CN1152013C - 一类左旋氨氯地平盐的水合物及其制剂 - Google Patents
一类左旋氨氯地平盐的水合物及其制剂 Download PDFInfo
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- HTIQEAQVCYTUBX-KRWDZBQOSA-N (S)-amlodipine Chemical class CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-KRWDZBQOSA-N 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title abstract description 9
- 229950008554 levamlodipine Drugs 0.000 claims abstract description 31
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 7
- 206010020772 Hypertension Diseases 0.000 claims abstract description 4
- 235000003704 aspartic acid Nutrition 0.000 claims abstract description 4
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims abstract description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims abstract 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 5
- 229940095064 tartrate Drugs 0.000 claims description 5
- 150000004677 hydrates Chemical class 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 3
- 230000003257 anti-anginal effect Effects 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 19
- 150000003839 salts Chemical class 0.000 abstract description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 abstract description 4
- 239000002253 acid Substances 0.000 abstract description 4
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 abstract description 3
- 206010002383 Angina Pectoris Diseases 0.000 abstract description 2
- 150000007522 mineralic acids Chemical class 0.000 abstract description 2
- 150000007524 organic acids Chemical class 0.000 abstract description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 abstract 3
- 150000007513 acids Chemical class 0.000 abstract 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 abstract 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 abstract 1
- 235000011054 acetic acid Nutrition 0.000 abstract 1
- 229940092714 benzenesulfonic acid Drugs 0.000 abstract 1
- 235000005985 organic acids Nutrition 0.000 abstract 1
- 235000002906 tartaric acid Nutrition 0.000 abstract 1
- 239000011975 tartaric acid Substances 0.000 abstract 1
- ZPBWCRDSRKPIDG-UHFFFAOYSA-N amlodipine benzenesulfonate Chemical compound OS(=O)(=O)C1=CC=CC=C1.CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl ZPBWCRDSRKPIDG-UHFFFAOYSA-N 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 229960000528 amlodipine Drugs 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 238000010494 dissociation reaction Methods 0.000 description 6
- 230000005593 dissociations Effects 0.000 description 6
- 230000000857 drug effect Effects 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 229940127291 Calcium channel antagonist Drugs 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229960004005 amlodipine besylate Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical class [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 239000000480 calcium channel blocker Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000012069 chiral reagent Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- IZEKFCXSFNUWAM-UHFFFAOYSA-N dipyridamole Chemical compound C=12N=C(N(CCO)CCO)N=C(N3CCCCC3)C2=NC(N(CCO)CCO)=NC=1N1CCCCC1 IZEKFCXSFNUWAM-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N hydrochloric acid Substances Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4422—1,4-Dihydropyridines, e.g. nifedipine, nicardipine
-
- 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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- 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
- A61P9/12—Antihypertensives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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Abstract
本发明涉及一类左旋氨氯地平盐的水合物，例如苯磺酸左旋氨氯地平水合物、天冬酸左旋氨氯地平水合物、乙酸左旋氨氯地平水合物、硫酸左旋氨氯地平水合物、氢溴酸左旋氨氯地平水合物和左旋氨氯地平-半-(R，R)-(+)-酒石酸盐双水合物。这些水合物比其非水合物更易溶于水，有更高的生物利用度和更好的药效。这些水合物可以制备成片剂，胶囊剂和透皮剂。
Description
本发明涉及一类左旋氨氯地平盐的水合物，例如苯磺酸左旋氨氯地平水合物、天冬酸左旋氨氯地平水合物、乙酸左旋氨氯地平水合物、硫酸左旋氨氯地平水合物、氢溴酸左旋氨氯地平水合物和左旋氨氯地平-半-(R，R)-(+)-酒石酸盐双水合物。这些水合物比其非水合物更易溶于水，有更高的生物利用度和更好的药效。这些水合物可以制备成片剂，胶囊剂和透皮剂。
1.背景
左旋氨氯地平和它的盐是长效钙通道拮抗剂，对于治疗高血压和心绞痛是有用的。
辉瑞公司(Pfizer)发明了一个氨氯地平对映体的拆分可行方法(WO9525722)，其光学纯度和收率都非常高。该方法的关键是同时应用二甲基亚砜(DMSO)及手性试剂酒石酸。
张喜田的发明指出六氘代二甲基亚砜(DMSO-d6)是一种比DMSO还好的手性助剂(WO 01/60799A1)其光学纯度可达100％e.e.，并且收率也相当高。
美国Sepracor公司申请了左旋氨氯地平及其盐的制剂专利(WO 93/10779)。但没有左旋氨氯地平盐水合物的描述。
中国1999年3月17日苯磺酸左旋氨氯地平及其片上市销售，该产品仅给出苯磺酸左旋氨氯地平干燥后的分子式C20H25N2O5Cl·C6H6O3S，但尚未公开其水合物的信息。
左旋氨氯地平盐水合物优于其非水合物，因为左旋氨氯地平盐水合物更易溶于水，因此其生物利用度更高，药效也就更高。
2.发明
氨氯地平由左旋氨氯地平和右旋氨氯地平等量组成，其中左旋氨氯地平是抗高血压和心绞痛的有效成分。氨氯地平能否被身体充分吸收是发挥其药效的关键，同样左旋氨氯地平能否被身体充分吸收也是发挥其药效的关键。左旋氨氯地平盐比非左旋氨氯盐地平更易溶于水，也就更易于身体吸收。但左旋氨氯地平盐的亲水性也是不同的，左旋氨氯地平盐水合物比不能生成水合物的左旋氨氯地平盐更易溶于水，更利于身体吸收。
一般钙拮抗剂的生物利用度8-10％，因为它们在水中的溶解度低，因此生物利用度也低。苯磺酸氨氯地平是盐类，故较容易于水，其生物利用度也就高。苯磺酸氨氯地平的生物利用度大约为60-80％，但还不是100％。苯磺酸左旋氨氯地平水合物更易溶于水，也就更易于吸收，药效也更高。
左旋氨氯地平盐水合物组成及性质见表。
表氨氯地平盐的结晶水数和结晶水解离温度
| 酸 | 氨氯地平 | 结晶水分子数 | 结晶水解离温度(℃) | |
| 第一解离温度 | 第二解离温度 | |||
| 苯磺酸 | 左旋体 | 2 | 41 | 67 |
| 消旋体 | - | - | - | |
| 甲磺酸 | 左旋体 | - | - | - |
| 消旋体 | 1 | 45 | ||
| 乙酸 | 左旋体 | 1 | 90 | - |
| 消旋体 | - | - | - | |
| 天冬酸 | 左旋体 | 2 | 93 | - |
| 消旋体 | 2 | 78 | - | |
| 酒石酸(S，S) | 左旋体 | 1 | 109 | - |
| 消旋体 | 2 | 33 | 63 | |
| 酒石酸(R，R) | 左旋体 | 2 | 36 | 58 |
| 消旋体 | 2 | 33 | 63 | |
| 马来酸 | 左旋体 | - | - | - |
| 消旋体 | - | - | - | |
| 硫酸 | 左旋体 | 2 | 102 | - |
| 消旋体 | 2 | 59 | - | |
| 盐酸 | 左旋体 | - | - | - |
| 消旋体 | 1 | 49 | - | |
| 氢溴酸 | 左旋体 | 1 | 81 | - |
| 消旋体 | - | - | - | |
结晶水含量和结晶水解离温度由PERKIN-ELMER 7 Series Thermal AnalysisSystem仪器测定或由1H-NMR谱仪测定。
氨氯地平盐水合物(左旋体及消旋体)的结晶水解离温度范围一般在110℃以内。
左旋氨氯地平盐水合物可在有水介质的合成过程中生成。
制备左旋氨氯地平盐水合物的溶剂是水，在氮气保护下，将左旋氨氯地平加入与左旋氨氯地平等当量60℃酸水溶液中，搅拌至溶解，停止搅拌、冷却、过滤，室温干燥至恒重，即可得到水合物。不同的左旋氨氯地平盐水合物溶解度不同，因此无机或有机酸的水溶液浓度要适当调节，也可将左旋氨氯地平盐水溶液进行适当浓缩然后再结晶。
3.关于实施例
实施例1 苯磺酸左旋氨氯地平水合物的制备5g左旋氨氯地平置120ml水中，然后加入1.4g苯磺酸并搅拌，在氮气保护下加热至60℃。溶解后，停止搅拌并冷却至室温，结晶过夜；过滤后，再经20ml水洗涤，得苯磺酸左旋氨氯地平，室温干燥至恒重，得6.6g(理论收率的90％)，(发现：C51.68％，H5.72％，N4.71％；C20H25N2O5Cl·C6H6O3S·2H2O的计算值：C51.74％，H5.80％，N4.64％)
实施例2苯磺酸左旋氨氯地平水合物片剂的制备
配方如下：
1.苯磺酸左旋氨氯地平水合物(n2＝2) 3.68g
2.微晶纤维素(M80) 15g
3.微晶纤维素(A300) 20g
4.乳糖 53.82g
5.淀粉 7g
6.硬脂酸镁 0.50g
1000片
上述物料混均后，经压制可得片重100mg含2.5mg左旋氨氯地平片剂。
实施例3苯磺酸左旋氨氯地平胶囊剂的制备
配方如下：
1.苯磺酸左旋氨氯地平水合物(n2＝2) 3.678g
2.淀粉 30g
1000粒
上述物料混均后，均匀装入1000粒胶囊中即可，每粒含2.5mg左旋氨氯地平。
4.本发明的实用性
本发明在工业上是可行的，不存在任何技术障碍。由于左旋氨氯地平盐水合物比不能生成水合物的左旋氨氯地平盐生物利用度高，因而提高了药效。
Claims (4)
1.一种左旋氨氯地平盐的水合物，所述的水合物不包括：左旋氨氯地平-(S，S)-(-)-半-酒石酸盐单水合物。
2.如权利要求1所述的一种左旋氨氯地平盐的水合物，它选自如下化合物：苯磺酸左旋氨氯地平水合物、天冬酸左旋氨氯地平水合物、乙酸左旋氨氯地平水合物、硫酸左旋氨氯地平水合物、氢溴酸左旋氨氯地平水合物和左旋氨氯地平-(R，R)-(+)-半-酒石酸盐双水合物。
3.一种药物组合物，由如权利要求1所述的左旋氨氯地平盐的水合物及相应的载体组成。
4.如权利要求1所述左旋氨氯地平盐的水合物在用于制备治疗抗高血压和抗心绞痛疾病的药物中的应用。
Priority Applications (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011400277A CN1152013C (zh) | 2001-11-22 | 2001-11-22 | 一类左旋氨氯地平盐的水合物及其制剂 |
| PCT/CN2002/000730 WO2003043989A1 (en) | 2001-11-22 | 2002-10-18 | Hydrophilic (s)-amlodipine salts or their hydrates and pharmaceutical compositions |
| EP02769861A EP1458681A4 (en) | 2001-11-22 | 2002-10-18 | HYDROPHILIC SALTS OF (S) -AMLODIPINE OR THEIR HYDRATES AND PHARMACEUTICAL COMPOSITIONS |
| KR1020047007566A KR20050037498A (ko) | 2001-11-22 | 2002-10-18 | 친수성 (ｓ)-암로디핀 염 또는 그 수화물 및 약리학적조성물 |
| AU2002336032A AU2002336032A1 (en) | 2001-11-22 | 2002-10-18 | Hydrophilic (s)-amlodipine salts or their hydrates and pharmaceutical compositions |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB011400277A CN1152013C (zh) | 2001-11-22 | 2001-11-22 | 一类左旋氨氯地平盐的水合物及其制剂 |
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| Publication Number | Publication Date |
|---|---|
| CN1355162A CN1355162A (zh) | 2002-06-26 |
| CN1152013C true CN1152013C (zh) | 2004-06-02 |
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|---|---|---|---|
| CNB011400277A Expired - Lifetime CN1152013C (zh) | 2001-11-22 | 2001-11-22 | 一类左旋氨氯地平盐的水合物及其制剂 |
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| Country | Link |
|---|---|
| EP (1) | EP1458681A4 (zh) |
| KR (1) | KR20050037498A (zh) |
| CN (1) | CN1152013C (zh) |
| AU (1) | AU2002336032A1 (zh) |
| WO (1) | WO2003043989A1 (zh) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2021088672A1 (zh) | 2019-11-08 | 2021-05-14 | 施慧达药业集团(吉林)有限公司 | 含苯磺酸左氨氯地平水合物的组合物及其制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4319148B2 (ja) | 2002-09-11 | 2009-08-26 | ハンリム ファーマシューティカル カンパニー リミテッド | Ｓ−（−）−アムロジピンニコチネート及びその製造方法 |
| US20050187262A1 (en) * | 2004-01-12 | 2005-08-25 | Grogan Donna R. | Compositions comprising (S)-amlodipine and an angiotensin receptor blocker and methods of their use |
| WO2005097191A2 (en) * | 2004-04-04 | 2005-10-20 | Sepracor Inc. | COMBINATIONS COMPRISING (S)- AMLODIPINE AND A HMG-CoA REDUCTASE INHIBITOR OR CHOLESTEROL ABSORPOTION INHIBITOR OR BOTH, AND METHODS FOR REDUCING HYPERTENSION |
| WO2005099699A1 (en) * | 2004-04-07 | 2005-10-27 | Sepracor Inc. | Combination of (s)-amlodipine and a beta-blocker, and methods for reducing hypertension |
| KR100913791B1 (ko) * | 2006-07-21 | 2009-08-26 | 한미약품 주식회사 | (ｓ)-(-)-암로디핀 캠실레이트 또는 이의 수화물 및 이를함유하는 약학적 조성물 |
| KR100830003B1 (ko) * | 2006-10-31 | 2008-05-15 | 씨제이제일제당 (주) | 결정성 ｓ-(-)-암로디핀 아디핀산 염 무수물 및 이의 제조방법 |
| KR100843400B1 (ko) * | 2006-11-14 | 2008-07-04 | 씨제이제일제당 (주) | 결정성 ｓ-(-)-암로디핀 말레익산 염 무수물 및 이의제조방법 |
| GB0624087D0 (en) * | 2006-12-01 | 2007-01-10 | Selamine Ltd | Ramipril combination salt |
| KR100843401B1 (ko) * | 2006-12-04 | 2008-07-04 | 씨제이제일제당 (주) | 결정성 ｓ-(-)-암로디핀 캠실레이트 무수물 및 이의제조방법 |
| KR100840069B1 (ko) * | 2007-01-23 | 2008-06-20 | 씨제이제일제당 (주) | 결정성 ｓ-(-)-암로디핀 오로테이트 무수물 및 이의제조방법 |
| CN105111137B (zh) * | 2015-08-21 | 2016-04-27 | 薛传校 | 苯磺酸左旋氨氯地平晶体、其制备方法和应用 |
| CN111689894B (zh) * | 2019-03-13 | 2023-05-02 | 鲁南制药集团股份有限公司 | 一种苯磺酸左旋氨氯地平晶型 |
| CN112110850B (zh) * | 2019-06-20 | 2023-05-02 | 鲁南制药集团股份有限公司 | 一种苯磺酸左旋氨氯地平新晶型 |
| CN112704667A (zh) * | 2021-02-24 | 2021-04-27 | 施慧达药业集团(吉林)有限公司 | 含苯磺酸左氨氯地平水合物的组合物及其制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2233974A (en) * | 1989-07-22 | 1991-01-23 | Pfizer Ltd | Dihydropyridine antiinflammatory agent |
| US6057344A (en) * | 1991-11-26 | 2000-05-02 | Sepracor, Inc. | Methods for treating hypertension, and angina using optically pure (-) amlodipine |
| CA2124445A1 (en) * | 1991-11-26 | 1993-06-10 | James W. Young | Methods and compositions for treating hypertension, angina and other disorders using optically pure (-) amlodipine |
| GB9317773D0 (en) * | 1993-08-26 | 1993-10-13 | Pfizer Ltd | Therapeutic compound |
| GB9405833D0 (en) * | 1994-03-24 | 1994-05-11 | Pfizer Ltd | Separation of the enantiomers of amlodipine |
| HN2000000050A (es) * | 1999-05-27 | 2001-02-02 | Pfizer Prod Inc | Sal mutua de amlodipino y atorvastatina |
| CN1100038C (zh) * | 2000-02-21 | 2003-01-29 | 张喜田 | 氨氯地平对映体的拆分 |
| AR037565A1 (es) * | 2001-11-21 | 2004-11-17 | Synthon Bv | Formas de sales de amlodipina y procedimientos para prepararlas. |
| WO2004096770A1 (en) * | 2003-04-25 | 2004-11-11 | Cipla Limited | Process for preparing almodipine mesylate monohydrate |
-
2001
- 2001-11-22 CN CNB011400277A patent/CN1152013C/zh not_active Expired - Lifetime
-
2002
- 2002-10-18 EP EP02769861A patent/EP1458681A4/en not_active Ceased
- 2002-10-18 WO PCT/CN2002/000730 patent/WO2003043989A1/en not_active Application Discontinuation
- 2002-10-18 KR KR1020047007566A patent/KR20050037498A/ko active Search and Examination
- 2002-10-18 AU AU2002336032A patent/AU2002336032A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2021088672A1 (zh) | 2019-11-08 | 2021-05-14 | 施慧达药业集团(吉林)有限公司 | 含苯磺酸左氨氯地平水合物的组合物及其制备方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1355162A (zh) | 2002-06-26 |
| AU2002336032A1 (en) | 2003-06-10 |
| EP1458681A1 (en) | 2004-09-22 |
| WO2003043989A1 (en) | 2003-05-30 |
| KR20050037498A (ko) | 2005-04-22 |
| EP1458681A4 (en) | 2005-04-27 |
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Application publication date: 20020626 Assignee: SHIHUIDA PHARMACEUTICALS GROUP (JILIN) Ltd. Assignor: Zhang Xitian Contract record no.: 2014220000018 Denomination of invention: Levo-amlodipine salt able to generate hydrate and its hydrate and preparation Granted publication date: 20040602 License type: Exclusive License Record date: 20140319 |
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