CN102746227B - 一种磷酸二甲啡烷晶型ⅱ及制备方法和药物组合物 - Google Patents
一种磷酸二甲啡烷晶型ⅱ及制备方法和药物组合物 Download PDFInfo
- Publication number
- CN102746227B CN102746227B CN201210234970.9A CN201210234970A CN102746227B CN 102746227 B CN102746227 B CN 102746227B CN 201210234970 A CN201210234970 A CN 201210234970A CN 102746227 B CN102746227 B CN 102746227B
- Authority
- CN
- China
- Prior art keywords
- crystal form
- dimemorfan phosphate
- phosphate crystal
- dimemorfan
- preparing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- KBEZZLAAKIIPFK-NJAFHUGGSA-N dimemorfan Chemical compound C1C2=CC=C(C)C=C2[C@@]23CCN(C)[C@@H]1[C@H]2CCCC3 KBEZZLAAKIIPFK-NJAFHUGGSA-N 0.000 title claims abstract description 75
- 229960001056 dimemorfan Drugs 0.000 title claims abstract description 75
- 239000013078 crystal Substances 0.000 title claims abstract description 71
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
- 238000002360 preparation method Methods 0.000 title abstract description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000008187 granular material Substances 0.000 claims abstract description 10
- 239000007788 liquid Substances 0.000 claims abstract description 10
- 239000002775 capsule Substances 0.000 claims abstract description 9
- 238000001035 drying Methods 0.000 claims abstract description 9
- 238000000034 method Methods 0.000 claims abstract description 9
- 238000010992 reflux Methods 0.000 claims abstract description 9
- 239000007787 solid Substances 0.000 claims abstract description 9
- 239000006188 syrup Substances 0.000 claims abstract description 9
- 235000020357 syrup Nutrition 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 16
- 239000012043 crude product Substances 0.000 claims description 5
- 238000002425 crystallisation Methods 0.000 claims description 5
- 230000008025 crystallization Effects 0.000 claims description 5
- 239000000706 filtrate Substances 0.000 claims description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- 239000011777 magnesium Substances 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- 241001269238 Data Species 0.000 claims description 3
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 235000014435 Mentha Nutrition 0.000 claims description 2
- 241001072983 Mentha Species 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- SOBHUZYZLFQYFK-UHFFFAOYSA-K trisodium;hydroxy-[[phosphonatomethyl(phosphonomethyl)amino]methyl]phosphinate Chemical compound [Na+].[Na+].[Na+].OP(O)(=O)CN(CP(O)([O-])=O)CP([O-])([O-])=O SOBHUZYZLFQYFK-UHFFFAOYSA-K 0.000 claims description 2
- 238000001816 cooling Methods 0.000 abstract description 3
- 238000001914 filtration Methods 0.000 abstract description 3
- 238000002347 injection Methods 0.000 abstract description 3
- 239000007924 injection Substances 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract 2
- 238000010586 diagram Methods 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 230000001766 physiological effect Effects 0.000 abstract 1
- 239000000843 powder Substances 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 7
- 206010011224 Cough Diseases 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 206010006451 bronchitis Diseases 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 206010006458 Bronchitis chronic Diseases 0.000 description 2
- 206010052804 Drug tolerance Diseases 0.000 description 2
- 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 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 206010035664 Pneumonia Diseases 0.000 description 2
- 206010057190 Respiratory tract infections Diseases 0.000 description 2
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 2
- 208000007451 chronic bronchitis Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000026781 habituation Effects 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 201000005202 lung cancer Diseases 0.000 description 2
- 208000020816 lung neoplasm Diseases 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 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
- 208000008128 pulmonary tuberculosis Diseases 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 235000013736 caramel Nutrition 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 1
- -1 crystal formation I Chemical compound 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- MKXZASYAUGDDCJ-NJAFHUGGSA-N dextromethorphan Chemical compound C([C@@H]12)CCC[C@]11CCN(C)[C@H]2CC2=CC=C(OC)C=C21 MKXZASYAUGDDCJ-NJAFHUGGSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004712 monophosphates Chemical class 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
2θ角数据 | d值数据 | 强度数据(%) |
5.5 | 16.1 | 100.0 |
11.0 | 8.0 | 2.7 |
12.2 | 7.3 | 4.6 |
12.8 | 6.9 | 3.1 |
13.6 | 6.5 | 6.2 |
14.3 | 6.2 | 3.7 |
14.6 | 6.0 | 3.5 |
15.7 | 5.6 | 8.8 |
16.6 | 5.3 | 28.4 |
17.2 | 5.1 | 5.3 |
19.3 | 4.6 | 3.1 |
21.1 | 4.2 | 4.7 |
24.7 | 3.6 | 9.6 |
28.3 | 3.2 | 2.4 |
2θ角数据 | d值数据 | 强度数据(%) |
5.5 | 16.1 | 100.0 |
11.0 | 8.0 | 2.7 |
12.2 | 7.3 | 4.6 |
12.8 | 6.9 | 3.1 |
13.6 | 6.5 | 6.2 |
14.3 | 6.2 | 3.7 |
14.6 | 6.0 | 3.5 |
15.7 | 5.6 | 8.8 |
16.6 | 5.3 | 28.4 |
17.2 | 5.1 | 5.3 |
19.3 | 4.6 | 3.1 |
21.1 | 4.2 | 4.7 |
24.7 | 3.6 | 9.6 |
28.3 | 3.2 | 2.4 |
Claims (7)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210234970.9A CN102746227B (zh) | 2012-07-09 | 2012-07-09 | 一种磷酸二甲啡烷晶型ⅱ及制备方法和药物组合物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201210234970.9A CN102746227B (zh) | 2012-07-09 | 2012-07-09 | 一种磷酸二甲啡烷晶型ⅱ及制备方法和药物组合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN102746227A CN102746227A (zh) | 2012-10-24 |
CN102746227B true CN102746227B (zh) | 2014-12-03 |
Family
ID=47026781
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201210234970.9A Active CN102746227B (zh) | 2012-07-09 | 2012-07-09 | 一种磷酸二甲啡烷晶型ⅱ及制备方法和药物组合物 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN102746227B (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103169681B (zh) * | 2013-03-29 | 2014-09-03 | 山东罗欣药业股份有限公司 | 磷酸二甲啡烷片组合物及其制备方法 |
CN105596312B (zh) * | 2016-01-08 | 2018-06-26 | 珠海联邦制药股份有限公司 | 一种磷酸二甲啡烷胶囊组合物及其制备方法 |
CN105963267A (zh) * | 2016-06-12 | 2016-09-28 | 佛山市腾瑞医药科技有限公司 | 一种磷酸二甲啡烷制剂及其应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101993417A (zh) * | 2009-08-10 | 2011-03-30 | 北京利乐生制药科技有限公司 | 磷酸二甲啡烷的稳定新晶型 |
-
2012
- 2012-07-09 CN CN201210234970.9A patent/CN102746227B/zh active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101993417A (zh) * | 2009-08-10 | 2011-03-30 | 北京利乐生制药科技有限公司 | 磷酸二甲啡烷的稳定新晶型 |
Also Published As
Publication number | Publication date |
---|---|
CN102746227A (zh) | 2012-10-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN102249975B (zh) | (s)-4-羟基-2-氧代-1-吡咯烷乙酰胺晶型ⅰ及其制备方法和用途 | |
AU2019202311B2 (en) | L-ornithine phenyl acetate and methods of making thereof | |
EP3686183A1 (en) | L-ornithine phenyl acetate and methods of making thereof | |
WO2014060449A1 (en) | Multicomponent crystalline system comprising nilotinib and selected co-crystal formers | |
JP2017526699A (ja) | (6s)−5−メチルテトラヒドロ葉酸又はその塩の組成物及びその調製と応用 | |
WO2008031284A1 (fr) | Procédé de résolution d'acide 5-méthyltétrahydrofolique et sa salinisation | |
CN103073542B (zh) | 一种枸橼酸托烷司琼晶型ⅱ的制备和应用 | |
CN103864760B (zh) | 一种盐酸法舒地尔化合物 | |
CN102746227B (zh) | 一种磷酸二甲啡烷晶型ⅱ及制备方法和药物组合物 | |
US9586904B2 (en) | Preparation of (−)-huperzine A | |
JP2023122634A (ja) | トリエチレンテトラミン四塩酸塩、その製造方法及び組成物 | |
CN107849002B (zh) | 一种线叶旋覆花内酯a衍生物 | |
CN108084177B (zh) | 一种小檗碱9-位吡唑衍生物及其制备和应用 | |
CN102775408B (zh) | 稳定的5-甲基四氢叶酸晶型及其制备方法 | |
CN109516991B (zh) | 一种枸橼酸托法替尼晶型化合物及其制备方法 | |
CN103073543B (zh) | 一种枸橼酸托烷司琼晶型ⅰ的制备和应用 | |
CN116041324A (zh) | 一种氘代吡唑二氯苯甲酰胺类化合物、药物组合物和用途 | |
JP7014719B2 (ja) | 置換アミノピラン誘導体の結晶形 | |
CN113045554A (zh) | 一种非索替尼晶型及其制备方法 | |
CN105985252B (zh) | 一种门冬氨酸鸟氨酸晶型iv及其制备方法 | |
CN115252583B (zh) | 复方盐酸替利定缓释制剂及其制备方法 | |
CN106478603B (zh) | 尼洛替尼盐酸盐的新晶型及其制备方法和医药用途 | |
CN115403538B (zh) | 一种依帕司他晶型及其制备方法和应用 | |
CN114105888B (zh) | 丙基硫氧嘧啶与具有抗氧化活性的营养素小分子的共晶及其制备方法 | |
WO2023160520A1 (zh) | 一种三亚乙基四胺四氢氯化物及其制备方法与组合物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
ASS | Succession or assignment of patent right |
Owner name: AOYI BAOLING PHARMACEUTICAL CO., LTD., HANGZHOU Free format text: FORMER OWNER: ZHEJIANG POLLEN PHARMACEUTICAL CO., LTD. Effective date: 20140911 |
|
C41 | Transfer of patent application or patent right or utility model | ||
COR | Change of bibliographic data |
Free format text: CORRECT: ADDRESS; FROM: 310018 HANGZHOU, ZHEJIANG PROVINCE TO: 310022 HANGZHOU, ZHEJIANG PROVINCE |
|
TA01 | Transfer of patent application right |
Effective date of registration: 20140911 Address after: Hangzhou City, Zhejiang province 310022 mid Baolinglu No. 5 Applicant after: Hangzhou Aoyi Baoling Pharmaceutical Co., Ltd. Address before: 310018 No. 668, No. 23, Hangzhou economic and Technological Development Zone, Zhejiang Applicant before: Zhejiang Baoling Pharmaceutical Co., Ltd. |
|
C53 | Correction of patent for invention or patent application | ||
CB02 | Change of applicant information |
Address after: 310018 No. 668, No. 23, Hangzhou economic and Technological Development Zone, Zhejiang Applicant after: Hangzhou Aoyi Baoling Pharmaceutical Co., Ltd. Address before: Hangzhou City, Zhejiang province 310022 mid Baolinglu No. 5 Applicant before: Hangzhou Aoyi Baoling Pharmaceutical Co., Ltd. |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CP03 | Change of name, title or address | ||
CP03 | Change of name, title or address |
Address after: 310018 no.668, No.23 street, Hangzhou Economic and Technological Development Zone, Hangzhou, Zhejiang Province Patentee after: Hangzhou Qianyuan Baoling Pharmaceutical Co., Ltd Address before: 310018 No. 668, No. 23, Hangzhou economic and Technological Development Zone, Zhejiang Patentee before: HANGZHOU AOYIPOLLEN PHARMACEUTICAL Co.,Ltd. |