CN113712928A - 经口腔粘膜吸收的溴夫定药物 - Google Patents
经口腔粘膜吸收的溴夫定药物 Download PDFInfo
- Publication number
- CN113712928A CN113712928A CN202111147785.1A CN202111147785A CN113712928A CN 113712928 A CN113712928 A CN 113712928A CN 202111147785 A CN202111147785 A CN 202111147785A CN 113712928 A CN113712928 A CN 113712928A
- Authority
- CN
- China
- Prior art keywords
- brivudine
- oral mucosa
- tablet
- preparation
- absorbed
- 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
- 229960001169 brivudine Drugs 0.000 title claims abstract description 76
- ODZBBRURCPAEIQ-PIXDULNESA-N helpin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(\C=C\Br)=C1 ODZBBRURCPAEIQ-PIXDULNESA-N 0.000 title claims abstract description 76
- 239000003814 drug Substances 0.000 title claims abstract description 42
- 210000002200 mouth mucosa Anatomy 0.000 title claims abstract description 26
- 229940079593 drug Drugs 0.000 title claims description 16
- 238000002360 preparation method Methods 0.000 claims description 33
- 239000003826 tablet Substances 0.000 claims description 33
- 239000006187 pill Substances 0.000 claims description 15
- 239000000843 powder Substances 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 10
- 239000000853 adhesive Substances 0.000 claims description 8
- 230000001070 adhesive effect Effects 0.000 claims description 8
- 239000010408 film Substances 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 6
- 239000004615 ingredient Substances 0.000 claims description 6
- 239000007962 solid dispersion Substances 0.000 claims description 5
- 239000002552 dosage form Substances 0.000 claims description 4
- 238000007908 dry granulation Methods 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 3
- 238000005550 wet granulation Methods 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 2
- -1 micropowder Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 238000010521 absorption reaction Methods 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 7
- 210000000214 mouth Anatomy 0.000 abstract description 6
- 230000007794 irritation Effects 0.000 abstract 1
- 238000002156 mixing Methods 0.000 description 31
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 24
- 229920002472 Starch Polymers 0.000 description 22
- 239000008107 starch Substances 0.000 description 22
- 229940032147 starch Drugs 0.000 description 22
- 235000019698 starch Nutrition 0.000 description 22
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 16
- 239000008108 microcrystalline cellulose Substances 0.000 description 16
- 229940016286 microcrystalline cellulose Drugs 0.000 description 16
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 16
- 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 description 14
- 229920000881 Modified starch Polymers 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 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 description 13
- 239000008101 lactose Substances 0.000 description 13
- 239000006190 sub-lingual tablet Substances 0.000 description 13
- 235000019359 magnesium stearate Nutrition 0.000 description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
- 229940098466 sublingual tablet Drugs 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 238000007873 sieving Methods 0.000 description 10
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 9
- 238000001035 drying Methods 0.000 description 9
- 229920002785 Croscarmellose sodium Polymers 0.000 description 8
- 239000004376 Sucralose Substances 0.000 description 8
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 8
- 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 8
- 229960001681 croscarmellose sodium Drugs 0.000 description 8
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 8
- 235000019408 sucralose Nutrition 0.000 description 8
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 8
- 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 description 7
- 208000007514 Herpes zoster Diseases 0.000 description 7
- 229930195725 Mannitol Natural products 0.000 description 7
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 7
- 208000002193 Pain Diseases 0.000 description 7
- 235000021355 Stearic acid Nutrition 0.000 description 7
- 239000000594 mannitol Substances 0.000 description 7
- 235000010355 mannitol Nutrition 0.000 description 7
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 7
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 7
- 229940023488 pill Drugs 0.000 description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- 239000008117 stearic acid Substances 0.000 description 7
- 239000000203 mixture Substances 0.000 description 6
- 210000004877 mucosa Anatomy 0.000 description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 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 description 5
- 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 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000002671 adjuvant Substances 0.000 description 5
- 210000005178 buccal mucosa Anatomy 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 241000701085 Human alphaherpesvirus 3 Species 0.000 description 4
- 230000000202 analgesic effect Effects 0.000 description 4
- 239000003443 antiviral agent Substances 0.000 description 4
- 239000006189 buccal tablet Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 235000011187 glycerol Nutrition 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- 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 4
- 210000004185 liver Anatomy 0.000 description 4
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 4
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 4
- 229940069328 povidone Drugs 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000004408 titanium dioxide Substances 0.000 description 4
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- 206010067484 Adverse reaction Diseases 0.000 description 3
- 229920002307 Dextran Polymers 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 239000004386 Erythritol Substances 0.000 description 3
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 239000005913 Maltodextrin Substances 0.000 description 3
- 229920002774 Maltodextrin Polymers 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 description 3
- 229920002125 Sokalan® Polymers 0.000 description 3
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 description 3
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 3
- 230000006838 adverse reaction Effects 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 239000000783 alginic acid Substances 0.000 description 3
- 229960001126 alginic acid Drugs 0.000 description 3
- 150000004781 alginic acids Chemical class 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 229940046011 buccal tablet Drugs 0.000 description 3
- 229960001631 carbomer Drugs 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 235000019414 erythritol Nutrition 0.000 description 3
- 229940009714 erythritol Drugs 0.000 description 3
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 3
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 3
- 239000003292 glue Substances 0.000 description 3
- 231100000334 hepatotoxic Toxicity 0.000 description 3
- 230000003082 hepatotoxic effect Effects 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 229940035034 maltodextrin Drugs 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 235000010413 sodium alginate Nutrition 0.000 description 3
- 239000000661 sodium alginate Substances 0.000 description 3
- 229940005550 sodium alginate Drugs 0.000 description 3
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229940013618 stevioside Drugs 0.000 description 3
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 description 3
- 235000019202 steviosides Nutrition 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000000080 wetting agent Substances 0.000 description 3
- 239000000811 xylitol Substances 0.000 description 3
- 235000010447 xylitol Nutrition 0.000 description 3
- 229960002675 xylitol Drugs 0.000 description 3
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 3
- 229910002012 Aerosil® Inorganic materials 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108010011485 Aspartame Proteins 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- UDIPTWFVPPPURJ-UHFFFAOYSA-M Cyclamate Chemical compound [Na+].[O-]S(=O)(=O)NC1CCCCC1 UDIPTWFVPPPURJ-UHFFFAOYSA-M 0.000 description 2
- 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 description 2
- 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 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 229920003083 Kollidon® VA64 Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920003081 Povidone K 30 Polymers 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 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 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 239000000605 aspartame Substances 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- 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 description 2
- 229960003438 aspartame Drugs 0.000 description 2
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229960000913 crospovidone Drugs 0.000 description 2
- 239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 238000010579 first pass effect Methods 0.000 description 2
- 239000001341 hydroxy propyl starch Substances 0.000 description 2
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229940057995 liquid paraffin Drugs 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 239000002777 nucleoside Substances 0.000 description 2
- 150000003833 nucleoside derivatives Chemical class 0.000 description 2
- 239000007935 oral tablet Substances 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 2
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 2
- 238000010298 pulverizing process Methods 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 235000019204 saccharin Nutrition 0.000 description 2
- 229940081974 saccharin Drugs 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 2
- 229960001462 sodium cyclamate Drugs 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- 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 description 1
- LQIAZOCLNBBZQK-UHFFFAOYSA-N 1-(1,2-Diphosphanylethyl)pyrrolidin-2-one Chemical compound PCC(P)N1CCCC1=O LQIAZOCLNBBZQK-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- ANRFTTXEGCYVMQ-UHFFFAOYSA-L C(C=CC(=O)[O-])(=O)[O-].[Na+].C(CCCCCCCCCCCCCCCCC)(=O)O.[Na+] Chemical compound C(C=CC(=O)[O-])(=O)[O-].[Na+].C(CCCCCCCCCCCCCCCCC)(=O)O.[Na+] ANRFTTXEGCYVMQ-UHFFFAOYSA-L 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 201000006082 Chickenpox Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 206010061598 Immunodeficiency Diseases 0.000 description 1
- 208000004404 Intractable Pain Diseases 0.000 description 1
- 206010023129 Jaundice cholestatic Diseases 0.000 description 1
- 229920003085 Kollidon® CL Polymers 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 201000005267 Obstructive Jaundice Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229920003072 Plasdone™ povidone Polymers 0.000 description 1
- HDSBZMRLPLPFLQ-UHFFFAOYSA-N Propylene glycol alginate Chemical compound OC1C(O)C(OC)OC(C(O)=O)C1OC1C(O)C(O)C(C)C(C(=O)OCC(C)O)O1 HDSBZMRLPLPFLQ-UHFFFAOYSA-N 0.000 description 1
- HDOVUKNUBWVHOX-QMMMGPOBSA-N Valacyclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCOC(=O)[C@@H](N)C(C)C)C=N2 HDOVUKNUBWVHOX-QMMMGPOBSA-N 0.000 description 1
- 206010046980 Varicella Diseases 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940124397 anti-herpes virus drug Drugs 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-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)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 WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 235000010410 calcium alginate Nutrition 0.000 description 1
- 239000000648 calcium alginate Substances 0.000 description 1
- 229960002681 calcium alginate Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- OKHHGHGGPDJQHR-YMOPUZKJSA-L calcium;(2s,3s,4s,5s,6r)-6-[(2r,3s,4r,5s,6r)-2-carboxy-6-[(2r,3s,4r,5s,6r)-2-carboxylato-4,5,6-trihydroxyoxan-3-yl]oxy-4,5-dihydroxyoxan-3-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylate Chemical compound [Ca+2].O[C@@H]1[C@H](O)[C@H](O)O[C@@H](C([O-])=O)[C@H]1O[C@H]1[C@@H](O)[C@@H](O)[C@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@H](O2)C([O-])=O)O)[C@H](C(O)=O)O1 OKHHGHGGPDJQHR-YMOPUZKJSA-L 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 230000001587 cholestatic effect Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 229960004396 famciclovir Drugs 0.000 description 1
- GGXKWVWZWMLJEH-UHFFFAOYSA-N famcyclovir Chemical compound N1=C(N)N=C2N(CCC(COC(=O)C)COC(C)=O)C=NC2=C1 GGXKWVWZWMLJEH-UHFFFAOYSA-N 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 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
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 230000002101 lytic effect Effects 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 229960002160 maltose Drugs 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000000554 physical therapy Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 235000010408 potassium alginate Nutrition 0.000 description 1
- 239000000737 potassium alginate Substances 0.000 description 1
- MZYRDLHIWXQJCQ-YZOKENDUSA-L potassium alginate Chemical compound [K+].[K+].O1[C@@H](C([O-])=O)[C@@H](OC)[C@H](O)[C@H](O)[C@@H]1O[C@@H]1[C@@H](C([O-])=O)O[C@@H](O)[C@@H](O)[C@H]1O MZYRDLHIWXQJCQ-YZOKENDUSA-L 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000010409 propane-1,2-diol alginate Nutrition 0.000 description 1
- 239000000770 propane-1,2-diol alginate Substances 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000007420 reactivation Effects 0.000 description 1
- 229940085605 saccharin sodium Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000000413 sensory ganglia Anatomy 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000037380 skin damage Effects 0.000 description 1
- 231100000046 skin rash Toxicity 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 229940080313 sodium starch Drugs 0.000 description 1
- 229940080350 sodium stearate Drugs 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 210000003901 trigeminal nerve Anatomy 0.000 description 1
- 229940093257 valacyclovir Drugs 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 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
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/20—Antivirals for DNA viruses
- A61P31/22—Antivirals for DNA viruses for herpes viruses
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Virology (AREA)
- Molecular Biology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Biophysics (AREA)
- Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
经口腔粘膜吸收的溴夫定药物，以溴夫定为有效药物成分，与口腔粘膜药物中可以接受的辅助成分共同组成，该药物对口腔无刺激性，起效更快，生物利用度更高，使患者具有满意的依从性。
Description
技术领域
本发明涉及一种经口腔粘膜吸收的药物，具体讲是一种可经口腔粘膜吸收的溴夫定药物，包括但不限于舌下片/颗粒/丸/膜、口颊含片/颗粒/丸/膜、含片/颗粒/丸/膜、口腔粘附片和口腔贴片等可全部或主要由舌下粘膜和/或口颊粘膜等口腔粘膜吸收的药物制剂。
背景技术
水痘-带状疱疹病毒(varicella-zoster virus, VZV)感染可导致两种临床表现形式不同的疾病。VZV的原发性感染将导致水痘，特点是面部、躯干和四肢出现不同进展阶段的水疱性皮损。带状疱疹是由感觉神经节中内源性潜伏性VZV感染的再激活所致。这种临床类型的特点是单侧疼痛性的水疱发疹，通常发生在局限的皮节分布区域。带状疱疹可发生于任何年龄，但主要发生于60岁以上的成人。
我国《带状疱疹后神经痛中国专家诊疗共识》明确指出，带状疱疹后遗神经痛（PHN）是皮疹愈合后持续 1 个月及以上的疼痛。PHN发病率占带状疱疹患者的5% ~ 30%，我国约有400万PHN患者。PHN多见于高龄、免疫功能低下患者，疼痛部位通常比疱疹区域有所扩大，常见于单侧胸部、三叉神经（主要是眼支）或颈部。疼痛性质多样，可为烧灼样、电击样、刀割样、针刺样或撕裂样。一种疼痛为主，或多样疼痛并存。明显扰乱患者的睡眠、情绪，影响工作和日常生活，严重可导致精神障碍和抑郁。30% ~ 50%的患者疼痛持续超过1年，部分病程可达10年或更长。
西医目前主要采用抗病毒和止痛的方法治疗带状疱疹及PHN。国内抗病毒药物的使用已趋规范，抗病毒常规治疗 7 天，但临床可见少数患者常规抗病毒 7 天后，皮损未见好转，因此抗病毒药物的疗程是否可以适当延长没有明确的指导意见。止痛方法多样，包括药物、介入和物理治疗等多种方法，各有优势和适应症。糖皮质激素的止痛作用主要凭经验用药，尚缺乏高质量证据。对于顽固性的疼痛，还需探索更有效的止痛措施。
溴夫定为核苷类抗疱疹病毒药物，可降低带状疱疹后神经痛（PHN）的发生率及持续时间，促进水疱的愈合。与阿昔洛韦、泛昔洛韦、伐昔洛韦相比，溴夫定抗病毒活性较强，治疗带状疱疹的疗效优于同类核苷类药物。安全性方面，溴夫定口服治疗带状疱疹耐受性良好，不良事件发生率低，与同类药物相比无差异。
溴夫定原料药性状为白色或类白色结晶性粉末，熔点为158℃ (分解），在DMF、稀碱中易溶，在甲醇中可溶，在乙腈、乙醇、稀酸中微溶，在水中极微溶解，在正己烷中几乎不溶。已上市的溴夫定剂型仅有口服片剂，规格为125mg，给药后由于肝酶降解而产生的首过效应，导致生物利用度较低，仅有30%。在溴夫定片的临床试验和上市后经验中均观察到肝毒性反应，包括胆汁郁积性或溶解性肝炎、胆汁郁积性黄疸或肝酶升高。
发明内容
针对上述情况，本发明拟提供一种经口腔粘膜吸收的溴夫定药物，包括但不限于舌下片/颗粒/丸/膜、口颊含片/颗粒/丸/膜、含片/颗粒/丸/膜、口腔粘附片和口腔贴片等可全部或主要由舌下粘膜和/或口颊粘膜等口腔粘膜吸收的药物制剂。
与其他非口服给药途径相比，口腔黏膜给药具有以下特点：①口腔黏膜中的颊黏膜和舌下黏膜部位的血流丰富，血流速度快；②口腔黏膜对外界刺激具有较强的耐受性，当黏膜组织受到制剂中的一些成分刺激和损伤，停止用药后能够较快地恢复；③剂型易定位，用药方便，可以随时撤去药物。溴夫定口腔黏膜给药，药物经舌下粘膜和/或口颊粘膜，通过舌静脉和面静脉等汇至颈内静脉而直接进入血液循环，迅速起效；可避开肝首过效应，减少肝药酶对药物的降解，提高生物利用度，可以较低给药剂量达到相同或更好的治疗效果，并减少不良反应；给药方便，患者依从性好。
综上所述，溴夫定的口腔黏膜制剂生物利用度提高，可以较低的给药剂量达到更好的治疗效果。由于本发明提供的药物不经过肝脏代谢，可降低不良反应风险，特别是降低肝毒性反应。
本发明经口腔粘膜吸收的溴夫定药物，同样以溴夫定为有效药物成分，与口腔粘膜药物中可以接受的辅助成分共同组成。其中，所说的口腔粘膜药物中可以接受的辅助成分，可以选择目前在口腔粘膜药物制剂中通常需要和/或使用的多种辅料成分，包括：
稀释剂：如微晶纤维素、乳糖、乳糖复合物Ludipress（由乳糖、Kollidon 30和Kollidon CL组成）、Ludipress LCE（由乳糖和Kollidon 30组成）、Ludiflash（由90%Mannitol、5% Kollidon® CL-SF 和5% Kollicoat® SR 30D组成）、Cellactose 80 、Tablettose 80、MicroceLac 100、StarLac、Prosolv HD 90、淀粉、预胶化淀粉、糖粉、葡萄糖、硫酸钙、糊精、甘露醇、赤藓糖醇、麦芽糖、麦芽糖醇、麦芽糖糊精、山梨醇、木糖醇中的一种或几种；
粘合剂：如常用的聚维酮类成分（如Kollidon VA 64、Kollidon VA 64 Fine、Plasdone S-630）、淀粉浆、羟丙基甲基纤维素、甲基纤维素、角叉菜胶、卡波姆、瓜尔胶、明胶、阿拉伯胶、黄原胶、海藻酸或如海藻酸钠、海藻酸钾、海藻酸钙等其盐类成分、海藻酸丙二醇酯等各种成分中的一种或几种、磷酸淀粉钠、壳聚糖、糊精和糖浆中的一种或几种；
润湿剂：如常用的水、乙醇、无水乙醇及不同浓度的乙醇溶液中的一种或几种；
崩解剂：如交联聚维酮、羧甲基淀粉钠、交联羧甲基纤维素钠、低取代羟丙基纤维素、微晶纤维素、微晶纤维素-微粉硅胶、预胶化淀粉、干淀粉、淀粉、海藻酸钠、海藻酸、羟丙基淀粉、羧甲基纤维素钙中的一种或几种，用量一般可为片剂总重量的0.1%~50%；
掩味（矫味）剂：如常用的甘草甜素、阿斯巴甜、晶状麦芽糖、处理琼脂（TAG）、甜菊苷、三氯蔗糖、黄原胶、糖精、维生素C、果糖、葡聚糖、甜蜜素、索马甜、糖精、薄荷醇等允许使用的甜味剂和/或食用香精成分中的一种或几种。
润滑剂：如常用的硬脂酸镁、硬脂酸、硬脂富马酸钠、十二烷基硫酸钠、聚乙二醇4000（或聚乙二醇6000）、微粉硅胶、滑石粉等成分中的一种或几种。
滴丸基质：聚乙二醇6000、聚乙二醇4000、聚乙二醇300、硬脂酸钠、甘油明胶中的一种或几种；
成膜材料：聚乙烯醇、乙烯-醋酸乙烯共聚物、羟丙基甲基纤维素、聚维酮、羟丙基纤维素，成膜增塑剂：甘油、山梨醇；表面活性剂聚山梨酯80、十二烷基硫酸钠，填充剂：碳酸钙、二氧化硅、淀粉，着色剂：色素、二氧化钛和脱膜剂液状石蜡中的一种或几种。
本发明上述经口腔粘膜吸收药物中的溴夫定，是在口腔的舌下、口颊或口腔的其它部位含化，全部或基本上是由包括舌下粘膜和口颊粘膜等口腔内的粘膜组织吸收起效，其具体制剂形式，可以包括目前已有使用的舌下片/颗粒/丸/膜、口颊含片/颗粒/丸/膜、含片/颗粒/丸/膜、口腔粘附片和口腔贴片等。
本发明上述药物中，所说有效药物成分溴夫定在药物制剂中的含量，一般可以为药物总重量的0.1%～100%，上述辅助成分的用量则可分别按目前各相应制剂的常规方式使用。
本发明上述经口腔粘膜吸收药物的制备，可以采用目前同类药物制剂的常规方式制备得到。以片剂为例，其典型的制备方式可以有：
a. 干法制粒压片方式：将有效药物成分溴夫定与所选择的辅助成分混合均匀，直接压成块，再破碎成颗粒，压片，制得成品。
b. 湿法制粒压片方式：将有效药物成分溴夫定与内加的辅助成分混合均匀，加入粘合剂和/或润湿剂制粒并干燥后，再加入（或不加入）外加辅料（润滑剂和/或崩解剂），充分混匀，压片，制得成品。
c. 粉末直接压片方式：将有效药物成分溴夫定与所选择的辅助成分混合均匀，直接压片，制得成品。
d. 半干法制粒压片方式：将所选择的辅助成分混合均匀，加入粘合剂和/或润湿剂制粒并干燥后，再加入有效药物成分（也可以与外加润滑剂和/或崩解剂等辅料一并加入）充分混匀，压片，制得成品。
e.冷冻干燥法制片方式：将有效药物成分溴夫定、赋形剂和其他辅料与溶剂进行混合，配制成药液，将配制好的药液灌装到泡罩内，置冷冻干燥机中进行冷冻干燥，制得成品。
上述片剂典型的制备方式中，有效药物成分溴夫定可经预处理或不经预处理，可以晶体、粉末、微粉、固体分散体和/或包合物等形式，与所选择的辅助成分（可预先粉碎或与溴夫定共粉碎）进行混合，制粒，干燥，整粒后压片；或与所选择的辅助成分（预先制备成空白颗粒）进行混合后压片；或与所选择的辅助成分混匀后直接压片。
本发明上述形式的药物，可以满意地解决口服片剂所存在的生物利用度较低、肝毒性反应较大等缺点，提高疗效，降低不良反应，具有理想的患者依从性，能让带状疱疹患者更快地得到安全有效的治疗，尽快减轻患者痛苦。
以下通过实施例的具体实施方式再对本发明的上述内容作进一步的详细说明。但不应将此理解为本发明上述主题的范围仅限于以下的实例。在不脱离本发明上述技术思想情况下，根据本领域普通技术知识和惯用手段做出的各种替换或变更，均应包括在本发明的范围内。
具体实施方式
实施例1（含片，130~160mg/片）
组成：
溴夫定（粉碎至D90=5~15µm） 130g~160g
淀粉 30g
预胶化淀粉 50g
阿斯巴甜 2g
5%聚维酮水溶液 适量
硬脂酸镁 2g
制成1000片
制备方法：将溴夫定进行微粉化预处理至D90=5~15µm，原料与淀粉、预胶化淀粉等辅助成分混合均匀后，加入5%聚维酮水溶液制粒，流化床干燥，整粒，加入硬脂酸镁，混合均匀，压片，即得。溶化性检查：15分钟~23分钟崩解溶化。服用时，置于口颊处含化。
实施例2（含片，100mg/片）
组成：
溴夫定（粉碎至D90=10~25µm） 100g
Ludipress LCE 33g
微晶纤维素 16g
甜蜜素 5g
硬脂富马酸钠 2g
制成1000片
制备方法：将溴夫定进行微粉化预处理至D90=10~25µm，与Ludipress LCE、微晶纤维素等辅助成分混合均匀后，加入硬脂酸镁，混合均匀，直接压片即得。溶化性检查：15分钟~20钟崩解溶化。服用时，置于口颊处含化。
实施例3（含片，70mg/片）
组成：
溴夫定（粉碎至D90=10~20µm） 70g
预胶化淀粉 35g
淀粉 20g
果糖 10g
硬脂酸 3g
制成1000片
制备方法：将溴夫定进行微粉化预处理至D90=10~20µm，与预胶化淀粉、淀粉等辅助成分混合均匀后，置流化床中，用纯化水制粒，干燥，整粒，加入硬脂酸，混合均匀，压片，即得。溶化性检查：13分钟~16分钟崩解溶化。服用时，置于口颊处含化。
实施例4（含片，38mg/片）
组成：
溴夫定（粉碎至D90=10~30µm） 38g
乳糖 20g
预胶化淀粉 20g
赤藓糖醇 10g
硬脂酸 3g
制成1000片
制备方法：将溴夫定进行微粉化预处理至D90=10~20µm，与乳糖、预胶化淀粉、赤藓糖醇等辅助成分混合均匀后，直接压片，即得。溶化性检查：12分钟~15分钟崩解溶化。服用时，置于口颊处含化。
实施例5（口腔贴片或口腔粘附片，88mg/片）
组成：
溴夫定（粉碎至D90=5~25µm） 88g
麦芽糖 25g
甘露醇 20g
卡波姆 8g
羟丙基甲基纤维素 6g
聚山梨酸酯80 5g
甜菊苷 6g
微粉硅胶 0。 2g
制成1000片
制备方法：将溴夫定进行微粉化预处理至D90=15~25µm，与麦芽糖、甘露醇、卡波姆和羟丙基甲基纤维素等辅助成分混合均匀，压片即得口腔粘附片，或按贴片工艺进行制备。释放度符合要求。服用时，贴于或粘附于口颊处或口腔内其他部位逐渐溶化。
实施例6（舌下片，60mg/片）
组成：
溴夫定（粉碎至D90=10~20µm） 60g
预胶化淀粉 25g
甘露醇 15g
羧甲基淀粉钠 10g
微粉硅胶 2g
制成1000片
制备方法：将溴夫定进行微粉化预处理至D90=10~20µm，与预胶化淀粉和甘露醇等辅助成分混合均匀，混合均匀，压片。崩解时限检查： 2分钟～3分钟。
实施例7（舌下片，50mg/片）
组成：
溴夫定（粉碎至D90=10~30µm） 50g
麦芽糖糊精 20g
微晶纤维素 20g
三氯蔗糖 3g
羧甲基淀粉钠 8g（内加60%，外加40%）
10%淀粉浆 适量
硬脂富马酸钠 0.8g
制成1000片
制备方法：将溴夫定进行微粉化预处理至D90=10~30µm，与麦芽糖糊精、微晶纤维素、羧甲基淀粉钠等辅助成分过100目筛，混合均匀，加入10%淀粉浆适量，制粒，干燥，整粒，加入外加羧甲基淀粉钠和硬脂富马酸钠，压片。崩解时限检查： 3分钟～4分钟。
实施例8（舌下片，40mg/片）
组成：
溴夫定（粉碎至D90=10~20µm） 40g
预胶化淀粉 30g
交联羧甲基纤维素钠 5g（内加3g，外加2g）
6%淀粉浆 适量
三氯蔗糖 3g
硬脂酸镁 0.5g
制成1000片
制备方法：将溴夫定进行微粉化预处理至D90=10~20µm，与淀粉、交联羧甲基纤维素钠等内加辅料过100目筛，混合均匀，加入6%淀粉浆，制粒，干燥，整粒，加入外加交联羧甲基纤维素钠和硬脂酸镁，混合均匀，压片。崩解时限检查：2分钟～3分钟。
实施例9（舌下片，30mg/片）
组成：
溴夫定 30g
木糖醇 20g
微晶纤维素 20g
羟丙基纤维素 10g
交联聚维酮 7g（内加70%，外加30%）
三氯蔗糖 2g
硬脂酸 1g
制成1000片
制备方法：将溴夫定与木糖醇、羟丙基纤维素等辅助成分过100目筛，混合均匀，加入干法制粒机制粒，整粒，加入硬脂酸和外加交联聚维酮，混合均匀，压片。崩解时限检查：2分钟～3分钟。
实施例10（舌下片，20mg/片）
组成：
溴夫定 20g
乳糖 25g
微晶纤维素 15g
低取代羟丙基纤维素 6g（内加70%，外加30%）
甜菊苷 1g
硬脂酸镁 0.6g
制成1000片
制备方法：将乳糖、微晶纤维素等辅助成分过100目筛，置流化床中，用纯化水制粒并干燥，整粒，加入溴夫定和外加低取代羟丙基纤维素，混合均匀，加入硬脂酸镁，总混，压片。崩解时限检查：1分钟～2分钟。
实施例11（舌下片，10mg/片）
组成：
溴夫定 10g
聚维酮K30 40g
乳糖 30g
微晶纤维素 15g
葡聚糖 6g
聚乙二醇6000 1.2g
制成1000片
制备方法：将溴夫定与聚维酮K30，以溶剂法（如以乙醇为溶剂）制备成溴夫定-聚维酮K30固体分散体，干燥，检测固体分散体中溴夫定含量，将固体分散体粉碎，过筛，与乳糖、微晶纤维素、葡聚糖等辅助成分过100目筛，混匀，压片即得。崩解时限检查：1分钟～3分钟。
实施例12（舌下片，7mg/片）
组成：
溴夫定 7g
β-环糊精 25g
乳糖 25g
微晶纤维素 15g
交联羧甲基纤维素钠 3g
三氯蔗糖 3g
硬脂酸 0.6g
制成1000片
制备方法：将溴夫定与羟丙基β-环糊精，以喷雾干燥法制备成包合物，检测包合物中溴夫定含量，将溴夫定-羟丙基β-环糊精包合物粉碎，过筛，将微晶纤维素、三氯蔗糖等辅助成分过100目筛，混合均匀，压片。崩解时限检查： 1分钟～3分钟。
实施例13（舌下片，1mg/片）
组成：
溴夫定 1g
乳糖 25g
微晶纤维素 15g
三氯蔗糖 3g
硬脂酸镁 0.5g
制成1000片
制备方法：将乳糖、微晶纤维素等辅助成分过100目筛，等量递加法加入溴夫定混合，加入硬脂酸镁总混，压片。崩解时限检查：1分钟～2分钟。
实施例14（舌下片，20mg/片）
组成：
溴夫定 20g
蔗糖 25g
微晶纤维素 25g
三氯蔗糖 3g
硬脂酸镁 0.5g
制成1000片
制备方法：将溴夫定和蔗糖、微晶纤维素等辅助成分过100目筛，加入挤出滚圆机，用纯化水挤出，滚圆，整粒，加入硬脂酸镁总混，压片即得。崩解时限检查：3分钟～4分钟。
实施例15（舌下片，10mg/片）
组成：
溴夫定 10g
甘露醇 20g
晶状麦芽糖 15g
制成 1000片
制备方法：按照处方量称取溴夫定和辅料溶于水中，然后放入冻干机内低温迅速冻结成型，将冻结后的药物在高真空低温条件下升华，除去水分并适当干燥除去残余水分，制片。崩解时限检查：30秒～60秒。
实施例16（滴丸，13mg/片）
组成：
溴夫定（粉碎至D90=3µm~15µm） 13g
聚乙二醇4000 80g
制成1000丸
制备方法：按滴制法，将溴夫定微粉加入熔融的聚乙二醇4000中，不断搅拌使全部熔融，趁热过滤，置贮液瓶中保温，用滴管滴至液状石蜡冷凝液中冷凝成丸（2mm～3mm），即得。溶散时限检查：30分钟内全部溶散。服用时，置于舌下或口颊处含化。
实施例17（微丸，10mg/粒）
组成：
溴夫定 10g
空白丸芯（糖丸） 25g
制成 1000粒
制备方法：将空白丸芯（糖丸）加入流化床，底喷加入溴夫定的水溶液，制成微丸。崩解时限检查：2分钟～4分钟。服用时，置于舌下或口颊处含化。
实施例18（舌下含服颗粒，30mg）
组成：
溴夫定 30g
10%淀粉浆 适量
预胶化淀粉 80g
交联羧甲基纤维素钠 6g
糖精钠 3g
制成1000袋
制备方法：将溴夫定与预胶化淀粉、交联羧甲基纤维素钠等辅料过80目筛，混合均匀，加入10%淀粉浆制粒后，干燥，整粒，装袋即得。崩解时限检查：2分钟～3分钟。
实施例19（膜剂，0.3%）
组成：
溴夫定 3g
聚乙烯醇 6g
二氧化钛 0.5g
甘油 1g
纯化水 30g
制成1000片
制备方法：称取溴夫定加入纯化水中，搅拌分散均匀，再称取二氧化钛、甘油加入纯化水中，搅拌分散均匀，再将聚乙烯醇加入分散均匀的溶液中，充分搅拌溶解形成胶液，胶液通过抽真空离心脱泡。将胶液注入涂布机，涂膜。按规格剪裁，包装。崩解时限检查：崩解溶化时间为1分钟～3分钟。服用时，置于舌下或口颊处含化。
以上虽然以实施例描述了本发明的精神，但是只用于说明目的而不是限制本发明，实施例的变化对于本领域一般的技术人员，在阅读本发明的技术路线后或者实施例后变得显而易见。因此，在不背离本发明范围和精神的情况下，可以对本发明的实施例进行调整和改变，这些调整和改变都属于本发明的等同替换。
Claims (6)
1.经口腔粘膜吸收的药物，以溴夫定为有效药物成分，与口腔粘膜药物中可以接受的辅助成分共同组成，其特征是每单位剂量中所含溴夫定为1mg～200mg。
2.如权利要求1所述的经口腔粘膜吸收的溴夫定药物，其特征是剂型为片剂、颗粒剂、丸剂、膜剂、口腔粘附片和口腔贴片等剂型。
3.如权利要求1、2所述的经口腔粘膜吸收的溴夫定药物，其特征是采用干法制粒、湿法制粒工艺制备的颗粒，以及干法制粒压片、湿法制粒压片、半干法制粒压片、粉末直接压片和冷冻干燥法制片工艺制备的片剂。
4.如权利要求1、2所述的经口腔粘膜吸收的溴夫定药物，其特征是采用常规滴丸制备方法，进行滴丸制备。
5.如权利要求1、2所述的经口腔粘膜吸收的溴夫定药物，其特征是采用常规膜剂制备方法，进行膜剂制备。
6.如权利要求3、4、5所述的经口腔粘膜吸收的溴夫定药物，其有效药物成分溴夫定可经预处理或不经预处理，可以晶体、粉末、微粉、固体分散体和/或包合物等形式，与所选择的辅助成分进行片剂、颗粒剂、丸剂、膜剂、口腔粘附片和口腔贴片等剂型的制备。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111147785.1A CN113712928A (zh) | 2021-09-29 | 2021-09-29 | 经口腔粘膜吸收的溴夫定药物 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111147785.1A CN113712928A (zh) | 2021-09-29 | 2021-09-29 | 经口腔粘膜吸收的溴夫定药物 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113712928A true CN113712928A (zh) | 2021-11-30 |
Family
ID=78685481
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111147785.1A Pending CN113712928A (zh) | 2021-09-29 | 2021-09-29 | 经口腔粘膜吸收的溴夫定药物 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113712928A (zh) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0110682D0 (en) * | 2001-01-03 | 2001-06-20 | Berlin Chemie Ag | Once-a-day pharmaceutical composition containing brivudine |
| US20040259835A1 (en) * | 2001-12-19 | 2004-12-23 | Christian Schnittker | Stabilized brivudine topical formulations |
| CN101272765A (zh) * | 2005-09-29 | 2008-09-24 | 柏林-化学股份公司 | 包含用于治疗疱疹性角膜炎的溴夫定的耐光药物组合物 |
| CN103156817A (zh) * | 2011-12-19 | 2013-06-19 | 重庆市力扬医药开发有限公司 | 经口腔粘膜吸收的利扎曲坦药物 |
-
2021
- 2021-09-29 CN CN202111147785.1A patent/CN113712928A/zh active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0110682D0 (en) * | 2001-01-03 | 2001-06-20 | Berlin Chemie Ag | Once-a-day pharmaceutical composition containing brivudine |
| US20040259835A1 (en) * | 2001-12-19 | 2004-12-23 | Christian Schnittker | Stabilized brivudine topical formulations |
| CN101272765A (zh) * | 2005-09-29 | 2008-09-24 | 柏林-化学股份公司 | 包含用于治疗疱疹性角膜炎的溴夫定的耐光药物组合物 |
| CN103156817A (zh) * | 2011-12-19 | 2013-06-19 | 重庆市力扬医药开发有限公司 | 经口腔粘膜吸收的利扎曲坦药物 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8613950B2 (en) | Pharmaceutical forms with improved pharmacokinetic properties | |
| JP5053865B2 (ja) | 口腔内崩壊性固形製剤の製造法 | |
| US20120171296A1 (en) | Rapidly disintegrating solid preparation | |
| JP2000103731A (ja) | 速崩壊性固形製剤 | |
| JP6154878B2 (ja) | アタザナビルを含む錠剤組成物 | |
| US10548847B2 (en) | Composition for manufacturing orally disintegrating dosage form to protect coating layer of active substance | |
| JP2010530889A (ja) | アタザナビルを含む錠剤組成物 | |
| CN113712895A (zh) | 经口腔粘膜吸收的s-氯胺酮药物 | |
| JP2010530892A (ja) | アタザナビルを含む錠剤組成物 | |
| CN105193772A (zh) | 一种沙格列汀口腔膜剂及其制备方法 | |
| CN104922143B (zh) | Egcg与壳寡糖的组合物及其制备方法和应用 | |
| CN107441068B (zh) | 一种盐酸可乐定口腔膜剂及其制备方法 | |
| EP3238712B1 (en) | Very rapidly disintegrating tablet, and method for producing same | |
| US20160136097A1 (en) | Ultrafast-disintegrating tablet and method for manufacturing same | |
| US10864165B2 (en) | Super-rapid disintegrating tablet, and method for producing same | |
| KR100604034B1 (ko) | 암로디핀 유리염기를 함유한 구강 속붕해정 및 그의 조성물 | |
| CN113712928A (zh) | 经口腔粘膜吸收的溴夫定药物 | |
| JP2010530890A (ja) | アタザナビルを含む錠剤組成物 | |
| KR20160141620A (ko) | 생체이용률이 개선된 프란루카스트 함유 고형 제제의 조성물 및 그 제조방법 | |
| KR20090086128A (ko) | 메만틴 약학 조성물 | |
| CN102048677B (zh) | 一种盐酸缬更昔洛韦固体制剂及其制备方法 | |
| CN113952312A (zh) | 经口腔粘膜吸收的赛洛多辛药物 | |
| CN100387226C (zh) | 一种千金藤素口腔崩解片及其制备方法 | |
| EP1608341A1 (en) | Water-soluble tablets of metformin | |
| CN116270509A (zh) | 一种含有替加氟、吉莫斯特和奥替拉西钾的口腔崩解制剂 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20211130 |