In the composition, a preferentially addictive drug represents opioid, while a non-addictive drug represents acetaminophen. Более предпочтительно, центральная часть дополнительно содержит ацетаминофен.

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2477995
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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
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=GAK
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95%
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HA:;�TU;M:;8;
95%
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95%
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99%
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[email protected];@T�A
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99%
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HA:;�TU;M:;8;
99%
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EABJ=HA:�;TU;M:;8;
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(Driam) (
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2).
"[email protected];[email protected]
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30, 50, 70, 90
120
:B=O;E=:9�AC;�=�[email protected];�A.9;A;HAL8NE9;
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(USP Dissolution Apparatus II
@AH=GE�A;
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C, 0,01M HCl, 50
[email protected];GEKA=LE9K&#x;-8.;G12;&#x.1E-;�.9K;&#x-17.;z-2;a.6;&#x=-7.;L-1;.1E; K-1;.70;ABA
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HCl,
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[email protected];EL9?;I�=�;G�;[email protected]�;A.70;ABAHAL8NE9D
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(USP Dissolution Apparatus II
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KNGKA?AFJ=;:[email protected];EALKG8;JPKAJ�ABA8=GEKA8=
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[email protected];�[email protected];EL=G
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120
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240
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#LA8AGE98=GEKA8;�[email protected];L=8GEK;��ABAG8;[email protected][email protected];@T�A�=
10%
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AH8;J;@[email protected];[email protected]=�GAC=8:=LAH;;#V'
@AH=GE�AMGHAGA?
, USP XXV;
C, 0,01M HCl, 50
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KNGKA?AFJ=;:ABA9I
[email protected];EALKG8;JPKA�JABA8=GEKA8=
HCl,
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�9E;[email protected]=:9
[email protected];EL=?;I�=��;G;[email protected];��AABAHAL8NE9D
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120
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240
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360
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480
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[email protected]�;[email protected];EL=GA
120
:B=O;E=:�9AC�;[email protected];�A�.90;A:HAL8NE99
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120
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240
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360
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480
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#LA8AGE98=GEKA8;�[email protected];L=8GEK;��ABAG8;[email protected][email protected];@T�A�=
25%
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H89GPEGEKPQ[;[email protected]�;�AA:HAL8NE99
4;GE98�AK=9;[email protected]
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Kollicoat
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LAEA8NM
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3AK;�8SAGET
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4;[email protected]
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Kollicoat
[email protected][email protected]
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3AL8NEN;[email protected];�[email protected];EL9
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[email protected];JA�K=9DGLA8AGE98=GEKA8;�9DK
40%
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[email protected]=ETGSAJ�N;GHAGA?N
[email protected]=GEKA8;�9DK
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: USP Dissolution Apparatus II (
@AH=GE�A;
40%
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: USP Dissolution Apparatus II (
@AH=GE�A;
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30/60/120/180/240/360/420/480/600/720/840/1080/1320/1560/1800
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280
III.
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65,42%
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150
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9,29%
[email protected];@@[email protected]
Ph. Eur. Type EF
2,99% Polaxamer 188 Ph. Eur./NF
2,8%
B9J8ALAJA�=f
1% Aerosil 200
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6027
12043
18057
24067
30076
36084
42090
48094
60098
72098
84098
108099
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156099
1800100
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���.: 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;:
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55,88%
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120
:B=O;E=:9�AC�;=
13,50% Eudragit RL-PO
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Kollicoat IR
11,0%
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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
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Xylisorb 90
2,21%
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1% Aerosil 200 Ph, Eur,/NF
"?[=D:=GG=O;�[email protected]�AM=GE9
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3017
6031
12046
18057
24067
30075
36082
42088
48091
60096
72097
84098
108099
132099
156099
1800100
���.: 42
RU2477995C2
XII(b)
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. HCl
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3034
6041
12047
18051
24056
30060
36065
42068
48071
60076
72080
84084
108089
1320100
1560100
1800100
IV.
40%
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40%
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65,42%
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150
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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%
B9J8ALAJ�A=f
1% Aerosil 200
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H8;[email protected];�NJ=��N;8=GEKA�8;[email protected]�A=
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XIV(a)
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B9J8ALAJA�=
���.: 43
RU2477995C2
36097
42097
48098
60098
72099
840100
108098
132099
156099
1800100
XIV(b)
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55,88%
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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%
B9J8ALAJ�A=f
1% Aerosil 200 Ph, Eur,/NF
"?[=D:=GG=O;�[email protected]�AM=GE9
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XVI
H8;[email protected];�NJ=��N;8=GEKA�8;[email protected]�A=
(XVI(a))
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XVI(a)
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1560101
1800100
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40%
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3033
6045
12062
18073
24080
30084
36087
42088
48089
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12017
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IX.
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XXII
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12,6% Eudragit RL-PO12,6% Eudragit RL-PO12,6% Eudragit RL-PO12,6% Eudragit RL-PO
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6,0%
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1,8%
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1% Aerosil 200
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1% Aerosil 200
Ph. Eur./NF
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3AL8NE9;f
50,0
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6030303028
12042434443
18051535453
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30064676867
36069727473
42074777978
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307151922
6011192326
12017252932
18022293336
24026333740
30030364043
36033394245
42036424548
48039454851
0,01
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KA�EAU;�99=O;E�=:9AC�;=
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XXV.
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XXIV
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65,42%
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9,29% Eudragit RL-PO
9,29%
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9,29%
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12027
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RU2477995C2
XXVI
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11,0%
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13,40%
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2,21%
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18065
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0, 0,25, 0,5, 0,75,
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AUC
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4,4
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14,0
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205
(19%)
209
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6,22
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447
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13,0
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204
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209
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5,93
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(N=20)
AUC
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150,74 (66%)206 (25%)21,2 (29%)22,9 (30%)9,85 (46%)24,0 (33%)
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160,82 (82%)2,41 (32%)22,1 (24%)
22,3 (25%)5,59 (21%)23,7 (24%)
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199,636
203,905
206,338
206,338
0,968
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204,492
208,867
210,187
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0,973
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20,580
22,363
21,732
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22,171
22,402
21,987
21,987
1,008
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60%
[email protected];@T�A
99%
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in vitro
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