CN103191075A - 他达拉非的口服药物制剂 - Google Patents
他达拉非的口服药物制剂 Download PDFInfo
- Publication number
- CN103191075A CN103191075A CN201310153588XA CN201310153588A CN103191075A CN 103191075 A CN103191075 A CN 103191075A CN 201310153588X A CN201310153588X A CN 201310153588XA CN 201310153588 A CN201310153588 A CN 201310153588A CN 103191075 A CN103191075 A CN 103191075A
- Authority
- CN
- China
- Prior art keywords
- preferred
- tadanafil
- preparation
- tadalafil
- oral
- 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.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 33
- 229960000835 tadalafil Drugs 0.000 title abstract description 10
- IEHKWSGCTWLXFU-IIBYNOLFSA-N tadalafil Chemical compound C1=C2OCOC2=CC([C@@H]2C3=C([C]4C=CC=CC4=N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 IEHKWSGCTWLXFU-IIBYNOLFSA-N 0.000 title abstract 8
- 210000000214 mouth Anatomy 0.000 claims abstract description 33
- 239000003814 drug Substances 0.000 claims abstract description 30
- 239000007910 chewable tablet Substances 0.000 claims abstract description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 208000010228 Erectile Dysfunction Diseases 0.000 claims abstract description 8
- 201000001881 impotence Diseases 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 4
- WOXKDUGGOYFFRN-IIBYNOLFSA-N tadalafil Chemical group C1=C2OCOC2=CC([C@@H]2C3=C(C4=CC=CC=C4N3)C[C@H]3N2C(=O)CN(C3=O)C)=C1 WOXKDUGGOYFFRN-IIBYNOLFSA-N 0.000 claims description 97
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 26
- 239000003826 tablet Substances 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- 239000008187 granular material Substances 0.000 claims description 20
- 239000003795 chemical substances by application Substances 0.000 claims description 19
- 229940068682 chewable tablet Drugs 0.000 claims description 19
- 229940037201 oris Drugs 0.000 claims description 18
- 238000001035 drying Methods 0.000 claims description 13
- 235000019359 magnesium stearate Nutrition 0.000 claims description 13
- 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 description 12
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 12
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 12
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 12
- 229920003081 Povidone K 30 Polymers 0.000 claims description 10
- 239000011230 binding agent Substances 0.000 claims description 10
- 238000004132 cross linking Methods 0.000 claims description 10
- 239000000945 filler Substances 0.000 claims description 10
- 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 description 9
- 239000008101 lactose Substances 0.000 claims description 9
- 239000000314 lubricant Substances 0.000 claims description 9
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 8
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 7
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 7
- 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 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 229920003023 plastic Polymers 0.000 claims description 6
- 239000004033 plastic Substances 0.000 claims description 6
- 235000010413 sodium alginate Nutrition 0.000 claims description 6
- 239000000661 sodium alginate Substances 0.000 claims description 6
- 229940005550 sodium alginate Drugs 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 claims description 6
- 108010011485 Aspartame Proteins 0.000 claims description 5
- 206010013786 Dry skin Diseases 0.000 claims description 5
- 238000010521 absorption reaction Methods 0.000 claims description 5
- 239000000605 aspartame Substances 0.000 claims description 5
- 235000010357 aspartame Nutrition 0.000 claims description 5
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 5
- 229960003438 aspartame Drugs 0.000 claims description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 5
- 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 description 5
- 229940126701 oral medication Drugs 0.000 claims description 5
- -1 polyethylene Polymers 0.000 claims description 5
- 229920000642 polymer Polymers 0.000 claims description 5
- 239000007779 soft material Substances 0.000 claims description 5
- 238000005303 weighing Methods 0.000 claims description 5
- 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 description 4
- 239000001856 Ethyl cellulose Substances 0.000 claims description 4
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 4
- 229920001249 ethyl cellulose Polymers 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 4
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- 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 description 3
- 239000011248 coating agent Substances 0.000 claims description 3
- 238000000576 coating method Methods 0.000 claims description 3
- 238000007766 curtain coating Methods 0.000 claims description 3
- 239000001087 glyceryl triacetate Substances 0.000 claims description 3
- 235000013773 glyceryl triacetate Nutrition 0.000 claims description 3
- 238000009413 insulation Methods 0.000 claims description 3
- 229920002521 macromolecule Polymers 0.000 claims description 3
- 239000011259 mixed solution Substances 0.000 claims description 3
- 238000012856 packing Methods 0.000 claims description 3
- 239000000049 pigment Substances 0.000 claims description 3
- 239000002002 slurry Substances 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- 229960002622 triacetin Drugs 0.000 claims description 3
- ZEMPKEQAKRGZGQ-AAKVHIHISA-N 2,3-bis[[(z)-12-hydroxyoctadec-9-enoyl]oxy]propyl (z)-12-hydroxyoctadec-9-enoate Chemical compound CCCCCCC(O)C\C=C/CCCCCCCC(=O)OCC(OC(=O)CCCCCCC\C=C/CC(O)CCCCCC)COC(=O)CCCCCCC\C=C/CC(O)CCCCCC ZEMPKEQAKRGZGQ-AAKVHIHISA-N 0.000 claims description 2
- 229920000856 Amylose Polymers 0.000 claims description 2
- 241000167854 Bourreria succulenta Species 0.000 claims description 2
- 240000004307 Citrus medica Species 0.000 claims description 2
- 239000004698 Polyethylene Substances 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 239000003945 anionic surfactant Substances 0.000 claims description 2
- 235000019693 cherries Nutrition 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 239000000576 food coloring agent Substances 0.000 claims description 2
- 229950005770 hyprolose Drugs 0.000 claims description 2
- 210000002200 mouth mucosa Anatomy 0.000 claims description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N o-dicarboxybenzene Natural products OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims description 2
- 235000010987 pectin Nutrition 0.000 claims description 2
- 239000001814 pectin Substances 0.000 claims description 2
- 229920001277 pectin Polymers 0.000 claims description 2
- 239000004014 plasticizer Substances 0.000 claims description 2
- 229920000573 polyethylene Polymers 0.000 claims description 2
- 229920003169 water-soluble polymer Polymers 0.000 claims description 2
- 239000012528 membrane Substances 0.000 abstract description 6
- 238000011160 research Methods 0.000 abstract description 5
- 238000009472 formulation Methods 0.000 abstract description 3
- 230000002411 adverse Effects 0.000 abstract 2
- 230000004393 visual impairment Effects 0.000 abstract 2
- 206010047571 Visual impairment Diseases 0.000 abstract 1
- 230000001524 infective effect Effects 0.000 abstract 1
- 239000006191 orally-disintegrating tablet Substances 0.000 abstract 1
- 208000029257 vision disease Diseases 0.000 abstract 1
- 238000013459 approach Methods 0.000 description 13
- 229940079593 drug Drugs 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- 235000009508 confectionery Nutrition 0.000 description 9
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 239000000796 flavoring agent Substances 0.000 description 8
- 235000019634 flavors Nutrition 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 229960001375 lactose Drugs 0.000 description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
- 210000004379 membrane Anatomy 0.000 description 5
- ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 4
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 4
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 4
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 229940034610 toothpaste Drugs 0.000 description 4
- 239000000606 toothpaste Substances 0.000 description 4
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 3
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 3
- 102000004654 Cyclic GMP-Dependent Protein Kinases Human genes 0.000 description 3
- 108010003591 Cyclic GMP-Dependent Protein Kinases Proteins 0.000 description 3
- XKMLYUALXHKNFT-UUOKFMHZSA-N Guanosine-5'-triphosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XKMLYUALXHKNFT-UUOKFMHZSA-N 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 229940112822 chewing gum Drugs 0.000 description 3
- 235000015218 chewing gum Nutrition 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000004576 sand Substances 0.000 description 3
- 210000002460 smooth muscle Anatomy 0.000 description 3
- 238000001694 spray drying Methods 0.000 description 3
- 230000009967 tasteless effect Effects 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- RQFCJASXJCIDSX-UHFFFAOYSA-N 14C-Guanosin-5'-monophosphat Natural products C1=2NC(N)=NC(=O)C=2N=CN1C1OC(COP(O)(O)=O)C(O)C1O RQFCJASXJCIDSX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000994 depressogenic effect Effects 0.000 description 2
- 210000003238 esophagus Anatomy 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 239000002590 phosphodiesterase V inhibitor Substances 0.000 description 2
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- 208000012201 sexual and gender identity disease Diseases 0.000 description 2
- 208000015891 sexual disease Diseases 0.000 description 2
- 230000000391 smoking effect Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 241000282806 Rhinoceros Species 0.000 description 1
- 201000001880 Sexual dysfunction Diseases 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000008321 arterial blood flow Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000005056 cell body Anatomy 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 229940117229 cialis Drugs 0.000 description 1
- 239000000701 coagulant Substances 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 210000003725 endotheliocyte Anatomy 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000010579 first pass effect Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 229960001021 lactose monohydrate Drugs 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 210000002464 muscle smooth vascular Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 210000003899 penis Anatomy 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 231100000872 sexual dysfunction Toxicity 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000036259 sexual stimuli Effects 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 210000004003 subcutaneous fat Anatomy 0.000 description 1
- 239000013595 supernatant sample Substances 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
Description
他达拉非 | 100g | 10.0% |
聚乙烯吡咯烷酮(PVP) | 125g | 12.5% |
甘露醇 | 700g | 70% |
硬脂酸镁 | 15g | 1.5% |
柠檬酸 | 30g | 3% |
碳酸氢钠 | 30g | 3% |
他达拉非 | 20g | 10.0% |
羧甲基淀粉钠 | 27g | 13.5% |
羟丙甲基纤维素 | 10g | 5.0% |
甘露醇 | 140g | 70.0% |
阿司帕坦 | 1g | 0.5% |
滑石粉 | 2g | 1.0% |
他达拉非 | 10g | 5.0% |
交联聚维酮 | 27g | 13.5% |
羟丙基纤维素 | 10g | 5.0% |
蔗糖 | 150g | 75.0% |
甜菊素 | 1g | 0.5% |
硬脂酸镁 | 2g | 1.0% |
他达拉非 | 20g | 10.0% |
交联羧甲基纤维素钠 | 25g | 12.5% |
聚维酮K30 | 8g | 4.0% |
乳糖 | 140g | 70.0% |
薄荷香精 | 4g | 2.0% |
硬脂酸镁 | 3g | 1.5% |
他达拉非 | 10g | 5.0% |
交联羧甲基纤维素钠 | 26g | 13.0% |
聚维酮K30 | 8g | 4.0% |
乳糖 | 150g | 75.0% |
薄荷香精 | 4g | 2.0% |
硬脂酸镁 | 2g | 1.0% |
崩解时间(s) | 口感 | |
实施例1 | 18 | 无味 |
实施例2 | 16 | 味甜 |
实施例3 | 15 | 味甜 |
实施例4 | 13 | 味甜且清新 |
实施例5 | 12 | 味甜且清新 |
他达拉非 | 100g | 34.6% |
聚乙烯醇1788 | 133g | 46.0% |
聚乙二醇400 | 33g | 11.4% |
海藻酸钠 | 13g | 4.5% |
纯化水 | 10g | 3.5% |
他达拉非 | 100g | 33.7% |
聚乙烯醇1788 | 133g | 44.8% |
聚乙二醇400 | 33g | 11.1% |
海藻酸钠 | 13g | 4.4% |
阿司帕坦 | 3g | 1.0% |
吐温80 | 5g | 1.7% |
日落黄 | 0.05g | 0.017% |
乙醇水 | 10g | 3.4% |
他达拉非 | 100g | 33.7% |
聚乙烯醇1788 | 133g | 44.8% |
聚乙二醇400 | 33g | 11.1% |
海藻酸钠 | 13g | 4.4% |
薄荷香精 | 3g | 1.0% |
十二烷基硫酸钠 | 5g | 1.7% |
日落黄 | 0.05g | 0.017% |
乙醇水 | 10g | 3.4% |
崩解时间(s) | 口感 | |
实施例7 | 58 | 苦涩味 |
实施例8 | 46 | 味甜 |
实施例9 | 43 | 味甜且清新 |
他达拉非 | 20g | 10.0% |
羧甲基淀粉钠 | 10g | 5.0% |
聚维酮K30 | 18g | 9.0% |
微晶纤维素 | 150g | 75.0% |
橙子香精 | 1g | 0.5% |
滑石粉 | 1g | 0.5% |
他达拉非 | 5g | 2.5% |
交联聚维酮 | 12g | 6.0% |
羟丙基纤维素 | 15g | 7.5% |
预胶化淀粉 | 165g | 82.5% |
阿司帕坦 | 1g | 0.5% |
滑石粉 | 2g | 1.0% |
他达拉非 | 20g | 10.0% |
交联羧甲基纤维素钠 | 8g | 4.0% |
聚维酮K30 | 8g | 4.0% |
乳糖 | 155g | 77.5% |
薄荷香精 | 6g | 3.0% |
硬脂酸镁 | 3g | 1.5% |
他达拉非 | 10g | 5.0% |
交联羧甲基纤维素钠 | 8g | 4.0% |
聚维酮K30 | 8g | 4.0% |
乳糖 | 165g | 82.5% |
薄荷香精 | 6g | 3.0% |
硬脂酸镁 | 3g | 1.5% |
他达拉非 | 5g | 2.5% |
交联羧甲基纤维素钠 | 9g | 4.5% |
聚维酮K30 | 9g | 4.5% |
乳糖 | 168g | 84% |
薄荷香精 | 5g | 2.5% |
硬脂酸镁 | 4g | 2.0% |
有无砂砾感 | 口感评分 | |
实施例11 | 有 | 6.5 |
实施例12 | 略有 | 7.2 |
实施例13 | 无 | 9.5 |
实施例14 | 无 | 9.2 |
实施例15 | 无 | 9.1 |
Claims (15)
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310153588.XA CN103191075B (zh) | 2013-04-28 | 2013-04-28 | 他达拉非的口服药物制剂 |
CN201410563329.9A CN104352461B (zh) | 2013-04-28 | 2013-04-28 | 他达拉非的口服药物制剂 |
CN201410563973.6A CN104274417B (zh) | 2013-04-28 | 2013-04-28 | 他达拉非的口服药物制剂 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201310153588.XA CN103191075B (zh) | 2013-04-28 | 2013-04-28 | 他达拉非的口服药物制剂 |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410563329.9A Division CN104352461B (zh) | 2013-04-28 | 2013-04-28 | 他达拉非的口服药物制剂 |
CN201410563973.6A Division CN104274417B (zh) | 2013-04-28 | 2013-04-28 | 他达拉非的口服药物制剂 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN103191075A true CN103191075A (zh) | 2013-07-10 |
CN103191075B CN103191075B (zh) | 2015-04-08 |
Family
ID=48714014
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201310153588.XA Active CN103191075B (zh) | 2013-04-28 | 2013-04-28 | 他达拉非的口服药物制剂 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN103191075B (zh) |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104758941A (zh) * | 2015-04-27 | 2015-07-08 | 浙江永宁药业股份有限公司 | 一种利用羟丙基纤维素为粘合剂实现快速溶出的口服片剂 |
CN105213333A (zh) * | 2014-06-30 | 2016-01-06 | 深圳海王药业有限公司 | 一种他达拉非药物组合物及其制备方法 |
CN105380912A (zh) * | 2014-09-03 | 2016-03-09 | 长春海悦药业有限公司 | 一种含有他达拉非的药物组合物 |
CN106389392A (zh) * | 2016-10-13 | 2017-02-15 | 常州市第四制药厂有限公司 | 一种他达拉非口腔溶膜剂及制备方法 |
CN108883074A (zh) * | 2016-03-31 | 2018-11-23 | 韩美药品株式会社 | 含有他达拉非和坦索罗辛并具有改善的稳定性和溶出率的复合胶囊制剂 |
CN110035756A (zh) * | 2016-11-30 | 2019-07-19 | 成药技术Ip控股有限公司 | 含有他达拉非的药物配制品 |
CN110664766A (zh) * | 2019-10-10 | 2020-01-10 | 甘肃普安制药股份有限公司 | 一种他达拉非片剂及其制备方法 |
CN112040984A (zh) * | 2018-02-07 | 2020-12-04 | 斯码瓦有限公司 | 药物制剂、制备药物制剂的方法和包含其的药物 |
CN113041228A (zh) * | 2021-03-30 | 2021-06-29 | 新乡市常乐制药有限责任公司 | 一种他达拉非片剂混合物及其制备方法 |
CN114246835A (zh) * | 2022-01-05 | 2022-03-29 | 河北龙海药业有限公司 | 一种枸橼酸西地那非口腔崩解片的制备方法 |
CN114948886A (zh) * | 2022-06-16 | 2022-08-30 | 南京正科医药股份有限公司 | 一种他达那非口崩片及其制备方法 |
CN115154429A (zh) * | 2021-04-06 | 2022-10-11 | 南京科默生物医药有限公司 | 一种他达拉非口腔崩解组合物 |
CN116196285A (zh) * | 2023-01-09 | 2023-06-02 | 广东西捷药业有限公司 | 一种纳米他达拉非口腔崩解组合物及其制备方法和应用 |
CN118384133A (zh) * | 2024-04-29 | 2024-07-26 | 上海欣峰制药有限公司 | 他达拉非口溶膜剂及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102716097A (zh) * | 2012-05-29 | 2012-10-10 | 浙江华海药业股份有限公司 | 控制口腔崩解片药物释放速率的方法 |
CN102727455A (zh) * | 2012-07-03 | 2012-10-17 | 北京科信必成医药科技发展有限公司 | 一种他达那非口腔崩解片及其制备方法 |
CN102824333A (zh) * | 2012-09-26 | 2012-12-19 | 苏州大学 | 一种口腔速溶膜剂及其制备方法 |
-
2013
- 2013-04-28 CN CN201310153588.XA patent/CN103191075B/zh active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102716097A (zh) * | 2012-05-29 | 2012-10-10 | 浙江华海药业股份有限公司 | 控制口腔崩解片药物释放速率的方法 |
CN102727455A (zh) * | 2012-07-03 | 2012-10-17 | 北京科信必成医药科技发展有限公司 | 一种他达那非口腔崩解片及其制备方法 |
CN102824333A (zh) * | 2012-09-26 | 2012-12-19 | 苏州大学 | 一种口腔速溶膜剂及其制备方法 |
Cited By (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105213333A (zh) * | 2014-06-30 | 2016-01-06 | 深圳海王药业有限公司 | 一种他达拉非药物组合物及其制备方法 |
CN105380912A (zh) * | 2014-09-03 | 2016-03-09 | 长春海悦药业有限公司 | 一种含有他达拉非的药物组合物 |
CN105380912B (zh) * | 2014-09-03 | 2018-09-11 | 长春海悦药业股份有限公司 | 一种含有他达拉非的药物组合物 |
CN104758941A (zh) * | 2015-04-27 | 2015-07-08 | 浙江永宁药业股份有限公司 | 一种利用羟丙基纤维素为粘合剂实现快速溶出的口服片剂 |
CN108883074A (zh) * | 2016-03-31 | 2018-11-23 | 韩美药品株式会社 | 含有他达拉非和坦索罗辛并具有改善的稳定性和溶出率的复合胶囊制剂 |
CN112999203A (zh) * | 2016-10-13 | 2021-06-22 | 常州市第四制药厂有限公司 | 一种他达拉非口腔溶膜剂及制备方法 |
CN106389392A (zh) * | 2016-10-13 | 2017-02-15 | 常州市第四制药厂有限公司 | 一种他达拉非口腔溶膜剂及制备方法 |
WO2018068498A1 (zh) * | 2016-10-13 | 2018-04-19 | 常州市第四制药厂有限公司 | 一种他达拉非口腔溶膜剂及制备方法 |
CN110035756A (zh) * | 2016-11-30 | 2019-07-19 | 成药技术Ip控股有限公司 | 含有他达拉非的药物配制品 |
CN112040984A (zh) * | 2018-02-07 | 2020-12-04 | 斯码瓦有限公司 | 药物制剂、制备药物制剂的方法和包含其的药物 |
CN110664766A (zh) * | 2019-10-10 | 2020-01-10 | 甘肃普安制药股份有限公司 | 一种他达拉非片剂及其制备方法 |
CN113041228A (zh) * | 2021-03-30 | 2021-06-29 | 新乡市常乐制药有限责任公司 | 一种他达拉非片剂混合物及其制备方法 |
CN115154429A (zh) * | 2021-04-06 | 2022-10-11 | 南京科默生物医药有限公司 | 一种他达拉非口腔崩解组合物 |
CN114246835A (zh) * | 2022-01-05 | 2022-03-29 | 河北龙海药业有限公司 | 一种枸橼酸西地那非口腔崩解片的制备方法 |
CN114948886A (zh) * | 2022-06-16 | 2022-08-30 | 南京正科医药股份有限公司 | 一种他达那非口崩片及其制备方法 |
CN116196285A (zh) * | 2023-01-09 | 2023-06-02 | 广东西捷药业有限公司 | 一种纳米他达拉非口腔崩解组合物及其制备方法和应用 |
CN118384133A (zh) * | 2024-04-29 | 2024-07-26 | 上海欣峰制药有限公司 | 他达拉非口溶膜剂及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN103191075B (zh) | 2015-04-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN103191075B (zh) | 他达拉非的口服药物制剂 | |
AU2006220100B2 (en) | Pharmaceutical forms with improved pharmacokinetic properties | |
CN101983054B (zh) | 含有咪达那新的口腔内迅速崩解性片剂 | |
CN100352432C (zh) | 含有那格列奈的制剂 | |
JP6827923B2 (ja) | デキサメタゾン口腔内フィルム | |
CN104168895A (zh) | 包含西地那非作为活性成分的掩蔽苦味的高含量快速溶解膜 | |
JP2002524534A (ja) | 非合法使用に適さない交感神経刺激性アミン塩を含んでなる組成物 | |
KR101304343B1 (ko) | Pde-5 억제제의 경구용 속용제형 | |
US20160045446A1 (en) | Oral administration preparation with masked bitterness of silodosin | |
MX2014004811A (es) | Composicion farmaceutica de sabor enmascarado para administracion oral, y proceso para la preparacion de la misma. | |
CA2984615C (en) | Vortioxetine pyroglutamate | |
CN105362240A (zh) | 口腔内速崩片 | |
KR20190089892A (ko) | 디아민 유도체를 함유하는 구강내 붕괴정 | |
CN103735525B (zh) | 一种达泊西汀片剂及制备方法 | |
TWI663990B (zh) | 包含他達拉非或其藥學上可接受之鹽類的咀嚼錠調配物 | |
WO2019151405A1 (ja) | 錠剤及びその製造方法 | |
JP2017526751A (ja) | タダラフィル口腔崩解フィルム及びこの製造方法 | |
CN101683324A (zh) | 一种枸橼酸西地那非口腔崩解片及其制备方法 | |
CN104644574B (zh) | 一种枸橼酸西地那非掩味制剂 | |
EP2563340A2 (en) | Water soluble pharmaceutical composition | |
KR20130003511A (ko) | 약제학적 활성 성분을 함유하는 경구용 속붕해성 필름 및 이의 제조 방법 | |
JP5818219B2 (ja) | 6,7−不飽和−7−カルバモイルモルヒナン誘導体含有製剤 | |
JP3228335B2 (ja) | 口腔内崩壊型組成物及びその製造方法 | |
CN107625734B (zh) | 一种无水吞服掩味制剂及其制备方法 | |
KR20130135611A (ko) | Pde-5 억제제를 포함하는 고미 개선된 경구용 조성물 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
DD01 | Delivery of document by public notice |
Addressee: NANJING HAIRONG PHARMACEUTICAL TECHNOLOGY CO.,LTD. Document name: Notification of Passing Preliminary Examination of the Application for Invention |
|
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
DD01 | Delivery of document by public notice |
Addressee: NANJING HAIRONG PHARMACEUTICAL TECHNOLOGY CO.,LTD. Document name: Notification of Publication and of Entering the Substantive Examination Stage of the Application for Invention |
|
DD01 | Delivery of document by public notice |
Addressee: Bao Yusheng Document name: Notification of Passing Examination on Formalities |
|
ASS | Succession or assignment of patent right |
Owner name: NANJING CHIA TAI TIANQING PHARMACEUTICAL CO., LTD. Effective date: 20150112 |
|
C41 | Transfer of patent application or patent right or utility model | ||
C53 | Correction of patent of invention or patent application | ||
CB03 | Change of inventor or designer information |
Inventor after: Chao Yang Inventor after: Bao Yusheng Inventor after: Ye Hai Inventor after: Guo Xuan Inventor after: Xu Dan Inventor after: Yang Zhimin Inventor before: Chao Yang Inventor before: Bao Yusheng Inventor before: Ye Hai |
|
COR | Change of bibliographic data |
Free format text: CORRECT: INVENTOR; FROM: CHAO YANG BAO YUSHENG YE HAI TO: CHAO YANG BAO YUSHENG YE HAI GUO XUAN XU DAN YANG ZHIMIN |
|
TA01 | Transfer of patent application right |
Effective date of registration: 20150112 Address after: The 211100 Nanjing Road, Jiangsu Jiangning Science Park No. 18 Applicant after: NANJING HAIRONG PHARMACEUTICAL TECHNOLOGY CO.,LTD. Applicant after: NANJING CHIA TAI TIANQING PHARMACEUTICAL Co.,Ltd. Address before: The 211100 Nanjing Road, Jiangsu Jiangning Science Park No. 18 Applicant before: NANJING HAIRONG PHARMACEUTICAL TECHNOLOGY CO.,LTD. |
|
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CP03 | Change of name, title or address | ||
CP03 | Change of name, title or address |
Address after: 211100 building 10, North District, Life Science Town, 568 longmian Avenue, Jiangning District, Nanjing City, Jiangsu Province Patentee after: NANJING HERON PHARMACEUTICAL SCIENCE AND TECHNOLOGY Co.,Ltd. Patentee after: NANJING CHIA TAI TIANQING PHARMACEUTICAL Co.,Ltd. Address before: No.18, Zhilan Road, Jiangning Science Park, Nanjing, Jiangsu, 211100 Patentee before: NANJING HAIRONG PHARMACEUTICAL TECHNOLOGY Co.,Ltd. Patentee before: NANJING CHIA TAI TIANQING PHARMACEUTICAL Co.,Ltd. |
|
TR01 | Transfer of patent right |
Effective date of registration: 20210602 Address after: 210038 9 Hui Ou Road, Nanjing economic and Technological Development Zone, Jiangsu Patentee after: NANJING CHIA TAI TIANQING PHARMACEUTICAL Co.,Ltd. Address before: 211100 building 10, North District, Life Science Town, 568 longmian Avenue, Jiangning District, Nanjing City, Jiangsu Province Patentee before: NANJING HERON PHARMACEUTICAL SCIENCE AND TECHNOLOGY Co.,Ltd. Patentee before: NANJING CHIA TAI TIANQING PHARMACEUTICAL Co.,Ltd. |
|
TR01 | Transfer of patent right |