CN104623671A - 含有乙酰胆碱酯酶抑制剂和二甲双胍的复方药用组合物 - Google Patents
含有乙酰胆碱酯酶抑制剂和二甲双胍的复方药用组合物 Download PDFInfo
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- CN104623671A CN104623671A CN201510066439.9A CN201510066439A CN104623671A CN 104623671 A CN104623671 A CN 104623671A CN 201510066439 A CN201510066439 A CN 201510066439A CN 104623671 A CN104623671 A CN 104623671A
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- CN
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- Prior art keywords
- metformin
- donepezil
- hydrochloride
- pharmaceutical composition
- pharmaceutically acceptable
- 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
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 239000003814 drug Substances 0.000 title claims abstract description 33
- 229960003105 metformin Drugs 0.000 title claims abstract description 25
- 239000000544 cholinesterase inhibitor Substances 0.000 title claims abstract description 18
- 239000000203 mixture Substances 0.000 title claims abstract description 18
- 150000001875 compounds Chemical class 0.000 title abstract description 17
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 title abstract 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims abstract description 32
- 229960003530 donepezil Drugs 0.000 claims abstract description 16
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims abstract description 15
- 229940079593 drug Drugs 0.000 claims abstract description 12
- 229960003980 galantamine Drugs 0.000 claims abstract description 9
- ZRJBHWIHUMBLCN-SEQYCRGISA-N Huperzine A Natural products N1C(=O)C=CC2=C1C[C@H]1/C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-SEQYCRGISA-N 0.000 claims abstract description 6
- ZRJBHWIHUMBLCN-UHFFFAOYSA-N Shuangyiping Natural products N1C(=O)C=CC2=C1CC1C(=CC)C2(N)CC(C)=C1 ZRJBHWIHUMBLCN-UHFFFAOYSA-N 0.000 claims abstract description 6
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims abstract description 6
- ZRJBHWIHUMBLCN-YQEJDHNASA-N huperzine A Chemical compound N1C(=O)C=CC2=C1C[C@H]1\C(=C/C)[C@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-YQEJDHNASA-N 0.000 claims abstract description 6
- ZRJBHWIHUMBLCN-BMIGLBTASA-N rac-huperzine A Natural products N1C(=O)C=CC2=C1C[C@@H]1C(=CC)[C@@]2(N)CC(C)=C1 ZRJBHWIHUMBLCN-BMIGLBTASA-N 0.000 claims abstract description 6
- HPOIPOPJGBKXIR-UHFFFAOYSA-N 3,6-dimethoxy-10-methyl-galantham-1-ene Natural products O1C(C(=CC=2)OC)=C3C=2CN(C)CCC23C1CC(OC)C=C2 HPOIPOPJGBKXIR-UHFFFAOYSA-N 0.000 claims abstract description 4
- LPCKPBWOSNVCEL-UHFFFAOYSA-N Chlidanthine Natural products O1C(C(=CC=2)O)=C3C=2CN(C)CCC23C1CC(OC)C=C2 LPCKPBWOSNVCEL-UHFFFAOYSA-N 0.000 claims abstract description 4
- BGLNUNCBNALFOZ-WMLDXEAASA-N galanthamine Natural products COc1ccc2CCCC[C@@]34C=CCC[C@@H]3Oc1c24 BGLNUNCBNALFOZ-WMLDXEAASA-N 0.000 claims abstract description 4
- IYVSXSLYJLAZAT-NOLJZWGESA-N lycoramine Natural products CN1CC[C@@]23CC[C@H](O)C[C@@H]2Oc4cccc(C1)c34 IYVSXSLYJLAZAT-NOLJZWGESA-N 0.000 claims abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 239000003112 inhibitor Substances 0.000 claims description 16
- 206010012289 Dementia Diseases 0.000 claims description 15
- 201000010099 disease Diseases 0.000 claims description 12
- 150000003839 salts Chemical class 0.000 claims description 10
- 238000009472 formulation Methods 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 239000000470 constituent Substances 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- 229950004288 tosilate Drugs 0.000 claims description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 10
- 239000003937 drug carrier Substances 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 abstract description 14
- 238000012360 testing method Methods 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 10
- 238000002360 preparation method Methods 0.000 abstract description 8
- 230000003285 pharmacodynamic effect Effects 0.000 abstract description 5
- 230000002195 synergetic effect Effects 0.000 abstract description 3
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 239000004480 active ingredient Substances 0.000 abstract 1
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 39
- XWAIAVWHZJNZQQ-UHFFFAOYSA-N donepezil hydrochloride Chemical compound [H+].[Cl-].O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 XWAIAVWHZJNZQQ-UHFFFAOYSA-N 0.000 description 37
- 229960004329 metformin hydrochloride Drugs 0.000 description 36
- 229960003135 donepezil hydrochloride Drugs 0.000 description 35
- 241000699670 Mus sp. Species 0.000 description 24
- 230000006886 spatial memory Effects 0.000 description 13
- 239000008187 granular material Substances 0.000 description 12
- 230000006870 function Effects 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 239000003826 tablet Substances 0.000 description 10
- 238000012549 training Methods 0.000 description 8
- 206010039966 Senile dementia Diseases 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000005550 wet granulation Methods 0.000 description 7
- 238000011825 3xTg-AD mouse Methods 0.000 description 6
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 6
- 230000000052 comparative effect Effects 0.000 description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 6
- 229960003943 hypromellose Drugs 0.000 description 6
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 6
- 239000008108 microcrystalline cellulose Substances 0.000 description 6
- 229940016286 microcrystalline cellulose Drugs 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- 238000003723 Smelting Methods 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 230000009261 transgenic effect Effects 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000012347 Morris Water Maze Methods 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 238000003304 gavage Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 2
- 229960004640 memantine Drugs 0.000 description 2
- 230000015654 memory Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229960001685 tacrine Drugs 0.000 description 2
- YLJREFDVOIBQDA-UHFFFAOYSA-N tacrine Chemical compound C1=CC=C2C(N)=C(CCCC3)C3=NC2=C1 YLJREFDVOIBQDA-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 1
- 229940123511 Excitatory amino acid receptor antagonist Drugs 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000007910 chewable tablet Substances 0.000 description 1
- 229940068682 chewable tablet Drugs 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- -1 metformin hydrochloride compound Chemical class 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 229940023488 pill Drugs 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000007962 solid dispersion Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
组分 | 用量 |
盐酸多奈哌齐 | 5g |
盐酸二甲双胍 | 500g |
微晶纤维素 | 45g |
交联羧甲基纤维素钠 | 10g |
硬脂酸镁 | 4g |
2%羟丙甲纤维素(固体重量) | 6g |
组分 | 用量 |
盐酸多奈哌齐 | 5g |
盐酸二甲双胍 | 250g |
微晶纤维素 | 30g |
硬脂酸镁 | 10g |
2%羟丙甲纤维素(固体重量) | 10g |
Claims (10)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510066439.9A CN104623671B (zh) | 2015-02-09 | 2015-02-09 | 含有乙酰胆碱酯酶抑制剂和二甲双胍的复方药用组合物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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CN201510066439.9A CN104623671B (zh) | 2015-02-09 | 2015-02-09 | 含有乙酰胆碱酯酶抑制剂和二甲双胍的复方药用组合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104623671A true CN104623671A (zh) | 2015-05-20 |
CN104623671B CN104623671B (zh) | 2017-11-17 |
Family
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CN201510066439.9A Active CN104623671B (zh) | 2015-02-09 | 2015-02-09 | 含有乙酰胆碱酯酶抑制剂和二甲双胍的复方药用组合物 |
Country Status (1)
Country | Link |
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CN (1) | CN104623671B (zh) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112076202A (zh) * | 2020-09-22 | 2020-12-15 | 中国农业大学 | 一种药物组合物及其在制备预防和/或治疗阿尔茨海默症药物中的应用 |
CN112654367A (zh) * | 2018-06-29 | 2021-04-13 | 再青春生物医药公司 | 用于年龄相关性和/或变性疾病的药物组合 |
CN113384552A (zh) * | 2021-05-14 | 2021-09-14 | 厦门大学 | 用于神经退行性疾病的双载药纳米制剂及其制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1960735A (zh) * | 2004-05-20 | 2007-05-09 | 代阿麦迪卡股份有限公司 | 药物组合在治疗胰岛素抗性中的应用 |
US20080286344A1 (en) * | 2007-05-16 | 2008-11-20 | Olivia Darmuzey | Solid form |
US20090081314A1 (en) * | 2007-09-18 | 2009-03-26 | Stephen Wills | Glycemic Control, Diabetes Treatment, and Other Treatments with Acetyl Cholinesterase Inhibitors |
CN103860532A (zh) * | 2014-03-11 | 2014-06-18 | 贡岳松 | 美金刚和二甲双胍的复方药用组合物及其制备方法 |
-
2015
- 2015-02-09 CN CN201510066439.9A patent/CN104623671B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1960735A (zh) * | 2004-05-20 | 2007-05-09 | 代阿麦迪卡股份有限公司 | 药物组合在治疗胰岛素抗性中的应用 |
US20080286344A1 (en) * | 2007-05-16 | 2008-11-20 | Olivia Darmuzey | Solid form |
US20090081314A1 (en) * | 2007-09-18 | 2009-03-26 | Stephen Wills | Glycemic Control, Diabetes Treatment, and Other Treatments with Acetyl Cholinesterase Inhibitors |
WO2009039313A1 (en) * | 2007-09-18 | 2009-03-26 | Stephen Wills | Glycemic control, diabetes treatment, and other treatments with acetyl cholinesterase inhibitors |
CN103860532A (zh) * | 2014-03-11 | 2014-06-18 | 贡岳松 | 美金刚和二甲双胍的复方药用组合物及其制备方法 |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112654367A (zh) * | 2018-06-29 | 2021-04-13 | 再青春生物医药公司 | 用于年龄相关性和/或变性疾病的药物组合 |
KR20210042312A (ko) * | 2018-06-29 | 2021-04-19 | 리주베나떼 바이오메드 | 노화-관련 질환 및/또는 퇴행성 질환에 사용하는 약제학적 결합물 |
CN112654367B (zh) * | 2018-06-29 | 2023-08-04 | 再青春生物医药公司 | 用于年龄相关性和/或变性疾病的药物组合 |
CN112076202A (zh) * | 2020-09-22 | 2020-12-15 | 中国农业大学 | 一种药物组合物及其在制备预防和/或治疗阿尔茨海默症药物中的应用 |
CN113384552A (zh) * | 2021-05-14 | 2021-09-14 | 厦门大学 | 用于神经退行性疾病的双载药纳米制剂及其制备方法 |
Also Published As
Publication number | Publication date |
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CN104623671B (zh) | 2017-11-17 |
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Effective date of registration: 20200628 Address after: Room 903B, Block A, 66 Hexi Street, Jianye District, Nanjing City, Jiangsu Province Co-patentee after: Xu Yungen Patentee after: Nanjing Qianhand Co-founding Biological Technology Co.,Ltd. Address before: Room 903B, Block A, 66 Hexi Street, Jianye District, Nanjing City, Jiangsu Province Patentee before: Nanjing Qianhand Co-founding Biological Technology Co.,Ltd. |