CN115768407A - Epipiprazole-containing pharmaceutical composition and preparation method thereof - Google Patents
Epipiprazole-containing pharmaceutical composition and preparation method thereof Download PDFInfo
- Publication number
- CN115768407A CN115768407A CN202180035664.XA CN202180035664A CN115768407A CN 115768407 A CN115768407 A CN 115768407A CN 202180035664 A CN202180035664 A CN 202180035664A CN 115768407 A CN115768407 A CN 115768407A
- Authority
- CN
- China
- Prior art keywords
- pharmaceutical composition
- brexpiprazole
- containing pharmaceutical
- sodium
- ipiprazole
- 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.)
- Pending
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract 37
- 238000002360 preparation method Methods 0.000 title claims abstract 6
- 239000002270 dispersing agent Substances 0.000 claims abstract 11
- 239000008280 blood Substances 0.000 claims abstract 4
- 210000004369 blood Anatomy 0.000 claims abstract 4
- ZKIAIYBUSXZPLP-UHFFFAOYSA-N brexpiprazole Chemical compound C1=C2NC(=O)C=CC2=CC=C1OCCCCN(CC1)CCN1C1=CC=CC2=C1C=CS2 ZKIAIYBUSXZPLP-UHFFFAOYSA-N 0.000 claims 22
- 229960001210 brexpiprazole Drugs 0.000 claims 22
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 9
- 108010010803 Gelatin Proteins 0.000 claims 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 6
- 229920000159 gelatin Polymers 0.000 claims 6
- 239000008273 gelatin Substances 0.000 claims 6
- 235000019322 gelatine Nutrition 0.000 claims 6
- 235000011852 gelatine desserts Nutrition 0.000 claims 6
- 239000000243 solution Substances 0.000 claims 6
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims 5
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims 5
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims 5
- 229920002385 Sodium hyaluronate Polymers 0.000 claims 5
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims 5
- 229920001983 poloxamer Polymers 0.000 claims 5
- 229960000502 poloxamer Drugs 0.000 claims 5
- 229940010747 sodium hyaluronate Drugs 0.000 claims 5
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims 5
- -1 span Polymers 0.000 claims 5
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims 4
- 239000000463 material Substances 0.000 claims 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 229920002472 Starch Polymers 0.000 claims 3
- 235000019438 castor oil Nutrition 0.000 claims 3
- 239000004359 castor oil Substances 0.000 claims 3
- 239000000945 filler Substances 0.000 claims 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims 3
- 239000008107 starch Substances 0.000 claims 3
- 235000019698 starch Nutrition 0.000 claims 3
- JQWAHKMIYCERGA-UHFFFAOYSA-N (2-nonanoyloxy-3-octadeca-9,12-dienoyloxypropoxy)-[2-(trimethylazaniumyl)ethyl]phosphinate Chemical compound CCCCCCCCC(=O)OC(COP([O-])(=O)CC[N+](C)(C)C)COC(=O)CCCCCCCC=CCC=CCCCCC JQWAHKMIYCERGA-UHFFFAOYSA-N 0.000 claims 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims 2
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims 2
- 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 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims 2
- 229930195725 Mannitol Natural products 0.000 claims 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims 2
- 239000002202 Polyethylene glycol Substances 0.000 claims 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims 2
- 239000007983 Tris buffer Substances 0.000 claims 2
- 239000000872 buffer Substances 0.000 claims 2
- 239000006172 buffering agent Substances 0.000 claims 2
- 239000004067 bulking agent Substances 0.000 claims 2
- 229910000019 calcium carbonate Inorganic materials 0.000 claims 2
- 235000011187 glycerol Nutrition 0.000 claims 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims 2
- 238000002347 injection Methods 0.000 claims 2
- 239000007924 injection Substances 0.000 claims 2
- 238000010255 intramuscular injection Methods 0.000 claims 2
- 239000007927 intramuscular injection Substances 0.000 claims 2
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims 2
- 239000000347 magnesium hydroxide Substances 0.000 claims 2
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims 2
- 239000000395 magnesium oxide Substances 0.000 claims 2
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims 2
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims 2
- 239000000594 mannitol Substances 0.000 claims 2
- 235000010355 mannitol Nutrition 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 229920001223 polyethylene glycol Polymers 0.000 claims 2
- 229920000136 polysorbate Polymers 0.000 claims 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims 2
- 235000013772 propylene glycol Nutrition 0.000 claims 2
- 239000011734 sodium Substances 0.000 claims 2
- 229910052708 sodium Inorganic materials 0.000 claims 2
- 235000015424 sodium Nutrition 0.000 claims 2
- ZIWRUEGECALFST-UHFFFAOYSA-M sodium 4-(4-dodecoxysulfonylphenoxy)benzenesulfonate Chemical compound [Na+].CCCCCCCCCCCCOS(=O)(=O)c1ccc(Oc2ccc(cc2)S([O-])(=O)=O)cc1 ZIWRUEGECALFST-UHFFFAOYSA-M 0.000 claims 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims 2
- 229940083466 soybean lecithin Drugs 0.000 claims 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical group OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 2
- 239000008215 water for injection Substances 0.000 claims 2
- 235000010493 xanthan gum Nutrition 0.000 claims 2
- 239000000230 xanthan gum Substances 0.000 claims 2
- 229920001285 xanthan gum Polymers 0.000 claims 2
- 229940082509 xanthan gum Drugs 0.000 claims 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims 1
- CDOUZKKFHVEKRI-UHFFFAOYSA-N 3-bromo-n-[(prop-2-enoylamino)methyl]propanamide Chemical compound BrCCC(=O)NCNC(=O)C=C CDOUZKKFHVEKRI-UHFFFAOYSA-N 0.000 claims 1
- 244000215068 Acacia senegal Species 0.000 claims 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
- 229920001817 Agar Polymers 0.000 claims 1
- 241000416162 Astragalus gummifer Species 0.000 claims 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims 1
- IELOKBJPULMYRW-NJQVLOCASA-N D-alpha-Tocopheryl Acid Succinate Chemical compound OC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C IELOKBJPULMYRW-NJQVLOCASA-N 0.000 claims 1
- 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 1
- 229920002907 Guar gum Polymers 0.000 claims 1
- 229920000084 Gum arabic Polymers 0.000 claims 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims 1
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- 239000004698 Polyethylene Substances 0.000 claims 1
- 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 1
- 229930006000 Sucrose Natural products 0.000 claims 1
- 229920001615 Tragacanth Polymers 0.000 claims 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims 1
- 229930003427 Vitamin E Natural products 0.000 claims 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims 1
- 235000010489 acacia gum Nutrition 0.000 claims 1
- 239000000205 acacia gum Substances 0.000 claims 1
- 239000008272 agar Substances 0.000 claims 1
- 229940023476 agar Drugs 0.000 claims 1
- 235000010419 agar Nutrition 0.000 claims 1
- 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 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 claims 1
- HLKZFSVWBQSKKH-UHFFFAOYSA-N but-3-enoic acid;1-ethenylpyrrolidin-2-one Chemical compound OC(=O)CC=C.C=CN1CCCC1=O HLKZFSVWBQSKKH-UHFFFAOYSA-N 0.000 claims 1
- 239000001768 carboxy methyl cellulose Substances 0.000 claims 1
- 235000010418 carrageenan Nutrition 0.000 claims 1
- 239000000679 carrageenan Substances 0.000 claims 1
- 229920001525 carrageenan Polymers 0.000 claims 1
- 229940113118 carrageenan Drugs 0.000 claims 1
- 235000019329 dioctyl sodium sulphosuccinate Nutrition 0.000 claims 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 claims 1
- 229940014259 gelatin Drugs 0.000 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- 235000001727 glucose Nutrition 0.000 claims 1
- 235000010417 guar gum Nutrition 0.000 claims 1
- 239000000665 guar gum Substances 0.000 claims 1
- 229960002154 guar gum Drugs 0.000 claims 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims 1
- 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 1
- 229960003943 hypromellose Drugs 0.000 claims 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims 1
- 229920000609 methyl cellulose Polymers 0.000 claims 1
- 235000010981 methylcellulose Nutrition 0.000 claims 1
- 239000001923 methylcellulose Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims 1
- 235000019799 monosodium phosphate Nutrition 0.000 claims 1
- 239000003002 pH adjusting agent Substances 0.000 claims 1
- 229920001277 pectin Polymers 0.000 claims 1
- 235000010987 pectin Nutrition 0.000 claims 1
- 239000001814 pectin Substances 0.000 claims 1
- 229960000292 pectin Drugs 0.000 claims 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- 229920000747 poly(lactic acid) Polymers 0.000 claims 1
- 229920000573 polyethylene Polymers 0.000 claims 1
- 239000004626 polylactic acid Substances 0.000 claims 1
- 229940051841 polyoxyethylene ether Drugs 0.000 claims 1
- 229920000056 polyoxyethylene ether Polymers 0.000 claims 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims 1
- 229920000053 polysorbate 80 Polymers 0.000 claims 1
- 238000000634 powder X-ray diffraction Methods 0.000 claims 1
- 229960004063 propylene glycol Drugs 0.000 claims 1
- 235000010413 sodium alginate Nutrition 0.000 claims 1
- 239000000661 sodium alginate Substances 0.000 claims 1
- 229940005550 sodium alginate Drugs 0.000 claims 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims 1
- 235000010356 sorbitol Nutrition 0.000 claims 1
- 239000000600 sorbitol Substances 0.000 claims 1
- 238000001228 spectrum Methods 0.000 claims 1
- 238000010254 subcutaneous injection Methods 0.000 claims 1
- 239000007929 subcutaneous injection Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims 1
- 239000005720 sucrose Substances 0.000 claims 1
- 235000010487 tragacanth Nutrition 0.000 claims 1
- 239000000196 tragacanth Substances 0.000 claims 1
- 229940116362 tragacanth Drugs 0.000 claims 1
- 229940046009 vitamin E Drugs 0.000 claims 1
- 235000019165 vitamin E Nutrition 0.000 claims 1
- 239000011709 vitamin E Substances 0.000 claims 1
- 235000010447 xylitol Nutrition 0.000 claims 1
- 239000000811 xylitol Substances 0.000 claims 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims 1
- 229960002675 xylitol Drugs 0.000 claims 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 2
- 230000000857 drug effect Effects 0.000 abstract 1
Images
Classifications
-
- 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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Biomedical Technology (AREA)
- Biochemistry (AREA)
- Psychiatry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
一种含依匹哌唑药物组合物及其制备方法，该药物组合物包括依匹哌唑和一种或多种分散剂。该药物组合物给药后无明显突释现象，药效时间长，血药浓度稳定，血药浓度波动幅度较小，起效速度快，其制备方法工艺简单，操作方便。
A pharmaceutical composition containing ebiprazole and a preparation method thereof, the pharmaceutical composition includes ebiprazole and one or more dispersants. The pharmaceutical composition has no obvious sudden release phenomenon after administration, has long drug effect time, stable blood drug concentration, small fluctuation range of blood drug concentration, fast onset speed, simple preparation process and convenient operation.
Description
PCT国内申请，说明书已公开。PCT domestic application, specification has been published.
Claims (24)
- A pharmaceutical composition comprising brexpiprazole, characterized in that said composition comprises: <xnotran> , , pH , , , , , , , , , , , , , , , , , , , , , , , α - , , , , , , , , , , , , , - , , , , E , , - , - β - , β - , , , , , , - - , , , , , , , , , , , , - , , . </xnotran>
- The brexpiprazole-containing pharmaceutical composition according to claim 1, characterized in that: the dispersing agent is selected from one or more of gelatin, sodium hyaluronate, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, sodium carboxymethyl starch, propylene glycol, sodium lauryl sulfate, poloxamer, span, gum arabic, tragacanth, pectin, xanthan gum, guar gum, carrageenan, sodium alginate, agar, alpha-tocopherol, succinate, microcrystalline cellulose-sodium carboxymethyl cellulose, polyoxyethylene castor oil, glycerol, vitamin E polyethylene glycol succinate, polyethylene glycol-polylactic acid, sodium dodecyl diphenyl ether disulfonate, dioctyl sodium sulfosuccinate, triethanolamine, soybean lecithin, egg yolk lecithin, polyvinyl alcohol polyethylene glycol copolymer, polyvinyl alcohol, vinyl pyrrolidone-vinyl acetate or hydrogenated castor oil polyoxyethylene ether.
- The brexpiprazole-containing pharmaceutical composition according to claim 2, characterized in that: the dispersing agent is selected from one or more of gelatin, sodium hyaluronate, hydroxypropyl cellulose, hypromellose, methylcellulose, hydroxyethyl cellulose, sodium carboxymethyl starch, propylene glycol, sodium lauryl sulfate, poloxamer, span, xanthan gum, polyoxyethylene castor oil, glycerol, sodium dodecyl diphenyl ether disulfonate, soybean lecithin or egg yolk lecithin.
- The brexpiprazole-containing pharmaceutical composition according to claim 3, characterized in that: the dispersing agent is selected from one or more of propylene glycol, hydroxyethyl cellulose, poloxamer, sodium hyaluronate or gelatin.
- The brexpiprazole-containing pharmaceutical composition according to claim 4, characterized in that: the dispersing agent is selected from one or more of propylene glycol, hydroxyethyl cellulose or poloxamer.
- The brexpiprazole-containing pharmaceutical composition according to claim 4, characterized in that: the dispersing agent is selected from one or more of sodium hyaluronate or gelatin, preferably gelatin.
- The brexpiprazole-containing pharmaceutical composition according to any one of claims 1 to 6, wherein: the dispersant further comprises tween, preferably tween 80.
- The brexpiprazole-containing pharmaceutical composition according to claim 1, characterized in that: the dispersant is selected from the group consisting of poloxamer and tween in combination, propylene glycol, hydroxyethyl cellulose, sodium hyaluronate or gelatin.
- The brexpiprazole-containing pharmaceutical composition according to any one of claims 1 to 8, characterized in that: the amount of the dispersant is 0.001 per thousand to 20wt%, preferably 0.005 per thousand to 15wt%, more preferably 0.005 per thousand to 10wt%, further preferably 0.5 per thousand to 10wt%, and further preferably 0.5 per thousand to 4wt% of the total amount of the pharmaceutical composition.
- The ipiprazole-containing pharmaceutical composition of any one of claims 1 to 9, wherein: the amount of the brexpiprazole is 1-30wt%, preferably 1-15wt%, more preferably 2-10wt%, further preferably 3-8wt%, still further preferably 4-5wt% of the total amount of the pharmaceutical composition.
- The ipiprazole-containing pharmaceutical composition of any one of claims 1 to 10, wherein: the buffer is selected from TRIS buffer, phosphate, citrate, acetate, preferably TRIS buffer, sodium salt of phosphoric acid, more preferably sodium dihydrogen phosphate.
- The ipiprazole-containing pharmaceutical composition of any one of claims 1 to 11, wherein: the amount of the buffer is 0.05 to 5wt%, preferably 0.05 to 0.5wt% of the total amount of the pharmaceutical composition.
- The brexpiprazole-containing pharmaceutical composition of any one of claims 1-12, wherein: the pH adjusting agent is a substance for adjusting the pH of the pharmaceutical composition to 4.0 to 9.0, preferably 6.0 to 8.0, more preferably 6.8 to 7.8, and further preferably 7.0.
- The ipiprazole-containing pharmaceutical composition of any one of claims 1 to 13, wherein: the pH regulator is selected from hydrochloric acid, acetic acid, sodium hydroxide, potassium hydroxide, calcium carbonate, sodium bicarbonate, magnesium oxide or magnesium hydroxide, preferably sodium hydroxide, potassium hydroxide, calcium carbonate, sodium bicarbonate, magnesium oxide or magnesium hydroxide, and more preferably sodium hydroxide.
- The ipiprazole-containing pharmaceutical composition of any one of claims 1 to 14, wherein: the pharmaceutical composition further comprises a bulking agent.
- The brexpiprazole-containing pharmaceutical composition of claim 15, wherein: the amount of the filler is 1-20wt%, preferably 4-5wt% of the total amount of the pharmaceutical composition.
- The ipiprazole-containing pharmaceutical composition of any one of claims 15 to 16, wherein: the bulking agent is selected from one or more of mannitol, sucrose, maltose, xylitol, glucose, starch and sorbitol, preferably mannitol.
- The brexpiprazole-containing pharmaceutical composition of any one of claims 1-17, wherein: the powder X-ray diffraction spectrum of the brexpiprazole has the following characteristic peaks: 2 θ =6.4, 13.5, 14.1, 14.5, 17.0, 18.8, 19.9, 21.0, and 22.9.
- The ipiprazole-containing pharmaceutical composition of any one of claims 1 to 18, wherein: the D50 of the brexpiprazole is 0.1-50 μm, preferably 0.1-30 μm, more preferably 1.8-21 μm, still more preferably 1.8-10.4 μm, and still more preferably 4-6 μm.
- The ipiprazole-containing pharmaceutical composition of any one of claims 1 to 18, wherein: the D50 of the brexpiprazole is 1-50 μm, preferably 1.2-30 μm, more preferably 1.5-3 μm, and still more preferably 1.8 μm.
- The ipiprazole-containing pharmaceutical composition of any one of claims 1 to 20, wherein: the pharmaceutical composition is used for injection administration, including intramuscular injection administration or subcutaneous injection administration, and preferably intramuscular injection administration.
- The ipiprazole-containing pharmaceutical composition of any one of claims 1 to 21, wherein: the blood concentration of the pharmaceutical composition is maintained to be more than 5ng/mL within 0 to 19 days after administration, and preferably the blood concentration of the pharmaceutical composition is maintained to be more than 5ng/mL within 0 to 26 days after administration.
- A process for the preparation of an brexpiprazole-containing pharmaceutical composition according to any one of claims 1 to 22, comprising: the preparation method comprises the steps of crushing the brexpiprazole, dissolving the filler, the buffering agent and the dispersing agent in water for injection, adjusting the pH of the solution by using a pH regulator to obtain an auxiliary material solution, and finally adding the crushed brexpiprazole into the auxiliary material solution to prepare the brexpiprazole.
- A process for the preparation of an brexpiprazole-containing pharmaceutical composition according to any one of claims 1 to 22, comprising: dissolving a filling agent, a buffering agent and a dispersing agent in water for injection, then adjusting the pH of the solution by using a pH regulator to obtain an auxiliary material solution, and finally adding the brexpiprazole into the auxiliary material solution to prepare the injection.
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| Application Number | Priority Date | Filing Date | Title |
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| CN202010436814 | 2020-05-21 | ||
| CN2020104368145 | 2020-05-21 | ||
| PCT/CN2021/095011 WO2021233402A1 (en) | 2020-05-21 | 2021-05-21 | Brexpiprazole-containing pharmaceutical composition and preparation method therefor |
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| CN115768407A true CN115768407A (en) | 2023-03-07 |
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| CN118201600A (en) * | 2021-11-10 | 2024-06-14 | 广东东阳光药业股份有限公司 | Quinoline medicine composition |
| CN116407539B (en) * | 2021-12-30 | 2025-01-10 | 上海现代药物制剂工程研究中心有限公司 | Use of epiprazole methyl fatty acid ester |
| CN114767663A (en) * | 2022-04-19 | 2022-07-22 | 浙江和泽医药科技股份有限公司 | Orally dissolving film agent and preparation method thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1870980A (en) * | 2003-10-23 | 2006-11-29 | 大冢制药株式会社 | Controlled release sterile injectable aripiprazole formulation and method |
| CN105106142A (en) * | 2015-09-22 | 2015-12-02 | 成都欣捷高新技术开发有限公司 | Brexpiprazole-containing freeze-dried oral preparation and preparation method thereof |
| CN106389357A (en) * | 2011-06-07 | 2017-02-15 | 大塚制药株式会社 | Freeze-dried aripiprazole formulation |
-
2021
- 2021-05-21 CN CN202180035664.XA patent/CN115768407A/en active Pending
- 2021-05-21 WO PCT/CN2021/095011 patent/WO2021233402A1/en active Application Filing
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1870980A (en) * | 2003-10-23 | 2006-11-29 | 大冢制药株式会社 | Controlled release sterile injectable aripiprazole formulation and method |
| CN106389357A (en) * | 2011-06-07 | 2017-02-15 | 大塚制药株式会社 | Freeze-dried aripiprazole formulation |
| CN105106142A (en) * | 2015-09-22 | 2015-12-02 | 成都欣捷高新技术开发有限公司 | Brexpiprazole-containing freeze-dried oral preparation and preparation method thereof |
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