JP5165582B2 - ジペプチジルペプチダーゼ−4インヒビターとメトホルミンとを組み合わせた医薬組成物 - Google Patents
ジペプチジルペプチダーゼ−4インヒビターとメトホルミンとを組み合わせた医薬組成物 Download PDFInfo
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- JP5165582B2 JP5165582B2 JP2008545737A JP2008545737A JP5165582B2 JP 5165582 B2 JP5165582 B2 JP 5165582B2 JP 2008545737 A JP2008545737 A JP 2008545737A JP 2008545737 A JP2008545737 A JP 2008545737A JP 5165582 B2 JP5165582 B2 JP 5165582B2
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- sitagliptin
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- FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 235000010386 dodecyl gallate Nutrition 0.000 description 1
- 239000000555 dodecyl gallate Substances 0.000 description 1
- 229940080643 dodecyl gallate Drugs 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000001258 dyslipidemic effect Effects 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 238000005243 fluidization Methods 0.000 description 1
- 235000019264 food flavour enhancer Nutrition 0.000 description 1
- 235000010382 gamma-tocopherol Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 229940112611 glucovance Drugs 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940090022 hyzaar Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 229960000519 losartan potassium Drugs 0.000 description 1
- 239000000391 magnesium silicate Substances 0.000 description 1
- 235000019792 magnesium silicate Nutrition 0.000 description 1
- 229910052919 magnesium silicate Inorganic materials 0.000 description 1
- 229960002366 magnesium silicate Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229940035732 metformin and rosiglitazone Drugs 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 235000010387 octyl gallate Nutrition 0.000 description 1
- 239000000574 octyl gallate Substances 0.000 description 1
- NRPKURNSADTHLJ-UHFFFAOYSA-N octyl gallate Chemical compound CCCCCCCCOC(=O)C1=CC(O)=C(O)C(O)=C1 NRPKURNSADTHLJ-UHFFFAOYSA-N 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960000540 polacrilin potassium Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- WVWZXTJUCNEUAE-UHFFFAOYSA-M potassium;1,2-bis(ethenyl)benzene;2-methylprop-2-enoate Chemical compound [K+].CC(=C)C([O-])=O.C=CC1=CC=CC=C1C=C WVWZXTJUCNEUAE-UHFFFAOYSA-M 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 208000037821 progressive disease Diseases 0.000 description 1
- 235000010388 propyl gallate Nutrition 0.000 description 1
- 239000000473 propyl gallate Substances 0.000 description 1
- 229940075579 propyl gallate Drugs 0.000 description 1
- 238000009490 roller compaction Methods 0.000 description 1
- SUFUKZSWUHZXAV-BTJKTKAUSA-N rosiglitazone maleate Chemical compound [H+].[H+].[O-]C(=O)\C=C/C([O-])=O.C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O SUFUKZSWUHZXAV-BTJKTKAUSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229940074790 simvastatin and ezetimibe Drugs 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- BTURAGWYSMTVOW-UHFFFAOYSA-M sodium dodecanoate Chemical compound [Na+].CCCCCCCCCCCC([O-])=O BTURAGWYSMTVOW-UHFFFAOYSA-M 0.000 description 1
- 229940082004 sodium laurate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- MWZFQMUXPSUDJQ-KVVVOXFISA-M sodium;[(z)-octadec-9-enyl] sulfate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCCOS([O-])(=O)=O MWZFQMUXPSUDJQ-KVVVOXFISA-M 0.000 description 1
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 229940009349 vytorin Drugs 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 239000002478 γ-tocopherol Substances 0.000 description 1
- QUEDXNHFTDJVIY-DQCZWYHMSA-N γ-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-DQCZWYHMSA-N 0.000 description 1
- 239000002446 δ-tocopherol Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2813—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Description
(1)50ミリグラムのシタグリプチン(64.25ミリグラムのリン酸シタグリプチン一水和物に等しい)及び500ミリグラムの塩酸メトホルミン;
(2)50ミリグラムのシタグリプチン(64.25ミリグラムのリン酸シタグリプチン一水和物に等しい)及び850ミリグラムの塩酸メトホルミン;
(3)50ミリグラムのシタグリプチン(64.25ミリグラムのリン酸シタグリプチン一水和物に等しい)及び1000ミリグラムの塩酸メトホルミン;
(4)100ミリグラムのシタグリプチン(128.5ミリグラムのリン酸シタグリプチン一水和物に等しい)及び500ミリグラムの塩酸メトホルミン;
(5)100ミリグラムのシタグリプチン(128.5ミリグラムのリン酸シタグリプチン一水和物に等しい)及び850ミリグラムの塩酸メトホルミン;並びに
(6)100ミリグラムのシタグリプチン(128.5ミリグラムのリン酸シタグリプチン一水和物に等しい)及び1000ミリグラムの塩酸メトホルミン。
約9重量%のDPP−4インヒビター;約73重量%の塩酸メトホルミン;約7重量%の結合剤;約1〜2重量%の潤滑剤;並びに任意に約10重量%の稀釈剤及び/又は約0.5重量%の界面活性剤。この実施態様の部類において、DPP−4インヒビターは、シタグリプチン、ビルダグリプチン又はサクサグリプチンであり;結合剤は、ポリビニルピロリドンであり、潤滑剤は、ステアリン酸マグネシウム又はステアリルフマル酸ナトリウムであり、稀釈剤は、微晶質セルロースであり、そして界面活性剤は、ラウリル硫酸ナトリウムである。この部類の下位分類において、DPP−4インヒビターはシタグリプチンである。
約6重量%のDPP−4インヒビター;約76重量%の塩酸メトホルミン;約7重量%の結合剤;約1〜2重量%の潤滑剤;並びに任意に約10重量%の稀釈剤及び/又は約0.5重量%の界面活性剤。この実施態様の部類において、DPP−4インヒビターは、シタグリプチン、ビルダグリプチン又はサクサグリプチンであり;結合剤は、ポリビニルピロリドンであり、潤滑剤は、ステアリン酸マグネシウム又はステアリルフマル酸ナトリウムであり、稀釈剤は、微晶質セルロースであり、そして界面活性剤は、ラウリル硫酸ナトリウムである。下位分類において、DPP−4インヒビターはシタグリプチンである。
約5重量%のDPP−4インヒビター;約77重量%の塩酸メトホルミン;約7重量%の結合剤;約1〜2重量%の潤滑剤;並びに任意に約10重量%の稀釈剤及び/又は約0.5重量%の界面活性剤。この実施態様の部類において、DPP−4インヒビターは、シタグリプチン、ビルダグリプチン又はサクサグリプチンであり;結合剤は、ポリビニルピロリドンであり、潤滑剤は、ステアリン酸マグネシウム又はステアリルフマル酸ナトリウムであり、稀釈剤は、微晶質セルロースであり、そして界面活性剤は、ラウリル硫酸ナトリウムである。下位分類において、DPP−4インヒビターはシタグリプチンである。
約17重量%のDPP−4インヒビター;約65重量%の塩酸メトホルミン;約7重量%の結合剤;約1〜2重量%の潤滑剤;並びに任意に約9重量%の稀釈剤及び/又は約0.5重量%の界面活性剤。この実施態様の部類において、DPP−4インヒビターは、シタグリプチン、ビルダグリプチン又はサクサグリプチンであり;結合剤は、ポリビニルピロリドンであり、潤滑剤は、ステアリン酸マグネシウム又はステアリルフマル酸ナトリウムであり、稀釈剤は、微晶質セルロースであり、そして界面活性剤は、ラウリル硫酸ナトリウムである。下位分類において、DPP−4インヒビターはシタグリプチンである。
約11重量%のDPP−4インヒビター;約75重量%の塩酸メトホルミン;約7重量%の結合剤;約1〜2重量%の潤滑剤;並びに任意に約4重量%の稀釈剤及び/又は約0.5重量%の界面活性剤。この実施態様の部類において、DPP−4インヒビターは、シタグリプチン、ビルダグリプチン又はサクサグリプチンであり;結合剤は、ポリビニルピロリドンであり、潤滑剤は、ステアリン酸マグネシウム又はステアリルフマル酸ナトリウムであり、稀釈剤は、微晶質セルロースであり、そして界面活性剤は、ラウリル硫酸ナトリウムである。下位分類において、DPP−4インヒビターはシタグリプチンである。
約10重量%のDPP−4インヒビター;約77重量%の塩酸メトホルミン;約7重量%の結合剤;約1〜2重量%の潤滑剤;並びに任意に約4重量%の稀釈剤及び/又は約0.5重量%の界面活性剤。この実施態様の部類において、DPP−4インヒビターは、シタグリプチン、ビルダグリプチン又はサクサグリプチンであり;結合剤は、ポリビニルピロリドンであり、潤滑剤は、ステアリン酸マグネシウム又はステアリルフマル酸ナトリウムであり、稀釈剤は、微晶質セルロースであり、そして界面活性剤は、ラウリル硫酸ナトリウムである。下位分類において、DPP−4インヒビターはシタグリプチンである。
(1)活性医薬成分の塩酸メトホルミンとDPP−4インヒビターを造粒ボウルに加える;
(2)任意の崩壊剤を工程1に加える;
(3)高剪断造粒のために、結合剤(例えば、ポリビニルピロリドン又はヒドロキシプロピルセルロース)を造粒ボウルに乾燥したままで加え、短時間乾燥混合し、続いて、界面活性剤(例えば、ラウリル硫酸ナトリウム)を伴うか又は伴わないで水を加える。流動層造粒のためには、両方の活性医薬成分を造粒ボウルに加え、界面活性剤を有するか又は有さない、水中の結合剤から構成される造粒溶液を、流動化の際に加える;
(4)高剪断造粒により調製された顆粒を、オーブンによりトレーで乾燥するか又は流動層ドライヤーで乾燥する。流動層造粒により調製される顆粒では、顆粒を流動層ドライヤーで乾燥する;
(5)乾燥した顆粒を適切なミルで大きさを変える;
(6)任意の稀釈剤(例えば、微晶質セルロース及び第二リン酸カルシウム二水和物)を適切なブレンダーで乾燥した顆粒と混合する;
(7)潤滑剤又は滑剤(例えば、ステアリン酸マグネシウム及びステアリルフマル酸ナトリウム)を適切なブレンダーで工程6の混合物に加える;
(8)工程7の潤滑した顆粒混合物をボトル、小袋(sachets)若しくはカプセルに充填するか、又は所望の錠剤に圧縮する;および、
(9)望ましい場合は、得られた錠剤を被膜することができる。
(1)活性医薬成分の塩酸メトホルミンとDPP−4インヒビターを適切なブレンダーに加える;
(2)任意の崩壊剤を工程1に加える;
(3)任意の結合剤及び/又は稀釈剤を工程2に加える;
(4)潤滑剤又は滑剤を工程3に加える;
(5)工程4の混合物をボトル、小袋(sachets)若しくはカプセルに充填するか、又は所望の錠剤像に圧縮するか、又はローラー圧密機で処理する;
(6)ローラー圧密機で処理する場合、必要であれば顆粒を適切なミルで大きさを変えることができる;
(7)任意の稀釈剤を、適切なブレンダー中の、得られた顆粒に加えて圧密性を改善することができる;
(8)任意の潤滑剤又は滑剤を工程7の混合物に加える;
(9)工程8の潤滑した顆粒混合物をボトル、小袋(sachets)若しくはカプセルに充填するか、又は所望の錠剤像に圧縮する;および、
(10)望ましい場合は、工程5又は工程9で得られた錠剤を被膜することができる。
1錠あたり50ミリグラムのシタグリプチンと500ミリグラムの塩酸メトホルミンの固定用量の組み合わせ−湿式造粒
リン酸シタグリプチン一水和物及び塩酸メトホルミンを、高剪断造粒機又は流動層造粒機に装填した。高剪断造粒の場合、ポリビニルピロリドン結合剤に加えて、ラウリル硫酸ナトリウムを含有する精製水を3〜5分間かけてAPIに加えた。湿潤した塊をトレーにより40℃で乾燥するか、又は流動層ドライヤーにより45〜60℃の入口温度で3〜6分間乾燥した。流動層造粒の場合、ポリビニルピロリドン及びラウリル硫酸ナトリウムを含有する精製水を、30〜60分間かけてAPIに加えた。湿潤した塊を流動層ドライヤーにより45〜60℃の入口温度で乾燥した。次に乾燥した物質を、コミル(co−mill)を使用して摩砕して微細顆粒を得た。摩砕した後、微晶質セルロースを顆粒に加え、ツインシェルブレンダー(twin shell−blender)で200回転して混合した。次に、潤滑剤(ステアリルフマル酸ナトリウム)を加え、更に100回転して混合した。潤滑した混合物を、ロータリー錠剤プレスを使用して圧縮し、689mgの素錠を得た。錠剤を、Opadry(登録商標)II懸濁液(ポリビニルアルコール、ポリエチレングリコール、二酸化チタン及びタルク、着色剤有り又は無し)で任意に被膜し、重量をおよそ2.5%増加して、706mgの被膜錠剤を得た。
1錠あたり50ミリグラムのシタグリプチンと850ミリグラムの塩酸メトホルミンの固定用量の組み合わせ−湿式造粒
錠剤を、実質的に実施例1の手順を使用する湿式造粒により調製して、1117mgの素錠を得た。錠剤を、27.9mgの標準OpadryII(登録商標)被膜配合物により任意に被膜して、1145mgの被膜錠剤を得た。
1錠あたり50ミリグラムのシタグリプチンと1000ミリグラムの塩酸メトホルミンの固定用量の組み合わせ−湿式造粒
錠剤を、実質的に実施例1の手順を使用する湿式造粒により調製して、1300mgの素錠を得た。錠剤を、OpadryII(登録商標)懸濁液(ポリビニルアルコール、ポリエチレングリコール、二酸化チタン及びタルク、着色剤を有り又は無し)で任意に被膜し、重量をおよそ2.5%増加して、1333mgの被膜錠剤を得た。
1錠あたり50ミリグラムのシタグリプチンと500ミリグラムの塩酸メトホルミンの固定用量の組み合わせ−湿式造粒
リン酸シタグリプチン一水和物及び塩酸メトホルミンを、高剪断造粒機又は流動層造粒機に装填した。高剪断造粒の場合、ポリビニルピロリドン結合剤に加えて、精製水を3〜5分間かけてAPIに加えた。湿潤した塊をトレーにより40℃で乾燥するか、又は流動層ドライヤーにより45〜60℃の入口温度で3〜6分間乾燥した。流動層造粒の場合、ポリビニルピロリドンを含有する精製水を、30〜60分間かけてAPIに加えた。湿潤した塊を流動層ドライヤーにより45〜60℃の入口温度で乾燥した。次に乾燥した物質を、コミルを使用して摩砕して微細顆粒を得た。摩砕した後、微晶質セルロースを顆粒に加え、ツインシェルブレンダーで200回転して混合した。次に、潤滑剤(ステアリン酸マグネシウム)を加え、更に100回転して混合した。潤滑した混合物を、ロータリー錠剤プレスを使用して圧縮し、689mgの素錠を得た。次に錠剤を、OpadryII(登録商標)懸濁液(ポリビニルアルコール、ポリエチレングリコール、二酸化チタン及びタルク、着色剤有り又は無し)で任意に被膜し、重量をおよそ2.5%増加して、706mgの被膜錠剤を得た。
1錠あたり50ミリグラムのシタグリプチンと1000ミリグラムの塩酸メトホルミンの固定用量の組み合わせ−湿式造粒
リン酸シタグリプチン一水和物及び塩酸メトホルミンを、高剪断造粒機又は流動層造粒機に装填した。高剪断造粒の場合、ポリビニルピロリドン結合剤に加えて、ラウリル硫酸ナトリウムを含有する精製水を3〜5分間かけてAPIに加えた。湿潤した塊をトレーにより40℃で乾燥するか、又は流動層ドライヤーにより45〜60℃の入口温度で3〜6分間乾燥した。流動層造粒の場合、ポリビニルピロリドン及びラウリル硫酸ナトリウムを含有する精製水を、30〜60分間かけてAPIに加えた。湿潤した塊を流動層ドライヤーにより45〜60℃の入口温度で乾燥した。次に乾燥した物質を、コミルを使用して摩砕して微細顆粒を得た。摩砕した後、微晶質セルロースを顆粒に加え、ツインシェルブレンダーで200回転して混合した。次に、潤滑剤(ステアリン酸マグネシウム)を加え、更に100回転して混合した。潤滑した混合物を、ロータリー錠剤プレスを使用して圧縮し、1300mgの素錠を得た。次に錠剤を、OpadryII(登録商標)懸濁液(ポリビニルアルコール、ポリエチレングリコール、二酸化チタン及びタルク、着色剤有り又は無し)で任意に被膜し、重量をおよそ2.5%増加して、1333mgの被膜錠剤を得た。
1錠あたり100ミリグラムのシタグリプチンと1000ミリグラムの塩酸メトホルミンの固定用量の組み合わせ−湿式造粒
錠剤を、実質的に実施例1の手順を使用する流動層造粒により調製して、1300mgの素錠を得た。
1錠あたり100ミリグラムのシタグリプチンと500ミリグラムの塩酸メトホルミンの固定用量の組み合わせ−湿式造粒
錠剤を、実質的に実施例1の手順を使用する流動層造粒により調製して、768mgの素錠を得た。
Claims (11)
- (a)3〜20重量%のシタグリプチン又はその薬学的に許容される塩;
(b)25〜94重量%の塩酸メトホルミン;
(c)0.1〜10重量%の滑沢剤;
(d)0〜35重量%の結合剤;
(e)0.5〜1重量%のラウリル硫酸ナトリウム;及び
(f)5〜15重量%の稀釈剤;
を含む、2型糖尿病の治療のための医薬組成物であって、前記シタグリプチンが、50ミリグラムの単位投与力価で存在し、そして前記塩酸メトホルミンが、1000ミリグラムの単位投与力価で存在する、医薬組成物。 - (a)崩壊剤;(b)湿潤剤;及び(c)酸化防止剤からなる群より選択される1つ以上の賦形剤をさらに含む、請求項1記載の医薬組成物。
- (a)5〜18重量%のシタグリプチン又はその薬学的に許容される塩;
(b)65〜77重量%の塩酸メトホルミン;
(c)1〜2重量%の滑沢剤;及び
(d)4〜9重量%の結合剤;
を含む、請求項1記載の医薬組成物。 - 前記滑沢剤が、ステアリン酸マグネシウム又はステアリルフマル酸ナトリウムであり、結合剤がポリビニルピロリドンである、請求項3記載の医薬組成物。
- (a)5重量%のシタグリプチン又はその薬学的に許容される塩;
(b)77重量%の塩酸メトホルミン;
(c)1〜2重量%の滑沢剤;
(d)7重量%の結合剤;
(e)0.5重量%のラウリル硫酸ナトリウム;及び
(f)10重量%の稀釈剤
を含む、請求項3記載の医薬組成物。 - 前記薬学的に許容される塩が、そのリン酸二水素塩である、請求項5記載の医薬組成物。
- (a)50ミリグラムの単位投与力価で存在するシタグリプチンと;
(b)1000ミリグラムの単位投与力価で存在する塩酸メトホルミン;
(c)1〜2重量%の滑沢剤;
(d)7重量%の結合剤;
(e)10重量%の稀釈剤;及び、
(f)0.5重量%のラウリル硫酸ナトリウム;
を含む、2型糖尿病の治療のための医薬組成物。 - 前記滑沢剤がステアリルフマル酸ナトリウムであり、前記結合剤がポリビニルピロリドンであり、前記稀釈剤が微晶質セルロースである、請求項7記載の医薬組成物。
- 前記組成物が錠剤の投与形態である、請求項1又は7記載の医薬組成物。
- 風味剤、着色剤及び甘味料からなる群より選択される1つ以上の物質をさらに含む、請求項1記載の医薬組成物。
- 湿式造粒法により調製される、請求項1又は3記載の医薬組成物。
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WO2007078726A2 (en) | 2007-07-12 |
JP2013047260A (ja) | 2013-03-07 |
WO2007078726A3 (en) | 2008-06-12 |
CN101365432B (zh) | 2011-06-22 |
EP1962827A2 (en) | 2008-09-03 |
US8414921B2 (en) | 2013-04-09 |
US20090105265A1 (en) | 2009-04-23 |
CN101365432A (zh) | 2009-02-11 |
AU2006333151B2 (en) | 2010-03-04 |
JP5779566B2 (ja) | 2015-09-16 |
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