CN113521024A - 一种碳酸锂缓释片 - Google Patents
一种碳酸锂缓释片 Download PDFInfo
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- CN113521024A CN113521024A CN202110812281.0A CN202110812281A CN113521024A CN 113521024 A CN113521024 A CN 113521024A CN 202110812281 A CN202110812281 A CN 202110812281A CN 113521024 A CN113521024 A CN 113521024A
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- sustained
- release tablet
- lithium carbonate
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- following
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- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 title claims abstract description 49
- 229910052808 lithium carbonate Inorganic materials 0.000 title claims abstract description 48
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 36
- 239000000463 material Substances 0.000 claims abstract description 22
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 6
- 238000013268 sustained release Methods 0.000 claims abstract description 6
- 239000012730 sustained-release form Substances 0.000 claims abstract description 6
- 239000000945 filler Substances 0.000 claims abstract description 5
- 239000000314 lubricant Substances 0.000 claims abstract description 5
- 239000004094 surface-active agent Substances 0.000 claims abstract description 5
- 239000000080 wetting agent Substances 0.000 claims abstract description 5
- 239000007884 disintegrant Substances 0.000 claims abstract description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 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
- 238000002360 preparation method Methods 0.000 claims description 13
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims description 10
- 239000008116 calcium stearate Substances 0.000 claims description 10
- 235000013539 calcium stearate Nutrition 0.000 claims description 10
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 10
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 10
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 10
- 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 10
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 10
- 229920002472 Starch Polymers 0.000 claims description 9
- 239000008107 starch Substances 0.000 claims description 9
- 235000019698 starch Nutrition 0.000 claims description 9
- 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 description 8
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 8
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 8
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 8
- 235000021355 Stearic acid Nutrition 0.000 claims 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 claims description 8
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 claims description 8
- 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 8
- 239000008101 lactose Substances 0.000 claims description 8
- 235000019359 magnesium stearate Nutrition 0.000 claims description 8
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 8
- 239000011780 sodium chloride Substances 0.000 claims description 8
- 229940083575 sodium dodecyl sulfate Drugs 0.000 claims description 8
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 8
- 239000008117 stearic acid Substances 0.000 claims description 8
- 239000003826 tablet Substances 0.000 claims description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 7
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 6
- 229930195725 Mannitol Natural products 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims 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 claims description 6
- 229930006000 Sucrose Natural products 0.000 claims description 6
- 239000000594 mannitol Substances 0.000 claims description 6
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- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 5
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- 229910002027 silica gel Inorganic materials 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 4
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 4
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 4
- 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 description 4
- 239000004375 Dextrin Substances 0.000 claims description 4
- 229920001353 Dextrin Polymers 0.000 claims description 4
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 4
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 4
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 4
- 239000004203 carnauba wax Substances 0.000 claims description 4
- 235000013869 carnauba wax Nutrition 0.000 claims description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 4
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 4
- 229960000913 crospovidone Drugs 0.000 claims description 4
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 4
- 235000019425 dextrin Nutrition 0.000 claims description 4
- 239000000499 gel Substances 0.000 claims description 4
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 4
- 235000010445 lecithin Nutrition 0.000 claims description 4
- 239000000787 lecithin Substances 0.000 claims description 4
- 229940067606 lecithin Drugs 0.000 claims description 4
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 4
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 4
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 4
- 239000001103 potassium chloride Substances 0.000 claims description 4
- 235000011164 potassium chloride Nutrition 0.000 claims description 4
- 239000000600 sorbitol Substances 0.000 claims description 4
- 235000010356 sorbitol Nutrition 0.000 claims description 4
- 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 description 3
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 239000011230 binding agent Substances 0.000 claims description 3
- 235000011132 calcium sulphate Nutrition 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
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- 235000019322 gelatine Nutrition 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 3
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 claims description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 229920002101 Chitin Polymers 0.000 claims description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 229920003064 carboxyethyl cellulose Polymers 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 235000012000 cholesterol Nutrition 0.000 claims description 2
- 229940107161 cholesterol Drugs 0.000 claims description 2
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 2
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000008103 glucose Substances 0.000 claims description 2
- 229940075507 glyceryl monostearate Drugs 0.000 claims description 2
- 229920003063 hydroxymethyl cellulose Polymers 0.000 claims description 2
- 229940031574 hydroxymethyl cellulose Drugs 0.000 claims description 2
- 239000011159 matrix material Substances 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 2
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 239000002002 slurry Substances 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 229940045902 sodium stearyl fumarate Drugs 0.000 claims description 2
- 229940083466 soybean lecithin Drugs 0.000 claims description 2
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- 238000013265 extended release Methods 0.000 claims 2
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- -1 glidant Substances 0.000 abstract description 2
- 238000007873 sieving Methods 0.000 description 25
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- 229940078456 calcium stearate Drugs 0.000 description 9
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- 206010067484 Adverse reaction Diseases 0.000 description 1
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- 206010028813 Nausea Diseases 0.000 description 1
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- 238000003321 atomic absorption spectrophotometry Methods 0.000 description 1
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- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
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- 238000007796 conventional method Methods 0.000 description 1
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- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 229960001375 lactose Drugs 0.000 description 1
- 229940089469 lithobid Drugs 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
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- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
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- 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
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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Abstract
本发明公开一种碳酸锂缓释片，该缓释片包括碳酸锂、缓释材料以及其他辅料。其中所述的缓释材料为亲水凝胶骨架材料或溶蚀性骨架材料；其中所述的其他辅料包括：粘合剂、致孔剂、表面活性剂、润滑剂、助流剂、填充剂、崩解剂和润湿剂。上述的碳酸锂缓释片，减少给药次数，避免或减小血药浓度的峰谷现象，提供平稳持久的有效血药浓度，提高药物的安全性和有效性。
Description
技术领域
本发明涉及一种缓释片剂，具体地，是碳酸锂缓释片。
背景技术
碳酸锂，主要用于治疗躁狂症，对躁狂和抑郁交替发作的双相情感性精神障碍有很好的治疗和预防复发作用，对反复发作的抑郁症也有预防发作作用。也用于治疗分裂-情感性精神病。
碳酸锂最初由苏威公司和诺华(Solvay and Novartis)合作开发，苏威公司后来被雅培收购。1939年最早在美国上市，商品名为Lithobid。
目前碳酸锂上市剂型包括普通片、胶囊剂、糖浆剂和缓释片剂，规格包括150mg、300mg、450mg、600mg。普通片每天需口服2～3次，多次服用易产生碳酸锂副作用，如口干、烦渴、多饮、多尿、便秘、腹泻、恶心、呕吐、上腹痛。制成口服缓释片剂可将服药次数降至每天1～2次，提高病人的顺应性。
美国专利US4264573公开了一种制备表面溶蚀型碳酸锂缓释片的方法： 1、将氯化钠通过Whilstler粉碎机粉碎；2、将粉碎后的氯化钠与碳酸锂在混合机中混匀，再在高速模式下通过Fitzmill粉碎机；3、将上述混合粉再次投入混合机，与聚维酮一起加水混合制软材；4、软材在高速模式下通过 Fitzmill粉碎机制粒；5、湿颗粒在55℃下干燥过夜；6、干颗粒在中速模式下通过Fitzmill粉碎机整粒；7、整粒后的干颗粒与山梨醇、Stearowet 
和羧甲基淀粉钠混合后压片。该制备方法需经过多次粉碎工序，粉尘多、损耗大，且干燥时间过长，不利于工业化大生产。
发明内容
本发明的目的在于提供一种口服碳酸锂缓释片，减少给药次数，避免或减小血药浓度的峰谷现象，提供平稳持久的有效血药浓度，提高药物的安全性和有效性。
为了实现本发明的目的，发明人提供如下一种碳酸锂缓释片，由碳酸锂、缓释材料以及其他辅料组成。其中，缓释材料占制剂重量的1～30％，优选地，所述缓释材料占制剂重量的1～10％。
本发明所用的缓释材料为亲水凝胶骨架材料或溶蚀性骨架材料。其中的亲水凝胶骨架材料为甲基纤维素、羟甲基纤维素、羟乙基纤维素、羟丙基纤维素、羟丙甲基纤维素、羧甲基纤维素、羧乙基纤维素、海藻酸钠、壳多糖和聚羧乙稀中的一种或它们的混合物；溶蚀性骨架材料包括巴西棕榈蜡、硬脂酸、硬脂酸盐、硬脂醇和单硬脂酸甘油酯中的一种或它们的混合物。
本发明所述的缓释片剂，处方中除上述的缓释材料外，其他的辅料还有、粘合剂、致孔剂、表面活性剂、润滑剂、填充剂、崩解剂和润湿剂。
所述粘合剂选自以下一种或多种：聚乙烯吡咯烷酮、羟丙甲基纤维素、淀粉浆、明胶、羧甲基纤维素钠；所述致孔剂选自以下一种或多种：聚乙二醇、甘露醇、葡萄糖、乳糖、糊精、蔗糖、氯化钠、氯化钾；表面活性剂选自以下一种或多种：吐温、司盘、卵磷脂、大豆磷脂、十二烷基硫酸钠、胆固醇；润滑剂选自以下一种或多种：硬脂酸镁、滑石粉、硬脂酸、硬脂酸钙、硬脂酰富马酸钠；所述填充剂选自以下一种或多种：微晶纤维素、乳糖、甘露醇、山梨醇、淀粉、磷酸氢钙、硫酸钙、糊精、蔗糖；所述崩解剂选自以下一种或多种：羧甲基淀粉钠、交联聚维酮、交联羧甲基纤维素钠、预胶化淀粉；所述润湿剂选自以下一种或多种：水、乙醇、乙醇水溶液。
本发明的缓释片剂，每个制剂单位含碳酸锂100～900mg，优选300～ 600mg，最优选为300mg。
本发明所述的缓释片剂，可以按照制药工业已知的片剂制备方法来生产。
碳酸锂治疗指数低，治疗浓度和中毒浓度较接近，将碳酸锂制成缓释制剂，确保血药浓度平稳且长时间维持在治疗窗范围内，可有效降低碳酸锂的不良反应。且与普通片剂或胶囊相比，只需1天给要1～2次，作用持久、疗效稳定，可有效提高病人顺应性。
附图说明
图1为根据实施例1制备的碳酸锂缓释片释放曲线图
图2为根据实施例2制备的碳酸锂缓释片释放曲线图
图3为根据实施例3制备的碳酸锂缓释片释放曲线图
图4为根据实施例4制备的碳酸锂缓释片释放曲线图
图5为根据实施例5制备的碳酸锂缓释片释放曲线图
图6为根据实施例6制备的碳酸锂缓释片释放曲线图
图7为根据实施例7制备的碳酸锂缓释片释放曲线图
具体实施方式
下面通过实施例的方式进一步说明本发明，但并不因此将本发明限制在所述的实施例范围之中。下列实施例中未注明具体条件的实验方法，按照常规方法和条件，或按照商品说明书选择。
下面结合实施例对本发明做进一步地说明，实施例仅为解释性的，决不意味着它以任何方式限制本发明的范围。
实施例1
处方：
制备方法：将碳酸锂过80目筛，羟丙甲纤维素、乳糖、硬脂酸、硬脂酸镁、滑石粉过60目筛；取处方量碳酸锂、羟丙甲纤维素、乳糖、硬脂酸混合均匀，用含吐温80的7.5％聚乙烯吡咯烷酮75％乙醇溶液制粒，沸腾床干燥，过20目筛整粒，加入硬脂酸镁、滑石粉混合后压片。
实施例2
处方：
制备方法：将碳酸锂过80目筛，羟丙甲纤维素K4M、羟丙甲纤维素 K15M、微晶纤维素、硬脂酸、十二烷基硫酸钠、硬脂酸钙、微粉硅胶过60 目筛；取处方量碳酸锂、羟丙甲纤维素K4M、羟丙甲纤维素K15M、微晶纤维素、十二烷基硫酸钠、硬脂酸混合均匀，用75％乙醇溶液制粒，沸腾床干燥，过20目筛整粒，加入硬脂酸钙、微粉硅胶混合后压片。
实施例3
处方：
制备方法：将碳酸锂过80目筛，羟乙基纤维素、硫酸钙、硬脂酸镁、微粉硅胶过60目筛；取处方量碳酸锂、羟乙基纤维素、硫酸钙混合均匀，用含卵磷脂的5％聚乙烯吡咯烷酮75％乙醇溶液制粒，沸腾床干燥，过20目筛整粒，加入硬脂酸镁、微粉硅胶混合后压片。
实施例4
处方：
制备方法：将碳酸锂过80目筛，氯化钠粉碎后过60目筛，十二烷基硫酸钠、聚乙烯吡咯烷酮、羧甲基淀粉钠、硬脂酸钙、微粉硅胶过60目筛，山梨醇过40目筛；取处方量碳酸锂、氯化钠、聚乙烯吡咯烷酮混合均匀，用75％乙醇溶液制粒，沸腾床干燥，过20目筛整粒，加入山梨醇、硬脂酸钙、十二烷基硫酸钠、羧甲基淀粉钠、微粉硅胶混合后压片。
实施例5
处方：
制备方法：将碳酸锂过80目筛，聚乙二醇、甘露醇、十二烷基硫酸钠、交联聚维酮、硬脂酸钙60目筛；取处方量碳酸锂、聚乙二醇、十二烷基硫酸钠、交联聚维酮混合均匀，用15％明胶水溶液制粒，沸腾床干燥，过20 目筛整粒，加入甘露醇、硬脂酸钙混合后压片。
实施例6
处方：
制备方法：将碳酸锂过80目筛，氯化钾粉碎后过60目筛，蔗糖、巴西棕榈蜡、预胶化淀粉、硬脂酸镁、滑石粉过60目筛；取处方量碳酸锂、蔗糖、氯化钾、巴西棕榈蜡、预胶化淀粉混合均匀，用含卵磷脂的1.5％羧甲基纤维素钠50％乙醇溶液制粒，沸腾床干燥，过20目筛整粒，加入硬脂酸镁、滑石粉混合后压片。
实施例7
处方：
制备方法：将碳酸锂过80目筛，氯化钠粉碎后过60目筛，乳糖、交联羧甲基纤维素钠、十六十八醇、硬脂酸钙、滑石粉过60目筛；取处方量碳酸锂、乳糖、氯化钠、十六十八醇、交联羧甲基纤维素钠混合均匀，用含吐温80的1.5％羧甲基纤维素钠50％乙醇溶液制粒，沸腾床干燥，过20目筛整粒，加入硬脂酸钙、滑石粉混合后压片。
试验方法：照溶出度测定法(中国药典2015版四部通则0931第一法)，以水900ml作为溶出介质，转速为100转/分，依法操作，照原子吸收分光光度法(中国药典2015版四部通则0406第一法)测定每片在0.5h、1h、 2h、3h、4h、5h、6h和8h的溶出量。
Claims (10)
1.一种碳酸锂缓释片，其特征在于，所述的缓释片包括碳酸锂、缓释材料以及其他辅料；所述缓释材料为亲水凝胶骨架材料或溶蚀性骨架材料；
其中所述的亲水凝胶骨架材料为甲基纤维素、羟甲基纤维素、羟乙基纤维素、羟丙基纤维素、羟丙甲基纤维素、羧甲基纤维素、羧乙基纤维素、海藻酸钠、壳多糖和聚羧乙稀中的一种或它们的混合物；其中所述的溶蚀性骨架材料包括巴西棕榈蜡、硬脂酸、硬脂酸盐、硬脂醇和单硬脂酸甘油酯中的一种或它们的混合物。
2.如权利要求1所述缓释片，其特征在于，所述缓释材料占制剂重量的1～30％。
3.如权利要求1所述缓释片，其特征在于，其他辅料包括：粘合剂、致孔剂、表面活性剂、润滑剂、助流剂、填充剂、崩解剂和润湿剂；所述粘合剂选自以下一种或多种：聚乙烯吡咯烷酮、羟丙甲基纤维素、淀粉浆、明胶、羧甲基纤维素钠；所述致孔剂选自以下一种或多种：聚乙二醇、甘露醇、葡萄糖、乳糖、糊精、蔗糖、氯化钠、氯化钾；表面活性剂选自以下一种或多种：吐温、司盘、卵磷脂、大豆磷脂、十二烷基硫酸钠、胆固醇；润滑剂选自以下一种或多种：硬脂酸镁、硬脂酸、硬脂酸钙、硬脂酰富马酸钠；助流剂选自以下一种或多种：微粉硅胶、滑石粉；所述填充剂选自以下一种或多种：微晶纤维素、乳糖、甘露醇、山梨醇、淀粉、磷酸氢钙、硫酸钙、糊精、蔗糖；所述崩解剂选自以下一种或多种：羧甲基淀粉钠、交联聚维酮、交联羧甲基纤维素钠、预胶化淀粉；所述润湿剂选自以下一种或多种：水、乙醇、乙醇水溶液。
4.一种碳酸锂缓释片，其特征在于，缓释片的处方如下：
5.一种碳酸锂缓释片，其特征在于，缓释片的处方如下：
6.一种碳酸锂缓释片，其特征在于，缓释片的处方如下：
7.一种碳酸锂缓释片，其特征在于，缓释片的处方如下：
8.一种碳酸锂缓释片，其特征在于，缓释片的处方如下：
9.一种碳酸锂缓释片，其特征在于，缓释片的处方如下：
10.如权利要求1所述的缓释片，其特征在于，缓释片的处方如下：
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