CN1211086C - 雷诺嗪持续释放制剂 - Google Patents
雷诺嗪持续释放制剂 Download PDFInfo
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- CN1211086C CN1211086C CNB998108359A CN99810835A CN1211086C CN 1211086 C CN1211086 C CN 1211086C CN B998108359 A CNB998108359 A CN B998108359A CN 99810835 A CN99810835 A CN 99810835A CN 1211086 C CN1211086 C CN 1211086C
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- ranolazine
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- General Health & Medical Sciences (AREA)
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- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
溶液pH | 溶解度(mg/mL) | USP溶解度级别 |
4.81 | 161 | 易溶的 |
4.89 | 73.8 | 可溶的 |
4.90 | 76.4 | 可溶的 |
5.04 | 49.4 | 可溶的 |
5.35 | 16.7 | 微溶的 |
5.82 | 5.48 | 微溶的 |
6.46 | 1.63 | 微溶的 |
6.73 | 0.83 | 极微溶的 |
7.08 | 0.39 | 极微溶的 |
7.59(未缓冲水) | 0.24 | 极微溶的 |
7.73 | 0.17 | 极微溶的 |
12.66 | 0.18 | 极微溶的 |
治疗 | |||||
平均运动变量(所有患者,分钟) | 双盲安慰剂 | 雷诺嗪400mg每天两次 | 雷诺嗪267mg每天三次 | 雷诺嗪400mg每天三次 | |
出现心绞痛发作的时间 | 峰值 | 9.01 | 9.33 | 9.40 | 9.33 |
谷值 | 8.58 | 8.77 | 8.78 | 8.65 | |
运动持续时间 | 峰值 | 10.67 | 10.83 | 10.87 | 10.84 |
谷值 | 10.50 | 10.55 | 10.56 | 10.60 | |
出现1mm ST压低的时间 | 峰值 | 9.58 | 9.86 | 9.99 | 9.94 |
谷值 | 9.04 | 9.22 | 9.22 | 9.31 |
雷诺嗪400mg每天两次 | 雷诺嗪267mg每天三次 | 雷诺嗪400mg每天三次 | |
峰值(ng/mL) | |||
所有患者 | 1882(1094) | 1346(823) | 2128(1198) |
男性 | 1762(999) | 1261(774) | 1917(1046) |
女性 | 2171(1253) | 1594(904) | 2654(1385) |
谷值(ng/Ml) | |||
所有患者 | 235(288) | 316(336) | 514(500) |
男性 | 235(264) | 316(336) | 518(494) |
女性 | 235(342) | 316(340) | 505(517) |
平均值±SD药物动力学参数(n=8,除外*n=7) | |||||
剂量SR(mg) | 组 | Cmax(ng/mL) | Ctrough(ng/mL) | TMAX(小时) | AUC0-30小时(ng·小时/mL) |
500 | 1 | 883±353 | 382±251 | 4.63±1.19 | 9380±4250 |
750 | 1 | 1300±1060 | 455±353 | 4.25±0.886 | 12500±9000 |
1000 | 1* | 1610±959 | 695±438 | 5.71±2.14 | 18100±9630 |
1250 | 2 | 2210±716 | 943±541 | 6.21±3.52 | 25000±8090 |
1500 | 3 | 1980±1050 | 1070±754 | 4.75±0.886 | 25400±16000 |
1750 | 2 | 3670±1570 | 2400±1260 | 5.25±2.31 | 49200±18200 |
2000 | 3 | 2440±1120 | 1640±937 | 5.21±2.30 | 35400±19100 |
第5天雷诺嗪药物动力学参数(平均值±SD) | |||
参数 | 雷诺嗪SR500mg每天两次(n=7) | 雷诺嗪SR750mg每天两次(n=7) | 雷诺嗪SR1000mg每天两次(n=7) |
CMAX(ng/mL)TMAX(小时)Cmin(ng/mL) | 1760±7152.00±1.15585±340 | 2710±6574.33±1.621260±501 | 3660±10904.17±2.481960±812 |
参数 | 1500mg SR 每天两次 | 2000mgSR每天两次 | ||
RS雷诺嗪 | (+)R雷诺嗪 | (-)S雷诺嗪 | RS雷诺嗪 | |
CMAX(ng/mL) | 5284±2434 | 2909±1308 | 2944±1426 | 7281±2700 |
Cmin(ng/mL) | 2932±1918 | 1436±1046 | 1514±1201 | 4149±2228 |
中间tMAX(小时) | 4.00 | 4.00 | 4.00 | 4.00 |
C96h(ng/ml) | 3656±1918 | 2009±1137 | 2399±1205 | 5042±1797 |
C108h(ng/ml) | 2942±1937 | 1447±1071 | 1541±1260 | 4398±2396 |
AUC96-108h(ng.h/ml) | 49516±23945 | 25731±13385 | 26407±14849 | 68459±25842 |
C平均(ng/ml) | 4126±1995 | 2144±1115 | 2201±1237 | 5705±2153 |
波动程度 | 0.664±0.336 | 0.833±0.402 | 0.824±0.443 | 0.591±0.240 |
Claims (18)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US9980498P | 1998-09-10 | 1998-09-10 | |
US60/099,804 | 1998-09-10 | ||
US09/321,522 US6303607B1 (en) | 1998-09-10 | 1999-05-27 | Method for administering a sustained release ranolanolazine formulation |
US09/321,522 | 2009-05-27 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1321088A CN1321088A (zh) | 2001-11-07 |
CN1211086C true CN1211086C (zh) | 2005-07-20 |
Family
ID=26796494
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB998108367A Expired - Lifetime CN1193757C (zh) | 1998-09-10 | 1999-09-09 | 雷诺嗪持续释放制剂 |
CNB998108359A Expired - Lifetime CN1211086C (zh) | 1998-09-10 | 1999-09-09 | 雷诺嗪持续释放制剂 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB998108367A Expired - Lifetime CN1193757C (zh) | 1998-09-10 | 1999-09-09 | 雷诺嗪持续释放制剂 |
Country Status (33)
Country | Link |
---|---|
US (14) | US6303607B1 (zh) |
EP (3) | EP1109558B1 (zh) |
JP (2) | JP3745621B2 (zh) |
KR (1) | KR100475759B1 (zh) |
CN (2) | CN1193757C (zh) |
AR (3) | AR022085A1 (zh) |
AT (2) | ATE285774T1 (zh) |
AU (4) | AU760435B2 (zh) |
BR (2) | BR9913626A (zh) |
CA (2) | CA2342390C (zh) |
CY (1) | CY2008020I1 (zh) |
CZ (2) | CZ301341B6 (zh) |
DE (3) | DE122008000065I1 (zh) |
DK (2) | DK1096937T3 (zh) |
ES (2) | ES2234302T3 (zh) |
FR (1) | FR09C0001I2 (zh) |
GE (1) | GEP20053420B (zh) |
HK (2) | HK1040060A1 (zh) |
HU (2) | HUP0104088A3 (zh) |
IL (6) | IL141892A0 (zh) |
LU (1) | LU91504I2 (zh) |
MX (2) | MXPA01002599A (zh) |
NL (1) | NL300371I2 (zh) |
NO (4) | NO320986B1 (zh) |
NZ (2) | NZ510386A (zh) |
PL (3) | PL196263B1 (zh) |
PT (2) | PT1096937E (zh) |
RU (2) | RU2207856C2 (zh) |
SI (2) | SI1109558T1 (zh) |
TR (2) | TR200101262T2 (zh) |
TW (1) | TWI241911B (zh) |
UA (2) | UA67793C2 (zh) |
WO (2) | WO2000013686A2 (zh) |
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-
1999
- 1999-05-27 US US09/321,522 patent/US6303607B1/en not_active Expired - Lifetime
- 1999-09-09 GE GE4322A patent/GEP20053420B/en unknown
- 1999-09-09 CN CNB998108367A patent/CN1193757C/zh not_active Expired - Lifetime
- 1999-09-09 CZ CZ20010880A patent/CZ301341B6/cs not_active IP Right Cessation
- 1999-09-09 UA UA2001031623A patent/UA67793C2/uk unknown
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