CN104086490B - 一种格列吡嗪化合物及含有该化合物的药物组合物及其制备方法 - Google Patents
一种格列吡嗪化合物及含有该化合物的药物组合物及其制备方法 Download PDFInfo
- Publication number
- CN104086490B CN104086490B CN201410341085.XA CN201410341085A CN104086490B CN 104086490 B CN104086490 B CN 104086490B CN 201410341085 A CN201410341085 A CN 201410341085A CN 104086490 B CN104086490 B CN 104086490B
- Authority
- CN
- China
- Prior art keywords
- glipizide
- preparation
- compound
- pharmaceutical composition
- metformin hydrochloride
- 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
- 229960001381 glipizide Drugs 0.000 title claims abstract description 115
- 238000002360 preparation method Methods 0.000 title claims abstract description 53
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 17
- -1 glipizide compound Chemical class 0.000 title abstract description 31
- 150000001875 compounds Chemical class 0.000 title abstract description 15
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 claims abstract description 84
- 239000003814 drug Substances 0.000 claims abstract description 60
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin hydrochloride Chemical class CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims abstract description 38
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical class Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 claims abstract description 33
- 229960004329 metformin hydrochloride Drugs 0.000 claims abstract description 33
- 239000000843 powder Substances 0.000 claims abstract description 20
- 239000013078 crystal Substances 0.000 claims abstract description 10
- 229910017488 Cu K Inorganic materials 0.000 claims abstract description 8
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- 229940079593 drug Drugs 0.000 claims description 47
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 42
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 28
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 24
- 239000011259 mixed solution Substances 0.000 claims description 23
- 239000000203 mixture Substances 0.000 claims description 20
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 14
- 238000003756 stirring Methods 0.000 claims description 12
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- 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 7
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- 238000012360 testing method Methods 0.000 description 28
- 238000000034 method Methods 0.000 description 16
- 238000009472 formulation Methods 0.000 description 11
- 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 10
- 239000008103 glucose Substances 0.000 description 10
- 239000008280 blood Substances 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
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- 235000012054 meals Nutrition 0.000 description 6
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- 230000002218 hypoglycaemic effect Effects 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 229960003105 metformin Drugs 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000011978 dissolution method Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229940006384 glipizide 2.5 mg Drugs 0.000 description 4
- 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 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 4
- 206010067484 Adverse reaction Diseases 0.000 description 3
- 102000001554 Hemoglobins Human genes 0.000 description 3
- 108010054147 Hemoglobins Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 230000006838 adverse reaction Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 150000002304 glucoses Chemical class 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
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- 238000002835 absorbance Methods 0.000 description 2
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- 239000002671 adjuvant Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
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- 239000012738 dissolution medium Substances 0.000 description 2
- 229940000406 drug candidate Drugs 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
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- 238000001764 infiltration Methods 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 230000010534 mechanism of action Effects 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- FMUIDSCDMUNUQP-UHFFFAOYSA-N n-[2-[4-(cyclohexylcarbamoylsulfamoyl)phenyl]ethyl]-5-methylpyrazine-2-carboxamide;3-(diaminomethylidene)-1,1-dimethylguanidine;hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N.C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 FMUIDSCDMUNUQP-UHFFFAOYSA-N 0.000 description 2
- 230000008520 organization Effects 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
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- 206010003211 Arteriosclerosis coronary artery Diseases 0.000 description 1
- 108010075254 C-Peptide Proteins 0.000 description 1
- LOZSMQANPHUIQN-UHFFFAOYSA-N CC(C1)=CC=CC1=C Chemical compound CC(C1)=CC=CC1=C LOZSMQANPHUIQN-UHFFFAOYSA-N 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
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- 238000002425 crystallisation Methods 0.000 description 1
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- 229940093462 metformin hydrochloride 250 mg Drugs 0.000 description 1
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- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
样品 | 溶解度(μg/mL)5 --> |
样品1 | 612 |
样品2 | 611 |
样品3 | 610 |
样品4 | 611 |
样品5 | 610 |
样品6 | 65 |
样品7 | 64 |
Claims (11)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN201410341085.XA CN104086490B (zh) | 2014-07-17 | 2014-07-17 | 一种格列吡嗪化合物及含有该化合物的药物组合物及其制备方法 |
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CN201410341085.XA CN104086490B (zh) | 2014-07-17 | 2014-07-17 | 一种格列吡嗪化合物及含有该化合物的药物组合物及其制备方法 |
Publications (2)
Publication Number | Publication Date |
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CN104086490A CN104086490A (zh) | 2014-10-08 |
CN104086490B true CN104086490B (zh) | 2016-07-06 |
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CN201410341085.XA Active CN104086490B (zh) | 2014-07-17 | 2014-07-17 | 一种格列吡嗪化合物及含有该化合物的药物组合物及其制备方法 |
Country Status (1)
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CN (1) | CN104086490B (zh) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
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CN105399692A (zh) * | 2015-12-18 | 2016-03-16 | 四川大学 | 格列吡嗪晶型iii及其制备方法 |
CN106187921B (zh) * | 2016-07-09 | 2018-06-15 | 威海迪素制药有限公司 | 一种格列吡嗪结晶的制备方法 |
CN106977466B (zh) * | 2017-03-21 | 2018-07-31 | 威海迪素制药有限公司 | 一种高堆密度格列吡嗪的结晶制备方法 |
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2014
- 2014-07-17 CN CN201410341085.XA patent/CN104086490B/zh active Active
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Publication number | Publication date |
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CN104086490A (zh) | 2014-10-08 |
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C41 | Transfer of patent application or patent right or utility model | ||
CB03 | Change of inventor or designer information |
Inventor after: Huang Bendong Inventor after: Xu Yan Inventor after: Xie Anyun Inventor after: Xu Xiaoqiang Inventor before: Xu Xiaoqiang |
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TR01 | Transfer of patent right |
Effective date of registration: 20161118 Address after: 410329 Liuyang Hunan Biomedical Park Patentee after: HUNAN WARRANT PHARMACEUTICAL CO., LTD. Address before: 410014 Hunan province Changsha Yuhua District No. 52 Kui Tang Lu Ying County love 9 building 601 room Patentee before: Xu Xiaoqiang |