CN117100712A - Pulse release drug 3D printed multi-unit gastric retention sheet - Google Patents
Pulse release drug 3D printed multi-unit gastric retention sheet Download PDFInfo
- Publication number
- CN117100712A CN117100712A CN202311266922.2A CN202311266922A CN117100712A CN 117100712 A CN117100712 A CN 117100712A CN 202311266922 A CN202311266922 A CN 202311266922A CN 117100712 A CN117100712 A CN 117100712A
- Authority
- CN
- China
- Prior art keywords
- unit
- release
- tablet
- drug
- artesunate
- 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
- 239000003814 drug Substances 0.000 title claims abstract description 105
- 230000002496 gastric effect Effects 0.000 title claims abstract description 102
- 230000014759 maintenance of location Effects 0.000 title claims abstract description 62
- 229940079593 drug Drugs 0.000 title claims description 75
- 210000002784 stomach Anatomy 0.000 claims abstract description 24
- 230000003111 delayed effect Effects 0.000 claims abstract description 20
- 238000010146 3D printing Methods 0.000 claims abstract description 19
- 230000000903 blocking effect Effects 0.000 claims abstract description 15
- 230000000694 effects Effects 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 8
- 206010002383 Angina Pectoris Diseases 0.000 claims abstract description 6
- 208000006673 asthma Diseases 0.000 claims abstract description 6
- 230000000717 retained effect Effects 0.000 claims abstract description 5
- 206010020772 Hypertension Diseases 0.000 claims abstract description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 4
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims abstract description 4
- 238000000034 method Methods 0.000 claims description 19
- 230000000541 pulsatile effect Effects 0.000 claims description 16
- 230000000979 retarding effect Effects 0.000 claims description 16
- 239000000463 material Substances 0.000 claims description 14
- 239000011230 binding agent Substances 0.000 claims description 9
- 239000007884 disintegrant Substances 0.000 claims description 7
- 230000002209 hydrophobic effect Effects 0.000 claims description 4
- FIHJKUPKCHIPAT-AHIGJZGOSA-N artesunate Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@@H](OC(=O)CCC(O)=O)[C@@H]4C FIHJKUPKCHIPAT-AHIGJZGOSA-N 0.000 description 124
- 229960004991 artesunate Drugs 0.000 description 124
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 20
- 239000000203 mixture Substances 0.000 description 19
- 239000012738 dissolution medium Substances 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 14
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 229920002785 Croscarmellose sodium Polymers 0.000 description 9
- 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 description 9
- 229960001681 croscarmellose sodium Drugs 0.000 description 9
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 9
- 238000012377 drug delivery Methods 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 238000007639 printing Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 238000004090 dissolution Methods 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 235000011837 pasties Nutrition 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 239000003430 antimalarial agent Substances 0.000 description 6
- 239000002872 contrast media Substances 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 6
- 239000006069 physical mixture Substances 0.000 description 6
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Natural products C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 5
- 238000013461 design Methods 0.000 description 5
- 238000007667 floating Methods 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 5
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 5
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000010521 absorption reaction Methods 0.000 description 4
- BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 description 4
- 229960004191 artemisinin Drugs 0.000 description 4
- 229930101531 artemisinin Natural products 0.000 description 4
- 229960002521 artenimol Drugs 0.000 description 4
- BJDCWCLMFKKGEE-ISOSDAIHSA-N artenimol Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2O[C@H](O)[C@@H]4C BJDCWCLMFKKGEE-ISOSDAIHSA-N 0.000 description 4
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 4
- 229930016266 dihydroartemisinin Natural products 0.000 description 4
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol group Chemical group C(CCCCCCCCCCCCCCC)O BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 4
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 235000001258 Cinchona calisaya Nutrition 0.000 description 3
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- -1 antibacterial drugs Substances 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000001186 cumulative effect Effects 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001125 extrusion Methods 0.000 description 3
- 238000000227 grinding Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 3
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 229960000948 quinine Drugs 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 239000007921 spray Substances 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- 239000012086 standard solution Substances 0.000 description 3
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- XEEQGYMUWCZPDN-DOMZBBRYSA-N (-)-(11S,2'R)-erythro-mefloquine Chemical compound C([C@@H]1[C@@H](O)C=2C3=CC=CC(=C3N=C(C=2)C(F)(F)F)C(F)(F)F)CCCN1 XEEQGYMUWCZPDN-DOMZBBRYSA-N 0.000 description 2
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 description 2
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 2
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 2
- FEDJGPQLLNQAIY-UHFFFAOYSA-N 2-[(6-oxo-1h-pyridazin-3-yl)oxy]acetic acid Chemical compound OC(=O)COC=1C=CC(=O)NN=1 FEDJGPQLLNQAIY-UHFFFAOYSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 2
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 2
- 239000002083 C09CA01 - Losartan Substances 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- 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 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 241000283977 Oryctolagus Species 0.000 description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000004098 Tetracycline Substances 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 2
- 229960000528 amlodipine Drugs 0.000 description 2
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 description 2
- 230000000078 anti-malarial effect Effects 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229960000981 artemether Drugs 0.000 description 2
- 229960002970 artemotil Drugs 0.000 description 2
- NLYNIRQVMRLPIQ-XQLAAWPRSA-N artemotil Chemical compound C1C[C@H]2[C@H](C)CC[C@H]3[C@@H](C)[C@@H](OCC)O[C@H]4[C@]32OO[C@@]1(C)O4 NLYNIRQVMRLPIQ-XQLAAWPRSA-N 0.000 description 2
- 229960002274 atenolol Drugs 0.000 description 2
- 229960005370 atorvastatin Drugs 0.000 description 2
- 229960004324 betaxolol Drugs 0.000 description 2
- NWIUTZDMDHAVTP-UHFFFAOYSA-N betaxolol Chemical compound C1=CC(OCC(O)CNC(C)C)=CC=C1CCOCC1CC1 NWIUTZDMDHAVTP-UHFFFAOYSA-N 0.000 description 2
- 229960000541 cetyl alcohol Drugs 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 229960003677 chloroquine Drugs 0.000 description 2
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 229960002227 clindamycin Drugs 0.000 description 2
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 description 2
- 229960000913 crospovidone Drugs 0.000 description 2
- 238000000151 deposition Methods 0.000 description 2
- SXYIRMFQILZOAM-HVNFFKDJSA-N dihydroartemisinin methyl ether Chemical compound C1C[C@H]2[C@H](C)CC[C@H]3[C@@H](C)[C@@H](OC)O[C@H]4[C@]32OO[C@@]1(C)O4 SXYIRMFQILZOAM-HVNFFKDJSA-N 0.000 description 2
- 229960005316 diltiazem hydrochloride Drugs 0.000 description 2
- 229960003722 doxycycline Drugs 0.000 description 2
- 238000005538 encapsulation Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229960003943 hypromellose Drugs 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229960004773 losartan Drugs 0.000 description 2
- KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229960001962 mefloquine Drugs 0.000 description 2
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 description 2
- 238000001471 micro-filtration Methods 0.000 description 2
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 2
- 229960001597 nifedipine Drugs 0.000 description 2
- 229960002582 perindopril Drugs 0.000 description 2
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 229960005179 primaquine Drugs 0.000 description 2
- INDBQLZJXZLFIT-UHFFFAOYSA-N primaquine Chemical compound N1=CC=CC2=CC(OC)=CC(NC(C)CCCN)=C21 INDBQLZJXZLFIT-UHFFFAOYSA-N 0.000 description 2
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 description 2
- 229960002052 salbutamol Drugs 0.000 description 2
- BNRNXUUZRGQAQC-UHFFFAOYSA-N sildenafil Chemical compound CCCC1=NN(C)C(C(N2)=O)=C1N=C2C(C(=CC=1)OCC)=CC=1S(=O)(=O)N1CCN(C)CC1 BNRNXUUZRGQAQC-UHFFFAOYSA-N 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 2
- 229960002180 tetracycline Drugs 0.000 description 2
- 229930101283 tetracycline Natural products 0.000 description 2
- 235000019364 tetracycline Nutrition 0.000 description 2
- 150000003522 tetracyclines Chemical class 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 238000002411 thermogravimetry Methods 0.000 description 2
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
- BIDNLKIUORFRQP-XYGFDPSESA-N (2s,4s)-4-cyclohexyl-1-[2-[[(1s)-2-methyl-1-propanoyloxypropoxy]-(4-phenylbutyl)phosphoryl]acetyl]pyrrolidine-2-carboxylic acid Chemical compound C([P@@](=O)(O[C@H](OC(=O)CC)C(C)C)CC(=O)N1[C@@H](C[C@H](C1)C1CCCCC1)C(O)=O)CCCC1=CC=CC=C1 BIDNLKIUORFRQP-XYGFDPSESA-N 0.000 description 1
- OBRNDARFFFHCGE-PERKLWIXSA-N (S,S)-formoterol fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1=CC(OC)=CC=C1C[C@H](C)NC[C@@H](O)C1=CC=C(O)C(NC=O)=C1.C1=CC(OC)=CC=C1C[C@H](C)NC[C@@H](O)C1=CC=C(O)C(NC=O)=C1 OBRNDARFFFHCGE-PERKLWIXSA-N 0.000 description 1
- RZPZLFIUFMNCLY-WLHGVMLRSA-N (e)-but-2-enedioic acid;1-(propan-2-ylamino)-3-[4-(2-propan-2-yloxyethoxymethyl)phenoxy]propan-2-ol Chemical compound OC(=O)\C=C\C(O)=O.CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 RZPZLFIUFMNCLY-WLHGVMLRSA-N 0.000 description 1
- LHNYXTULDSJZRB-UHFFFAOYSA-N 1-(9h-carbazol-4-yloxy)-3-[2-(2-methoxyphenoxy)ethylamino]propan-2-ol;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.OP(O)(O)=O.COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=C1C1=CC=CC=C1N2.COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=C1C1=CC=CC=C1N2 LHNYXTULDSJZRB-UHFFFAOYSA-N 0.000 description 1
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 description 1
- ZKLPARSLTMPFCP-OAQYLSRUSA-N 2-[2-[4-[(R)-(4-chlorophenyl)-phenylmethyl]-1-piperazinyl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCN1[C@@H](C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-OAQYLSRUSA-N 0.000 description 1
- JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 description 1
- RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 description 1
- IBSREHMXUMOFBB-JFUDTMANSA-N 5u8924t11h Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O3)C=C[C@H](C)[C@@H](C(C)C)O4)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 IBSREHMXUMOFBB-JFUDTMANSA-N 0.000 description 1
- VHRSUDSXCMQTMA-PJHHCJLFSA-N 6alpha-methylprednisolone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)CO)CC[C@H]21 VHRSUDSXCMQTMA-PJHHCJLFSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- 239000005660 Abamectin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 102220487426 Actin-related protein 2/3 complex subunit 3_K15M_mutation Human genes 0.000 description 1
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 0.000 description 1
- 239000002947 C09CA04 - Irbesartan Substances 0.000 description 1
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- KJEBULYHNRNJTE-DHZHZOJOSA-N Cinalong Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC\C=C\C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 KJEBULYHNRNJTE-DHZHZOJOSA-N 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
- 108010061435 Enalapril Proteins 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- VPNYRYCIDCJBOM-UHFFFAOYSA-M Glycopyrronium bromide Chemical compound [Br-].C1[N+](C)(C)CCC1OC(=O)C(O)(C=1C=CC=CC=1)C1CCCC1 VPNYRYCIDCJBOM-UHFFFAOYSA-M 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- 239000005906 Imidacloprid Substances 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
- 108010007859 Lisinopril Proteins 0.000 description 1
- RGHAZVBIOOEVQX-UHFFFAOYSA-N Metoprolol succinate Chemical compound OC(=O)CCC(O)=O.COCCC1=CC=C(OCC(O)CNC(C)C)C=C1.COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 RGHAZVBIOOEVQX-UHFFFAOYSA-N 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- FAIIFDPAEUKBEP-UHFFFAOYSA-N Nilvadipine Chemical compound COC(=O)C1=C(C#N)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC([N+]([O-])=O)=C1 FAIIFDPAEUKBEP-UHFFFAOYSA-N 0.000 description 1
- SNIOPGDIGTZGOP-UHFFFAOYSA-N Nitroglycerin Chemical compound [O-][N+](=O)OCC(O[N+]([O-])=O)CO[N+]([O-])=O SNIOPGDIGTZGOP-UHFFFAOYSA-N 0.000 description 1
- 239000000006 Nitroglycerin Substances 0.000 description 1
- 239000005480 Olmesartan Substances 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 description 1
- 229950008167 abamectin Drugs 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940124350 antibacterial drug Drugs 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 229940092705 beclomethasone Drugs 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 229960004530 benazepril Drugs 0.000 description 1
- 229960004916 benidipine Drugs 0.000 description 1
- QZVNQOLPLYWLHQ-ZEQKJWHPSA-N benidipine Chemical compound C1([C@H]2C(=C(C)NC(C)=C2C(=O)OC)C(=O)O[C@H]2CN(CC=3C=CC=CC=3)CCC2)=CC=CC([N+]([O-])=O)=C1 QZVNQOLPLYWLHQ-ZEQKJWHPSA-N 0.000 description 1
- BNQDCRGUHNALGH-UHFFFAOYSA-N benserazide Chemical compound OCC(N)C(=O)NNCC1=CC=C(O)C(O)=C1O BNQDCRGUHNALGH-UHFFFAOYSA-N 0.000 description 1
- 229960000911 benserazide Drugs 0.000 description 1
- 239000000227 bioadhesive Substances 0.000 description 1
- 229960002781 bisoprolol Drugs 0.000 description 1
- VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 description 1
- 229960005400 bisoprolol fumarate Drugs 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 229960004195 carvedilol Drugs 0.000 description 1
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 1
- 229960000370 carvedilol phosphate Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229960001523 chlortalidone Drugs 0.000 description 1
- 229960003020 cilnidipine Drugs 0.000 description 1
- RRGUKTPIGVIEKM-UHFFFAOYSA-N cilostazol Chemical compound C=1C=C2NC(=O)CCC2=CC=1OCCCCC1=NN=NN1C1CCCCC1 RRGUKTPIGVIEKM-UHFFFAOYSA-N 0.000 description 1
- 229960004588 cilostazol Drugs 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229960002448 dasatinib Drugs 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229960004483 doxofylline Drugs 0.000 description 1
- HWXIGFIVGWUZAO-UHFFFAOYSA-N doxofylline Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2N=CN1CC1OCCO1 HWXIGFIVGWUZAO-UHFFFAOYSA-N 0.000 description 1
- 229960001971 ebastine Drugs 0.000 description 1
- MJJALKDDGIKVBE-UHFFFAOYSA-N ebastine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)CCCN1CCC(OC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 MJJALKDDGIKVBE-UHFFFAOYSA-N 0.000 description 1
- 229960000873 enalapril Drugs 0.000 description 1
- GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 description 1
- 229960002548 epinastine hydrochloride Drugs 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 229960003580 felodipine Drugs 0.000 description 1
- 229960000676 flunisolide Drugs 0.000 description 1
- 229960001469 fluticasone furoate Drugs 0.000 description 1
- XTULMSXFIHGYFS-VLSRWLAYSA-N fluticasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(F)[C@@]4(C)C=CC(=O)C=C4[C@@H](F)C[C@H]3[C@@H]2C[C@H]1C)C(=O)SCF)C(=O)C1=CC=CO1 XTULMSXFIHGYFS-VLSRWLAYSA-N 0.000 description 1
- 229960000193 formoterol fumarate Drugs 0.000 description 1
- 229960002490 fosinopril Drugs 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960003711 glyceryl trinitrate Drugs 0.000 description 1
- 229940015042 glycopyrrolate Drugs 0.000 description 1
- 229960002003 hydrochlorothiazide Drugs 0.000 description 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 description 1
- 229960002240 iloprost Drugs 0.000 description 1
- HIFJCPQKFCZDDL-ACWOEMLNSA-N iloprost Chemical compound C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)C(C)CC#CC)[C@H](O)C[C@@H]21 HIFJCPQKFCZDDL-ACWOEMLNSA-N 0.000 description 1
- 229960002411 imatinib Drugs 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- YWTYJOPNNQFBPC-UHFFFAOYSA-N imidacloprid Chemical compound [O-][N+](=O)\N=C1/NCCN1CC1=CC=C(Cl)N=C1 YWTYJOPNNQFBPC-UHFFFAOYSA-N 0.000 description 1
- 229940056881 imidacloprid Drugs 0.000 description 1
- NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 description 1
- 229960004569 indapamide Drugs 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 229960001361 ipratropium bromide Drugs 0.000 description 1
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
- 229960002198 irbesartan Drugs 0.000 description 1
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 description 1
- MOYKHGMNXAOIAT-JGWLITMVSA-N isosorbide dinitrate Chemical compound [O-][N+](=O)O[C@H]1CO[C@@H]2[C@H](O[N+](=O)[O-])CO[C@@H]21 MOYKHGMNXAOIAT-JGWLITMVSA-N 0.000 description 1
- 229960000201 isosorbide dinitrate Drugs 0.000 description 1
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
- 229960003827 isosorbide mononitrate Drugs 0.000 description 1
- 229960001632 labetalol Drugs 0.000 description 1
- ZDXUKAKRHYTAKV-UHFFFAOYSA-N lercanidipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)(C)CN(C)CCC(C=2C=CC=CC=2)C=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZDXUKAKRHYTAKV-UHFFFAOYSA-N 0.000 description 1
- 229960004294 lercanidipine Drugs 0.000 description 1
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 description 1
- 229960004002 levetiracetam Drugs 0.000 description 1
- 229960001508 levocetirizine Drugs 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960002394 lisinopril Drugs 0.000 description 1
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229960004329 metformin hydrochloride Drugs 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin hydrochloride Natural products CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 229960002237 metoprolol Drugs 0.000 description 1
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 1
- 229960000939 metoprolol succinate Drugs 0.000 description 1
- 238000001000 micrograph Methods 0.000 description 1
- 229960001664 mometasone Drugs 0.000 description 1
- QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 description 1
- 229960002744 mometasone furoate Drugs 0.000 description 1
- WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 description 1
- 229960001951 montelukast sodium Drugs 0.000 description 1
- LBFBRXGCXUHRJY-HKHDRNBDSA-M montelukast sodium Chemical compound [Na+].CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC([O-])=O)CC1 LBFBRXGCXUHRJY-HKHDRNBDSA-M 0.000 description 1
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 description 1
- 229960004398 nedocromil Drugs 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- LBHIOVVIQHSOQN-UHFFFAOYSA-N nicorandil Chemical compound [O-][N+](=O)OCCNC(=O)C1=CC=CN=C1 LBHIOVVIQHSOQN-UHFFFAOYSA-N 0.000 description 1
- 229960002497 nicorandil Drugs 0.000 description 1
- 229960005366 nilvadipine Drugs 0.000 description 1
- DCUJJWWUNKIJPH-UHFFFAOYSA-N nitrapyrin Chemical compound ClC1=CC=CC(C(Cl)(Cl)Cl)=N1 DCUJJWWUNKIJPH-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 description 1
- 229960005117 olmesartan Drugs 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229960004439 pemirolast Drugs 0.000 description 1
- HIANJWSAHKJQTH-UHFFFAOYSA-N pemirolast Chemical compound CC1=CC=CN(C2=O)C1=NC=C2C=1N=NNN=1 HIANJWSAHKJQTH-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 229960004583 pranlukast Drugs 0.000 description 1
- UAJUXJSXCLUTNU-UHFFFAOYSA-N pranlukast Chemical compound C=1C=C(OCCCCC=2C=CC=CC=2)C=CC=1C(=O)NC(C=1)=CC=C(C(C=2)=O)C=1OC=2C=1N=NNN=1 UAJUXJSXCLUTNU-UHFFFAOYSA-N 0.000 description 1
- IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 1
- 229960001289 prazosin Drugs 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960002288 procaterol Drugs 0.000 description 1
- FKNXQNWAXFXVNW-BLLLJJGKSA-N procaterol Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)[C@@H](NC(C)C)CC FKNXQNWAXFXVNW-BLLLJJGKSA-N 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 229960003712 propranolol Drugs 0.000 description 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- IBBLRJGOOANPTQ-JKVLGAQCSA-N quinapril hydrochloride Chemical compound Cl.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 IBBLRJGOOANPTQ-JKVLGAQCSA-N 0.000 description 1
- 229960003042 quinapril hydrochloride Drugs 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 125000003410 quininyl group Chemical group 0.000 description 1
- 229960003401 ramipril Drugs 0.000 description 1
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 229960003310 sildenafil Drugs 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- LXMSZDCAJNLERA-ZHYRCANASA-N spironolactone Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CCC(=O)C=C4C[C@H]([C@@H]13)SC(=O)C)C[C@@]21CCC(=O)O1 LXMSZDCAJNLERA-ZHYRCANASA-N 0.000 description 1
- 229960002256 spironolactone Drugs 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 229960005187 telmisartan Drugs 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 229960004929 tirofiban hydrochloride Drugs 0.000 description 1
- HWAAPJPFZPHHBC-FGJQBABTSA-N tirofiban hydrochloride Chemical compound O.Cl.C1=CC(C[C@H](NS(=O)(=O)CCCC)C(O)=O)=CC=C1OCCCCC1CCNCC1 HWAAPJPFZPHHBC-FGJQBABTSA-N 0.000 description 1
- 229960005342 tranilast Drugs 0.000 description 1
- NZHGWWWHIYHZNX-CSKARUKUSA-N tranilast Chemical compound C1=C(OC)C(OC)=CC=C1\C=C\C(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-CSKARUKUSA-N 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
- 229960001722 verapamil Drugs 0.000 description 1
- 229960004764 zafirlukast Drugs 0.000 description 1
- 229960002769 zofenopril Drugs 0.000 description 1
- IAIDUHCBNLFXEF-MNEFBYGVSA-N zofenopril Chemical compound C([C@@H](C)C(=O)N1[C@@H](C[C@@H](C1)SC=1C=CC=CC=1)C(O)=O)SC(=O)C1=CC=CC=C1 IAIDUHCBNLFXEF-MNEFBYGVSA-N 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
-
- 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
-
- 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
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y70/00—Materials specially adapted for additive manufacturing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y80/00—Products made by additive manufacturing
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Materials Engineering (AREA)
- Manufacturing & Machinery (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a multi-unit gastric retention tablet capable of pulse releasing medicine, which can be retained in stomach for a long time and can pulse releasing medicine, and application of the tablet in preparation of medicine for treating hypertension, angina pectoris, bronchial asthma, rheumatism and diabetes. The multi-unit gastric retention sheet comprises a quick release unit, a blocking unit and a delayed release unit. The quick release unit quickly releases the medicine in the stomach, the blocking unit slowly dissolves, the delay release unit starts to release the medicine after a certain delay time, the pulse release medicine effect is obtained, and the medicine is released in the stomach all the time. The volume of the quick release unit is designed according to the dosage required by the medicine to be released for the first time, the volume of the blocking unit is designed according to the length of the delay time, and the volume of the delay release unit is designed according to the dosage required by the medicine to be released by the pulse. The form and volume of these units can be individually designed according to the treatment requirements and the patient's needs. The multi-unit gastric retentive sheet is preferably a 3D printing preparation method.
Description
Technical Field
The invention relates to the technical field of medical treatment and health, in particular to a multi-unit gastric retention tablet for pulse release of medicines.
Background
The Gastric Retention Drug Delivery System (GRDDS) is a type of drug delivery system which can be retained in the stomach for a long time after being orally taken, prolongs the release time of the drug in the stomach, can obtain the effects of slowly and controllably releasing the drug, improving the drug absorption, enhancing the local treatment effect of the drug in the stomach, reducing adverse reaction and administration times, improving clinical curative effect and the like. Gastric retentive drug delivery systems typically include gastric floating formulations, gastric distending formulations, bioadhesive formulations, and high density formulations.
Gastric retentive drug delivery systems are advantageous for achieving adequate efficacy of a variety of drugs, such as drugs with sites of action in the stomach, drugs with a narrow absorption window in the stomach or upper small intestine. In addition, drugs that degrade in the intestinal or colonic environment and drugs that are poorly soluble at alkaline pH values are also suitable for formulation into gastric retentive drug delivery systems.
Currently, most of the gastric retentive drug delivery systems are sustained release formulations, which release drugs in the stomach. Gastric retention administration has the advantages of reducing the administration times, improving the patient compliance, improving the drug bioavailability and the like, and the gastric retention preparations on the market comprise Madopa HbS (drug: levodopa and benserazide) of Roche company, varelease (drug: diazepam), glucophage XR (drug: metformin hydrochloride) of Shinobel company, cifranod (drug: ciprofloxacin) of Lanbosai company and the like. They are all capable of slowly releasing the drug in the stomach.
A pulsatile drug delivery system is defined as a drug delivery system that rapidly releases a drug in a predetermined pattern. Pulse release is similar to physiological release of hormones in humans, such as the release of hormones like insulin. Has rhythmicity on the onset of illness without long-time maintenance of the constant drug concentration in the body, such as hypertension, angina pectoris, bronchial asthma, rheumatism, diabetes and the like, and has good curative effect by pulse administration and reduced adverse reaction of the drug.
3D printing, also known as additive manufacturing, is a rapid prototyping technology developed by the university of Massachusetts at the end of the 80 s of the 20 th century, and the basic principle is to bind powders together with viscous liquids to form a three-dimensional structure. The U.S. FDA approved the first new drug of levetiracetam 3D print tablet worldwide using 3D printing technology in 8 months 2015. The 3D printed formulation represents a perfect combination of pharmaceutical raw materials, pharmaceutical excipients, pharmaceutical dosage forms, pharmaceutical equipment and manufacturing techniques (including software design and computer control). The 3D printing preparation is characterized by being capable of being personalized and individually designed according to the disease treatment characteristics and individual requirements, and realizing accurate drug delivery and treatment.
Disclosure of Invention
The present inventors devised and prepared a multi-unit gastric retentive tablet of a pulsatile release drug which can be retained in the stomach for a long period of time and which can pulsatively release the drug.
The invention discloses an application of a pulse-release drug multi-unit gastric retention tablet in preparing drugs for treating hypertension, angina pectoris, bronchial asthma, rheumatism and diabetes.
The invention discloses a multi-unit gastric retention tablet for pulse release of medicines, which comprises a quick release unit, a blocking unit and a delay release unit. The quick release unit comprises a drug, a binder, and a disintegrant. The retarding element comprises a hydrophobic material and an adhesive. The delayed release unit comprises a drug, a binder, and a disintegrant. The medicament in the quick release unit and the delayed release unit may or may not be the same medicament, preferably the same medicament. The binder and disintegrant in the quick release unit and the delayed release unit may be the same or different, preferably the same binder and disintegrant. The delay release unit is completely surrounded by the blocking unit. The quick release unit is outermost.
The multi-unit gastric retention tablet for pulse release of the medicine in the invention has the advantages that the quick release unit quickly releases the medicine in the stomach, the blocking unit slowly dissolves, the delay release unit starts to release the medicine after a certain delay time, the effect of pulse release of the medicine is obtained, and the medicine is always released in the stomach.
The volume of the quick release unit of the pulse drug release multi-unit gastric retention tablet is designed according to the dosage required by the drug release for the first time, the volume of the blocking unit is designed according to the length of delay time, and the volume of the delay release unit is designed according to the dosage required by the pulse drug release.
The pulse drug-releasing multi-unit gastric retention tablet can be personalized according to the treatment requirements and the patient requirements by the form and the volume of the quick release unit, the blocking unit and the delay release unit.
The pulse-released drug multi-unit gastric retention tablet of the invention stays in the stomach for more than 8 hours, and the pulse-released drug takes more than 6 hours.
The preparation method of the pulse-release drug multi-unit gastric retentive tablet is not limited, and is preferably a 3D printing method. The 3D printing method is selected from fused deposition type 3D printing method, optical three-dimensional printing 3D printing method, laser fused 3D printing method, powder bonding 3D printing method, semisolid extrusion 3D printing method, preferably semisolid extrusion 3D printing method.
When the semisolid extrusion 3D printing method is used for preparing the pulse release drug multi-unit gastric retention tablet, the preparation process is as follows:
(1) Adding wetting agent into the medicine, the adhesive and the disintegrating agent to prepare a medicine-containing pasty mixture, and filling the mixture into a charging barrel;
(2) Adding wetting agent into hydrophobic material and adhesive to prepare blank pasty mixture, and filling into a charging barrel;
(3) Printing by adopting double spray heads, wherein one spray head is loaded with a medicine-containing pasty mixture, the other spray head is loaded with a blank pasty mixture, extruding from the tip of a 3D printer charging barrel according to designed model parameters, and depositing onto a platform layer by layer to obtain a wet multi-cell sheet:
(4) Naturally drying the wet multi-unit tablet at room temperature or heating and drying or decompressing and drying to obtain the multi-unit gastric retention tablet for pulse release medicine.
The wetting agent in the above preparation is selected from water, ethanol, water and ethanol mixture, preferably water.
The binder in the quick release unit, the retarding unit and the delayed release unit is selected from polyvinylpyrrolidone, hypromellose, methylcellulose, gelatin and poloxamer, preferably polyvinylpyrrolidone and hypromellose. The disintegrating agent in the quick release unit and the delayed release unit is selected from pregelatinized starch, croscarmellose sodium, low substituted hydroxypropylcellulose, sodium carboxymethyl starch, crospovidone, further preferably from croscarmellose sodium, sodium carboxymethyl starch, crospovidone, most preferably croscarmellose sodium. The hydrophobic material in the retardation unit is selected from cetyl alcohol, stearyl alcohol, ethyl cellulose, cellulose acetate, acrylic resin, and polycaprolactone, preferably from cetyl alcohol, stearyl alcohol, and ethyl cellulose.
The pulse-release drug multi-unit gastric retention tablet is not limited, and can select various drugs, preferably antimalarial drugs, antibacterial drugs, drugs for treating angina pectoris, antihypertensive drugs and drugs for treating asthma.
The antimalarial agent is selected from quinine antimalarial agent and artemisinin antimalarial agent. The quinine antimalarial is selected from chloroquine, quinidine, mefloquine and primaquine. The artemisinin antimalarial is selected from artemisinin, dihydroartemisinin, artesunate, artemether, arteether and dihydroartemisinin, preferably artesunate. The antibacterial agent is selected from tetracycline, doxycycline, and clindamycin. Correspondingly, the multi-unit gastric retention tablet of the pulsatile release drug is selected from the group consisting of chloroquine pulsatile release multi-unit gastric retention tablet, quinine Ding Maichong release multi-unit gastric retention tablet, mefloquine pulsatile release multi-unit gastric retention tablet, primaquine pulsatile release multi-unit gastric retention tablet, artemisinin pulsatile release multi-unit gastric retention tablet, dihydroartemisinin pulsatile release multi-unit gastric retention tablet, artemether pulsatile release multi-unit gastric retention tablet, arteether pulsatile release multi-unit gastric retention tablet, dihydroartemisinin pulsatile release multi-unit gastric retention tablet, tetracycline pulsatile release multi-unit gastric retention tablet, doxycycline pulsatile release multi-unit gastric retention tablet, clindamycin pulsatile release multi-unit gastric retention tablet, preferably artesunate pulsatile release multi-unit gastric retention tablet.
The medicine for treating angina pectoris is selected from nitroglycerin, isosorbide dinitrate, isosorbide mononitrate, betaxolol, metoprolol succinate, nifedipine, atorvastatin, amlodipine, cilostazol, verapamil, diltiazem hydrochloride, lercanidipine, carvedilol, nilvadipine, nicorandil, benidipine, bisoprolol fumarate, atenolol, celecoxib, trinitrate, progesterone, tirofiban hydrochloride, and efodipine hydrochloride.
Antihypertensive agents include, but are not limited to, sildenafil, amlodipine, felodipine, cilnidipine, nifedipine, nitrapyrin, enalapril, fosinopril, lisinopril, perindopril, imidacloprid, ramipril, perindopril, spiropril, zofenopril, quinapril hydrochloride, benazepril, losartan, valsartan, irbesartan, telmisartan, losartan, olmesartan, hydrochlorothiazide, chlorthalidone, indapamide, metoprolol, bisoprolol, atenolol, labetalol, propranolol, carvedilol phosphate, clonidine, betaxolol, atorvastatin, diltiazem hydrochloride, spirolactone, iloprost, prazosin.
Drugs for the treatment of asthma include, but are not limited to, theophylline, fluticasone furoate, etanercept, abamectin, glycopyrrolate, budesonide, formoterol fumarate, dasatinib, beclomethasone propionate, montelukast sodium, imatinib, ipratropium bromide, mometasone furoate, triamcinolone, dexamethasone, salbutamol, terbutaline, procaterol, scopolamine isopropyl, albuterol, mometasone, levocetirizine hydrochloride, prednisolone, ebastine, pranlukast, doxofylline, flunisolide, cromolyn sodium, zafirlukast, pemirolast hydrochloride, epinastine hydrochloride, nedocromil, tolterol, mizostatin, promulgated, tranilast, methylprednisolone, and rapiroxostat.
The pulse released medicine multi-unit gastric retention tablet features that the pulse released medicine is released in stomach and the material, form and volume of the retarding unit are regulated to obtain different delay time and gastric retention time.
Drawings
FIG. 1. 3D model design of artesunate tablet, (A) artesunate quick release tablet, (B) artesunate pulse release multi-unit gastric retention tablet of 7mm diameter, (C) artesunate pulse release multi-unit gastric retention tablet of 8mm, (D) artesunate quick release tablet cross-sectional view, (E) artesunate pulse release multi-unit gastric retention tablet of 7mm diameter, and (F) artesunate pulse release multi-unit gastric retention tablet cross-sectional view of 8 mm.
FIG. 2 scanning electron microscope image (A) artesunate, (B) physical mixture, (C) artesunate immediate release tablet, (D) artesunate pulse release multi-unit gastric retention tablet.
Figure 3. IR spectrum. Artesunate, polyvinylpyrrolidone, croscarmellose sodium, physical mixture, artesunate quick release tablet, artesunate pulse release multi-unit gastric retentive tablet are shown in figure 3.
Figure 4. X-ray diffraction pattern. Artesunate, polyvinylpyrrolidone, croscarmellose sodium, physical mixture, artesunate immediate release tablet, artesunate pulse release multicell gastric retentive tablet are illustrated in figure 4.
Figure 5 thermogravimetric analysis of artesunate, polyvinylpyrrolidone, croscarmellose sodium, physical mixture, immediate release tablet of artesunate is shown in figure 5.
FIG. 6 in vitro release profile of artesunate pulse release multiple unit gastric retentive tablets of different diameter sizes.
FIG. 7. In vitro residence time of artesunate pulse release multiple units of gastric retentive tablets of different diameter sizes.
Figure 8.6 mm artesunate immediate release tablet image and in vivo residence time under X-ray.
FIG. 9.7 mm artesunate pulse release multi-unit gastric retentive tablet images and in vivo residence time under X-ray.
FIG. 10.8 mm artesunate pulse release multi-unit gastric retentive tablet images and in vivo residence time under X-ray.
Detailed Description
EXAMPLE 1 artesunate pulse release multiple unit gastric retentive tablet
Weighing 4g artesunate, 0.56g polyvinylpyrrolidone K30 and 0.44g croscarmellose sodium, grinding and mixing uniformly for 10 minutes, adding 4mL of water, stirring continuously to obtain an artesunate pasty mixture, and loading into a 3D printer charging barrel; weighing 3g of stearyl alcohol, 1g of hydroxypropyl methylcellulose K15M and 0.5g of polyvinylpyrrolidone K30, grinding and uniformly mixing for 10 minutes, adding 4mL of ethanol into 0.2g of poloxamer 188 for dissolution, then adding into the mixture, continuously stirring, adding 1mL of water, continuously stirring to obtain a blank pasty mixture, and loading into a 3D printer charging barrel; modeling by using 3D design software, and designing the forms and volumes of a quick release unit, a retarding unit and a delay release unit, wherein the quick release unit is a cylinder with the diameter of 6.93mm and the height of 1.5mm and is positioned at the top of the retarding unit, the retarding unit is a cylinder with the diameter of 7mm and the height of 4mm, and the center inside the retarding unit is provided with a cylinder with the diameter of 6mm and the height of 2 mm; the model is converted into a recognizable parameter file of a 3D printer, the printing parameters comprise a quick release unit containing medicine and a delay release unit, the printing speed is 10mm/s, the printing temperature is 25 ℃, the layer height is 0.5mm, the printing speed of a retarding unit is 10mm/s, the printing temperature is 4 ℃, the layer height is 0.5mm, and the artesunate pulse release multi-unit gastric retentive tablet with the diameter of 7mm is prepared.
The 3D printing design diagram is shown in fig. 1B, the cross section diagram is shown in fig. 1E, and the 3D printing design diagram consists of a quick release unit, a blocking unit and a delay release unit at the top.
The artesunate is replaced by other medicines, so that the corresponding multi-unit gastric retention tablet for pulse release of medicines can be achieved. The form and volume of each unit can be appropriately adjusted according to the requirements.
The artesunate pulse release multi-unit gastric retention tablet with the diameter of 8mm is obtained by setting the diameter of the retarding unit to 8mm, the 3D printing design drawing is shown in fig. 1C, the sectional drawing is shown in fig. 1F, and the artesunate pulse release multi-unit gastric retention tablet consists of a quick release unit, a retarding unit and a delayed release unit at the top.
Experimental example 1 artesunate quick-release tablet
Weighing 4g artesunate, 0.56g polyvinylpyrrolidone K30 and 0.44g croscarmellose sodium, grinding and mixing uniformly for 10 minutes, adding 4mL of water, stirring continuously to obtain an artesunate pasty mixture, and loading into a 3D printer charging barrel; modeling by using 3D design software to obtain a cylinder with the diameter of 6mm and the height of 4 mm; and converting the model into a 3D printer identifiable parameter file, wherein the printing parameters are that the printing speed is 10mm/s, the printing temperature is 25 ℃, the layer height is 0.5mm, and the artesunate quick-release tablet with the diameter of 6mm is prepared.
The 3D printing design drawing of the artesunate quick-release tablet is shown in figure 1A, and the cross-sectional drawing of the artesunate quick-release tablet is shown in figure 1D.
Experimental example 2 Property investigation of artesunate pulse-released Multi-Unit gastric-retentive tablet
Materials: a6 mm diameter quick release tablet of artesunate prepared according to experimental example 1, a 7mm and 8mm diameter pulse release multi-unit gastric retentive tablet of artesunate prepared according to example 2, artesunate, croscarmellose sodium, polyvinylpyrrolidone K30.
The method comprises the following steps: samples were taken and analyzed by Fourier transform infrared spectrometer (FTIR, spectrum Two) with a scan range of 4000cm -1 ～650cm -1 Resolution of 1cm -1 The number of scans was 8. Samples were taken and analyzed by an X-ray powder diffractometer (Empyrean) under conditions of Cu target, X-ray wavelength 0.15406nm, tube voltage 40kV, tube current 40mA, step size 0.02 DEG, scan speed 5 DEG/min, scan range 5 DEG-60 DEG, nitrogen atmosphere 60mL/min. The sample is taken and measured by a differential scanning calorimeter (Q20) under the condition that the heating rate is 10 ℃/min and the heating range is 30-200 ℃. Taking artesunate, artesunate quick release tablet and artesunate pulse release multi-unit gastric retention tablet, and performing scanning electron microscope (CUBE 2) observation and photographing record on the cross sections.
Results: the observation result of the artesunate bulk drug on a scanning electron microscope shows (figure 2A), and the artesunate exists mainly in a block form. It can be observed that the drug is present in the physical mixture in a large amount in the physical mixture (fig. 2B). The presence of artesunate particles inside the tablet was also observed on the surface of the 3D printed artesunate immediate release tablet and in the section of the 3D printed artesunate pulse release multi-unit gastroretentive tablet (figures 2C and 2D). The infrared spectra show (figure 3) that both the 3D printed artesunate quick release tablet and the 3D printed artesunate pulse release multi-unit gastric retentive tablet show the same telescopic vibration peaks as artesunate at the above wavelengths, and the characteristic peaks have no obvious deviation, disappearance or new peak types. The X-ray diffraction pattern showed (FIG. 4) that the peak pattern of the rapid 3D printed artesunate release tablet and the 3D printed artesunate pulse release multi-unit gastric retentive tablet was substantially the same as the five peak patterns described above. The thermogram shows that artesunate bulk drug has sharp endothermic peak at 141 ℃ (figure 5), and in 3D printed artesunate immediate release tablet, endothermic peak is found near 153 ℃, which is presumed to be artesunate endothermic peak. The absorption peak is basically the same as that of the artesunate bulk drug, but the heat absorption quantity is smaller than that of the artesunate bulk drug, which is related to the content of the drug. In conclusion, the characterization results of XRD, FTIR, thermogravimetric analysis and the like are combined, so that the medicine exists in the 3D printed artesunate quick-release tablet, does not react with auxiliary materials, does not generate a new crystal form, and has good compatibility with the auxiliary materials.
Experimental example 3 drug Release of artesunate immediate Release tablet
Materials: a6 mm diameter artesunate gastric retentive tablet prepared according to experimental example 1.
The method comprises the following steps: the artesunate gastric retention tablets with the diameter of 6mm are respectively placed in stainless steel rotary baskets, hydrochloric acid solution with the pH value of 1 is used as a dissolution medium, 900mL of dissolution medium is taken out from each dissolution cup, the rotary basket rotating speed is 75rpm, the water bath temperature is 37 ℃, 5mL of the dissolution medium is respectively sampled at a sampling point at fixed time, the sample is filtered through a microporous filter membrane with the diameter of 0.45 mu m, the subsequent filtrate is taken, isothermal and equivalent fresh dissolution medium is supplemented, and the cumulative release amount of the artesunate gastric retention tablets is measured by an ultraviolet spectrophotometer. Samples were taken at 0, 0.083, 0.167, 0.25, 0.5, 0.75, 1, 2, 4 and 6 hours, 5mL each time, the samples were passed through a 0.45 μm microfiltration membrane, the subsequent filtrate was taken and replenished with an isothermal equivalent amount of fresh dissolution medium, and the absorbance of the subsequent filtrate at 237nm was measured with an ultraviolet-visible spectrophotometer. The dissolution assay was performed with 3 artesunate gastric-retentive tablets of 6mm diameter. Comparing the measured filtrate with artesunate standard solution, calculating to obtain artesunate amount in the solution, and drawing artesunate release curve of artesunate gastric retention tablet with diameter of 6 mm.
Results: the in vitro release profile of the 6mm diameter artesunate immediate release tablet is shown in figure 6. The artesunate quick-release tablet with the diameter of 6mm can reach more than 85% after 1 hour of in-vitro drug release.
Experimental example 4 drug Release of artesunate pulse-released Multi-Unit gastric-retentive tablet
Materials: a7 mm diameter artesunate pulse release multi-unit gastric retentive tablet prepared as in example 1.
The method comprises the following steps: the artesunate pulse release multi-unit gastric retention tablets with the diameter of 7mm are respectively placed in stainless steel rotary baskets, hydrochloric acid solution with the pH value of 1 is used as a dissolution medium, 900mL of each dissolution cup is used as a dissolution medium, the rotary basket rotating speed is 75rpm, the water bath temperature is 37 ℃, 5mL of each sample is sampled at the sampling point at fixed time, the samples are respectively filtered through a microporous filter membrane with the diameter of 0.45 mu m, continuous filtrate is taken, isothermal and equivalent fresh dissolution medium is supplemented, and the cumulative release amount of the artesunate pulse release multi-unit gastric retention tablets is measured by an ultraviolet spectrophotometer. Samples were taken at 0, 0.083, 0.167, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 20 hours, 5mL each, and the samples were passed through a 0.45 μm microfiltration membrane to obtain a subsequent filtrate, and an isothermal equivalent of fresh dissolution medium was supplemented, and the absorbance of the subsequent filtrate at 237nm was measured with an ultraviolet-visible spectrophotometer. The dissolution assay was performed with 37 mm diameter artesunate pulse release multi-unit gastric retentive tablets. Comparing the measured filtrate with artesunate standard solution, calculating to obtain artesunate amount in the filtrate, and drawing artesunate release curve chart of artesunate pulse release multi-unit gastric retention tablet with diameter of 7 mm.
Results: the in vitro release profile of the 7mm diameter artesunate pulse release multi-unit gastric retentive tablet is shown in figure 6. The artesunate pulse release multi-unit gastric retention tablet with the diameter of 7mm can release more than 60% of the drug within 2 hours. From 2 hours to 6 hours, there is little drug release due to the retarding action of the retarding element, limiting the drug release of the internal delayed release element. After 6 hours, a rapid release period is entered, up to 12 hours, which is a pulse release.
Experimental example 5.8 mm diameter artesunate pulse-release drug Release of Multi-Unit gastric-retentive tablet
Materials: the 8mm diameter artesunate pulse release multi-unit gastric retentive tablet prepared in reference example 1.
The method comprises the following steps: the artesunate pulse release multi-unit gastric retention tablets with the diameter of 8mm are respectively placed in stainless steel rotary baskets, hydrochloric acid solution with the pH value of 1 is used as a dissolution medium, 900mL of each dissolution cup is used as a dissolution medium, the rotary basket rotating speed is 75r/min, the water bath temperature is 37 ℃, 5mL of each sample is sampled at the sampling point at fixed time, the samples are respectively filtered through a microporous filter membrane with the diameter of 0.45 mu m, continuous filtrate is obtained, isothermal and equivalent fresh dissolution medium is supplemented, and the cumulative release amount of the artesunate pulse release multi-unit gastric retention tablets is measured by an ultraviolet spectrophotometer. Samples were taken at 0, 0.083, 0.167, 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, 14, 16, 20 and 24 hours, 5mL each, the samples were passed through a 0.45 μm microporous filter membrane, the subsequent filtrate was taken, and an isothermal equivalent amount of fresh dissolution medium was replenished, and the absorbance of the subsequent filtrate at 237nm was measured with an ultraviolet-visible spectrophotometer. Dissolution assays were performed with 3 8mm diameter artesunate pulse release multi-unit gastric retentive tablets. Comparing the measured filtrate with artesunate standard solution, calculating to obtain artesunate amount in the filtrate, and drawing artesunate release curve chart of artesunate pulse release multi-unit gastric retention tablet with diameter of 8 mm.
Results: the in vitro release profile of the 8mm diameter artesunate pulse release multi-unit gastric retentive tablet is shown in figure 6. The artesunate pulse release multi-unit gastric retention tablet with the diameter of 8mm can release more than 30% of the drug within 2 hours. From 2 hours to 8 hours, there is little drug release due to the retarding action of the retarding element, limiting the drug release of the internal delayed release element. After 8 hours, a rapid release period is entered, until 15 hours, which is a pulse release.
The experiment proves that the initial time of pulse release can be adjusted by adjusting the thickness of the blocking unit in the artesunate pulse release multi-unit gastric retentive tablet.
Experimental example 6 in vitro Floating time of artesunate pulse released multiple units gastric retentive tablet
Materials: a7 mm and 8mm diameter artesunate pulse release multi-unit gastric retentive tablet prepared as in example 1.
The method comprises the following steps: the artesunate pulse release multi-unit gastric retentive tablets with the diameters of 7mm and 8mm are respectively placed in a 250mL conical flask, hydrochloric acid solution with the pH value of 1 is used as a dissolution medium, the dissolution medium is placed in a shaking table for simulating gastric floating time, the rotation speed of the shaking table is 75rpm, the temperature is 37 ℃, and the floating condition of the tablet is observed in 0, 1, 2, 4, 6, 8, 12, 16 and 24 hours respectively.
Results: the 7mm diameter artesunate pulse release multi-unit gastric retentive tablet floats in vitro for up to 8 hours (figure 7). The 8mm diameter artesunate pulse release multi-unit gastric retentive tablet floats in vitro for up to 12 hours (figure 7). The artesunate pulse release multi-unit gastric retention tablets with the diameters of 7mm and 8mm have strong floating capacity and can be retained in the stomach for a long time.
Experimental example 7 in vivo residence time of artesunate immediate Release tablet
Materials: a6 mm diameter immediate release tablet of artesunate (with the addition of contrast agent barium sulphate to the drug-containing mixture) was prepared as in experimental example 1.
The method comprises the following steps: the artesunate quick-release tablet containing the contrast agent is pushed into the stomach of New Zealand rabbits by a catheter, and the retention condition of the artesunate quick-release tablet containing the contrast agent is observed by a portable X-ray machine at 0, 2, 4 and 6 hours respectively.
Results: x-ray shows that in the artesunate quick-release tablet containing barium sulfate, the whole tablet is black, and is shown in figure 8. With the extension of time, the artesunate quick-release tablet containing barium sulfate is gradually dissolved, and after the artesunate quick-release tablet stays in the body for 4 hours, the medicine is not seen, so that the artesunate quick-release tablet has no obvious gastric retention effect and is always at the bottom of the stomach.
Experimental example 8 in vivo residence time of artesunate gastric-retentive tablet
Materials: a7 mm and 8mm diameter artesunate pulse release multi-unit gastric retentive tablet prepared as in example 1, wherein the contrast agent barium sulfate was added to the drug-containing mixture.
The method comprises the following steps: the artesunate pulse release multi-unit gastric retention tablet containing the contrast agent is pushed into the stomach of New Zealand rabbits by a catheter, and the retention condition of the artesunate pulse release multi-unit gastric retention tablet containing the contrast agent is observed by a portable X-ray machine at different times.
Results: x-rays show that in the artesunate pulse release multi-unit gastric retentive tablet containing barium sulfate and with the diameter of 7mm, the quick release unit is a shaded part in the figure, and comprises a quick release unit and a delayed release unit, and is shown in figure 9. The 7mm diameter artesunate pulse release multicell gastroretentive tablet containing barium sulfate was gradually dissolved and at 0 to 2 hours, the shaded portion of the quick release unit was seen. After 4 hours, only the shadow of the delayed release unit was observed and after 12 hours of residence time in the body, the tablet disappeared, demonstrating that the 7mm diameter size artesunate pulse release multi-unit gastric retentive tablet containing barium sulfate was capable of residence in the stomach for 12 hours with a longer residence time than the artesunate immediate release tablet, which was associated with the encapsulation of the former by the blank layer retardation unit.
X-ray shows that in the 8mm diameter artesunate pulse release multi-unit gastric retentive tablet containing barium sulfate, the quick release part is a shaded part in the figure, and comprises a quick release unit and a delayed release unit, and is shown in figure 10. The 8mm diameter artesunate pulse release multicell gastroretentive tablet containing barium sulfate was gradually dissolved and at 0 to 2 hours, the shaded portion of the quick release unit was seen. At 2 hours, the quick release unit gradually dissolved and detached from the tablet. After 4 hours, only the shadow of the delayed release unit was observed and after 20 hours of residence in the body, the contrast of the sheet gradually decreased, demonstrating that the 8mm diameter artesunate pulse release multi-unit gastric retentive sheet containing barium sulfate was capable of residence in the stomach for 20 hours, with a residence time longer than the artesunate immediate release sheet and the 7mm diameter artesunate pulse release multi-unit gastric retentive sheet, which was related to the encapsulation of the former by the blocking unit.
In the future, a proper prescription and a proper process of the artesunate pulse release multi-unit gastric retention tablet can be selected according to the requirements of drug treatment so as to realize long-time retention.
Claims (10)
1. A multi-unit gastric retentive tablet for pulse releasing medicine comprises a quick release unit, a blocking unit, and a delayed release unit.
2. The application of pulse released medicine multi-unit gastric retention tablet in preparing medicine for treating hypertension, angina pectoris, bronchial asthma, rheumatism and diabetes includes fast release unit, retarding unit and delayed release unit.
3. The multi-unit gastroretentive tablet of claim 1 and the use of claim 2, wherein the quick release unit comprises a drug, a binder, a disintegrant, the retarding unit comprises a hydrophobic material, a binder, and the delayed release unit comprises a drug, a binder, a disintegrant.
4. The multi-unit gastroretentive tablet of claim 1 and the use of claim 2, wherein the drug in the quick release unit and the delayed release unit is the same drug.
5. The multi-unit gastroretentive tablet of claim 1 and the use of claim 2, wherein the binder and disintegrant in the quick release unit and the delayed release unit are the same.
6. The multi-unit gastroretentive sheet of claim 1 and the use of claim 2, wherein the delayed release unit is fully enclosed by the blocking unit, the quick release unit being outermost.
7. The multi-unit gastroretentive tablet of claim 1 and the use of claim 2, wherein the quick release unit releases the drug quickly in the stomach, the blocking unit dissolves slowly, the delayed release unit starts to release the drug after a certain delay, the effect of pulse release of the drug is obtained, and the drug is released in the stomach at all times.
8. The multi-unit gastroretentive tablet of claim 1 and the use of claim 2, wherein the volume of the quick release unit is designed according to the dose required for the first release of the drug, the volume of the blocking unit is designed according to the length of the delay time, and the volume of the delay release unit is designed according to the dose required for the pulsed release of the drug.
9. The multi-unit gastric retentive sheet of claim 1 and the use of claim 2, wherein the multi-unit gastric retentive sheet is retained in the stomach for a period of time exceeding 8 hours and the time for pulsatile release of the drug is greater than 6 hours.
10. The multi-unit gastroretentive sheet of claim 1 and the use of claim 2, wherein the preparation method of the multi-unit gastroretentive sheet is a 3D printing method.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311266922.2A CN117100712A (en) | 2023-09-28 | 2023-09-28 | Pulse release drug 3D printed multi-unit gastric retention sheet |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311266922.2A CN117100712A (en) | 2023-09-28 | 2023-09-28 | Pulse release drug 3D printed multi-unit gastric retention sheet |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117100712A true CN117100712A (en) | 2023-11-24 |
Family
ID=88796580
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311266922.2A Pending CN117100712A (en) | 2023-09-28 | 2023-09-28 | Pulse release drug 3D printed multi-unit gastric retention sheet |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117100712A (en) |
-
2023
- 2023-09-28 CN CN202311266922.2A patent/CN117100712A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101641517B1 (en) | Solid pharmaceutical formulations comprising BIBW 2992 | |
| CN109432039B (en) | Pharmaceutical dosage forms and uses thereof | |
| CA2822265C (en) | Process for the preparation of a pharmaceutical composition comprising a low soluble pharmaceutically active ingredient | |
| DK2313087T3 (en) | PHARMACEUTICAL DOSAGE FORM FOR IMMEDIATE RELEASE OF AN INDOLINE DERIVATIVE | |
| JP2012255017A (en) | Low dose entecavir formulation and use of the same | |
| CN116018131A (en) | Fast orodispersible tablet with inner cavity | |
| Priyanka et al. | A comprehensive review on pharmaceutical mini tablets | |
| AU2014224238B2 (en) | Formulations of organic compounds | |
| ES2693580T3 (en) | HIV treatment formulation of atazanavir and cobicistat | |
| CN114146062B (en) | Composition and preparation method and application thereof | |
| CN117100712A (en) | Pulse release drug 3D printed multi-unit gastric retention sheet | |
| TWI651084B (en) | Anti-tuberculosis stable pharmaceutical composition containing isoniazid amide (ISONIAZID) granules and rifapentine granules and preparation method thereof | |
| EP2915526B1 (en) | Pharmaceutical compositions comprising anagrelide | |
| JP2007023043A (en) | Controlled release medicinal composition of sleeping drug and method for producing the same | |
| CN114948883A (en) | Digoxin micro tablet and preparation method thereof | |
| Pattanayak et al. | Formulation and development of sustained release bilayer tablet for biphasic drug release: A novel approach in management of diabetes | |
| CN109721557A (en) | Letrozole crystalline substance II type solid matter and preparation method and its pharmaceutical composition and purposes | |
| US11672804B1 (en) | Pharmaceutical composition containing palbociclib and letrozole | |
| CN105636580A (en) | Pharmaceutical dosage forms containing sodium-1-[6-(morpholin-4-yl)pyrimidin-4-yl]-4-(1h-1,2,3-triazol-1-yl)-1h-pyrazol-5-olate | |
| Rajaram et al. | Chronomodulated Pulsatile Therapeutic System of Lisinopril for Blood Pressure on Early Morning Surge-Design and Quantification | |
| WO2021118403A1 (en) | System for delivering 2-ethyl-6-methyl-3-hydroxypyridine succinate for peroral administration | |
| WO2021252793A1 (en) | 3d laser sintering processes for improved drug delivery | |
| RU2207130C2 (en) | Hypnotic and sedative agent | |
| Patel | Formulation, Development and Evaluation of Expectorant Extended Release Tablet | |
| AU2015210331A1 (en) | Pharmaceutical dosage form for immediate release of an indolinone derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication |