CN101683325A - Cydiodine buccal tablets and preparation method thereof - Google Patents
Cydiodine buccal tablets and preparation method thereof Download PDFInfo
- Publication number
- CN101683325A CN101683325A CN200810223386A CN200810223386A CN101683325A CN 101683325 A CN101683325 A CN 101683325A CN 200810223386 A CN200810223386 A CN 200810223386A CN 200810223386 A CN200810223386 A CN 200810223386A CN 101683325 A CN101683325 A CN 101683325A
- Authority
- CN
- China
- Prior art keywords
- cydiodine
- buccal tablet
- component
- binding agent
- cyclodextrin
- 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
- 239000006189 buccal tablet Substances 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 claims abstract description 30
- 239000000945 filler Substances 0.000 claims abstract description 15
- 239000003814 drug Substances 0.000 claims abstract description 11
- 239000000314 lubricant Substances 0.000 claims abstract description 11
- 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 abstract description 7
- 229930195725 Mannitol Natural products 0.000 claims abstract description 7
- 229920002472 Starch Polymers 0.000 claims abstract description 7
- 239000000594 mannitol Substances 0.000 claims abstract description 7
- 235000010355 mannitol Nutrition 0.000 claims abstract description 7
- 238000002156 mixing Methods 0.000 claims abstract description 7
- 239000008107 starch Substances 0.000 claims abstract description 7
- 235000019698 starch Nutrition 0.000 claims abstract description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 6
- 238000005303 weighing Methods 0.000 claims abstract description 6
- 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 abstract description 5
- 239000008101 lactose Substances 0.000 claims abstract description 5
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims abstract description 4
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000811 xylitol Substances 0.000 claims abstract description 4
- 235000010447 xylitol Nutrition 0.000 claims abstract description 4
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims abstract description 4
- 229960002675 xylitol Drugs 0.000 claims abstract description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims abstract description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims abstract description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims abstract description 3
- 229920001353 Dextrin Polymers 0.000 claims abstract description 3
- 239000004375 Dextrin Substances 0.000 claims abstract description 3
- 239000004386 Erythritol Substances 0.000 claims abstract description 3
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000005715 Fructose Substances 0.000 claims abstract description 3
- 229930091371 Fructose Natural products 0.000 claims abstract description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 claims abstract description 3
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 3
- 235000019425 dextrin Nutrition 0.000 claims abstract description 3
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims abstract description 3
- 235000019414 erythritol Nutrition 0.000 claims abstract description 3
- 229940009714 erythritol Drugs 0.000 claims abstract description 3
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 3
- 239000011780 sodium chloride Substances 0.000 claims abstract description 3
- 239000000600 sorbitol Substances 0.000 claims abstract description 3
- 235000010356 sorbitol Nutrition 0.000 claims abstract description 3
- 229940046011 buccal tablet Drugs 0.000 claims description 43
- 210000004556 brain Anatomy 0.000 claims description 23
- 239000011230 binding agent Substances 0.000 claims description 18
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 17
- 229920000858 Cyclodextrin Polymers 0.000 claims description 16
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 16
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 12
- 229910052740 iodine Inorganic materials 0.000 claims description 12
- 239000011630 iodine Substances 0.000 claims description 12
- 239000007779 soft material Substances 0.000 claims description 11
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 10
- 239000004615 ingredient Substances 0.000 claims description 10
- 239000008187 granular material Substances 0.000 claims description 9
- -1 hydroxyl isomaltulose Chemical compound 0.000 claims description 9
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 9
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 9
- 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 9
- 239000000203 mixture Substances 0.000 claims description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 9
- 235000019359 magnesium stearate Nutrition 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 7
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 6
- 108010011485 Aspartame Proteins 0.000 claims description 5
- 239000000605 aspartame Substances 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
- 235000010357 aspartame Nutrition 0.000 claims description 5
- 229960003438 aspartame Drugs 0.000 claims description 5
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 claims description 3
- 229920001450 Alpha-Cyclodextrin Polymers 0.000 claims description 3
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 claims description 3
- 229940043377 alpha-cyclodextrin Drugs 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 claims description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 claims description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims 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 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- 239000004141 Sodium laurylsulphate Substances 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 235000006092 Stevia rebaudiana Nutrition 0.000 claims description 2
- 241000543392 Symplocos Species 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- 235000010489 acacia gum Nutrition 0.000 claims description 2
- 239000001785 acacia senegal l. willd gum Substances 0.000 claims description 2
- 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 2
- 239000001361 adipic acid Substances 0.000 claims description 2
- 235000011037 adipic acid Nutrition 0.000 claims description 2
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 claims description 2
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 2
- 239000008116 calcium stearate Substances 0.000 claims description 2
- 235000013539 calcium stearate Nutrition 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 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 claims description 2
- 239000000686 essence Substances 0.000 claims description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 238000004108 freeze drying Methods 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 claims description 2
- 229940080345 gamma-cyclodextrin Drugs 0.000 claims description 2
- 239000008172 hydrogenated vegetable oil Substances 0.000 claims description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 238000005498 polishing Methods 0.000 claims description 2
- 229940093429 polyethylene glycol 6000 Drugs 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 238000007670 refining Methods 0.000 claims description 2
- 229940085605 saccharin sodium Drugs 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 239000002002 slurry Substances 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000004334 sorbic acid Substances 0.000 claims description 2
- 229940075582 sorbic acid Drugs 0.000 claims description 2
- 235000010199 sorbic acid Nutrition 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims 1
- 230000001476 alcoholic effect Effects 0.000 claims 1
- 229930006000 Sucrose Natural products 0.000 abstract description 6
- 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 abstract description 6
- 239000005720 sucrose Substances 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 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 abstract 4
- 229960003310 sildenafil Drugs 0.000 abstract 2
- SERLAGPUMNYUCK-DCUALPFSSA-N 1-O-alpha-D-glucopyranosyl-D-mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O SERLAGPUMNYUCK-DCUALPFSSA-N 0.000 abstract 1
- 229920000881 Modified starch Polymers 0.000 abstract 1
- 239000000905 isomalt Substances 0.000 abstract 1
- 235000010439 isomalt Nutrition 0.000 abstract 1
- HPIGCVXMBGOWTF-UHFFFAOYSA-N isomaltol Natural products CC(=O)C=1OC=CC=1O HPIGCVXMBGOWTF-UHFFFAOYSA-N 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- JVFGXECLSQXABC-UHFFFAOYSA-N ac1l3obq Chemical compound O1C(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(O)C2O)C(COCC(O)C)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC2C(O)C(O)C1OC2COCC(C)O JVFGXECLSQXABC-UHFFFAOYSA-N 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000002574 poison Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to cydiodine buccal tablets and a preparation method thereof. The cydiodine buccal tablets comprise the following components in percentage by mass: 0.1 to 6 percent of cydiodine,0.5 to 5 percent of sildenafil, 0 to 2 percent of lubricant, and 84.4 to 98.5 percent of filler. The filler is one or combination of the following components: mannitol, lactose, xylitol, sorbitol, erythritol, fructose, isomalt, dextrin, microcrystalline cellulose, starch, pregelatinized starch, sodium chloride. The invention also proposes a method for preparing the buccal tablets, which comprisesthe following steps: preparing cydiodine and sildenafil; weighing the components according to proportioning rate, granulating and mixing the components; determining the content of every component inmixed medicaments and calculating the weight difference of products; and tabletting the mixed medicament. In the process of treating oral or other diseases, the cydiodine buccal tablets prepared by the method have the advantages of reducing the amount of sucrose taken in by patients and reducing harm to the patients.
Description
Technical field
The present invention relates to a kind of Cydiodine buccal tablet and preparation method thereof, belong to cydiodine goods field.
Background technology
Iodine is used the history in existing more than 100 year as disinfectant, and it all has or not optionally killing action to antibacterial, fungus, virus etc.Be made into the iodo-cydiodine of molecular state, this I by the inclusion technique of cyclodextrin
2Physics, the chemical property of clathrate relatively stable, do not have I yet
2Zest and stink, can be made into various preparations, extensive use and treatment oral cavity, laryngopharyngeal diseases.
China Poison ﹠ Medicine Inst. of Military Medicial Sciences Academy has applied for the patent (patent No.: ZL90106682.6) of " compound xidi iodine sucked tablet and preparation method thereof " August 16 nineteen ninety, use sucrose as filler in this patent in the prescription, make tablet have comparatively good mouldability, can well regulate mouthfeel again, extensive in clinical practice, determined curative effect.
Yet along with the raising day by day of living standard, the cases relevant with diet such as obesity, diabetes constantly rise, and make people pay attention to the safety of diet, medication more.For this reason, increased the intake of patient's sucrose as the xidi iodine sucked tablet of filler, and be not suitable for patients such as obesity, diabetes and take, brought potential harm to patient's body with sucrose.
Summary of the invention
Technical problem to be solved by this invention provides a kind of Sugarless type Cydiodine buccal tablet, in treatment oral cavity, laryngopharyngeal diseases, reduces the sucrose amount that the user takes in, and reduces the potential hazard that brings to the patient.
The technical scheme that the present invention solves the problems of the technologies described above is as follows: a kind of Cydiodine buccal tablet, its composition comprise cydiodine, west ground brain and lubricant, it is characterized in that: also comprise filler, according to the mass percent meter, the ratio of each component is:
Cydiodine: 0.1～6%
Ground, west brain: 0.5～5%
Lubricant: 0～2%
Filler: 84.4～98.5%
Wherein said filler is one or more the combination in the following ingredients:
Mannitol, lactose, xylitol, sorbitol, erythritol, fructose, hydroxyl isomaltulose, dextrin, microcrystalline Cellulose, starch, pre-paying starch, sodium chloride.
The invention has the beneficial effects as follows: employing mannitol etc. can reduce the sucrose amount that the user takes in as filler in treatment oral cavity, laryngopharyngeal diseases, reduce the potential hazard that brings to the patient.
On the basis of technique scheme, the present invention can also do following improvement.
Further, according to the mass percent meter, the component of described Cydiodine buccal tablet also comprises 0～3% correctives, and described correctives is one or more the combination in the following ingredients:
Sweetleaf centautin, aspartame, glucide, saccharin sodium, compound essence, citric acid, tartaric acid, fumaric acid, maleic acid, sorbic acid, Oleum menthae, Borneolum Syntheticum.
Further, according to the mass percent meter, the component of described Cydiodine buccal tablet also comprises 0～0.5% binding agent, and described binding agent is one or more the combination in the following ingredients:
Starch slurry, maltose, arabic gum, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose (HPMC), ethyl cellulose, polyvinylpyrrolidone.
Further, according to the mass percent meter, described cydiodine the ratio of each component is:
Iodine: 3～20%
Potassium iodide: 1.5～15%
Cyclodextrin: 65～95.5%
Further, according to the mass percent meter, ground, described west brain the ratio of each component is:
Mentholum: 3～30%
Cyclodextrin: 70～97%
Further, described cyclodextrin is one or more in the following ingredients:
Alpha-cyclodextrin, beta-schardinger dextrin-, gamma-cyclodextrin, cyclodextrin derivative.Cyclodextrin derivative wherein can be hydroxypropyl alpha-cyclodextrin, hydroxypropyl, hydroxypropyl gamma-cyclodextrin, methylol beta-schardinger dextrin-, dimethyl-, iodine butyl ether beta-schardinger dextrin-, maltose beta-schardinger dextrin-etc.
Further, described lubricant is one or more the combination in the following ingredients:
Stearic acid, magnesium stearate, calcium stearate, zinc stearate, refining hydrogenated vegetable oil, Macrogol 4000, polyethylene glycol 6000, Pulvis Talci, sodium lauryl sulphate, Stepanol MG, adipic acid, micropowder silica gel.
Adopt the beneficial effect of above-mentioned further scheme to be: each component in the buccal tablet can have multiple choices, has increased the source of raw material greatly, makes the preparation of buccal tablet also reduce cost of drugs more easily simultaneously.
The invention allows for a kind of method for preparing the described Cydiodine buccal tablet of claim 1, this method may further comprise the steps:
1) preparation cydiodine and ground, west brain;
2) take by weighing each component according to the described proportioning of claim 1, component is granulated and mixing;
3) measure each components contents in the mixed medicine and calculate the weight differential of product;
4) with mixed medicine tabletting.
Based on the above method, the present invention can also do following improvement.
Further, described cydiodine and ground, west brain adopt the cyclodextrin inclusion technique preparation, and described cyclodextrin inclusion technique can be saturated water solution method or polishing or freeze-drying.
Further, described component also comprises binding agent, described component is granulated and is mixed specifically may further comprise the steps:
A. with cydiodine and filler uniform mixing;
B. in the mixture of cydiodine and filler, add the solution of an amount of binding agent, make soft material;
C. described soft material is made granule, and with particle drying;
D. binding agent, lubricant and ground, west brain are mixed with described dried uniform particles.
Further, described component can also comprise correctives, in described steps d correctives, Xi Dinao, lubricant and binding agent is mixed with described dried uniform particles.
Further, the solution of described binding agent, its solvent are that mass percent concentration is 10～80% ethanol water.
Further, the solution of described binding agent is that mass percent concentration is 3% hydroxypropyl methylcellulose aqueous solution.
Further, particulate 10 orders～30 orders that are of a size of made of described soft material.
Further, the granule that described soft material is made carries out drying under 40～60 ℃ temperature.
Further, described component also comprises one or both in correctives, the binding agent, described component is granulated and mixes specifically be meant each component made granule, and uniform mixing.Described granular size can be 60 orders.
Adopt the beneficial effect of above-mentioned further scheme to be: for the Cydiodine buccal tablet of different component provides different preparation methoies, be that the preparation of medicine is faster, better effects if.
The specific embodiment
Below in conjunction with accompanying drawing principle of the present invention and feature are described, institute gives an actual example and only is used to explain the present invention, is not to be used to limit scope of the present invention.
Embodiment 1
Each component and the weight of Cydiodine buccal tablet are:
Cydiodine 8g, ground, west brain 18g, lactose 400g, magnesium stearate 4g, mass percent concentration are 3% HPMC (hydroxypropyl methylcellulose) aqueous solution.
Wherein, the component of cydiodine and weight are: iodine 6.97g, potassium iodide 5.06g, β～cyclodextrin 35g.The component and the weight of ground, west brain are: Mentholum 5.5g, beta-schardinger dextrin-55g.
The preparation method of Cydiodine buccal tablet:
1) preparation cydiodine and ground, west brain: described cydiodine and ground, west brain adopt the cyclodextrin inclusion technique preparation, and described cyclodextrin inclusion technique is a saturated water solution method.
2) press group component with cydiodine and lactose with equivalent incremental method mix homogeneously after, adding an amount of mass percent concentration is the 3%HPMC aqueous solution, makes soft material;
3) described soft material is made 14 purpose granules, and dry under 60 ℃ of temperature;
4) take by weighing west ground brain and magnesium stearate by group component, and with described dried granule mix homogeneously;
5) measure each components contents in the mixed medicine and calculate the weight differential of product;
6) use the circular flat oblique impact tabletting of Φ 11mm with mixed sample tabletting.
Embodiment 2
Each component and the weight of Cydiodine buccal tablet are:
Cydiodine 8g, mannitol 400g, ground, west brain 18g, aspartame 2g, magnesium stearate 4g, mass percent concentration are the 3%HPMC aqueous solution.
Wherein, the component of cydiodine and ground, west brain and weight are with embodiment 1.
The preparation method of Cydiodine buccal tablet:
1) the 1st step with embodiment 1 is identical;
2) press group component with cydiodine and mannitol with equivalent incremental method mix homogeneously after, adding an amount of mass percent concentration is the 3%HPMC aqueous solution, makes soft material;
3) the 3rd step with embodiment 1 is identical;
4) take by weighing Xi Dinao, aspartame and magnesium stearate by group component, and with described dried granule mix homogeneously;
5) following steps are identical with the 5th, 6 steps of embodiment 1.
Embodiment 3
Each component and the weight of Cydiodine buccal tablet are:
Cydiodine 8g, xylitol 80g, ground, west brain 18g, hydroxyl isomaltulose 320g, magnesium stearate 4g.
Wherein, the component of cydiodine and ground, west brain and weight are with embodiment 1.
The preparation method of Cydiodine buccal tablet:
1) the 1st step with embodiment 1 is identical;
2) taking by weighing each component according to quantity also screens with 60 mesh sieves;
The 60 purpose components that 3) will filter out equivalent incremental method mix homogeneously;
4) following steps are identical with the 5th, 6 steps of embodiment 1.
Embodiment 4
Each component and the weight of Cydiodine buccal tablet are:
Cydiodine 8g, mannitol 400g, aspartame 2g, ground, west brain 18g, magnesium stearate 4g.
Wherein, the component of cydiodine and ground, west brain and weight are with embodiment 1.
The preparation method of Cydiodine buccal tablet is identical with the preparation method of embodiment 3.
The stability of the Cydiodine buccal tablet of above embodiment under different affecting factors compares:
The Cydiodine buccal tablet of above embodiment is carried out simple and easy aluminium strip packing, under the varying environment condition, placed 10 days then, investigate the situation of change of its content of iodine.Described different environmental condition is respectively: ((illumination is 4500Lx ± 500Lx) to high humidity for 90%RH ± 5%RH), high temperature (60 ℃), high light.Experimental study result such as following table:
Result of the test shows Cydiodine buccal tablet of the present invention after placing 10 days under high temperature, high humidity, the high light condition, and content of iodine is all qualified, and is wherein best according to the Cydiodine buccal tablet effect of embodiment 2 preparations.
The Cydiodine buccal tablet of embodiment 2 preparations is reached accelerated stability test for a long time.
Experimental condition:
1) accelerated test: press commercially available back, it is that 40 ℃ ± 2 ℃, relative humidity are in the water isolation type constant incubator of 75% ± 5%RH that Cydiodine buccal tablet is placed on temperature, in sampling in the 1st, 2,3,6 month, carries out content of iodine and measures;
2) long term test: press commercially available back, it is to preserve under 25 ℃ ± 2 ℃, the condition of relative humidity 60% ± 10%RH that Cydiodine buccal tablet is placed on temperature.In sampling in the 0th, 3,6,9,12 month, carry out content of iodine and measure.Experimental study result such as following table:
Stability accelerated test result:
Above result of the test shows, Cydiodine buccal tablet of the present invention, and its stability is better, and content of iodine reduces slow.
The above only is preferred embodiment of the present invention, and is in order to restriction the present invention, within the spirit and principles in the present invention not all, any modification of being done, is equal to replacement, improvement etc., all should be included within protection scope of the present invention.
Claims (16)
1. Cydiodine buccal tablet, its composition comprise cydiodine, west ground brain and lubricant, it is characterized in that: also comprise filler, according to the mass percent meter, the ratio of each component is:
Cydiodine: 0.1～6%
Ground, west brain: 0.5～5%
Lubricant: 0～2%
Filler: 84.4～98.5%
Wherein said filler is one or more the combination in the following ingredients:
Mannitol, lactose, xylitol, sorbitol, erythritol, fructose, hydroxyl isomaltulose, dextrin, microcrystalline Cellulose, starch, pre-paying starch, sodium chloride.
2. Cydiodine buccal tablet according to claim 1 is characterized in that: according to the mass percent meter, the component of described Cydiodine buccal tablet also comprises 0～3% correctives, and described correctives is one or more the combination in the following ingredients:
Sweetleaf centautin, aspartame, glucide, saccharin sodium, compound essence, citric acid, tartaric acid, fumaric acid, maleic acid, sorbic acid, Oleum menthae, Borneolum Syntheticum.
3. Cydiodine buccal tablet according to claim 1 and 2 is characterized in that: according to the mass percent meter, the component of described Cydiodine buccal tablet also comprises 0～0.5% binding agent, and described binding agent is one or more the combination in the following ingredients:
Starch slurry, maltose, arabic gum, methylcellulose, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, ethyl cellulose, polyvinylpyrrolidone.
4. Cydiodine buccal tablet according to claim 1 is characterized in that: according to the mass percent meter, described cydiodine the ratio of each component is:
Iodine: 3～20%
Potassium iodide: 1.5～15%
Cyclodextrin: 65～95.5%.
5. Cydiodine buccal tablet according to claim 1 is characterized in that: according to the mass percent meter, ground, described west brain the ratio of each component is:
Mentholum: 3～30%
Cyclodextrin: 70～97%.
6. according to claim 4 or 5 described Cydiodine buccal tablets, it is characterized in that: described cyclodextrin is one or more in the following ingredients:
Alpha-cyclodextrin, beta-schardinger dextrin-, gamma-cyclodextrin, cyclodextrin derivative.
7. Cydiodine buccal tablet according to claim 1 is characterized in that: described lubricant is one or more the combination in the following ingredients:
Stearic acid, magnesium stearate, calcium stearate, zinc stearate, refining hydrogenated vegetable oil, Macrogol 4000, polyethylene glycol 6000, Pulvis Talci, sodium lauryl sulphate, Stepanol MG, adipic acid, micropowder silica gel.
8. method for preparing the described Cydiodine buccal tablet of claim 1, it is characterized in that: this method may further comprise the steps:
1) preparation cydiodine and ground, west brain;
2) take by weighing each component according to the described proportioning of claim 1, component is granulated and mixing;
3) measure each components contents in the mixed medicine and calculate the weight differential of product;
4) with mixed medicine tabletting.
9. the method for preparing Cydiodine buccal tablet according to claim 8 is characterized in that: described cydiodine and ground, west brain adopt the cyclodextrin inclusion technique preparation, and described cyclodextrin inclusion technique can be saturated water solution method or polishing or freeze-drying.
10. the method for preparing Cydiodine buccal tablet according to claim 8 is characterized in that: described component also comprises binding agent, described component is granulated and is mixed specifically may further comprise the steps:
A. with cydiodine and filler uniform mixing;
B. in the mixture of cydiodine and filler, add the solution of an amount of binding agent, make soft material;
C. described soft material is made granule, and with particle drying;
D. binding agent, lubricant and ground, west brain are mixed with described dried uniform particles.
11. the method for preparing Cydiodine buccal tablet according to claim 10 is characterized in that: described component can also comprise correctives, in described steps d correctives, Xi Dinao, lubricant and binding agent is mixed with described dried uniform particles.
12. according to claim 10 or the 11 described methods that prepare Cydiodine buccal tablet, it is characterized in that: the solution of described binding agent, its solvent are that mass percent concentration is 10～80% alcoholic acid aqueous solution.
13. according to claim 10 or the 11 described methods that prepare Cydiodine buccal tablet, it is characterized in that: the solution of described binding agent is that mass percent concentration is the aqueous solution of 3% hydroxypropyl methylcellulose.
14., it is characterized in that: particulate 10 orders～30 orders that are of a size of that described soft material is made according to claim 10 or the 11 described methods that prepare Cydiodine buccal tablet.
15. according to claim 10 or the 11 described methods that prepare Cydiodine buccal tablet, it is characterized in that: the granule that described soft material is made carries out drying under 40～60 ℃ temperature.
16. the method for preparing Cydiodine buccal tablet according to claim 8 is characterized in that: described component also comprises one or both in correctives, the binding agent, described component is granulated and mixes specifically be meant each component made granule, and uniform mixing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810223386A CN101683325A (en) | 2008-09-28 | 2008-09-28 | Cydiodine buccal tablets and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810223386A CN101683325A (en) | 2008-09-28 | 2008-09-28 | Cydiodine buccal tablets and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101683325A true CN101683325A (en) | 2010-03-31 |
Family
ID=42046860
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200810223386A Pending CN101683325A (en) | 2008-09-28 | 2008-09-28 | Cydiodine buccal tablets and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101683325A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103251002A (en) * | 2013-05-17 | 2013-08-21 | 邹桂怀 | Water shield buccal tablet and preparation method thereof |
| CN103385894A (en) * | 2013-07-29 | 2013-11-13 | 李春艳 | Buccal tablets prepared from ganoderma broken-down wall spore powder |
| CN104337786A (en) * | 2014-11-08 | 2015-02-11 | 山东新时代药业有限公司 | Cetyl pyridinium chloride buccal tablet |
| CN107517963A (en) * | 2017-08-31 | 2017-12-29 | 山东省农业科学院家禽研究所 | A kind of high stability BETA Cyclodextrin Inclusion Compound of Iodine powder and its preparation, application method |
-
2008
- 2008-09-28 CN CN200810223386A patent/CN101683325A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103251002A (en) * | 2013-05-17 | 2013-08-21 | 邹桂怀 | Water shield buccal tablet and preparation method thereof |
| CN103251002B (en) * | 2013-05-17 | 2014-06-04 | 邹桂怀 | Water shield buccal tablet and preparation method thereof |
| CN103385894A (en) * | 2013-07-29 | 2013-11-13 | 李春艳 | Buccal tablets prepared from ganoderma broken-down wall spore powder |
| CN104337786A (en) * | 2014-11-08 | 2015-02-11 | 山东新时代药业有限公司 | Cetyl pyridinium chloride buccal tablet |
| CN107517963A (en) * | 2017-08-31 | 2017-12-29 | 山东省农业科学院家禽研究所 | A kind of high stability BETA Cyclodextrin Inclusion Compound of Iodine powder and its preparation, application method |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5759113B2 (en) | Extract powder combination tablets | |
| JP5610865B2 (en) | Solid preparation | |
| CN101647785B (en) | Gliclazide sustained-release tablet and preparation method thereof | |
| CN113575958B (en) | Health care composition and capsule for improving immunity and preparation method thereof | |
| CN101683325A (en) | Cydiodine buccal tablets and preparation method thereof | |
| CN101053572A (en) | Citicoline enteric coated preparation and its preparation method | |
| CN111214443A (en) | Bismuth potassium citrate granules and preparation method thereof | |
| CN101548972A (en) | Solid pharmaceutical composition containing repaglinide | |
| CN107582536A (en) | A kind of CBS oral cavity adherent emplastrum and preparation method thereof | |
| CN106074681A (en) | A kind of dispersible tablets of Chinese medicine of anti-hepatic fibrosis and preparation method thereof | |
| CN100584353C (en) | A kind of pharmaceutical composition for treating oral ulcer and preparation method thereof | |
| JPWO2005084703A1 (en) | Sustained release oral composition | |
| CN109010514A (en) | Composition, health care product and the preparation method of altitude sickness prevention | |
| CN101120928B (en) | Vitamin K1 orally disintegrating tablets preparation and preparation method thereof | |
| WO2013177833A1 (en) | Dysmenorrhea-treating medicament and preparation method therefor | |
| CN100542526C (en) | Drug chewable tablet for antipyretic and pain relief and preparation method thereof | |
| CN1739666A (en) | Capsule prepn for treating laryngopharyngitis and tonsillitis and its prepn process | |
| CN102908328A (en) | Fudosteine composition tablet and preparation method thereof | |
| CN115252547A (en) | Lingzhu powder dry suspension and its preparation method and use | |
| CN101919864A (en) | Tolvaptan medicinal composition and preparation method thereof | |
| CN102600093B (en) | Moxifloxacin tablet and preparation method thereof | |
| CN1660107A (en) | Compound methoxyphenamine oral solid preparation and preparation method thereof | |
| CN110575440A (en) | Preparation method of calcium carbonate pharmaceutical composition | |
| CN108159008A (en) | The preparation method of Valsartan chewable tablets | |
| CN101091738A (en) | Composition of medicine in use for treating cardiovascular disease and cerebrovascular disease, and preparation method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20100331 |