FI3804716T3 - Farmaseuttinen yhdistelmä, koostumus ja yhdistelmävalmiste, joka käsittää glukokinaasin aktivaattorin ja sglt-2:n estäjän ja niiden valmistusmenetelmiä ja käyttöjä - Google Patents
Farmaseuttinen yhdistelmä, koostumus ja yhdistelmävalmiste, joka käsittää glukokinaasin aktivaattorin ja sglt-2:n estäjän ja niiden valmistusmenetelmiä ja käyttöjä Download PDFInfo
- Publication number
- FI3804716T3 FI3804716T3 FIEP19811691.5T FI19811691T FI3804716T3 FI 3804716 T3 FI3804716 T3 FI 3804716T3 FI 19811691 T FI19811691 T FI 19811691T FI 3804716 T3 FI3804716 T3 FI 3804716T3
- Authority
- FI
- Finland
- Prior art keywords
- hms5552
- solid dispersion
- lubricant
- fudragit
- empagliflozin
- Prior art date
Links
- 229940124828 glucokinase activator Drugs 0.000 title claims 15
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 title claims 12
- 238000000034 method Methods 0.000 title claims 4
- 239000000203 mixture Substances 0.000 title claims 4
- 238000002360 preparation method Methods 0.000 title claims 3
- HMUMWSORCUWQJO-QAPCUYQASA-N (2s)-2-[3-(2-chlorophenoxy)-5-oxo-2h-pyrrol-1-yl]-n-[1-[(2r)-2,3-dihydroxypropyl]pyrazol-3-yl]-4-methylpentanamide Chemical compound C=1C(=O)N([C@@H](CC(C)C)C(=O)NC2=NN(C[C@@H](O)CO)C=C2)CC=1OC1=CC=CC=C1Cl HMUMWSORCUWQJO-QAPCUYQASA-N 0.000 claims 126
- 239000007962 solid dispersion Substances 0.000 claims 105
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims 54
- 239000000314 lubricant Substances 0.000 claims 48
- 229960001713 canagliflozin Drugs 0.000 claims 36
- VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 claims 36
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims 28
- 229960003345 empagliflozin Drugs 0.000 claims 28
- OBWASQILIWPZMG-QZMOQZSNSA-N empagliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(Cl)C(CC=2C=CC(O[C@@H]3COCC3)=CC=2)=C1 OBWASQILIWPZMG-QZMOQZSNSA-N 0.000 claims 28
- 229940016286 microcrystalline cellulose Drugs 0.000 claims 28
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims 28
- 239000008108 microcrystalline cellulose Substances 0.000 claims 28
- 229920002785 Croscarmellose sodium Polymers 0.000 claims 27
- 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 claims 27
- 229960001681 croscarmellose sodium Drugs 0.000 claims 27
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims 27
- 235000019359 magnesium stearate Nutrition 0.000 claims 27
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims 26
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims 26
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims 26
- 239000003826 tablet Substances 0.000 claims 26
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- 239000008194 pharmaceutical composition Substances 0.000 claims 24
- 239000011230 binding agent Substances 0.000 claims 23
- 239000007884 disintegrant Substances 0.000 claims 23
- 229920000642 polymer Polymers 0.000 claims 23
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- GOADIQFWSVMMRJ-UPGAGZFNSA-N dapagliflozin propanediol monohydrate Chemical compound O.C[C@H](O)CO.C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl GOADIQFWSVMMRJ-UPGAGZFNSA-N 0.000 claims 21
- 239000004615 ingredient Substances 0.000 claims 20
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 claims 16
- 229960003834 dapagliflozin Drugs 0.000 claims 16
- 229920003139 Eudragit® L 100 Polymers 0.000 claims 12
- 238000000576 coating method Methods 0.000 claims 9
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims 7
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims 7
- 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 4
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 claims 4
- 239000004480 active ingredient Substances 0.000 claims 4
- 150000001875 compounds Chemical class 0.000 claims 4
- 239000008103 glucose Substances 0.000 claims 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims 3
- 239000008280 blood Substances 0.000 claims 3
- 210000004369 blood Anatomy 0.000 claims 3
- 239000007888 film coating Substances 0.000 claims 3
- 238000009501 film coating Methods 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 claims 2
- 239000002775 capsule Substances 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 239000003086 colorant Substances 0.000 claims 2
- -1 glidants Substances 0.000 claims 2
- 238000005469 granulation Methods 0.000 claims 2
- 230000003179 granulation Effects 0.000 claims 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims 2
- 201000001421 hyperglycemia Diseases 0.000 claims 2
- 208000030159 metabolic disease Diseases 0.000 claims 2
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims 2
- 229910002055 micronized silica Inorganic materials 0.000 claims 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims 2
- 239000000741 silica gel Substances 0.000 claims 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 2
- 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 1
- 229920002261 Corn starch Polymers 0.000 claims 1
- 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 1
- 208000002249 Diabetes Complications Diseases 0.000 claims 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
- 229920003134 Eudragit® polymer Polymers 0.000 claims 1
- 208000002705 Glucose Intolerance Diseases 0.000 claims 1
- 102000017011 Glycated Hemoglobin A Human genes 0.000 claims 1
- 108010014663 Glycated Hemoglobin A Proteins 0.000 claims 1
- 206010020772 Hypertension Diseases 0.000 claims 1
- 206010022489 Insulin Resistance Diseases 0.000 claims 1
- 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 1
- WHSOLWOTCHFFBK-ZQGJOIPISA-N Luseogliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)S2)O)=C(OC)C=C1C WHSOLWOTCHFFBK-ZQGJOIPISA-N 0.000 claims 1
- 229930195725 Mannitol Natural products 0.000 claims 1
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 1
- 229920000881 Modified starch Polymers 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- 206010033307 Overweight Diseases 0.000 claims 1
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- 239000004372 Polyvinyl alcohol Substances 0.000 claims 1
- 206010062237 Renal impairment Diseases 0.000 claims 1
- ZXOCGDDVNPDRIW-NHFZGCSJSA-N Tofogliflozin Chemical compound O.C1=CC(CC)=CC=C1CC1=CC=C(CO[C@@]23[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C2=C1 ZXOCGDDVNPDRIW-NHFZGCSJSA-N 0.000 claims 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 1
- 125000000129 anionic group Chemical group 0.000 claims 1
- 239000003963 antioxidant agent Substances 0.000 claims 1
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 claims 1
- 229940062672 calcium dihydrogen phosphate Drugs 0.000 claims 1
- 229910000389 calcium phosphate Inorganic materials 0.000 claims 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims 1
- 239000008120 corn starch Substances 0.000 claims 1
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- 229960000913 crospovidone Drugs 0.000 claims 1
- 208000033679 diabetic kidney disease Diseases 0.000 claims 1
- 238000007907 direct compression Methods 0.000 claims 1
- 238000007908 dry granulation Methods 0.000 claims 1
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- 235000003599 food sweetener Nutrition 0.000 claims 1
- 230000001771 impaired effect Effects 0.000 claims 1
- 229950000991 ipragliflozin Drugs 0.000 claims 1
- AHFWIQIYAXSLBA-RQXATKFSSA-N ipragliflozin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1C1=CC=C(F)C(CC=2SC3=CC=CC=C3C=2)=C1 AHFWIQIYAXSLBA-RQXATKFSSA-N 0.000 claims 1
- 239000008101 lactose Substances 0.000 claims 1
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- 239000007937 lozenge Substances 0.000 claims 1
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- 239000003605 opacifier Substances 0.000 claims 1
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- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims 1
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- 231100000857 poor renal function Toxicity 0.000 claims 1
- 230000000291 postprandial effect Effects 0.000 claims 1
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Classifications
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- A61K31/00—Medicinal preparations containing organic active ingredients
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- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
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- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810556685 | 2018-05-31 | ||
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| CA3181882A1 (en) * | 2020-04-22 | 2021-10-28 | Hua Medicine (Shanghai) Ltd. | Treating untreated or treatment-resistant diabetes with glucokinase activator and sodium-glucose cotransporter-2 inhibitor |
| US11857536B2 (en) | 2020-06-04 | 2024-01-02 | Hua Medicine (Shanghai) Ltd. | Glucokinase activator for treating diabetes with renal impairment |
| AU2020451588A1 (en) * | 2020-06-04 | 2023-01-19 | Hua Medicine (Shanghai) Ltd. | Glucokinase activator for treating diabetes with renal impairment |
| AU2020451966A1 (en) * | 2020-06-04 | 2023-01-19 | Hua Medicine (Shanghai) Ltd. | Glucokinase activator for treating diabetes with hepatic impairment |
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2020
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2022
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2023
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2024
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