CN100482220C - Oral preparation of bilobalide with high bioavailability and preparation method thereof - Google Patents
Oral preparation of bilobalide with high bioavailability and preparation method thereof Download PDFInfo
- Publication number
- CN100482220C CN100482220C CNB2007100200968A CN200710020096A CN100482220C CN 100482220 C CN100482220 C CN 100482220C CN B2007100200968 A CNB2007100200968 A CN B2007100200968A CN 200710020096 A CN200710020096 A CN 200710020096A CN 100482220 C CN100482220 C CN 100482220C
- Authority
- CN
- China
- Prior art keywords
- bilobalide
- ginkalide
- active component
- preparation
- adjuvant
- 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.)
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Links
- MOLPUWBMSBJXER-YDGSQGCISA-N bilobalide Chemical compound O([C@H]1OC2=O)C(=O)[C@H](O)[C@@]11[C@@](C(C)(C)C)(O)C[C@H]3[C@@]21CC(=O)O3 MOLPUWBMSBJXER-YDGSQGCISA-N 0.000 title claims abstract description 144
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims abstract description 18
- 241000218628 Ginkgo Species 0.000 claims abstract description 7
- 235000011201 Ginkgo Nutrition 0.000 claims abstract description 7
- 235000008100 Ginkgo biloba Nutrition 0.000 claims abstract description 7
- 210000002784 stomach Anatomy 0.000 claims abstract description 6
- 239000000203 mixture Substances 0.000 claims description 37
- 238000009472 formulation Methods 0.000 claims description 18
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 12
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 12
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 12
- 239000002671 adjuvant Substances 0.000 claims description 11
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 10
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 7
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 7
- -1 hydroxypropyl Chemical group 0.000 claims description 7
- 150000002596 lactones Chemical class 0.000 claims description 7
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 7
- 239000003826 tablet Substances 0.000 claims description 7
- 239000001856 Ethyl cellulose Substances 0.000 claims description 6
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 6
- 239000011230 binding agent Substances 0.000 claims description 6
- 238000007907 direct compression Methods 0.000 claims description 6
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 6
- 229920001249 ethyl cellulose Polymers 0.000 claims description 6
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 6
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 6
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 6
- 239000006187 pill Substances 0.000 claims description 6
- 239000011347 resin Substances 0.000 claims description 6
- 229920005989 resin Polymers 0.000 claims description 6
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 5
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 5
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 5
- 229910000019 calcium carbonate Inorganic materials 0.000 claims description 5
- 239000011248 coating agent Substances 0.000 claims description 5
- 238000000576 coating method Methods 0.000 claims description 5
- 239000004088 foaming agent Substances 0.000 claims description 5
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 5
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 5
- 235000019359 magnesium stearate Nutrition 0.000 claims description 5
- 229920000609 methyl cellulose Polymers 0.000 claims description 5
- 239000001923 methylcellulose Substances 0.000 claims description 5
- 239000000178 monomer Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 239000000375 suspending agent Substances 0.000 claims description 5
- 229920002125 Sokalan® Polymers 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 4
- 229960001631 carbomer Drugs 0.000 claims description 4
- 230000003196 chaotropic effect Effects 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 4
- 229920000053 polysorbate 80 Polymers 0.000 claims description 4
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 4
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 4
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 4
- 229920001661 Chitosan Polymers 0.000 claims description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 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 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims 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 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- 239000000783 alginic acid Substances 0.000 claims description 3
- 235000010443 alginic acid Nutrition 0.000 claims description 3
- 229920000615 alginic acid Polymers 0.000 claims description 3
- 229960001126 alginic acid Drugs 0.000 claims description 3
- 150000004781 alginic acids Chemical class 0.000 claims description 3
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 3
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 3
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 claims description 3
- 238000005516 engineering process Methods 0.000 claims description 3
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 3
- 239000001095 magnesium carbonate Substances 0.000 claims description 3
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- 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 claims description 2
- 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
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 238000007908 dry granulation Methods 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 235000001727 glucose Nutrition 0.000 claims description 2
- 238000001727 in vivo Methods 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 239000008188 pellet Substances 0.000 claims description 2
- 238000007670 refining Methods 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 238000005550 wet granulation Methods 0.000 claims description 2
- 229940079593 drug Drugs 0.000 abstract description 9
- 238000001035 drying Methods 0.000 abstract description 4
- 238000000227 grinding Methods 0.000 abstract 2
- 239000002245 particle Substances 0.000 abstract 2
- 229930063422 Bilobalide A Natural products 0.000 abstract 1
- SQOJOAFXDQDRGF-ZMVGXLHTSA-N ginkgolide b Chemical compound O[C@H]([C@]12[C@H](C(C)(C)C)C[C@H]3OC4=O)C(=O)O[C@H]2O[C@]24[C@@]13[C@H](O)[C@@H]1OC(=O)[C@@H](C)[C@]21O SQOJOAFXDQDRGF-ZMVGXLHTSA-N 0.000 abstract 1
- 238000009736 wetting Methods 0.000 abstract 1
- 238000002156 mixing Methods 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 239000000243 solution Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000000825 pharmaceutical preparation Substances 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 3
- 238000001647 drug administration Methods 0.000 description 3
- 230000000857 drug effect Effects 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000007779 soft material Substances 0.000 description 3
- 206010013786 Dry skin Diseases 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- 210000004051 gastric juice Anatomy 0.000 description 2
- 230000000968 intestinal effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- HVAUUPRFYPCOCA-AREMUKBSSA-N 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCOC[C@@H](OC(C)=O)COP([O-])(=O)OCC[N+](C)(C)C HVAUUPRFYPCOCA-AREMUKBSSA-N 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 108010003541 Platelet Activating Factor Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002212 flavone derivatives Chemical group 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
Description
Claims (5)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2007100200968A CN100482220C (en) | 2007-02-12 | 2007-02-12 | Oral preparation of bilobalide with high bioavailability and preparation method thereof |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CNB2007100200968A CN100482220C (en) | 2007-02-12 | 2007-02-12 | Oral preparation of bilobalide with high bioavailability and preparation method thereof |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101011382A CN101011382A (en) | 2007-08-08 |
CN100482220C true CN100482220C (en) | 2009-04-29 |
Family
ID=38699218
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB2007100200968A Active CN100482220C (en) | 2007-02-12 | 2007-02-12 | Oral preparation of bilobalide with high bioavailability and preparation method thereof |
Country Status (1)
Country | Link |
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CN (1) | CN100482220C (en) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104188959B (en) * | 2014-09-28 | 2016-08-24 | 顾玉奎 | A kind of ginkolide B composition and preparation method thereof |
CN105541861A (en) * | 2016-01-27 | 2016-05-04 | 河北润茂制药有限公司 | Refined ginkgolide extraction process |
CN105663073A (en) * | 2016-04-06 | 2016-06-15 | 刘建军 | Method for preparing traditional Chinese medicine tablet granulated by adhesive foam state |
-
2007
- 2007-02-12 CN CNB2007100200968A patent/CN100482220C/en active Active
Also Published As
Publication number | Publication date |
---|---|
CN101011382A (en) | 2007-08-08 |
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SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
ASS | Succession or assignment of patent right |
Owner name: JIANGSU PENGYAO PHARMACEUTICAL CO., LTD. Free format text: FORMER OWNER: ZHANG GUOQING Effective date: 20100407 |
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C41 | Transfer of patent application or patent right or utility model | ||
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Free format text: CORRECT: ADDRESS; FROM: 214205 JIANGSU PENGYAO PHARMACEUTICAL CO., LTD., NO.69, LONGCHI ROAD, YICHENG TOWN, YIXING CITY, JIANGSU PROVINCE TO: 214205 NO.69, LONGCHI ROAD, YICHENG TOWN, YIXING CITY, JIANGSU PROVINCE |
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TR01 | Transfer of patent right |
Effective date of registration: 20100407 Address after: 214205 Jiangsu province Yixing Yicheng town dragon Chi Lu No. 69 Patentee after: Jiangsu Pengyao Pharmaceutical Inc. Address before: 214205 Jiangsu province Yixing Yicheng town dragon Chi Lu No. 69 Jiangsu Pengyao Pharmaceutical Co., Ltd. Patentee before: Zhang Guoqing |