CN103735518B - The preparation method of timolol maleate sustained-release micro-spheres - Google Patents
The preparation method of timolol maleate sustained-release micro-spheres Download PDFInfo
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- CN103735518B CN103735518B CN201310697827.8A CN201310697827A CN103735518B CN 103735518 B CN103735518 B CN 103735518B CN 201310697827 A CN201310697827 A CN 201310697827A CN 103735518 B CN103735518 B CN 103735518B
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- timolol maleate
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- 239000004005 microsphere Substances 0.000 title claims abstract description 38
- WLRMANUAADYWEA-NWASOUNVSA-N (S)-timolol maleate Chemical compound OC(=O)\C=C/C(O)=O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 WLRMANUAADYWEA-NWASOUNVSA-N 0.000 title claims abstract description 35
- 229960005221 timolol maleate Drugs 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 27
- 238000013268 sustained release Methods 0.000 title claims abstract description 26
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 29
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical class O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000004925 Acrylic resin Substances 0.000 claims abstract description 18
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- 238000013019 agitation Methods 0.000 claims abstract description 13
- 239000004014 plasticizer Substances 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 13
- 238000001704 evaporation Methods 0.000 claims abstract description 11
- 230000008020 evaporation Effects 0.000 claims abstract description 11
- 235000015112 vegetable and seed oil Nutrition 0.000 claims abstract description 11
- 239000008158 vegetable oil Substances 0.000 claims abstract description 11
- 229920000136 polysorbate Polymers 0.000 claims abstract description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- 239000000839 emulsion Substances 0.000 claims description 14
- 238000002156 mixing Methods 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 9
- 230000007935 neutral effect Effects 0.000 claims description 7
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 239000001069 triethyl citrate Substances 0.000 claims description 5
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 5
- 235000013769 triethyl citrate Nutrition 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 230000004913 activation Effects 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 28
- 230000004410 intraocular pressure Effects 0.000 abstract description 6
- 238000000338 in vitro Methods 0.000 abstract description 5
- 238000005507 spraying Methods 0.000 abstract description 3
- 239000003921 oil Substances 0.000 abstract description 2
- 235000019198 oils Nutrition 0.000 abstract description 2
- 239000012071 phase Substances 0.000 description 19
- 229940079593 drug Drugs 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 239000000463 material Substances 0.000 description 8
- 238000001035 drying Methods 0.000 description 7
- 238000011068 loading method Methods 0.000 description 7
- NWGKJDSIEKMTRX-MDZDMXLPSA-N Sorbitan oleate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(O)C1OCC(O)C1O NWGKJDSIEKMTRX-MDZDMXLPSA-N 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 230000003213 activating effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000003889 eye drop Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 239000000607 artificial tear Substances 0.000 description 3
- 210000000481 breast Anatomy 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 239000001117 sulphuric acid Substances 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000006065 biodegradation reaction Methods 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 239000011806 microball Substances 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229920001661 Chitosan Polymers 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 102000002265 Human Growth Hormone Human genes 0.000 description 1
- 108010000521 Human Growth Hormone Proteins 0.000 description 1
- 239000000854 Human Growth Hormone Substances 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 206010030348 Open-Angle Glaucoma Diseases 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000011805 ball Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 210000003022 colostrum Anatomy 0.000 description 1
- 235000021277 colostrum Nutrition 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000004446 light reflex Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 210000004083 nasolacrimal duct Anatomy 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 239000002861 polymer material Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 201000006366 primary open angle glaucoma Diseases 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
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- 239000002904 solvent Substances 0.000 description 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims (9)
Priority Applications (1)
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CN201310697827.8A CN103735518B (en) | 2013-12-17 | 2013-12-17 | The preparation method of timolol maleate sustained-release micro-spheres |
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CN201310697827.8A CN103735518B (en) | 2013-12-17 | 2013-12-17 | The preparation method of timolol maleate sustained-release micro-spheres |
Publications (2)
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CN103735518A CN103735518A (en) | 2014-04-23 |
CN103735518B true CN103735518B (en) | 2016-02-17 |
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CN201310697827.8A Active CN103735518B (en) | 2013-12-17 | 2013-12-17 | The preparation method of timolol maleate sustained-release micro-spheres |
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Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN104491867B (en) * | 2014-11-27 | 2018-07-17 | 广东药科大学 | A kind of preparation method of the novel Drug Delivery Systems of chitosan package load medicine montmorillonite |
CN109646422A (en) * | 2019-01-18 | 2019-04-19 | 广东药科大学 | A kind of preparation method of the ophthalmic administration system of polyacrylic resin package load medicine montmorillonite |
CN112451478A (en) * | 2020-11-26 | 2021-03-09 | 江苏远恒药业有限公司 | Timolol maleate eye drops and preparation process thereof |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1278162A (en) * | 1997-11-05 | 2000-12-27 | 千寿制药株式会社 | Sustained release eyedrops |
WO2008157614A2 (en) * | 2007-06-21 | 2008-12-24 | Yale University | Sustained intraocular delivery of drugs from biodegradable polymeric microparticles |
-
2013
- 2013-12-17 CN CN201310697827.8A patent/CN103735518B/en active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1278162A (en) * | 1997-11-05 | 2000-12-27 | 千寿制药株式会社 | Sustained release eyedrops |
WO2008157614A2 (en) * | 2007-06-21 | 2008-12-24 | Yale University | Sustained intraocular delivery of drugs from biodegradable polymeric microparticles |
Non-Patent Citations (2)
Title |
---|
Montmorillonite as a drug delivery system: Intercalation and in vitro release of timolol maleate;Ghanshyam V. Joshi等;《International Journal of Pharmaceutics》;20090319(第374期);第53-57页,第57页第4节 * |
镶嵌蒙脱石载体的离子交换微球给药***的研制;侯永恒等;《西北药学杂志》;20121130;第27卷(第6期);第560-563页,第562页第3.1、3.2.4节 * |
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CN103735518A (en) | 2014-04-23 |
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C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
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Address after: 528458 Guangdong province Zhongshan city mayor Shan five life water Road No. 9-13 Patentee after: Guangdong Pharmaceutical University Address before: 528458 Guangdong province Zhongshan city mayor Shan five life water Road No. 9-13 Patentee before: Guangdong Pharmaceutical University |
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CP01 | Change in the name or title of a patent holder | ||
TR01 | Transfer of patent right |
Effective date of registration: 20200120 Address after: 510130 room 850, No. 333, jiufo Jianshe Road, Zhongxin Guangzhou Knowledge City, Guangzhou City, Guangdong Province Patentee after: Guangzhou Bosia Biomedical Technology Co.,Ltd. Address before: 528458 Guangdong province Zhongshan city mayor Shan five life water Road No. 9-13 Patentee before: Guangdong Pharmaceutical University |
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Effective date of registration: 20240516 Address after: Building C1, 6th Floor, Guangzhou Development Zone Technology Enterprise Accelerator, No. 11 Kaiyuan Avenue, Guangzhou Science City, Huangpu District, Guangzhou City, Guangdong Province, 510530 Patentee after: GUANGZHOU BOSITAO CONTROLLED RELEASE PHARMACEUTICAL Co.,Ltd. Country or region after: China Address before: Room 850, No. 333, jiufo Jianshe Road, Zhongxin Guangzhou Knowledge City, Guangzhou 510130, Guangdong Province Patentee before: Guangzhou Bosia Biomedical Technology Co.,Ltd. Country or region before: China |