;@1;.6T;-28.;лEP
;@AK;LPC=8:=O;KE9;GL=DLA:HAI9O9D
A?;GH;9K=;[email protected]@=I:;
S=8=LE;89IPQ[9MGD
[email protected]=AE
[email protected];@TA
0,6
:[email protected];@TA
1,4
:B9
[email protected]
=O;E=:9AC;[email protected];@TA
2,8
:B9
7,9
[email protected];AJAL8=EAM
JAIN
5J8PBA:K=89=E;AGP[;[email protected];9D
C=8:=O;KE9;GL=DLA:HAI9O9DA?;GH;9K=;E
[email protected]@=I:;
S=8=LE;89IPQ[9MGD
[email protected][email protected];@TA
0,4
:[email protected];@TA
1,9
:B9
[email protected]=O;E=:9AC;=AE
[email protected];@TA
2,0
:[email protected];@TA
10,4
[email protected];AJAL8=EAM
JAIN
5J8PBA:K=89=E;AGP[;[email protected];9D
C=8:=O;KE9;GL=DLA:HAI9O9DA?;GH;9K=;E
[email protected]@=I:;
S=8=LE;89IPQ[9MGD
[email protected][email protected];@TA
0,6
:[email protected];@TA
1,0
:B9
[email protected]=O;E=:9AC;=AE
[email protected];@TA
3,0
:[email protected];@TA
5,2
[email protected];AJAL8=EAMJAIN
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
H8;JHAE9E;@T-7.5;ພ-;.5;11.;[email protected];.5T-;.9;[email protected];EGD
H8;[email protected];NM9F;C=8:=LAL9;E9;[email protected]
LABJ=AJAL8=E=DJAI=
GAJ;[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
[email protected];@TA
500
:B=O;E=:9AC;=
H89KK;J;99H=O9;EP=EA[=L
389KK;J;99
H=O9;EP
;@AK;LPJAI98AK= .4;;[email protected];.4A1;K-1;.4;;.4;LP-2;f.5;JA10;I7.6;.4;K=;退 .4;;[email protected];.4A1;K-1;.4;;.4;LP-2;f.5;JA10;I7.6;.4;K=;退=DCA8:=A?;GH;9K=;E
AUC
[email protected]JA=AE
[email protected];@TA
9,1
:[email protected];@TA
19,9
:B9
AUC
=O;E=:9AC;[email protected];@TA
28,6
:[email protected];@TA
59,1
5J8PBA:K=89=E;AGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
AUC
B9J8ALAJ[email protected];@TA
7,0
:[email protected];@TA
26,2
AUC
[email protected]=O;E=:9AC;[email protected];@TA
18,4
:[email protected];@TA
79,9
5J8PBA:K=89=E;AGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
AUC
[email protected][email protected];@TA
11,3
:[email protected];@TA
18,7
:B9
AUC
[email protected]=O;E=:9AC;[email protected];@TA
28,7
:BJA
[email protected];@TA
53,5
38;JHAE9E;@T-9.2;ພ-;.2;@-1;.2T;-8.4;AK\EA:K=89-9.2;ພ-;.2;@-1;.2T;-8.4;=E;AGP[;[email protected];-9.2;ພ-;.2;@-1;.2T;-8.4;9D
GLA8AGETKNGKA?AFJ;9DC=8:=O;KE9;GLAMLA:HAI9O99
in vitro
9:;;EJKPSC=INM
[email protected]?AFJ;9D
9BJ;[email protected]=FJAMC=INGLA8AGETKNGKA?AFJ;9D
in vitro
9:;;E[email protected];[email protected];[email protected]=O;E=:9AC;=9[email protected];KAMHA8DJAL
[email protected];[email protected]A=?9E=8E8=E=H;E=B;:9B9J8=E=
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
H8;JHAE9E;@T-7.5;ພ-;.5;11.;[email protected];.5T-;.9;[email protected];EGD
H8;[email protected];NM9F;C=8:=LAL9;E9;[email protected]
LABJ=AJAL8=E=DJAI=
GAJ;[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
[email protected];@TA
500
:B=O;E=:9AC;=
H89KK;J;99H=O9;EP=EA[=L
38;JHAE9E;@T-12;.89E;-12.;@1;.6T;-28.;лAH89KK;J-12;.89E;-12.;@1;.6T;-28.;л;99H=O9;-12;.89E;-12.;@1;.6T;-28.;лEP
;@AK;LPC=8:=O;KE9;GL=DLA:HAI9O9D
A?;GH;9K=;EL.7;.7;K-10;.1=;; .5E;-258;.6L4;.7A0;AO;.7;.7;K-10;.1=;; .5E;-258;.6L4;.7A0;[email protected]=I:;;8;I
(C1)
[email protected]A=AE
[email protected];@TA
0,18
:[email protected];@TA
1,51
:B9LAO;E8=O9QK
[email protected]=I:;
;8;I
[email protected]=O;E=:=-8.;G-2;d.4;J2.1;[email protected];-2;V.2;=O-2;.7;;.1;-12;.1=-;.5:;-5.8;退9AC;=-8.;G-2;d.4;J2.1;[email protected];-2;V.2;=O-2;.7;;.1;-12;.1=-;.5:;-5.8;退[email protected];@T=-8.;G-2;d.4;J2.1;[email protected];-2;V.2;=O-2;.7;;.1;-12;.1=-;.5:;-5.8;退A
2,34
:BJA
[email protected];@TA
7,24
5H8;JHAE9E;@T.1;ç.1;9;[email protected];.1T;-8.5;NSK=89=.1;ç.1;9;[email protected];.1T;-8.5;E=SAGP[;[email protected];.1;ç.1;9;[email protected];.1T;-8.5;9D
E=L9SL=LGAGE=K
15,
JAI98AK==D
CA8:=A?;GH;9K=;E
[email protected][email protected];@TA
0,32
:BJA
[email protected];@TA
1,51
:B9
[email protected]=O;E=:9AC;[email protected];@TA
2,34
:[email protected];@TA
5,50
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
H8;JHAE9E;@T-7.5;ພ-;.5;11.;[email protected];.5T-;.9;[email protected];EGD
H8;[email protected];NM9F;C=8:=LAL9;E9;[email protected]
LABJ=AJAL8=E=DJAI=
GAJ;[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
[email protected];@TA
500
:B=O;E=:9AC;=
H89KK;J;99H=O9;EP=EA[=L
38;JHAE9E;@T-12;.89E;-12.;@1;.6T;-28.;лAH89KK;J-12;.89E;-12.;@1;.6T;-28.;л;99H=O9;-12;.89E;-12.;@1;.6T;-28.;лEP
;@AK;LPC=8:=O;KE9;GL=DLA:HAI9O9D
.: 16
RU2477995C2
A?;GH;9K=;EL.7;.7;K-10;.1=;; .5E;-258;.6L4;.7A0;AO;.7;.7;K-10;.1=;; .5E;-258;.6L4;.7A0;[email protected]=I:;;8;I
(C1)
[email protected]A=AE
[email protected];@TA
0,30
:[email protected];@TA
1,06
:B9
=O;E=:9AC;[email protected];@TA
2,75
:[email protected];@TA
5,57
H8;JHAE9E;@T-8.7;ພ-;.7;@-9;.7T-;.90;NSK=89=-8.7;ພ-;.7;@-9;.7T-;.90;E=SAGP[;[email protected];-8.7;ພ-;.7;@-9;.7T-;.90;9D
JAI98AK==DCA8:=A?;GH;9K=;E
[email protected][email protected];@TA
0,45
:[email protected];@TA
1,06
[email protected]=O;E=:9AC;[email protected];@TA
2,75
:[email protected];@TA
4,43
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=
A?;GH;9K=;ELA:?9 .69;.6K;-11.;=;8;.4E-;ə.;L3.;j:?;.6;98AK= .69;.6K;-11.;=;8;.4E-;ə.;L3.;j:?;.6; .69;.6K;-11.;=;8;.4E-;ə.;L3.;j:?;.6;PQ
[email protected]A=9=O;E=:9AC;=AE
[email protected];@TA
1,18
:LB
:@[email protected];@TA
3,63
[email protected];AJAL8=EAM
JAIN
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
H8;JHAE9E;@T-8.7;ພ-;.7;@-9;.7T-;.90;NSK=89=-8.7;ພ-;.7;@-9;.7T-;.90;E=SAGP[;[email protected];-8.7;ພ-;.7;@-9;.7T-;.90;9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;[email protected];@TA
1,18
:LB
:@[email protected];@TA
2,76
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=
?9E=8E8=E=H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;[email protected];@TA
1,38
:LB
:@[email protected];@TA
2,79
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=
?9E=8E8=E=H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5H8;JHAE9E;@T.4;.4;1;[email protected];.4;T-7.; NS
K=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;ELA:-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;?998A-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;K=-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;PQ
[email protected]=9=O;E=:9AC;[email protected];@TA
1,38
:LB
:@JA
[email protected];@TA
2,23
:LB
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5H8;JHAE9E;@T.1;ç.1;9;[email protected];.1T;-8.5;NSK=89=.1;ç.1;9;[email protected];.1T;-8.5;E=SAGP[;[email protected];.1;ç.1;9;[email protected];.1T;-8.5;9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;=
1,80
0,42
:LB
:@G
95%
JAK;89E;@TN:9E;[email protected]:[email protected];J;BAI=.2;;;[email protected];@T.2;;A
1,61
:@JA
[email protected];@TA
2,00
:LB
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
. 95%
JAK;89E;@TNM9E;[email protected]@D
LA:?998AK=AM
[email protected]=9=O;E=:9AC;[email protected]=;H8;JHAE9E;@T-12;.69E;-12.;@T;-180;NS
K=89=EAKAGP[;[email protected];9D9LA[email protected];8;L8NK=;EGD
. 95%
JAK;89E;@TNM9E;[email protected]
[email protected];J;BAI=;.8;16.;«9DLA:?9.8;16.;«98AK=.8;16.;«.8;16.;«AM
[email protected]A=9=O;E=:9AC;[email protected]
[email protected]=SAJ9EGDKJ9=H=IA;[email protected];@TAAE
1,46
1,96
:LB
[email protected];
KK;J;9DKL=;GEK;AJ.6;16.;G16;.4E1;.6K;-23;.7A;.2;J7.4;AL8=E.6;16.;G16;.4E1;.6K;-23;.7A;.2;J7.4;AMJAIN
:BB9J8ALAJA=9
500
:B=O;E=:9AC;=
H=O9;EP
;@AK;LP
[email protected]?;GH;9K=;EJAGE=EA .70;N;P8AK .70;[email protected]=I:;AH9A9J .70;ABA
9;AH9A9JABA=[email protected];[email protected]?;GH;-8.5;000;;9D-8.5;000;G9F;-8.5;000;9D9-8.5;000;E;-8.5;000;G9K-8.5;000;[email protected];J;@=S
[email protected];@TA
[email protected];KK;=-20;.2G9;.6=-;ɵ.;H-2;.6A;.2G;[email protected];.6;-;ɕ.;K-1;K-1;-0;.6J;;J;9D
389KK;J;[email protected];K;8NS=:;89L=O;[email protected]=H=JNS
;K8AH;MO;K
K=G.8=;G11.;踀EAGE9
LABJ=GAGE=K=J=HE98AK=
EA?NA-14;.3A?;N-27;.3A;-9.7;[email protected];-14;.3A?;N-27;.3A;-9.7;[email protected]
H8;J=I=;.6;26.;«[email protected];J;.6;26.;«9D;@AK;LPL=FJN;
=GAKH89-9.8;=-10;.2G9;.4A-; .2K;-275;.5H-;.6;-2;h.9;;A?SAJ9:AGE9
[email protected];@TA
20-45%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-6;1;.20;9;[email protected];@T-6;1;.20;A
[email protected];@T-9=-; .4G;=-27;.79;-268;.1H-;.8;-1;[email protected];-13I; .69;-23;.2;1;[email protected];-10T;-18.;лA
20-45%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.7;;.7;9;[email protected];@T.7;;.7;A
=G=K
0,01
. HCl
H89
:9H89
5J8PBA:K=89=E;AGP[;[email protected];9D
[email protected];@TA
25-35%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-6;1;.20;9;[email protected];@T-6;1;.20;A
[email protected];@T-9=-; .4G;=-27;.79;-268;.1H-;.8;-1;[email protected];-13I; .69;-23;.2;1;[email protected];-10T;-18.;лA
25-35%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.7;;.7;9;[email protected];@T.7;;.7;A
=G=K
0,01
. HCl
H89
:9H89
&8A:;EABA
KJ8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
.: 17
RU2477995C2
[email protected];@TA
=GAK
9HA:;TU;M:;8;AE
60%
[email protected];@TA
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
8,5
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7;1;.20;9;:;-7;1;.20;;;;:[email protected];@T.2;;.2;:-27;H-1;.88;-6.4; ?-6;[email protected];-0;.8I9;@T;-26.;«A
=GAK
9HA
:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-5.7;13.;у9;:;-5.7;13.;у;;;:[email protected];@T-5.7;13.;:-2;h.7;H-12;.58-;.19;?-5.;[email protected]; .7I;.9; -9.;~-;[email protected];.7;T-15;.100;A
=GAK
"J=LALABJ=K=89=EGI=:;[email protected];N:KNGKA?AFJ;9;:GAGE=K==J=HE98AK=
EA?NA-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];J-13;.8A?;-9.2;N-26;.6A;-19.;л-13;.8A?;-9.2;N-26;.6A;-19.;л=I=;-9.8;9.4;[email protected];J;-9.8;9.4;9D;@AK;LPJK=8=I=KGPEL9
;A?SAJ9:AGE9
EABJ=HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=G=JA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=G=JA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D\EABAK=89=E=
AGP[;[email protected];9DGI=:;[email protected];N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
B9J8ALAJA=
KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.7;; .70;9;[email protected];@T.7;; .70;A
[email protected];@T=-9G; -8K;-264;.1J1;.6A-;ɳ.;H-5;.28-;.2; -2.;[email protected]; .69;I9E;;-9.8;[email protected];∞A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.1;;.1;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
.: 18
RU2477995C2
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;:;.5;9.3;;;;:
[email protected];@TA
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.5;12.;Δ9;:-6.5;12.;Δ;;;;:[email protected];@T-6.5;12.;:-2;i.5;H-13;.38-;.99;-0.3;?-5.;[email protected];.59I;.1; -10;.5E-;.3;;[email protected];.90;A
=GAK
5H8;JHAE9E;@T-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;A:K=89=-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;E;AGP[;[email protected]-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;;9D
=GEAD[;;9IA?8;E;9;AEAG9EGDL
LA:HAI9O99
BJ;O;[email protected][email protected];8F9E\LGO9H9;E
GHAGA?NMLA[email protected]=ET
KNGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
9;O;[email protected][email protected];8F9E\LGO9H9;E
RU2477995C2
*[email protected];E9NSPL=I=9M
KG;E;S9;GL9;9GL9;-27;.29;-266;.800;=PN;E;8:9N
[email protected];:N;K
=GEAD[;:JALP:;E;
9:;QEE;F;I=;Ɇ.;26;.30;9D
LAEA8N;A?N-8.9;AHA-8.9;DE-8.9;NGH;[email protected]
[email protected]=GE9
LLAEA8AMAEAG9EGD9IA?8;E;9;
[email protected]?N;GHAGA?N9:=E;[email protected]
GSAJN;[email protected]\[email protected];EN;GHAGA?=:9:=E;[email protected]=:
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EK;8JN:8=GEKA8A:
4K;8JN;
8=GEKA8NKNINK=Q[9SI=K9G9:AGET=LE9KNSK;[;[email protected];JHAE9E;@T .9;.7;1;[email protected];-0.5;T-8.;退N:9
4=LF;GAGE=K:AF;EGAJ;8F=ETAJ[email protected];[email protected]?=KAL
KN?8=NS9IGH98EAK
[email protected]NS
:[email protected];LGE89AK
C=8:=O;KE9;GL9H89;:@;:NS
HAK;8SAGEA
=LE9KNSK;[;GEK
8;[email protected];LP;GE9
J;I9E;B898PQ[9SK;[;GEK
=HA@9E;@;M9G:=INK=Q[9SK;[;GEK
389:;8=:9H89BAJNSGH98EAKG=S=8AK
[email protected]:=9E
GA8?9E
[email protected]
H89BAJN;H8A9IKAJN;[email protected]=QE
A;AB8=99K=QEGD9:99IA:[email protected]
B9J8AB;9I98AK=PQ
LAJ;G98AK=PQ
[email protected]=E9AIP9J8PB9;H8A9IKAJN;
LAEA8N;@9?AGSAJN
@9?A;GSAJNG9:9
)=8:=O;KE9;GL9H89;:@;:N;HAK;8.6;-0.;G19;.6L-;.69;-258;.7H-;.48;.2;.6;:@9;.6;9;.4:N;-25;.9H;-6.4; K10;.2;8;.2;S000;SAG.6;-0.;G19;.6L-;.69;-258;.7H-;.48;.2;.6;:@9;.6;9;.4:N;-25;.9H;-6.4; K10;.2;8;.2;S000;EA
=LE9KN;K;[;GEK=H8;JHAE9E;@T-24;.196;.5E-;.9;@T-;).5;A
H8;[email protected]?AMC=8:=O;KE9;GL9H89;:@;:A;5;.6G2;L9-;ɒ.;H81;.69;5;.6:9;[email protected];15;.8:-;.1A;.6;-24; .50;;9A5;.6G2;L9-;ɒ.;H81;.69;5;.6:9;[email protected];15;.8:-;.1A;.6;-24; .50;5;.6G2;L9-;ɒ.;H81;.69;5;.6:9;[email protected];15;.8:-;.1A;.6;-24; .50;A;HAK;8S5;.6G2;L9-;ɒ.;H81;.69;5;.6:9;[email protected];15;.8:-;.1A;.6;-24; .50;AGE5;.6G2;L9-;ɒ.;H81;.69;5;.6:9;[email protected];15;.8:-;.1A;.6;-24; .50;A
=LE9KA;
K;[;GEKA
[email protected];19.;က9;HAK;8S19.;ကAG19.;ကEA
=LE9KNSK;[;[email protected];EGDAGA?;A
H8;JHAE9E;@T.1E;.3;औ.;Ϥ.;17;[email protected];.1T8;.900;N:[email protected]=;:=E89LGAK
GAJ;8F=[9S:[email protected]=GEKA89:N;KKAJ;
=LE9KN;9B8;J9;EN9
[email protected]@DH89J=9DGAGE=KPG:=9K=;:AGE9
3AK;8SAGEA
=LE9KA;K;[;GEKA:AF;EAGP[;[email protected]:BAK;A;\:[email protected]=9;=LE9KABA
9B8;J9;E=
KNGKA?AFJ=;:ABA9IJAI98AK=AMCA8:N
9H8;JAEK8=[=ETAG=FJ;9;
=LE9KABA9B8;J9;E=KKAJNSF9JLAGEDSF;@PJA.5;A
L9U;.90;ABAE8=LE=
/;LAEA8N;H8;JHAE9E;@T.6E;.8;21;[email protected];.8T;-170;N;[email protected][email protected]@T.8;=QE-;ɖ.;=2.;[email protected];.8L6;[email protected];.8;T-6.;∞N;H8AGEN;\C98N
[email protected]\[email protected];=
=H89:;[email protected][email protected]\[email protected]\[email protected];=
(3),
O;[email protected]\[email protected]\E[email protected];=
(5),
GE;[email protected]\C98
[email protected]\[email protected];=
(2),
GE;[email protected]\[email protected]\[email protected];=
(5);
[email protected]@[email protected]N;
H8AGEN;\[email protected]\[email protected];=
=H89:;8A[email protected];[email protected]\C98
[email protected]\[email protected];=
(2),
A[email protected];[email protected]\[email protected]\[email protected];=
(3),
A[email protected];[email protected]\[email protected]\E9@;=
(4)
[email protected]@C;[email protected]
.: 30
RU2477995C2
\[email protected]\[email protected];=
(3);
[email protected]AFN;\C98NF9[email protected]@9\[email protected];[email protected]@D
=H89:;8:A[email protected]=P8=E
PEG-200,
[email protected]=P8=E
PEG-200,
[email protected]=P8=E
PEG-300,
[email protected]=P8=E
PEG-
400,
J9GE;=8=E
PEG-300
[email protected]@;=E
PEG-300;
[email protected]N;:AA\C98NF98[email protected]
[email protected]@;[email protected]@D
=H89:;8:AA
[email protected][email protected];[email protected]@D
(Lauroglycol
[email protected]N;\C98NF9[email protected]=S=8AIN
=H89:;8:A
GE;=8=EG=S=8AIN
J9GE;=8=EG=S=8AIN
:A[email protected][email protected]@=P8=EG=S=8AI=
[email protected]AFN;:AA9J9
\C98NF98[email protected]?9E==
E=L9;L=L:A[email protected]=P8=E=GA8?9E==
(Span
20),
:[email protected];=EGA8?9E==
:A[email protected]:9E=EGA8?9E==
(Span
40),
[email protected];=8=EGA8?9E==
[email protected]\[email protected];AKN;H8A9IKAJN;L=GEA8AKABA:[email protected]=
=H89:;8
[email protected]\[email protected];[email protected];89=E8989O9[email protected];[email protected]@[email protected]
-35-
L=GEA8AKA;
:[email protected]
(Cremophor
EL; BASF Corp.)
[email protected]@9ALG9\E9@;[email protected];[email protected]=ALG9GE;=8=E
E=LAM
[email protected]\[email protected];[email protected]@T
-40-
B9J8AB;9I98AK=A;L=GEA8AKA;:[email protected]
(Cremophor
RH 40)
[email protected]@9\[email protected];[email protected]@T
-60-
B9J8AB;9I98AK=A;L=GEA8AKA;:[email protected]
(Cremophor
60);
[email protected][email protected]
[email protected]:;8NALG9J=\[email protected];[email protected];=
E=LF;9IK;GEN;
L=L
[email protected]
[email protected]:;[email protected]\[email protected];[email protected]@;[email protected]@9ALG9\[email protected];=9
[email protected]@;[email protected]@D
E=L9;L=L
Pluronic
F68, Pluronic
F127, Poloxamer
124,
Poloxamer
188, Poloxamer
237, Poloxamer
388,
Poloxamer
407 (BASF Wyandotte
Corp.);
[email protected]@AFN;:AA\C98NF98[email protected]@9ALG9\E9@;=
(20)
GA8?9E==
=H89:;[email protected]\[email protected];=
(20)
GA8?9E==:A[email protected];=E
(Tween
80),
[email protected]\[email protected];=
(20)
GA8?9E==:AAGE;=8=E
(Tween
60),
[email protected]\E[email protected];=
(20)
GA8?9E==:A[email protected]:9E=E
(Tween
40),
[email protected]\[email protected];=
(20)
GA8?9E==
:[email protected]=P8=E
(Tween
20)
=E=LF;G:;G9JKPS
E8;S
;EN8;S
[email protected][email protected];;9I
9S
[email protected]=K:AF[email protected][email protected]N;J8PB9;JA?=KL9
=H89:;88;[email protected]
E;LP;GE9
E=L9;[email protected]@A9JNMJ9ALG9JL8;:9D
G:=INK=Q[9;K;[;GEK=
[email protected]9E;@9
J;I9E;B898PQ[9;K;[;GEK=
[email protected]=GE9C9L=EA8N
[email protected]=EA8N
E=L9;
L=L=E9ALG9J=EN
GK;[email protected]=EA8N
=LO;[email protected]@[email protected]=EA8N
H8AE9KKAIJ;MGEK9D:9L8A?AK
&8A:;EABA
[email protected];8F=[9M=O;E=:9AC;
=8PF[email protected][email protected]=J=;EBA8TL9:KLPGA:[email protected];JGEK9;G=:ABA=O;E=:9AC;=
:AFA
RU2477995C2
=GE=-9.;GE-;.4;AGE9
H89BAJN:[email protected]\LGE8PJ;[email protected]:;[email protected]N;:=U9N
389BAJN;
\LGE8PJ;[email protected]=QEAJ=-10;.3Q-;ľ-;⚚-9.3;J0.3;AU=-10;.3Q-;ľ-;⚚-9.3;J0.3;;LAKN;\LGE8PJ;8N
\LGE8PJ;8NGAGO;H@;N:9
U;L=:99:ABAU;LAKN;\LGE8PJ;8N
H8;JHAE9E;@-4.;8.;[email protected];.2T0;TAJ-4.;8.;[email protected];.2T0;KPSU;LAKN;\LGE8PJ;8N
LAEA8N;:ABPEK8=[=ETGDKAJA:[email protected];[email protected]=[[email protected]FNS
[email protected];9DS9;A?DI=E;@TAA?A8PJAK=NJ9GL=:[email protected];8;:;U9K=9D
2PJ;E
HADEA
EA8=?A9;E;:H;8=EP8NE=LF;?PJPEAH8;J;@DETGDE9HA:\LGE8PJ;[email protected]
E9HA:[email protected];:AMLAC9BP8=O99\LGE8PJ;8=
k=GET\;8B99
E8;?P;:[email protected]
[email protected][email protected];9D
RU2477995C2
I=K9G9:[email protected];L=8GEK;NSG8;JGEK
[email protected];[email protected];@TAH;8KABA=G=
H8;JHAE9E;@T.3E;.5;ऒ.;ע.;15;[email protected];.3T7;.100;[email protected][;GEKPHAGEA.3E;.5;ऒ.;ע.;15;[email protected];.3T7;.100;D.3E;.5;ऒ.;ע.;15;[email protected];.3T7;.100;N:9KE;;.3;;.3;9;HA:;.3;;.3;TU;M:;8;
[email protected];@TA
6, 8, 10, 12
[email protected]
=GAK
4=L9:A?8=IA:
K=89=ENAGP[;[email protected];9D
\EABA9IA?8;E;9DA?;GH;9K=QEAJ -12;.5K-;.9=;.3Q;-11.;n-2;w.8; -7.; J1.;ΔAC= -12;.5K-;.9=;.3Q;-11.;n-2;w.8; -7.; J1.;Δ[email protected];L=8GEK -12;.5K-;.9=;.3Q;-11.;n-2;w.8; -7.; J1.;Δ; -12;.5K-;.9=;.3Q;-11.;n-2;w.8; -7.; J1.;ΔABAG8;JGEK=
RU2477995C2
KNINK=Q[;;I=K9G9:[email protected];L=8GEK;A;G8;JGEKA
RU2477995C2
[email protected]\EABAE8;[email protected]=KNGALA:P8AK;
RU2477995C2
9ILAMAEAG9E;@T[email protected]=[email protected];E=.2;15E;=5.;«99
?;I8=GE8;GL9K=9D
=JB;I99
[email protected];9DHAL8NE9D9E
.).
/;AF9J=A
KJ=AM8=?AE;[email protected]@;A
EAPL=I=ê-2;U.1;P9.2;L-6.;=-1;I7.8;=-10;ê-2;U.1;P9.2;L-6.;=-1;I7.8;=-10;N;KNU;E8;?AK=ê-2;U.1;P9.2;L-6.;=-1;I7.8;=-10;9D
RU2477995C2
A?;GH;9K=QEGDH89;:@;:N;GKAMGEK=GH8;[email protected] K-1;.6=;-8.4;Q-0.;-1;G1D;-256;.1H-;.8;-7.;I-1;.8;:;-15.;[email protected];:;-15.; N-3;.7;-;ɔ.;G1K;-8.4;¢.8;MG-9;.2EK;-8.4;=-27;.7G;H-1;.88;-7.4;11.;--2;f.3;=-1;.6G;.2;-12;K-8.;Ң.;-1;.6=;-263;[email protected]; -26;.1G;P-8;.4G-; .2H;000;H;I99
J=F;H89
[email protected]=99KNGALABAA?[;BAGAJ;8F=9DEK;8JNSK;[;GEK
PHA:DPENSKNU;
389BAJN;[email protected]:;[email protected]=QE
;9AN;[email protected]:;8NO;@@[email protected]
E=L9;L=L
[email protected];@@[email protected]=
[email protected]:;[email protected];@@[email protected]=
B9J8ALG9\[email protected];@@[email protected]=
L=E9AN;[email protected]:;[email protected]=EN
E=L9;L=L
Eudragit
E, Eudragit
NE30D, Eudragit
RL,
Eudragit
RS;
[email protected][email protected]
[email protected]\[email protected];=
KNGALA:[email protected];[email protected]N;
[email protected]\[email protected];[email protected]@9G:[email protected];LP@D8AM:=GGAM
(MW)100,000);
H89K9EN;[email protected]:;8N
[email protected][email protected]
[email protected]\[email protected];=
(Kollicoat
IR).
38;JHAE9E;@T鹙-5.2;å7;[email protected];T-10;.600;A
H89BAJN;[email protected]:;[email protected]:;[email protected];@@[email protected]
, Eudragit
NE30D
[email protected][email protected]=
[email protected];E.1;E9.;=00;=9M
[email protected];;H8;JHAE9E;@T.8E;࢞;[email protected];-7.6;A
H89BAJN:9
[email protected]:;8=:[email protected];[email protected]:;[email protected][email protected]
AL9GT
[email protected]\[email protected];=
=H89:;8
, Kollicoat
IR, BASF).
'LE9KNM9B8;J9;E
H8;JHAE9E;@.6;æ.6;০.;@9;.6T0;TA
=O;E=:9AC;
XA:AB;PQHA8AULAKPQG:;GT
GAGEAD[PQ9I
61,8%
HA:=GG;=O;E=:9AC;=
12,6%
HA:=GG;
Eudragit
RL, 12,6%
HA:=GG;[email protected]=
, 6%
HA:=GG;
[email protected]:;[email protected];@@[email protected]
(Methocel
K100), 6%
HA:=GG;[email protected]
:;[email protected];@@[email protected]=
(Methocel
K100M)
1,0%
HA:=GG;
Aerosil
200
AE:;[email protected]
GLA8AGETQ
KJ-256;.3K-;ɦ.; J9K;PSU0;KPSU;LAKNM\LGE8PJ;8GK8=[;-256;.3K-;ɦ.; J9K;PSU0;9;:KA-256;.3K-;ɦ.; J9K;PSU0;JA:-256;.3K-;ɦ.; J9K;PSU0;[email protected];-256;.3K-;ɦ.; J9K;PSU0;99
(ZSK-
40)
9\[email protected];:H;8=EP8;[email protected];@TA
140
[email protected];.6;9.4;9;:
BA:AB;AM?;@[email protected][email protected];[email protected];EN
3AL=A=;[;[email protected][email protected]=GE9-0.6;A:
GAGEAD99
\[email protected][email protected];[email protected];[email protected][;@[email protected]=CA8:PQ[;BA
[email protected][email protected]=[email protected]N:K8=[;9;:
[email protected]:;@9
[email protected][email protected];9D=9SHAK;8SAGE9
RU2477995C2
:=GGP
720
:[email protected];[email protected]=FJ;[email protected]AK=9D
3AK;8S[email protected];[email protected]=
U;8ASAK=EAM9:;GE=:9;8=KA:;8AM
'O;E=:9AC;G8=I:;8A:=GE9O
13%
H8;KNU=Q[9:
0,25
::9=
68%
H8;KNU=Q[9:
0,063
GPGH;[email protected];H;8;:;U9K=9;:
'LE9KNM
9B8;J9;EAG;[email protected]0;;[email protected];[email protected];190;9D:;[email protected]
#PGH;I9Q9I:;@[email protected]
9BA:AB;[email protected]
H8AHPGL=D;;;8;[email protected]@A9J8;;I-25;.9L;-15.;ʡ.;[email protected]@-;.2; -8.;ڗ.;J-9;.200;PQ:;@T8;;I-25;.9L;-15.;ʡ.;[email protected]@-;.2; -8.;ڗ.;J-9;.200;9OP
[email protected];9I:;@T;.2;;Δ9D
\EAMGPGH;[email protected]@9EK;[email protected]:;8
(Kollicoat
IR, BASF)
AEAU;9;:=GG=O;E=:9AC;
/Kollicoat
IR = 75:25)
[email protected]-9;0;;9;:A?[;M
LAO;E8=O99EK;8JNSK;[;GEK
30%
HA:=GG;
+=F;[email protected];[email protected];[email protected]:;8=
=O;E=:9AC;KG;;[;J;:[email protected]=F;PQE;J;O9QLAG=FJ;9Q
389
;H8;8NKA:H;8;:;U9K=99\EPGPGH;[email protected]@9[email protected];EL9
AH9G=N;K
H89:;8;
KPGE8AMGEK;[email protected]=;G;[email protected];A-7.8;ABAHAL8NE9D
(Driam).
"?8=ION
[email protected];[email protected]@;=;G;9D
30, 50, 70
:B=O;E=:9AC;==H@;AA;
HAL8NE9;
5AKG;[email protected]=DS.2;=D17;.2S-;ɥ.;Δ[email protected][email protected].2;000;;TSA8AU;;GO;[email protected];.2;000;9;HAL8NE9DG
[email protected];EL=:9
SAEDHAK;8SAGETHAL8NENS9GEA?;@[email protected];.5; G9.;Ϧ.;Z-2;T.2;?-9.;19;[email protected];.1;M-25;.8H;-6.5;[email protected];9.3;[email protected];[email protected]=KG;;[;
;:ABAU;[email protected];JGEK9;KG;;[;AEAG9E;@T[email protected]=GE9O
=O;E=:9AC;=
0:;TU;9;H89KNGPU9K=[email protected];[email protected]@A
HA:=GG;JA9
[email protected];=;G;[email protected];[email protected];SCA8:
3=8=:;E8NH8AO;GG==;G;[email protected];A.90;ABA
HAL8NE9D
LBO;[email protected]NS=GE;[email protected];EAL
'O;E=:9AC;G8=I:;8A:=GE9O
1% -
[email protected];;;:
0,25
, 5% -
[email protected];;;:
0,1
16% -
[email protected];;;:
0,063
GPGH;[email protected];H;8;:;U9K=9;:
'LE9KNM
9B8;J9;[email protected]9F;PQE;J;O9QLAG=FJ;[email protected];[email protected];'.2;260;9D:;[email protected]
HAG8=K;9QG:=E;[email protected]:
[email protected][email protected]:;8;
7=E;:L\EAM
GPGH;[email protected]@9EK;[email protected]:;8
(Kollicoat
IR, BASF) (
AEAU;9;
:=GG=O;E=:9AC;
/Kollicoat IR
[email protected]-7.4;000;;9;:A?[;MLA-7.4;000;O;-7.4;000;E8=O99EK;8JNS
K;[;GEK
30%
HA:=GG;
[email protected];[email protected];[email protected]:;8==O;E=:9AC;HAE9-9.5;-3.;9-2;h.6;;[email protected]
@9?AE;J;O99LAG=FJ;9Q
7=E;:\EPGPGH;[email protected]@9[email protected];EL9
LAEA8N;[email protected][email protected]
L=LAH9G=AKH89:;8;
AJ=LAG;:ABA
:AJ9C9O98AK=AMB;A:;E89;[email protected];EAL
KPGE8AMGEK;[email protected]=;G;[email protected];A.5;ABA
HAL8NE9D
(Driam) (
H=8=:;E8NH8AO;GG=L=LKH89:;8;
2).
"[email protected];[email protected]
[email protected];=;G;9D
30, 50, 70, 90
120
:B=O;E=:9AC;=[email protected];A.9;A;HAL8NE9;
5AKG;S
[email protected]=DS=8.4;Õ.6;S-26;.10;[email protected][email protected];-1.4;7.6;TKNGALPQ=JB;I9QHAL8NE9D-1.4;7.6;[email protected];EL=S
3AK;8SAGET
HAL8NENS9GEA?;@[email protected]-7.8; -1.;GE-;.8; -26;.3?;-7.2;@AM;-266;.9H-;.6;[email protected];00;;[email protected];[email protected][email protected]=JLAM9A-7.8; -1.;GE-;.8; -26;.3?;-7.2;@AM;-266;.9H-;.6;[email protected];00;JA8AJ-7.8; -1.;GE-;.8; -26;.3?;-7.2;@AM;-266;.9H-;.6;[email protected];00;AM
!=GEKA8;9;@;L=8GEK;ABAG8;[email protected];EALKGAAEK;EGEK99GH89:;8A:
AH8;J;@[email protected];[email protected]=GAC=8:=LAH;;#V'
(USP Dissolution Apparatus II
@AH=GEA;
), USP XXV; 37
C, 0,01M HCl, 50
[email protected];GEKA=LE9K-8.;G12;.1E-;.9K;-17.;z-2;a.6;=-7.;L-1;.1E; K-1;.70;ABA
9B8;J9;E=
KNGKA?AFJ=;:[email protected];EALKG8;JPKAJABA8=GEKA8=
HCl,
AH8;J;@[email protected]
HAG8;JGEKA:5^[email protected]".1;N:99".1;E;[email protected]=:9
[email protected];EL9?;I=;G;[email protected];A.70;ABAHAL8NE9D
.: 38
RU2477995C2
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
120
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
240
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;[email protected];EALKGAAEK;EGEK99GH89:;8A:
AH8;J;@[email protected];[email protected]=GAC=8:=LAH;;#V'
(USP Dissolution Apparatus II
@AH=GEA;
), USP XXV; 37
C, 0,01M HCl, 50
[email protected];GEKA=LE9K-8.;G12;.1E-;.9K;-17.;z-2;a.6;=-7.;L-1;.1E; K-1;.70;ABA
9B8;J9;E=
KNGKA?AFJ=;:[email protected];EALKG8;JPKAJABA8=GEKA8=
HCl,
AH8;J;@[email protected]
HAG8;JGEKA:5^[email protected]".1;N:99".1;E;[email protected]=:9
[email protected];[email protected];EL=G
:B=O;E=:9AC;[email protected];A.10;A:HAL8NE99
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
120
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
240
:9PE
#LA8AGE98=GEKA8;[email protected];L=8GEK;ABAG8;[email protected][email protected];@TA=
10%
H89L=FJA:E;GE98P;:A:9E;[email protected];[email protected];JGEK9;9GSAJA?NGE8ABAKNGKA?AFJ;9D
=LE9KABA9B8;J9;E=
H89GPEGEKPQ[;[email protected];AA:HAL8NE99
!=GEKA8;9;@;L=8GEK;ABAG8;[email protected];EALKGAAEK;EGEK99GH89:;8A:
AH8;J;@[email protected];[email protected]=GAC=8:=LAH;;#V'
@AH=GEAMGHAGA?
, USP XXV;
C, 0,01M HCl, 50
:9
[email protected];GEKA=LE9K22.;GE9;.3KA;-251;.4=L;.3E; K12;.900;ABA22.;GE9;.3KA;-251;.4=L;.3E; K12;.900;9B8;J9;22.;GE9;.3KA;-251;.4=L;.3E; K12;.900;E=
KNGKA?AFJ=;:ABA9I
[email protected];EALKG8;JPKAJABA8=GEKA8=
HCl,
AH8;J;@[email protected];JGEKA:5^[email protected]9N:9
9E;[email protected]=:9
[email protected];EL=?;I=;G;[email protected];AABAHAL8NE9D
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
120
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
240
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
360
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
480
:9PE
[email protected];[email protected];EL=GA
120
:B=O;E=:9AC;[email protected];A.90;A:HAL8NE99
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
120
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
240
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
360
:9PE
!=GEKA8;9;@;L=8GEK;ABAG8;JGEK=
9I:;8;A;;8;I
480
:9PE
#LA8AGE98=GEKA8;[email protected];L=8GEK;ABAG8;[email protected][email protected];@TA=
25%
H89L=FJA:E;GE98P;:A:9E;[email protected];[email protected];JGEK9;?NGE8ABA9GSAJABAKNGKA?AFJ;9D
=LE9KABA9B8;J9;E=
H89GPEGEKPQ[;[email protected];AA:HAL8NE99
4;GE98AK=9;[email protected]
L=L9KH89:;8;
AJ=LAK:;GEA
Kollicoat
[email protected][email protected];8JNMHA8AUAL=AGAK;[email protected]:;[email protected];@@[email protected]
LAEA8NM
RU2477995C2
/[email protected][email protected]; .4;;-200;TKNGALA;GO;[email protected]; .4;;-200;9;[email protected];EL=:9
3AK;8SAGET
L8=GAK=ENS
LA89.10;;[email protected].10;;[email protected];[email protected][email protected]=JLAM9A.10;JA8AJ.10;AM
4;[email protected]
L=LKH89:;8;
AJ=LAK:;GEA
Kollicoat
[email protected][email protected]
EK;8JNMHA8AUAL=AGAK;[email protected][email protected]=
3AL8NEN;[email protected];[email protected];EL9
[email protected];.9;;(.1;.9;;(.1;N;KGAAEK;EGEK99GH89:;8=:9
3, 7
S8[email protected]=L8NENSGE;[email protected][email protected]=SH89E;:H;8=EP8=S
k;8;I
:;GDO;[email protected]=:;EAE8;[9[email protected];EL=S9;[email protected][email protected]@;MLAGE9
!=GEKA8;9;
@;L=8GEK;ABAG8;JGEK=
9I:;8;A;GHAGA?A:
AH9G=N:KH89:;8;
;[email protected]
9I:;;9MHAG8=K;9QGAI=.6;;;9D:9
I=8;B9GE898AK=N:9K[email protected];S8= .8=;[email protected];-25;.7S;-0.8;=9.;л; .8=;[email protected];-25;.7S;-0.8;=9.;л9D
[email protected][email protected][email protected]=-8.;[email protected];ɦ.;-7;.1?-;.18;.1=;-8.1;I0.7;O-11;.1N-;ɘ.;H-1;.5A;.1L;-13.;x-7;.1NE;-11.;NS-;ɣ.;H-1;[email protected];.5;;;[email protected];EAL
[email protected];NSKGAAEK;EGEK99G
H89:;8A:
:B=O;E=:9AC;[email protected];[email protected];A.60;ABAHAL8NE9D
9J;@[email protected]L9MG8;I
[email protected];EL9KHAH;8;A:[email protected];99GHA:A[TQ:9L8AEA:[email protected];[email protected]
:9L8AGLAHA:
/=9IA?8=F;[email protected]@;A.50;[email protected]@;[email protected]:AE
O;[email protected][email protected];EL9
#HA:A[TQ9IA?8=F;9MAH8;J;@[email protected]
[email protected]
[email protected];A.9;[email protected]@
300
:9L8A:;E8AK
#[email protected]=F9K=Q[9M\CC;LEGPGH;I99
[email protected]=HAK;8SAGE9U;[email protected];[email protected]?;AI=:;E;
EA
E=LF;K9JA=C9B
.1, 3
11:
HCl
/9F;H8;[email protected];AAH9G=9;[email protected]@QGE8=E9K[email protected];JAK=9DGLA8AGE9
8=GEKA8;9DAH8;J;@;NSLA:HAI9O9MK
HCl
20%
KAJA:8=GEKA8;\E=[email protected]=
[email protected]
[email protected];JAK=9DGLA8AGE98=GEKA8;9DK
40%
KAJA:8=GEKA8;\E=[email protected]=:AFA
[email protected]=ETGSAJN;GHAGA?N
[email protected]=GEKA8;9DK
0,01
[email protected][email protected];9
20/40%
KAJA:8=GEKA8;
\E=[email protected][email protected][email protected]@;JPQ[;;PGE8AMGEKA9GHAGA?N
(I)
0,01
. HCl
0GE8AMGEKA
: USP Dissolution Apparatus II (
@AH=GEA;
40%
0GE8AMGEKA
: USP Dissolution Apparatus II (
@AH=GEA;
RU2477995C2
"?e;:G8;JN
4;:H;8=EP8=
58;:[email protected];GE98AK=9DKNGKA?AFJ;9DKE;;.5;9.3;9;
30/60/120/180/240/360/420/480/600/720/840/1080/1320/1560/1800
:9PE
"?e;:A?8=IO=
?;II=:;[;9DA?e;:=
[email protected];9;A?8=IO=
[email protected];EGDL=L;GET
"LA=-6.9;=-27;.700;9;=-6.9;=-27;.700;[email protected]=
J;E;LO9D
[email protected][email protected]N
280
III.
0,01
. HCl
#AGE=KG?NGE8N:KNGKA?AFJ;9;:
KAEAU;99=O;E=:9AC;=
0,01
. HCl
H89
H8;[email protected];[email protected];
[email protected];
H8;[email protected];GAGE=KO;[email protected]AM
=GE99HAL8NE9DGAGE=K=
#AGE=K
,;[email protected]=D=GET3AL8NE9;
65,42%
=O;E=:9AC;=
150
:B=O;E=:9AC;=
9,29% Eudragit RL-PO48
Kollicoat IR
9,29%
B9H8A:;@@AIN
Ph. Eur. USP 2208 Type V 100 (Methocel K100)
9,29%
[email protected];@@[email protected]
Ph. Eur. Type EF
2,99% Polaxamer 188 Ph. Eur./NF
2,8%
B9J8ALAJA=f
1% Aerosil 200
"?[=D:=GG=O;[email protected]AM=GE9
:Bf
"?[=D:[email protected];EL9
:Bf
[email protected];
H8;[email protected];NJ=N;HA8=GEKA8;[email protected]=
(X(a))
=O;E=:9AC;=
(X(b)).
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=B9J8ALAJA=5
0,01
. HCl
6A:;EK8;:;9E;GE98AK=9D
:9
#8;J;;I=;-30;.900;9;
3014
6027
12043
18057
24067
30076
36084
42090
48094
60098
72098
84098
108099
132099
156099
1800100
X(b)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
=O;E=:9AC;=
0,01
. HCl
6A:;EK8;:;9E;GE98AK=9D
:9
#8;J;;I=-17.; 00;;9;
.: 41
RU2477995C2
3033
6039
12046
18056
24064
30071
36078
42085
48090
60098
720100
840101
1080100
1320100
1560100
1800100
#AGE=KGI=:;J@;N:KNGKA?AFJ;9;:
KAEAU;99=O;E=:9AC;=
0,01
HCl
H89
H8;[email protected];[email protected];
XII.
[email protected];
H8;[email protected];GAGE=KO;[email protected]AM
=GE99HAL8NE9DGAGE=K=
#AGE=K
,;[email protected]=D=GET
3AL8NE9;
55,88%
=O;E=:9AC;=
120
:B=O;E=:9AC;=
13,50% Eudragit RL-PO
38,4
Kollicoat IR
11,0%
B9H8A:;@@AIN
Ph, Eur, USP 2208 Type V 100 (Methocel K100)
3,01%
B9H8A:;@@AIN
Ph, Eur, 2208 Type V 20000 (Methocel K100M)
13,40%
[email protected]=
Ph, Eur,/NF
4P8
Xylisorb 90
2,21%
B9J8ALAJAf
1% Aerosil 200 Ph, Eur,/NF
"?[=D:=GG=O;[email protected]AM=GE9
:Bf
"?[=D:[email protected];EL9
:Bf
+=N;8=GEKA8;[email protected]=
(XII(a)
9=O;E=:9AC;=
XII(b))
XII(a)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
B9J8ALAJA=
0,01
. HCl
6A:;EK8;:;9E;GE98AK=9D
#8;J;;I=000;;9;
3017
6031
12046
18057
24067
30075
36082
42088
48091
60096
72097
84098
108099
132099
156099
1800100
.: 42
RU2477995C2
XII(b)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
=O;E=:9AC;=
0,01
. HCl
6A:;EK8;:;9E;GE98AK=9D
:9
#8;J;;I=).5;000;;9;
3034
6041
12047
18051
24056
30060
36065
42068
48071
60076
72080
84084
108089
1320100
1560100
1800100
IV.
40%
#AGE=KG?NGE8N:KNGKA?AFJ;9;:
KAEAU;99=O;E=:9AC;=
40%
KAJA:
8=GEKA8;\[email protected]=H89
H8;[email protected];[email protected];
XIV.
[email protected];
XIII
H8;[email protected];
GAGE=KO;[email protected]AM=GE99HAL8NE9DGAGE=K=
XIII
#AGE=K
,;[email protected]=D=GET3AL8NE9;
65,42%
=O;E=:9AC;=
150
:B=O;E=:9AC;=
9,29% Eudragit RL-PO
Kollicoat IR
9,29%
B9H8A:;@@AIN
Ph, Eur, USP 2208 Type V 100 (Methocel K100)
9,29%
[email protected];@@[email protected]
Ph, Eur, Type EF
2,99% Polaxamer 188 Ph, Eur,/NF
2,8%
B9J8ALAJA=f
1% Aerosil 200
"?[=D:=GG=O;[email protected]AM=GE9
:Bf
"?[=D:[email protected];EL9
:Bf
[email protected];
XIV
H8;[email protected];NJ=N;8=GEKA8;[email protected]A=
(XIV (a))
=O;E=:9AC;=
(XIV (b)).
XIV(a)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
B9J8ALAJA=
.: 43
RU2477995C2
36097
42097
48098
60098
72099
840100
108098
132099
156099
1800100
XIV(b)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
=O;E=:9AC;=
#AGE=KGI=:;J@;N:KNGKA?AFJ;9;:
KAEAU;99=O;E=:9AC;=
40%
KAJA:8=GEKA8;\E=[email protected]=H89
H8;[email protected];[email protected];
XVI.
[email protected];
H8;[email protected];GAGE=KO;[email protected]AM=GE99HAL8NE9DGAGE=K=
#AGE=K
,;[email protected]=D=GET3AL8NE9;
55,88%
=O;E=:9AC;=
120
:B=O;E=:9AC;=
13,50% Eudragit RL-PO
38,4
Kollicoat IR
11,0%
B9H8A:;@@AIN
Ph, Eur, USP 2208 Type V 100 (Methocel K100)
3,01%
B9H8A:;@@AIN
Ph, Eur, 2208 Type V 20000 (Methocel K100M)
13,40%
[email protected]=
Ph, Eur,/NF
4P8
Xylisorb 90
2,21%
B9J8ALAJA=f
1% Aerosil 200 Ph, Eur,/NF
"?[=D:=GG=O;[email protected]AM=GE9
:Bf
"?[=D:[email protected];EL9
:Bf
[email protected];
XVI
H8;[email protected];NJ=N;8=GEKA8;[email protected]A=
(XVI(a))
=O;E=:9AC;=
(XVI(b)).
XVI(a)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
B9J8ALAJA=
.: 44
RU2477995C2
6A:;EK8;:;9E;GE98AK=9D
:9
#8;J;;I=;-16.;-3;.10;9;
3012
6024
12038
18051
24062
30072
36080
42085
48091
60096
72099
840100
1080100
1320102
1560101
1800100
XVI(b)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
=O;E=:9AC;=
, 60
40%
5?NEAKAMLAC;:[email protected];
\LGE8PJ98AK=[email protected];EL99I:;@[email protected];;.6;;-10.;∞9;
H89
~20000-50000
:9
[email protected]@9;GEKA
\[email protected];EA;AJAM
[email protected];EL;
RU2477995C2
8=GEKA8;\[email protected]=H89
H8;[email protected];[email protected];
XVII.
+=N;HA8=GEKA8;[email protected]
B9J8ALAJA=
(XVII(a))
9=O;E=:9AC;=
(XVII(b))
H8;[email protected];N9F;
XVII(a)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
B9J8ALAJA=
XVII(b)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK==O;E=:9AC;=5
#AGE=KGI=:;J@;N:KNGKA?AFJ;9;:
KAEAU;99=O;E=:9AC;=
40%
KAJA:8=GEKA8;\E=[email protected]=H89
H8;[email protected];[email protected];
XVIII.
+=N;HA
8=GEKA8;[email protected]A=
(XVIII(a))
9=O;E=:9AC;=
(XVIII(b))
H8;[email protected];N
9F;
XVIII(a)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
B9J8ALAJA=
XVIII(b)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK==O;E=:9AC;=5
.: 46
RU2477995C2
3033
6045
12062
18073
24080
30084
36087
42088
48089
VI.
0,01
. HCl
#AGE=KG?NGE8N:KNGKA?AFJ;9;:
KAEAU;99=O;E=:9AC;=
0,01
. HCl
H89
H8;[email protected];[email protected];
XIX.
+=N;HA8=GEKA8;[email protected]=
(XIX(a))
9=O;E=:9AC;=
(XIX(b))
H8;[email protected];N9F;
XIX(a)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
B9J8ALAJA=
XIX(b)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK==O;E=:9AC;=5
#AGE=KGI=:;J@;N:KNGKA?AFJ;9;:
KAEAU;99=O;E=:9AC;=
0,01
HCl
H89
H8;[email protected];[email protected];
XX.
+=N;HA8=GEKA8;[email protected]
B9J8ALAJA=
(XX(a))
9=O;E=:9AC;=
(XX(b))
H8;[email protected];N9F;
XX(a)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
B9J8ALAJA=
.: 47
RU2477995C2
12017
18023
24028
30032
36037
42041
48044
XX(b)
5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK==O;E=:9AC;=5
VIII.
3AL8NE9;\LGE8PJ98AK=[email protected];[email protected]=9E;@T-99E;@T-;(.6;A:[email protected]=F9K=-99E;@T-;(.6;9Q
HAK;8S[email protected];EL9
"?[[email protected]=
[email protected]@=
4,69
8=GGEAD9;:;FJPU=B=:[email protected]@A
[email protected]=K=?;IHAL8NE9D
CLA=0,56,
LABJ=
(N=69),
L=LHAL=I=A=C9B
.3.
6;FJPE;:
[email protected]=K=GHAL8NE9;:
CLA=0,15,
LABJ=
(N=69),
L=LHAL=I=A=C9B
.4.
IX.
0,01
. HCl
#AGE=KGI=:;[email protected];N:KNGKA?AFJ;9;:
KAEAU;99=O;E=:9AC;=
0,01
. Cl
H89
H8;[email protected];[email protected][email protected]NSGAGE=KAK
9-12
[email protected]=S
XXII
XXIII.
&A:HAI9O99GAGE=KAKH8;[email protected];[email protected];
XXI.
[email protected]=
XXI
#AGE=K#AGE=K
#AGE=K
#AGE=K
#AGE=K
&A:HAI9O9D
=O;E=:9AC;=
=O;E=:9AC;=
=O;E=:9AC;=
=O;E=:9AC;=
12,6% Eudragit RL-PO12,6% Eudragit RL-PO12,6% Eudragit RL-PO12,6% Eudragit RL-PO
.: 48
RU2477995C2
6,0%
B9H8A:;@@AIN
Ph.
Eur. USP 2208 Type V 100
(Methocel
100)
6,0%
B9H8A:;@@AIN
Ph.
Eur. USP 2208 Type V 100
(Methocel
100)
6,0%
B9H8A:;@@AIN
Ph.
Eur. USP 2208 Type V 100
(Methocel
100)
6,0%
B9H8A:;@@AIN
Ph.
Eur. USP 2208 Type V 100
(Methocel K100)
6,0%
B9H8A:;@@AIN
Ph.
Eur. 2208 TypeV 20000
(Methocel K100M)
6,0%
B9H8A:;@@AIN
Ph.
Eur. 2208 Type V 20000
(Methocel K100M)
6,0%
B9H8A:;@@AIN
Ph.
Eur. 2208 Type V 20000
(Methocel K100M)
6,0%
B9H8A:;@@AIN
Ph.
Eur. 2208 Type V 20000
(Methocel K100M)
12,6% X
[email protected]=
Ph.
Eur./NF
4P8
Xylisorb 90
12,6%
[email protected]=
Ph. Eur./NF
4P8
Xylisorb 90
12,6%
[email protected]=
Ph. Eur./NF
4P8
Xylisorb 90
12,6%
[email protected]=
Ph. Eur./NF
4P8
Xylisorb 90
1,8%
B9J8ALAJA=
1,8%
B9J8ALAJA=
1,8%
B9J8ALAJA=
1,8%
B9J8ALAJA=
1% Aerosil 200 Ph.
Eur./NF
1% Aerosil 200
Ph. Eur./NF
1% Aerosil 200
Ph. Eur./NF
1% Aerosil 200 Ph. Eur./NF
3AL8NE9;f
50,0
:B=O;E=:9AC;=
85,0
:B=O;E=:9AC;=
120,0
:B=O;E=:9AC;=
16,0
Kollicoat IR27,2
Kollicoat IR38,39
Kollicoat IR
7=J==D:=GG=
833
899
945,2
99,39
XXII
5NGKA?AFJ;9;
@;L=8GEK;ABAG8;JGEK=
B9J8ALAJA=
#AGE=K
#AGE=K
#AGE=K
#AGE=K
6A:;EE;GE98AK=9D
:9
#8;J;;I=).5;000;;9;K
#8;J;;I=;).5;-15;.900;9;K
#8;J;;I=;-;.5;9;K
#8;J;;I=;).5;-15;.900;9;K
00000
3021201916
6030303028
12042434443
18051535453
24058606261
30064676867
36069727473
42074777978
48078818382
XXIII
5NGKA?AFJ;9;@;L=8GEK;ABA
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307151922
6011192326
12017252932
18022293336
24026333740
30030364043
36033394245
42036424548
48039454851
0,01
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#AGE=KG?NGE8N:KNGKA?AFJ;9;:
KAEAU;99=O;E=:9AC;=
0,01
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H89
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XXV.
[email protected];
XXIV
H8;JGE=K@;GAGE=K
O;[email protected]AM=GE9GAGE=K=
13.
XXIV
#AGE=K
,;[email protected]=D=GET2;IHAL8NE9D
65,42%
=O;E=:9AC;=
9,29% Eudragit RL-PO
9,29%
B9H8A:;@@AIN
Ph. Eur. USP 2208 Type V 100 (Methocel K10)
.: 49
RU2477995C2
9,29%
[email protected];@@[email protected]
Ph. Eur. Type EF
2,99% Polaxamer 188 Ph. Eur./NF
2,8%
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1% Aerosil 200
"?[=D:=GG=
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6A:;EK8;:;9E;GE98AK=9D
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3028
6038
12050
18062
24072
30080
36088
42095
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600100
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3013
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12027
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1320104
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H89
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XXVII.
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XXVI
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13.
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XXVI
#AGE=K
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55,88%
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Ph, Eur, 2208 Type V 20000 (Methocel K100M)
13,40%
[email protected]=
Ph, Eur./NF
4P8
Xylisorb 90
2,21%
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1% Aerosil 200 Ph, Eur./NF
"?[=D:=GG=
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3030
6042
12054
18065
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30079
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5NGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK==O;E=:9AC;=5
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3011
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12025
18031
24036
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42053
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60063
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84074
108091
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RU2477995C2
1800103
12:
7=J=;[email protected];JAK=-9.1;10.;M-2;h.2; -2.; G-1;.3G;.1;[email protected];.1;-;.1J; -8.;K=-;.7;[email protected]=K-9.1;10.;M-2;h.2; -2.; G-1;.3G;.1;[email protected];.1;-;.1J; -8.;K=-;.7;-9.1;10.;M-2;h.2; -2.; G-1;.3G;.1;[email protected];.1;-;.1J; -8.;K=-;.7;;9;?9AJAGEPH-9.1;10.;M-2;h.2; -2.; G-1;.3G;.1;[email protected];.1;-;.1J; -8.;K=-;.7;AGE9JKPSE;GE98P;:NS
GAGE=KAK
G?9AJAGEPHAGETQLA[email protected]@DG8=K;9D
H8;[email protected];ABAK
[email protected];
#S;:=9GH[email protected][email protected]=AEL8NEA;
GAGEAD[;;9IE8;SH;89AJAK
H;8;L8;GEA;9GHNE=9;AJAL8=EAMJAIN=EA[=LP
GP?e;LE=
[email protected][email protected]=
AJ[email protected];ELPGAGE=K=
15;
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[email protected][email protected]=AJ=-9.;[email protected]=-;❚J-9.;У[email protected];ELPGAGE=K=
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[email protected][email protected]=AJ.4=;[email protected];.8=-;ɘ.;ΨJ;.6;[email protected];ELPLA.4=;[email protected];.8=-;ɘ.;ΨJ;.6;[email protected]
"[email protected];8;I
0, 0,25, 0,5, 0,75,
1, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36
[email protected];JAIN=9.6;G8.8; .4;K-26;.9H;.2A;G8.8;[email protected];-;ɖ.;JA1;.6I;.4;N-26;.20;=
GPEL99GHNE=9D
H8;[email protected];AM9F;[email protected];
XXVIII
[email protected]@QGE898AK=NGAGE=KNE;GE98P;:NS
GAGE=KAK
15, 16
9L[email protected]
E=LF;C9B
[email protected];J9SLAO;E8=O9M
B9J8ALAJA=9=O;E=:9AC;[email protected]=KAK
15, 16
9L[email protected]
#AGE=KN
5, 7
[email protected][;GEKP9J;E9.5;N:9J8PBJ8PBP
AJ=LAA9H8AP:;8AK=NHA
8=IA:[email protected].4;AM.4;P:;8=O99E;GEAK9\LGH;89:;.4;EAK
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GAGE=KN9
6, 8
[email protected][;GEKP9J;E9-8.5;N:9J8PBJ8PBP
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H8AP:;8AK=NHA
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8=IA:[email protected]ကAMကP:;8=O99E;GEAK9
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JAI98AK=AMCA8:[email protected];EGDGAGE=K
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[email protected]=K
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GKAMGEK=G:;U9K=9D
;:GAGE=K
16,
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;:GAGE=K
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9:;;[email protected];PJ;8F9K=Q[9;AEI=K9G9:AGE9GKAMGEK=
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[email protected];GEKA
[email protected];EL=#AGE=K
#AGE=K
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15, 16
LA[email protected]
H8;[email protected];N9F;[email protected];
XXIX.
XXIX
#S;:=
)=8:=LAL9;E9;GL9;H=8=:;E8N
X9J8ABAJA
(N=20)
AUC
AUC
CL/F (
#AGE=K
4,4
(33%)
14,0
(17%)
205
(19%)
209
(l8%)
6,22
(18%)
447
(19%)
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4,4
(32%)
13,0
(19%)
204
(20%)
209
(20%)
5,93
(22%)
45,0
(18%)
&A[email protected]
4,8
(63%)
12,6
(20%)
211
(18%)
214
(18%)
5,68
(19%)
43,5
(16%)
.: 52
RU2477995C2
'O;E=:9AC;
(N=20)
AUC
:LB
AUC
:LB
CL/F (
#AGE=K
150,74 (66%)206 (25%)21,2 (29%)22,9 (30%)9,85 (46%)24,0 (33%)
#AGE=K
160,82 (82%)2,41 (32%)22,1 (24%)
22,3 (25%)5,59 (21%)23,7 (24%)
&A[email protected]
10,83 (22%)2,23 (24%)22,1 (26%)
22,4 (26%)6,47 (24%)23,7 (24%)
*N=18
38;JK=89E;@TN;J=N;HAAEAG9E;@TAM?9AJAGEPHAGE9GAGE=KAK
H8AE9KLA[email protected]
H8;[email protected];N9F;[email protected];
XXX.
XXX
"EAG9E;@T=D?9AJAGEPHAGET
#S;:N
4;GEH8AE9K\[email protected]=
3=8=:;E8
,;[email protected]A;I=;-47;.100;9;
4A;-900;=D
AO;L=
JAK;89E;@TNM
9E;[email protected]
4;GE^[email protected]A
X9J8ALAJAf
#AGE=K
H8AE9KLA[email protected]
#AGE=K
H8AE9KLA[email protected]
13,950
13,240
12,626
12,626
1,105
1,049
0,985-1,116
#AGE=K
H8AE9KLA[email protected]
#AGE=K
H8AE9KLA[email protected]
AUC
AUC
199,636
203,905
206,338
206,338
0,968
0,988
0,919-1,019
0,937-1,042
#AGE=K
H8AE9KLA[email protected]
#AGE=K
H8AE9KLA[email protected]
AUC
AUC
204,492
208,867
210,187
210,187
0,973
0,994
0,926-1,022
0,944-1,046
'O;E=:9AC;f
#AGE=K
H8AE9KLA[email protected]
#AGE=K
H8AE9KLA[email protected]
2,014
2,395
2,193
0,918
1,092
0,858-0,983
1,018-1,172
#AGE=K
H8AE9KLA[email protected]
#AGE=K
H8AE9KLA[email protected]
AUC
AUC
20,580
22,363
21,732
21,732
0,947
1,029
0,899-0,998
0,975-1,086
#AGE=K
H8AE9KLA[email protected]
#AGE=K
H8AE9KLA[email protected]
AUC
AUC
22,171
22,402
21,987
21,987
1,008
1,023
0,944-1,077
0,956-1,095
'[email protected]=89C:G8;J;LK=J8=E9NSG8;J9SI=;.1;-0.;у[email protected]@AB=89C:AK
'[email protected]=89C:8=I9ON
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$GSAJD9IH8;JK=89E;@TNSJ=NSJK=E;GE98P;:NSGAGE=K=
[email protected]
[email protected];GL9\[email protected];.1;;-11.;G9.;L-5;.99-;ɩ.;-24;.7L-;.9K;-10.;Y-1;.1K;=-20;[email protected];; .10;E.1;;-11.;G9.;L-5;.99-;ɩ.;-24;.7L-;.9K;-10.;Y-1;.1K;=-20;[email protected];; .10;N:9LA.1;;-11.;G9.;L-5;.99-;ɩ.;-24;.7L-;.9K;-10.;Y-1;.1K;=-20;[email protected];; .10;[email protected]
KAEAU;99L=L
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AUC
3;8KA[email protected]-8.9;[email protected];(.5;=DGLA8AGETKG=GNK=-8.9;[email protected];(.5;9DB9J8ALA-8.9;[email protected];(.5;[email protected];EGD-8.9;[email protected];(.5;;:-8.9;[email protected];(.5;[email protected];;-8.9;[email protected];(.5;9ILAM
[email protected];GE98P;:NSGAGE=KAK
HAG8=K;9QGLA[email protected];:
13:
in vitro
#@;JPQ[9;GAGE=KN
18,
L=LH8;[email protected];A9F;[email protected];
XXXI,
[email protected];[email protected]
[email protected]@;MKNGKA?AFJ;[email protected];L=8GEK;ABAG8;JGEK=
in vitro
9\[email protected]
G8=K[email protected];[email protected]AM=GETQ?;IHAL8NE9D
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L=LHAL=I=A=
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(b).
XXXI
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[email protected];EL=
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USP
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15,9
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15,9
(2,2%)
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USP
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380,0
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350,0
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RL-PONF/Ph. Eur.
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I=:;[email protected];ABAKNGKA?AFJ;9D
91,8
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49,7
(9,3%)
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2208,
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49,7
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.: 53
RU2477995C2
[email protected]
NF/Ph. Eur.
6AJ9C9L=EA8KNGKA?AFJ;9D
91,1
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Poioxarner 188NF/Ph. Eur.
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16,0
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LA;AM\LGE8PJ98AK=[email protected];EL9
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49H
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13,4
12,612,6
Poloxamer 188 Ph. Eur./NF
49H
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2,79
:LB
:@[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=
500
:B=O;E=:9AC;=
5H8;JHAE9E;@T.9;ຘ.;1;[email protected];.9;T-16;.900;NSK=8.9;ຘ.;1;[email protected];.9;T-16;.900;9=E=SAGP[;[email protected];.9;ຘ.;1;[email protected];.9;T-16;.900;9D
JAI98AK==DCA8:=A?;GH;9K=;ELA:?9-0.9;.3;K-11;.5=8;.9;8;.1E-;ɠL;-6.9;©.9;:-8.;?95;.300;98AK=-0.9;.3;K-11;.5=8;.9;8;.1E-;ɠL;-6.9;©.9;:-8.;?95;.300;-0.9;.3;K-11;.5=8;.9;8;.1E-;ɠL;-6.9;©.9;:-8.;?95;.300;PQ
[email protected]=9
=O;E=:9AC;[email protected];@TA
1,38
:@[email protected];@TA
2,23
:LB
:@[email protected];
AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
500
=O;E=:9AC;=
5H8;JHAE9E;@T.1;ç.1;9;[email protected];.1T;-8.5;NSK=89=.1;ç.1;9;[email protected];.1T;-8.5;E=SAGP[;[email protected];.1;ç.1;9;[email protected];.1T;-8.5;9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;=
1,80
0,42
:LB
:@G
95%
JAK;89E;@TN:9E;[email protected]:[email protected];J;BAI=.2;;;[email protected];@T.2;;A
1,61
:@JA
[email protected];@TA
2,00
:LB
:@[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
. 95%
JAK;89E;@TNM9E;[email protected]@D
LA:?998AK=AM
[email protected]=9=O;E=:9AC;[email protected]=;H8;JHAE9E;@T-12;.69E;-12.;@T;-180;NS
K=89=EAKAGP[;[email protected];9D9LA[email protected];8;L8NK=;EGD
. 95%
JAK;89E;@TNM9E;[email protected]
[email protected];J;BAI=;.8;16.;«9DLA:?9.8;16.;«98AK=.8;16.;«.8;16.;«AM
[email protected]A=9=O;E=:9AC;[email protected]
[email protected]=SAJ9EGDKJ9=H=IA;[email protected];@TAAE
1,46
1,96
:LB
[email protected];
KK;J;9DKL=;GEK;AJ.6;16.;G16;.4E1;.6K;-23;.7A;.2;J7.4;AL8=E.6;16.;G16;.4E1;.6K;-23;.7A;.2;J7.4;AMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=H=O9;EP
;@AK;LP
&A[email protected]?;GH;9K=;E
JAGE=EA .50;N;P .50;[email protected]=I:;AH9A9J .50;ABA9 .50;;AH9A9J .50;ABA= .50;[email protected];[email protected]
A?;GH000;;;9D000;G9F000;;9D9000;E;000;G000;[email protected];J;@[email protected];@T000;A
[email protected];
KK;J;9D
389KK;J;[email protected];K;8NS=:;89L=O;[email protected]=H=JNS
;K8AH;MO;K
K=G.8=;G11.;踀EAGE9
LABJ=GAGE=K=J=HE98AK=
EA?NA-14;.3A?;N-27;.3A;-9.7;[email protected];-14;.3A?;N-27;.3A;-9.7;[email protected]
H8;J=I=;.6;26.;«[email protected];J;.6;26.;«9D;@AK;LPL=FJN;
=GAKH89-9.8;=-10;.2G9;.4A-; .2K;-275;.5H-;.6;-2;h.9;;A?SAJ9:AGE9
[email protected];@TA
20-45%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-6;1;.20;9;[email protected];@T-6;1;.20;A
[email protected];@T-9=-; .4G;=-27;.79;-268;.1H-;.8;-1;[email protected];-13I; .69;-23;.2;1;[email protected];-10T;-18.;лA
20-45%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.7;;.7;9;[email protected];@T.7;;.7;A
=G=K
0,01
. HCl
H89
:9H89
5J8PBA:K=89=E;AGP[;[email protected];9D
[email protected];@TA
25-35%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-6;1;.20;9;[email protected];@T-6;1;.20;A
=G=9H8[email protected];@T-9=-; .4G;=-27;.79;-268;.1H-;.8;-1;[email protected];-13I; .69;-23;.2;1;[email protected];-10T;-18.;лA
25-35%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.7;;.7;9;[email protected];@T.7;;.7;A
=G=K
0,01
. HCl
H89
:9H89
&8A:;EABA
KJ8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
.: 65
RU2477995C2
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;AE
60%
[email protected];@TA
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
8,5
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7;1;.20;9;:;-7;1;.20;;;;:[email protected];@T.2;;.2;:-27;H-1;.88;-6.4; ?-6;[email protected];-0;.8I9;@T;-26.;«A
=GAK
9HA
:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-5.7;13.;у9;:;-5.7;13.;у;;;:[email protected];@T-5.7;13.;:-2;h.7;H-12;.58-;.19;?-5.;[email protected]; .7I;.9; -9.;~-;[email protected];.7;T-15;.100;A
=GAK
"J=LALABJ=K=89=EGI=:;[email protected];N:KNGKA?AFJ;9;:GAGE=K==J=HE98AK=
EA?NA-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];J-13;.8A?;-9.2;N-26;.6A;-19.;л-13;.8A?;-9.2;N-26;.6A;-19.;л=I=;-9.8;9.4;[email protected];J;-9.8;9.4;9D;@AK;LPJK=8=I=KGPEL9
;A?SAJ9:AGE9
EABJ=HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D\EABAK=89=E=
AGP[;[email protected];9DGI=:;[email protected];N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
B9J8ALAJA=
KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.7;; .70;9;[email protected];@T.7;; .70;A
[email protected];@T=-9G; -8K;-264;.1J1;.6A-;ɳ.;H-5;.28-;.2; -2.;[email protected]; .69;I9E;;-9.8;[email protected];∞A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.1;;.1;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
.: 66
RU2477995C2
AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;:;.5;9.3;;;;:
[email protected];@TA
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.5;12.;Δ9;:-6.5;12.;Δ;;;;:[email protected];@T-6.5;12.;:-2;i.5;H-13;.38-;.99;-0.3;?-5.;[email protected];.59I;.1; -10;.5E-;.3;;[email protected];.90;A
=GAK
5H8;JHAE9E;@T-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;A:K=89=-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;E;AGP[;[email protected]-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;;9D
=GEAD[;;9IA?8;E;9;AEAG9EGDL
LA:HAI9O99
BJ;O;[email protected][email protected];8F9E\LGO9H9;[email protected]:;GT\LGO9H9;EAK
GHAGA?NSLA[email protected]=ETKNGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=
;O;[email protected][email protected];8F9E\LGO9H9;E
GHAGA?NM;:;[email protected];AKNGKA?AFJ=ET
@;L=8GEK;A;G8;JGEKA
&8A:;EABA
KH8;JHAE9E;@T.4E;.6;22;[email protected];-600;A:K=89=.4E;.6;22;[email protected];-600;E;AGP[;[email protected].4E;.6;22;[email protected];-600;;9D
O;[email protected][email protected]@P;.7;9.5;HPE;:\LGE8PJ98A.7;9.5;[email protected][email protected];JPQ[9:
H8D:N:H89J=9;:CA8:NGAJ;8F=[;:[email protected];L=8GEK;A;G8;[email protected]=KP
;O;[email protected][email protected]=;G;[email protected];9;:=O;[email protected][email protected]
/[email protected];;
H8;JHAE9E;@T.8E;᎑Ϣ.;15;[email protected];.8T7;.600;A
LA:HAI9O9DGAJ;[email protected];@TA
500
:B=O;E=:9AC;=9
[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=
5J8PBA:K=89=E;
AGP[;[email protected];9D
;O;[email protected][email protected]
[email protected];[email protected];EL9
:AF[email protected]=ETJ8PB9:
GHAGA?A:
5\EA:GHAGA?;
[email protected]@;A.60;[email protected]=QEAEJ;@T.60;A
\LGE8PJ98AK=9;:9\LGE8PJ=EPH89J=QECA8:[email protected];L9
^[email protected];[email protected]=J8
[email protected];99O;[email protected]TNS=GE;M
^EAEGHAGA?AGA?;AH89BAJ;[email protected]@GENS
[email protected];K
EAPGE8=-11;.7A-;ɢ.;P-1;.3G;.5;-1.;X-1;.3=;.10;D;[email protected];@T-11;.7A-;ɢ.;P-1;.3G;.5;-1.;X-1;.3=;.10;A;K8;:D-11;.7A-;ɢ.;P-1;.3G;.5;-1.;X-1;.3=;.10;=-11;.7A-;ɢ.;P-1;.3G;.5;-1.;X-1;.3=;.10;;G-11;.7A-;ɢ.;P-1;.3G;.5;-1.;X-1;.3=;.10;;[email protected];-11;.7A-;ɢ.;P-1;.3G;.5;-1.;X-1;.3=;.10;9;:
9A
H8;[email protected];EGA?AMH8AO;GG?;I8=GEKA89E;@D
^E=E;S[email protected]=LF;9IK;GE=L=L
E;S[email protected]
Xellex.
5J8PBA:[email protected]@QGE8=E9KA:K=89=E;AGP[;[email protected];9D
=GEAD[;;9IA?8;E;9;
AEAG9EGDLC=8:=O;KE9;GLAMLA:HAI9O99
9:;Q[;MO;[email protected]NM9;O;[email protected]NM
GAJ;8F=[;M
: (a)
RU2477995C2
G8;JGEK=H899I:;@T;.5;;-9.9;99HAKNU=;EGD:;.5;;-9.9;;;;:K
2-3
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HAG8=K;9QGO;@AM
[email protected];ELAM
LABJ=LA:HAI9O9Q9I:;@T=QEKE;;-9.; 9;
:9PENLAC;:[email protected]
20000-
50000
:9
40%
KAJA:8=GEKA8;\[email protected]=KE;;.8;9.6;9;
=G=H89
9I:;@T;.3;16.;က.3;16.;က=DLA:HAI9O9DGAJ;8F9E=GE9ON8=I:;8A:[email protected];@T.1=;.9;G16.;ẑ.3O;.9;N-25;.98;=16.; I25;.7:-;.8;;.1;ࠗ.;:-;ɕ.;騗.9E-;ɒH;.7;ओ.;?7.;[email protected];.393;.1I2;.79;.1E;.3;16.;[email protected];.3T-;.30;A
[email protected];@TA
355
:9L8A:;[email protected][email protected];@TA
20%
C8=LO99
[email protected];;;:
[email protected];@TA
:9L8A:;E8AK9:;;;;:[email protected];.4;:-2;Y.8;H6.6;.8; ?14;[email protected];I-0;.8I2;.89; .4E;12.;[email protected];@TA
355
:9L8A:;[email protected]
[email protected];@TA
66%
C8=LO999:;;;;:[email protected];@T.1;-0.;:-2;Q.9;H-5.;颗[email protected];.1;.1;I9.3;.1;-3.;9.;[email protected];.1T-;.50;A
:9L8A:;[email protected]
[email protected];@TA
14%
C8=LO99
H899I:;8;99GHA:A[TQE;GE=H8AG;9K=9;:
[email protected]
viii)
LA:[email protected];EGDHAGP[;GEKPAJA8AJAM
BJ;G8;J;;I=;.1;;#.3;9;
O;[email protected][email protected]999
(CLA)
[email protected];[email protected];@TA
0,1
[email protected];@TA
0,6,
H8;JHAE9E;@T-8.2;ພ-;.2;@-9;.2T-;.40;[email protected];@T-8.2;ພ-;.2;@-9;.2T-;.40;A
0,1
[email protected];@TA
0,4,
[email protected];;
H8;JHAE9E;@T-8.2;ພ-;.2;@-9;.2T-;.40;[email protected];@T-8.2;ພ-;.2;@-9;.2T-;.40;A
0,1
[email protected];@TA
0,2.
5\EAMLA:HAI9O99
[email protected];GEKAKNINK=Q[;BAI=K9G9:[email protected];L=8GEK;GE-;.8;K-8.;*-2;b.3;K-8.;N-3;.5IN;K=-1;.4Q;-10.; [-4;.3;B;-14.;*-2;r.5;I10.;=K-;.4; G-9; :AG;-11;.8T-;ɲ.;[email protected];.8;1;.2L=;-8.2;-7.;G1.;.K-;.2;;-900;GE-;.8;K-8.;*-2;b.3;K-8.;N-3;.5IN;K=-1;.4Q;-10.; [-4;.3;B;-14.;*-2;r.5;I10.;=K-;.4; G-9; :AG;-11;.8T-;ɲ.;[email protected];.8;1;.2L=;-8.2;-7.;G1.;.K-;.2;;-900;ABA
G8;JGEK=
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40%
KAJN:8=GEKA8A:\E=[email protected]=KE000;;;9;
AJABA=G=H89
[email protected];[email protected];@TA
70%
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130%
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5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
H8;JHAE9E;@T-19.;.-2;.29;-13E;-23.;@-; .2;T-28;.600;[email protected];EGD
H8;[email protected];NM9F;C=8:=LAL9;E9;[email protected]
LABJ=AJAL8=E=DJAI=
GAJ;[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
[email protected];@TA
500
:B=O;E=:9AC;=
H89KK;J;99H=O9;EP=EA[=L
389KK;J;99
H=O9;EP
;@AK;LP
JAI98AK==DCA8:=A?;GH;9K=;E
AUC
[email protected]=AE
[email protected];@TA
9,1
:[email protected];@TA
19,9
:B9
AUC
=O;E=:9AC;[email protected];@TA
28,6
:[email protected];@TA
59,1
5J8PBA:K=89=E;AGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
AUC
B9J8ALAJ[email protected];@TA
7,0
:[email protected];@TA
26,2
AUC
[email protected]=O;E=:9AC;[email protected];@TA
18,4
:[email protected];@TA
79,9
5J8PBA:K=89=E;AGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
AUC
[email protected][email protected];@TA
11,3
:[email protected];@TA
18,7
:B9
AUC
[email protected]=O;E=:9AC;[email protected];@TA
28,7
:BJA
[email protected];@TA
53,5
38;JHAE9E;@T-9.2;ພ-;.2;@-1;.2T;-8.4;AK\EA:K=89-9.2;ພ-;.2;@-1;.2T;-8.4;=E;AGP[;[email protected];-9.2;ພ-;.2;@-1;.2T;-8.4;9D
GLA8AGETKNGKA?AFJ;9DC=8:=O;KE9;GLAMLA:HAI9O99
in vitro
9:;;EJKPSC=INM
[email protected]?AFJ;9D
9BJ;[email protected]=FJAMC=INGLA8AGETKNGKA?AFJ;9D
in vitro
9:;;E[email protected];[email protected];[email protected]=O;E=:9AC;=9[email protected];KAMHA8DJAL
[email protected];[email protected]=
389KK;J;[email protected];K;8NS=:;89L=O;[email protected]=H=JNS
;K8AH;MO;K
K=G.8=;G11.;踀EAGE9
LABJ=GAGE=K=J=HE98AK=
EA?NA-14;.3A?;N-27;.3A;-9.7;[email protected];-14;.3A?;N-27;.3A;-9.7;[email protected]
H8;J=I=;.6;26.;«[email protected];J;.6;26.;«9D;@AK;LPL=FJN;
=GAKH89-9.8;=-10;.2G9;.4A-; .2K;-275;.5H-;.6;-2;h.9;;A?SAJ9:AGE9
[email protected];@TA
20-45%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-6;1;.20;9;[email protected];@T-6;1;.20;A
[email protected];@T-9=-; .4G;=-27;.79;-268;.1H-;.8;-1;[email protected];-13I; .69;-23;.2;1;[email protected];-10T;-18.;лA
20-45%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.7;;.7;9;[email protected];@T.7;;.7;A
=G=K
0,01
. HCl
H89
:9H89
5J8PBA:K=89=E;AGP[;[email protected];9D
[email protected];@TA
25-35%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-6;1;.20;9;[email protected];@T-6;1;.20;A
[email protected];@T-9=-; .4G;=-27;.79;-268;.1H-;.8;-1;[email protected];-13I; .69;-23;.2;1;[email protected];-10T;-18.;лA
25-35%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.7;;.7;9;[email protected];@T.7;;.7;A
=G=K
0,01
. HCl
H89
:9H89
&8A:;EABA
KJ8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;AE
60%
[email protected];@TA
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
.: 71
RU2477995C2
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
8,5
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7;1;.20;9;:;-7;1;.20;;;;:[email protected];@T.2;;.2;:-27;H-1;.88;-6.4; ?-6;[email protected];-0;.8I9;@T;-26.;«A
=GAK
9HA
:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-5.7;13.;у9;:;-5.7;13.;у;;;:[email protected];@T-5.7;13.;:-2;h.7;H-12;.58-;.19;?-5.;[email protected]; .7I;.9; -9.;~-;[email protected];.7;T-15;.100;A
=GAK
"J=LALABJ=K=89=EGI=:;[email protected];N:KNGKA?AFJ;9;:GAGE=K==J=HE98AK=
EA?NA-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];J-13;.8A?;-9.2;N-26;.6A;-19.;л-13;.8A?;-9.2;N-26;.6A;-19.;л=I=;-9.8;9.4;[email protected];J;-9.8;9.4;9D;@AK;LPJK=8=I=KGPEL9
;A?SAJ9:AGE9
EABJ=HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D\EABAK=89=E=
AGP[;[email protected];9DGI=:;[email protected];N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
B9J8ALAJA=
KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.7;; .70;9;[email protected];@T.7;; .70;A
[email protected];@T=-9G; -8K;-264;.1J1;.6A-;ɳ.;H-5;.28-;.2; -2.;[email protected]; .69;I9E;;-9.8;[email protected];∞A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.1;;.1;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;:;.5;9.3;;;;:
[email protected];@TA
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
.: 72
RU2477995C2
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.5;12.;Δ9;:-6.5;12.;Δ;;;;:[email protected];@T-6.5;12.;:-2;i.5;H-13;.38-;.99;-0.3;?-5.;[email protected];.59I;.1; -10;.5E-;.3;;[email protected];.90;A
=GAK
5H8;JHAE9E;@T-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;A:K=89=-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;E;AGP[;[email protected]-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;;9D
=GEAD[;;9IA?8;E;9;AEAG9EGDL
LA:HAI9O99
BJ;O;[email protected][email protected];8F9E\LGO9H9;E
GHAGA?NMLA[email protected]=ET
KNGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=9;O;[email protected][email protected];8F9E\LGO9H9;E
RU2477995C2
GAJ;[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
[email protected];@TA
500
:B=O;E=:9AC;=
H89KK;J;99H=O9;EP=EA[=L
38;JHAE9E;@T-12;.89E;-12.;@1;.6T;-28.;лAH89KK;J-12;.89E;-12.;@1;.6T;-28.;л;99H=O9;-12;.89E;-12.;@1;.6T;-28.;лEP
;@AK;LPC=8:=O;KE9;GL=DLA:HAI9O9D
A?;GH;9K=;EL.7;.7;K-10;.1=;; .5E;-258;.6L4;.7A0;AO;.7;.7;K-10;.1=;; .5E;-258;.6L4;.7A0;[email protected]=I:;;8;I
(C1)
[email protected]A=AE
[email protected];@TA
0,18
:[email protected];@TA
1,51
9LAO;E8=O9QK
[email protected]=I:;
;8;I
[email protected]=O;E=:=-8.;G-2;d.4;J2.1;[email protected];-2;V.2;=O-2;.7;;.1;-12;.1=-;.5:;-5.8;退9AC;=-8.;G-2;d.4;J2.1;[email protected];-2;V.2;=O-2;.7;;.1;-12;.1=-;.5:;-5.8;退[email protected];@T=-8.;G-2;d.4;J2.1;[email protected];-2;V.2;=O-2;.7;;.1;-12;.1=-;.5:;-5.8;退A
2,34
:BJA
[email protected];@TA
7,24
5H8;JHAE9E;@T.1;ç.1;9;[email protected];.1T;-8.5;NSK=89=.1;ç.1;9;[email protected];.1T;-8.5;E=SAGP[;[email protected];.1;ç.1;9;[email protected];.1T;-8.5;9D
E=L9SL=LGAGE=K
15,
JAI98AK==D
CA8:=A?;GH;9K=;E
[email protected][email protected];@TA
0,32
:BJA
[email protected];@TA
1,51
:B9
[email protected]=O;E=:9AC;[email protected];@TA
2,34
:[email protected];@TA
5,50
5;LAEA8NSJ8PB9SK=89=E=SAGP[;[email protected];9D
H8;JHAE9E;@T.5E;-6.7;@;.5T;-22.;У[email protected];EGD
H8;[email protected];NM9F;C=8:=LAL9;E9;[email protected]
LABJ=AJAL8=E=DJAI=
GAJ;[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
[email protected];@TA
500
:B=O;E=:9AC;=
H89KK;J;99H=O9;EP=EA[=L
38;JHAE9E;@T-12;.89E;-12.;@1;.6T;-28.;лAH89KK;J-12;.89E;-12.;@1;.6T;-28.;л;99H=O9;-12;.89E;-12.;@1;.6T;-28.;лEP
;@AK;LPC=8:=O;KE9;GL=DLA:HAI9O9D
A?;GH;9K=;EL.7;.7;K-10;.1=;; .5E;-258;.6L4;.7A0;AO;.7;.7;K-10;.1=;; .5E;-258;.6L4;.7A0;[email protected]=I:;;8;I
(C1)
[email protected]A=AE
[email protected];@TA
0,30
:[email protected];@TA
1,06
[email protected]
=O;E=:9AC;[email protected];@TA
2,75
:[email protected];@TA
5,57
H8;JHAE9E;@T-8.7;ພ-;.7;@-9;.7T-;.90;NSK=89=-8.7;ພ-;.7;@-9;.7T-;.90;E=SAGP[;[email protected];-8.7;ພ-;.7;@-9;.7T-;.90;9D
JAI98AK==DCA8:=A?;GH;9K=;E
[email protected][email protected];@TA
0,45
:[email protected];@TA
1,06
[email protected]=O;E=:9AC;[email protected];@TA
2,75
:[email protected];@TA
4,43
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;[email protected];@TA
1,18
:LB
:@[email protected];@TA
3,63
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=
?9E=8E8=E=H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5H8;JHAE9E;@T.4;.4;1;[email protected];.4;T-7.; NS
K=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;ELA:-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;?998A-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;K=-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;PQ
[email protected]=9=O;E=:9AC;[email protected];@TA
1,18
:LB
:@JA
[email protected];@TA
2,76
:LB
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;[email protected];@TA
1,38
:LB
:@[email protected];@TA
2,79
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=
?9E=8E8=E=H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5H8;JHAE9E;@T.4;.4;1;[email protected];.4;T-7.; NS
K=89=E=SAGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;ELA:-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;?998A-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;K=-0.3;.9;K=;8;.7E-;ə.;L-6;.3A1;.5:;?90;PQ
[email protected]=9=O;E=:9AC;[email protected];@TA
1,38
:LB
:@JA
[email protected];@TA
2,23
:LB
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
5H8;JHAE9E;@T.1;ç.1;9;[email protected];.1T;-8.5;NSK=89=.1;ç.1;9;[email protected];.1T;-8.5;E=SAGP[;[email protected];.1;ç.1;9;[email protected];.1T;-8.5;9D
JAI98AK==DCA8:=A?;GH;9K=;E
LA:?998AK=PQ
[email protected]JA=9=O;E=:9AC;=
1,80
0,42
:LB
:@G
95%
JAK;89E;@TN:9E;[email protected]:[email protected];J;BAI=.2;;;[email protected];@T.2;;A
1,61
:@JA
[email protected];@TA
2,00
:LB
[email protected];AJAL8=EAMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=
. 95%
JAK;89E;@TNM9E;[email protected]@D
LA:?998AK=AM
[email protected]=9=O;E=:9AC;[email protected]=;H8;JHAE9E;@T-12;.69E;-12.;@T;-180;NS
K=89=EAKAGP[;[email protected];9D9LA[email protected];8;L8NK=QEGD
. 95%
JAK;89E;@TNM9E;[email protected]
[email protected];J;BAI=;.8;16.;«9DLA:?9.8;16.;«98AK=.8;16.;«.8;16.;«AM
[email protected]A=9=O;E=:9AC;[email protected]
[email protected]=SAJ9EGDKJ9=H=IA;[email protected];@TAAE
1,46
1,96
:LB
[email protected];
.: 74
RU2477995C2
KK;J;9DKL=;GEK;AJ.6;16.;G16;.4E1;.6K;-23;.7A;.2;J7.4;AL8=E.6;16.;G16;.4E1;.6K;-23;.7A;.2;J7.4;AMJAIN
:BB9J8ALAJA=?9E=8E8=E=
H;E=B;:9B9J8=E=9
500
:B=O;E=:9AC;=H=O9;EP
;@AK;LP
&A[email protected]?;GH;9K=;E
JAGE=EA .50;N;P .50;[email protected]=I:;AH9A9J .50;ABA9 .50;;AH9A9J .50;ABA= .50;[email protected];[email protected]
A?;GH000;;;9D000;G9F000;;9D9000;E;000;G000;[email protected];J;@[email protected];@T000;A
[email protected];
KK;J;9D
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
H8;JHAE9E;@T-7.5;ພ-;.5;11.;[email protected];.5T-;.9;[email protected];EGD
H8;[email protected];NM9F;C=8:=LAL9;E9;[email protected]
LABJ=AJAL8=E=DJAI=
GAJ;[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
[email protected];@TA
500
:B=O;E=:9AC;=
H89KK;J;99H=O9;EP=EA[=L
38;JHAE9E;@T-12;.89E;-12.;@1;.6T;-28.;лAH89KK;J-12;.89E;-12.;@1;.6T;-28.;л;99H=O9;-12;.89E;-12.;@1;.6T;-28.;лEP
;@AK;LPC=8:=O;KE9;GL=DLA:HAI9O9D
A?;GH;9K=;[email protected]@=I:;
S=8=LE;89IPQ[9MGD
[email protected]=AE
[email protected];@TA
0,6
:[email protected];@TA
1,4
:B9
[email protected]
=O;E=:9AC;[email protected];@TA
2,8
:B9
7,9
[email protected];AJAL8=EAM
JAIN
5J8PBA:K=89=E;AGP[;[email protected];9D
C=8:=O;KE9;GL=DLA:HAI9O9DA?;GH;9K=;E
[email protected]@=I:;
S=8=LE;89IPQ[9MGD
[email protected][email protected];@TA
0,4
:[email protected];@TA
1,9
:B9
[email protected]=O;E=:9AC;=AE
[email protected];@TA
2,0
:[email protected];@TA
10,4
[email protected];AJAL8=EAM
JAIN
5J8PBA:K=89=E;AGP[;[email protected];9D
C=8:=O;KE9;GL=DLA:HAI9O9DA?;GH;9K=;E
[email protected]@=I:;
S=8=LE;89IPQ[9MGD
[email protected][email protected];@TA
0,6
:[email protected];@TA
1,0
:B9
[email protected]=O;E=:9AC;=AE
[email protected];@TA
3,0
:[email protected];@TA
5,2
[email protected];AJAL8=EAM
JAIN
5AH8;J;@;NSK=89=E=SAGP[;[email protected];9D
H8;JHAE9E;@T-19.;.-2;.29;-13E;-23.;@-; .2;T-28;.600;[email protected];EGD
H8;[email protected];NM9F;C=8:=LAL9;E9;[email protected]
LABJ=AJAL8=E=DJAI=
GAJ;[email protected];@TA
:BB9J8ALAJA=?9E=8E8=E=H;E=B;:9B9J8=E=9
[email protected];@TA
500
:B=O;E=:9AC;=
H89KK;J;99H=O9;EP=EA[=L
389KK;J;99
H=O9;EP
;@AK;LP
JAI98AK==DCA8:=A?;GH;9K=;E
AUC
[email protected]=AE
[email protected];@TA
9,1
:[email protected];@TA
19,9
:B9
AUC
=O;E=:9AC;[email protected];@TA
28,6
:[email protected];@TA
59,1
5J8PBA:K=89=E;AGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
AUC
B9J8ALAJ[email protected];@TA
7,0
:[email protected];@TA
26,2
AUC
[email protected]=O;E=:9AC;[email protected];@TA
18,4
:[email protected];@TA
79,9
5J8PBA:K=89=E;AGP[;[email protected];9D
JAI98AK==DCA8:=A?;GH;9K=;E
AUC
[email protected][email protected];@TA
11,3
:[email protected];@TA
18,7
:B9
AUC
[email protected]=O;E=:9AC;[email protected];@TA
28,7
:BJA
[email protected];@TA
53,5
38;JHAE9E;@T-9.2;ພ-;.2;@-1;.2T;-8.4;AK\EA:K=89-9.2;ພ-;.2;@-1;.2T;-8.4;=E;AGP[;[email protected];-9.2;ພ-;.2;@-1;.2T;-8.4;9D
GLA8AGETKNGKA?AFJ;9DC=8:=O;KE9;GLAMLA:HAI9O99
in vitro
9:;;EJKPSC=INM
[email protected]?AFJ;9D
9BJ;[email protected]=FJAMC=INGLA8AGETKNGKA?AFJ;9D
in vitro
9:;;E[email protected];[email protected];[email protected]=O;E=:9AC;=9[email protected];KAMHA8DJAL
[email protected];[email protected]=
389KK;J;[email protected];K;8NS
=:;89L=O;[email protected]=H=JNS;K8AH;MO;K
K=GEɵ.; =26;.3G;ɴ.;縦.70;AGE9
LABJ=GAGE=K=J=HE98AK=
EA?N
A[email protected]J;[email protected];J=I=;-9.6;9.6;[email protected];-9.6;9.6;J;9D;@AK;LPL=FJN;
=GAKH89
;A?SAJ9:AGE9
[email protected];@TA
20-45%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
C=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;[email protected];@T000;A
[email protected];@T=G-9;.9=-;ɤ.;)-2;g.8;H-15;.58-;.19;-2.5;[email protected];.79I;-1;.7;;[email protected];.10;A
20-
45%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MK
E;;120;9;[email protected];@T120;A
=G=K
0,01
. HCl
H89
:9H89
5J8PBA:
K=89=E;AGP[;[email protected];9D
[email protected];@TA
25-35%
B9J8ALAJA=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.9;;-7.5;9;[email protected];@T.9;;-7.5;A
=G=9
[email protected];@TA
25-35%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
.: 75
RU2477995C2
LA:HAI9O9MKE;;-6;1;.20;9;[email protected];@T-6;1;.20;A
=G=K
0,01
. HCl
H89
:9H89
&8A:;EABA
KJ8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=
KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.7;; .70;9;[email protected];@T.7;; .70;A
[email protected];@T=-9G; -8K;-264;.1J1;.6A-;ɳ.;H-5;.28-;.2; -2.;[email protected]; .69;I9E;;-9.8;[email protected];∞A
=GAK
9HA:;TU;M:;8;AE
60%
[email protected];@TA
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
8,5
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@.4;=-7.;G22;.4A3;.8K-;ɢ.;J13;.4A-;ɡ.;H6.;ډ?;[email protected];.49;I21.;觩.4;1;[email protected];.2T;TA
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE000;;;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9D
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7;1;.20;9;:;-7;1;.20;;;;:[email protected];@T.2;;.2;:-27;H-1;.88;-6.4; ?-6;[email protected];-0;.8I9;@T;-26.;«A
=GAK
9HA
:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9S
LA:HAI9O9MKE;;-5.7;13.;у9;:;-5.7;13.;у;;;:[email protected];@T-5.7;13.;:-2;h.7;H-12;.58-;.19;?-5.;[email protected]; .7I;.9; -9.;~-;[email protected];.7;T-15;.100;A
=GAK
"J=LALABJ=K=89=EGI=:;[email protected];N:KNGKA?AFJ;9;:GAGE=K==J=HE98AK=
EA?NA-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];-13;.8A?;-9.2;N-26;.6A;-19.;л[email protected];J-13;.8A?;-9.2;N-26;.6A;-19.;л-13;.8A?;-9.2;N-26;.6A;-19.;л=I=;-9.8;9.4;[email protected];J;-9.8;9.4;9D;@AK;LPJK=8=I=KGPEL9
;A?SAJ9:AGE9
EABJ=HA:;TU;M:;8;
90%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
90%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:
KNGKA?AFJ;9;:
HA:;TU;M:;8;
95%
B9J8ALAJA=KNGKA?AFJ=;EGD9I
C=8:=O;KE9;GLAMLA:HAI9O99KE;;-7.7;11.;у9;[email protected];@T-7.7;11.;уA
=GAKJA
[email protected];@TA
=GAK
9HA:;TU;M:;8;
95%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.2;130;9;[email protected];@T-6.2;130;A
=GAKJA
[email protected];@TA
=GAK
5J8PBA:K=89=E;AGP[;[email protected];9D\EABAK=89=E=
AGP[;[email protected];9DGI=:;[email protected];N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
B9J8ALAJA=
KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.7;; .70;9;[email protected];@T.7;; .70;A
[email protected];@T=-9G; -8K;-264;.1J1;.6A-;ɳ.;H-5;.28-;.2; -2.;[email protected]; .69;I9E;;-9.8;[email protected];∞A
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=
.: 76
RU2477995C2
KNGKA?AFJ=;EGD
in vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;.1;;.1;9;AE
[email protected];@TA
[email protected];@T-8.1;=-8.;GAK;-273;.8J2;.1A-;ɢ.;H-2;.18; ?-7;[email protected];.19I;-9.9;@;T-27;.700;A
=GAK
5J8PBA:K=89=E;
AGP[;[email protected];9DGAGE=K=GI=:;[email protected];N:KNGKA?AFJ;9;:
HA:;TU;M:;8;
99%
B9J8ALAJA=KNGKA?AFJ=;EGD9IC=8:=O;KE9;GLAMLA:HAI9O99KE;;.5;9.3;9;:;.5;9.3;;;;:
[email protected];@TA
=GAK
9HA:;TU;M:;8;
99%
=O;E=:9AC;=KNGKA?AFJ=;EGD
vitro
9IC=8:=O;KE9;GL9SLA:HAI9O9MKE;;-6.5;12.;Δ9;:-6.5;12.;Δ;;;;:[email protected];@T-6.5;12.;:-2;i.5;H-13;.38-;.99;-0.3;?-5.;[email protected];.59I;.1; -10;.5E-;.3;;[email protected];.90;A
=GAK
5H8;JHAE9E;@T-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;A:K=89=-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;E;AGP[;[email protected]-9E-;Ĺ-;#.2;-23;.2;-;.2;[email protected];T-28;.600;;9D
=GEAD[;;9IA?8;E;9;AEAG9EGDL
LA:HAI9O99
BJ;O;[email protected][email protected];8F9E\LGO9H9;E
GHAGA?NMLA[email protected]=ET
KNGKA?AFJ;9;@;L=8GEK;ABAG8;JGEK=9;O;[email protected][email protected];8F9E\LGO9H9;E
RU2477995C2
AH8;J;@D;[email protected]@=B=;:AMCA8:[email protected]?8;E;9D9;;\[email protected];E=:9
[email protected]9N;9I:;;9D9:AJ9C9L=O99AH9G=NSK=89=EAKAGP[;GEK@;9D?PJPE
A;K.9;;.9;K-18;.99J;9JNGH;[email protected]=:KJ=.9;;.9;K-18;.99J;.9;;.9;K-18;.99J;[email protected][email protected]=GETQ.9=;-18.; G10;.9E-;".5;T-7.;Q-2;v.7;=GEAD[;BA9IA?8;E;.9=;-18.; G10;.9E-;".5;T-7.;Q-2;v.7;9D
4=L9;9I:;;9D9:AJ9C9L=O99
[email protected]=D
A;AB8=99K=DGT9:9
9I:;;9D9
:AJ9C9L=O99
GKDI=N;GS9:9;GLAMGE8PLEP8AM
I=:;GE9E;@D:9
H8A9IKAJN:9
H8A:;FPEA.1;N:9GA;J.1;9;.1;9D:9
G9E;IA:
GAGE=K=:99
[email protected]?=:9H89:;;9D
9IA?8;E;9D
:AFAH8AKAJ9ET?;[email protected];9DAE;BAGP[AGE99A?e;:=
)A8:[email protected]=9IA?8;E;9D
)=8:=O;KE9;GL=DLA:HAI9O9D
9:;Q[=DO;[email protected]NM9;O;[email protected][email protected]
GAJ;8F=[=D
(a)
B9J8ALAJA
;BAC=8:=O;KE9;GL9H89;:@;:[email protected]@9B9J8=E
(b)
=O;E=:9AC;[email protected]?PH8AC;
BJ;HA:;TU;M:;8;
75%
B9J8ALAJA=
;BAC=8:=O;KE9;GL9H89;:@;:[email protected]@9
B9J8=E==SAJ9EGDKO;[email protected]AM=GE9
BJ;=O;E=:9AC;[email protected]?PH8AC;=SAJ9EGDK;O;[email protected]A:[email protected];
BJ;LA:HAI9O9D=J=HE98AK==E=L
EA?NA-14;.4A?;-9.8;N-27;.4A;-9.8;[email protected]=H89BAJ-14;.4A?;-9.8;N-27;.4A;-9.8;[email protected];[email protected]-14;.4A?;-9.8;N-27;.4A;-9.8;ABA
KK;J;9D;@AK;LP
3, 2
8=IKGPEL9
BJ;O;[email protected][email protected]@D;EGD:A[email protected]EN:
O;[email protected]N:[email protected];:
[email protected];N:HPE;:\LGE8PJ98AK=[email protected]=K=G
[email protected];JPQ[9:H8D:N:H89J=9;:CA8:NGAJ;8F=[;:[email protected];L=8GEK;A;G8;JGEKA
[email protected]=KP
?;IH8A:;FPEA-9.5;[email protected];-9.5;[email protected]:;@T000;;9D
H89;::A.5;;.3:;-255;.5:-;.6; -2.;က[email protected].5;;.3:;-255;.5:-;.6; -2.;ကNMO;.5;;.3:;-255;.5:-;.6; -2.;က[email protected].5;;.3:;-255;.5:-;.6; -2.;က[email protected];8F9EHA:;.5;;.3:;-255;.5:-;.6; -2.;ကTU;M:;8;AJ.5;;.3:;-255;.5:-;.6; -2.;က9
9I:;DQ[9MGLA8AGET
[email protected]@9:;89HA:;TU;M:;8;AJAH8A9IKAJA;
O;@@[email protected]=LE9KN;9B8;J9;ENKO;[email protected]A:[email protected];H8;[email protected];NKK9J;
EK;8JABA8=GEKA8=A?8=IAK=[email protected]:;8=:9KO;[email protected]A:[email protected];
BJ;O;[email protected]NM
[email protected];[email protected];EGA?AM\@;:;E;J9ABAEK;8JABA8=GEKA8=9
BJ;;O;[email protected][email protected];[email protected];[email protected]=JL9MK;U9M;O;[email protected][email protected]
GAJ;8F=[9MHA:;TU;M:;8;AJ9;AH9A9JNM=[email protected];[email protected]:;8
[email protected][email protected][email protected]\E9@;[email protected]@;:
BJ;;O;[email protected][email protected];GAJ;8F9E
AH9A9JNM=[email protected];E9L9BJ;;O;[email protected][email protected]=AG9EGD=O;[email protected][email protected]
K9J;KAJ[email protected];I99GA?[;MLAO;E8=O9;MEK;8JNSK;[;GEKHA
:;TU;M:;8;
20%
HA:=GG;9GAJ;8F=9;=LE9KABA9B8;J9;[email protected];EHA
:;TU;M:;8;
50%.
&A:HAI9O9DHAH
.1,
BJ;[email protected];;;:
90%
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.16,
BJ;[email protected]=;EB9J8ALAJAɨ.;=25;.6;;♾뉑.692;TJ2;h.2;艨.8A2;H.4;L262;.2A2;h.8;J258;ꉨ.800;9H;8KNM9KEA8AM
;AH9A9JNM=[email protected];[email protected]=;E=O;E=:-8.4;=-8.;E-;ɷ.;=O-;.8;E-1;.4=;-8.8;:-6.;ᤀ9-8.4;=-8.;E-;ɷ.;=O-;.8;E-1;.4=;-8.8;:-6.;ᤀAC;[email protected]?PH8AC-8.4;=-8.;E-;ɷ.;=O-;.8;E-1;.4=;-8.8;:-6.;ᤀ;
18.
&A:HAI9O9DHAH
.16,
BJ;[email protected]=;EB9J8ALAJAɨ.;=25;.6;;♾뉑.692;TJ2;h.2;艨.8A2;H.4;L262;.2A2;h.8;J258;ꉨ.800;9H;8KNM9KEA8AM
;AH9A9JNM=[email protected];[email protected]=;E=O;E=:-8.4;=-8.;E-;ɷ.;=O-;.8;E-1;.4=;-8.8;:-6.;ᤀ9-8.4;=-8.;E-;ɷ.;=O-;.8;E-1;.4=;-8.8;:-6.;ᤀAC;
19.
&A:HAI9O9DHAH
.16,
BJ;;O;[email protected][email protected];8F9E
=O;E=:9AC;
HA:;TU;M:;8;AJ99I:;DQ[9MGLA8AGETC=8:=O;KE9;GL9H89;:@;:NM
[email protected]:;8
[email protected]:;[email protected];E=-9.4;9.8;-23;.6=0;.400;9D
20.
&A:HAI9O9DHAH
.19,
BJ;[email protected]:;[email protected]@9:;8KN?8=9IB8PHHN
GAGEAD[;M
[email protected];@@[email protected]
[email protected]:;[email protected];@@[email protected]
B9J8ALG9\[email protected];@@[email protected]
[email protected]:;[email protected]=E=
[email protected][email protected]=
AL9G9
[email protected]\[email protected];=99SGA;E=E=-;.4;9M
21.
&A:HAI9O9DHAH
.19,
BJ;[email protected]:;[email protected]@9:;8KN?8=9IB8PHHN
GAGEAD[;M
[email protected]:;[email protected];@@[email protected]@9K[email protected]=
[email protected];E.8;;.8;ฐ=;=9M
.: 82
RU2477995C2
22.
&A:HAI9O9DHAH
.19,
BJ;[email protected]:;[email protected]@9:;8KN?8=9IB8PHHN
GAGEAD[;M
[email protected]:;[email protected][email protected][email protected]\[email protected];=
23.
&A:HAI9O9DHAH
.19,
BJ;GAAEAU;9;=O;E=:9AC;=9LA[email protected][;BA
[email protected]:;[email protected]@9:;[email protected];E=-10;=-9;.200;[email protected];[email protected];@T-10;=-9;.200;A
[email protected];@TA
10:1.
24.
&A:HAI9O9DHAH
.19,
BJ;GAAEAU;9;=O;E=:9AC;=9LA[email protected][;BA
[email protected]:;[email protected]@9:;[email protected];E=-10;=-9;.200;[email protected];[email protected];@T-10;=-9;.200;A
[email protected];@TA
5:1.
25.
&A:[email protected]?A:P9IHH
.16-24,
BJ;;O;[email protected][email protected]:;;EHA:;TU;M
:;8;AJ9[email protected];JPQ[9SH89I=LAK
(a)
HAGP[;GEKP
;8=GE8;GL9K=;[email protected];
:;GDO;KH89
C, 75%
AEAG9E;@TAM
[email protected]=FAGE9K9JPLO9A[email protected]=S
HDPE;
(b)
HAGP[;GEKP
GPSAM
;[email protected];ML9M
A?;GH;9K=;E?NGE8A;8=GEKA8;.89;-13.;K-9;.8=-; 9;.8E-;ɨ.;?-8;.8N-;.1G;-0.4;è-1;-;ɕ.;X-8;.8=-; .8G;-13;.4K-; .8A;.48;-8.8;-0.;л9;K
0,01
. HCl
H89
AEL8NK=DO;[email protected]NM
KNGKA?AFJ=;EHA:;TU;M:;8;
80%
=O;E=:9AC;=K;O;[email protected]A:[email protected];K
H8;J;@=S
:9[email protected];KK;J;9DH=O9;EP
;@AK;LP
[email protected]
(c)
A?;GH;9K=;E?;@PQH9B:;椒.2K5;.6=5;.6;1;^-2;S.1;?6.6;[email protected];.2;P5.6;Q-26;.4H;ऒ.;+-1;.6:;.3;;%.2;E=O9QGAGE=K=?;[email protected]椒.2K5;.6=5;.6;1;^-2;S.1;?6.6;[email protected];.2;P5.6;Q-26;.4H;ऒ.;+-1;.6:;.3;;%.2;9E;@T椒.2K5;.6=5;.6;1;^-2;S.1;?6.6;[email protected];.2;P5.6;Q-26;.4H;ऒ.;+-1;.6:;.3;;%.2;NSH9B:;椒.2K5;.6=5;.6;1;^-2;S.1;?6.6;[email protected];.2;P5.6;Q-26;.4H;ऒ.;+-1;.6:;.3;;%.2;EAK
26.
&A:[email protected]?A:P9IHH
.16-24,
BJ;LA:HAI9O9DS=8=LE;89IP;EGDHA
:;TU;M:;8;AJ9:[email protected];JPQ[9SH89I=LAK
[email protected];GEKAB9J8ALAJGE-;.1;K-10;.5A-;ɤ.;k-2;.79;-3.9;J8-9;.5AL;-5.9; -19;.7J0;.1A0;A=
LAEA8A;\LGE8=B98P;EGD9ILA:HAI9O99
40%-
N:
KAJN:8=GEKA8A:\E[email protected]=KE;;-10.;90;9;AJ-10.;90;ABA=G=H89
C in vitro,
[email protected];EGD:;TU9:
[email protected][email protected];GEKPB9J8ALAJ.2;9G9;æ.2;K-10;.6P-;ɥ.;J;.2;LA;.8;J0A0;A=
LAEA8A;\LGE8=B98P;EGD
0,01
[email protected][email protected]
in vitro
KE000;;;9;AJ000;ABA=G=H89
P:AF;A:P
1,5,
ii)
LA:HAI9O9D;8=I8PU=;EGDH89KAIJ;[email protected]
150
H8;JHAE9E;@Tž-;.49;#.2;-7.;26;[email protected];-12.;∞A
300
[email protected];;H8;JHAE9E;@T.5;ຖ.;צ.;-0;[email protected]; .7T;-19.;УA
450
[email protected];;H8;JHAE9E;@T.6;ç.6;1;[email protected];.6;T-80;A
500
/H899I:;8;99G
HA:A[[email protected]=9D=EK;8JAGET
"Pharma Test PTB 501",
iii)
LA:HAI9O9DKNGKA?AFJ=;EHA:;TU;M:;8;
20%
B9J8ALAJA=9;[email protected];;
45%
B9J8ALAJA=KE;;100;9;H;8KABA=G=E;GE98AK=-9.2;=-9.;G=-;ɴ.;1;G-1;.4E;-39-;.2;-8.;jK-; .6=;-9.6;9D8=GEKA-9.2;=-9.;G=-;ɴ.;1;G-1;.4E;-39-;.2;-8.;jK-; .6=;-9.6;8;9D
in vitro
H8;JHAE9E;@T-7.2;ພ-;.2;@-8;.2T-;.40;AE=LF;KE;;12;9;H;8KABA=G=E;GE98AK-7.2;=-7.;G12;=-27;.9E;-11.;GE; -11;.28-;.6A;K-17;.8=0;=9D
in vivo,
LA:HAI9O9DKNGKA?AFJ=;EE;8=H;KE9;GL9\CC;LE9K18.;G8.;L-6;.69-;ə.;-5C;-7.;18;.6L3;.6E-;.8;.6;K9.2;PQJAIP=O;E=:918.;G8.;L-6;.69-;ə.;-5C;-7.;18;.6L3;.6E-;.8;.6;K9.2;AC18.;G8.;L-6;.69-;ə.;-5C;-7.;18;.6L3;.6E-;.8;.6;K9.2;;=K
E;;110;9;AE
[email protected];AJ-265;.3H-;źG;-11.;[email protected];-;ɖ.;:J-;.2;AL8=E-265;.3H-;źG;-11.;[email protected];-;ɖ.;:J-;.2;AMJAIN
LA:HAI9O9DKNGKA?AFJ=;EE;8=H;KE9;GL9\CC;LE9K.8;;.8;G-9.;L-4;.29-;ɗ.;-23;-5.;-1;.3;;.8;L-14;.4E9;K-19;PQJAIP=O;E=:9.8;;.8;G-9.;L-4;.29-;ɗ.;-23;-5.;-1;.3;;.8;L-14;.4E9;K-19;AC;.8;;.8;G-9.;L-4;.29-;ɗ.;-23;-5.;-1;.3;;.8;L-14;.4E9;K-19;=
[email protected]=;8;I
9;8;I
[email protected];AJ-255;.7H-;.4A;G8.4;[email protected];-25;.9A;J9.6;AL8-255;.7H-;.4A;G8.4;[email protected];-25;.9A;J9.6;=EAMJAIN
KLA:HAI9O99KNGKA?AFJ;9;B9J8ALAJA=H899I:;@T-9.5;000;;99KAI8=GE=;[email protected];;
;:K
2-3
8=I=HAG8=K;9QGO;@[email protected];ELAM
LABJ=LA:HAI9O9Q9I:;@T=QEK
E;;110;9;
:9LAC;:[email protected]
20000-50000
40%-
A:KAJA:8=GEKA8;
\[email protected]=KE;;11.; 9;
H89
9I:;@T;.3;16.;က.3;16.;က=DLA:HAI9O9DGAJ;8F9E=GE9ON8=I:;8A:[email protected];@T.1=;.9;G16.;ẑ.3O;.9;N-25;.98;=16.; I25;.7:-;.8;;.1;ࠗ.;:-;ɕ.;騗.9E-;ɒH;.7;ओ.;?7.;[email protected];.393;.1I2;.79;.1E;.3;16.;[email protected];.3T-;.30;A
[email protected];@TA
355
:L:[email protected][email protected];@TA
20%
C8=LO99
[email protected];;;:
[email protected];@TA
:L:9:;;;;:[email protected];@T.9;;.9;:-25;.1H;ࠖ.;y?1;[email protected];.1;.9;I24.;֞;.9;[email protected];T-3;.500;A
355
:L:[email protected][email protected];@TA
66%
C8=LO999:;;;;:[email protected];@T.3;-1.;:-2;R.7;H-16;.981;.99;.3?;[email protected];.3;I8.5;.3;-3.; 9.;[email protected];T-1; .50;A
:L:[email protected][email protected];@TA
14%
C8=LO99
H89
9I:;8;99GHA:A[TQE;GE=H8AG;9K=9;:
viii)
LA:[email protected];EGD
HAGP[;GEKP
AJA8AJAM
BJ;G8;J;;I=;&.8;25.;«9;
O;[email protected][email protected]999
(CLA)
[email protected];[email protected];@TA
0,1
[email protected];@TA
0,6,
H8;JHAE9E;@T-8.2;ພ-;.2;@-9;.2T-;.40;[email protected];@T-8.2;ພ-;.2;@-9;.2T-;.40;A
0,1
[email protected];@TA
0,4,
[email protected];;
H8;JHAE9E;@T-8.2;ພ-;.2;@-9;.2T-;.40;[email protected];@T-8.2;ພ-;.2;@-9;.2T-;.40;A
0,1
[email protected];@TA
0,2.
.: 83
RU2477995C2
27.
&A:[email protected]?A:P9IHH
.16-24,
BJ;O;E8[email protected]@AM9[email protected];HPE;:
\LGE8PJ98AK=[email protected][email protected];JPQ[9:H8D:N:H89J=9;:CA8:N
GAJ;8F=[;:[email protected];L=8GEK;A;G8;[email protected]=KP
9;O;[email protected][email protected]=;G;
[email protected];9;:=O;[email protected][email protected]
.: 84
RU2477995C2
.: 85
RU2477995C2
.: 86
RU2477995C2
.: 87
RU2477995C2
.: 88
RU2477995C2
.: 89