CN1194827A - 自由流动的干燥颗粒 - Google Patents
自由流动的干燥颗粒 Download PDFInfo
- Publication number
- CN1194827A CN1194827A CN98105288A CN98105288A CN1194827A CN 1194827 A CN1194827 A CN 1194827A CN 98105288 A CN98105288 A CN 98105288A CN 98105288 A CN98105288 A CN 98105288A CN 1194827 A CN1194827 A CN 1194827A
- Authority
- CN
- China
- Prior art keywords
- dried particles
- weight
- vitamin
- calcium
- calcium silicates
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000002245 particle Substances 0.000 title claims abstract description 24
- 235000012241 calcium silicate Nutrition 0.000 claims abstract description 40
- 239000000203 mixture Substances 0.000 claims abstract description 27
- 239000000126 substance Substances 0.000 claims abstract description 24
- 239000011248 coating agent Substances 0.000 claims abstract description 23
- 238000000576 coating method Methods 0.000 claims abstract description 23
- 230000009969 flowable effect Effects 0.000 claims abstract description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims abstract description 12
- 239000012876 carrier material Substances 0.000 claims abstract description 11
- 235000012239 silicon dioxide Nutrition 0.000 claims abstract description 9
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims abstract description 8
- 239000008108 microcrystalline cellulose Substances 0.000 claims abstract description 8
- 229940016286 microcrystalline cellulose Drugs 0.000 claims abstract description 8
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims abstract description 8
- 235000021355 Stearic acid Nutrition 0.000 claims abstract description 6
- 235000019359 magnesium stearate Nutrition 0.000 claims abstract description 6
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims abstract description 6
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000008117 stearic acid Substances 0.000 claims abstract description 6
- 239000005995 Aluminium silicate Substances 0.000 claims abstract description 4
- 235000012211 aluminium silicate Nutrition 0.000 claims abstract description 4
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 claims abstract description 4
- 239000008116 calcium stearate Substances 0.000 claims abstract description 4
- 235000013539 calcium stearate Nutrition 0.000 claims abstract description 4
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 claims abstract description 4
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000395 magnesium oxide Substances 0.000 claims abstract description 4
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims abstract description 4
- 235000012245 magnesium oxide Nutrition 0.000 claims abstract description 4
- 239000000391 magnesium silicate Substances 0.000 claims abstract description 4
- 235000019792 magnesium silicate Nutrition 0.000 claims abstract description 4
- 229910052919 magnesium silicate Inorganic materials 0.000 claims abstract description 4
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims abstract description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 42
- 239000008187 granular material Substances 0.000 claims description 36
- 235000019165 vitamin E Nutrition 0.000 claims description 20
- 239000011709 vitamin E Substances 0.000 claims description 20
- 229930003427 Vitamin E Natural products 0.000 claims description 18
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 18
- 229940046009 vitamin E Drugs 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 229940088594 vitamin Drugs 0.000 claims description 12
- 229930003231 vitamin Natural products 0.000 claims description 12
- 235000013343 vitamin Nutrition 0.000 claims description 12
- 239000011782 vitamin Substances 0.000 claims description 12
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- 150000003722 vitamin derivatives Chemical class 0.000 claims description 9
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- 239000000839 emulsion Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims description 8
- 239000008107 starch Substances 0.000 claims description 8
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- 239000000758 substrate Substances 0.000 claims description 8
- 241000206672 Gelidium Species 0.000 claims description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- 229910004298 SiO 2 Inorganic materials 0.000 claims description 6
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 claims description 6
- 235000013734 beta-carotene Nutrition 0.000 claims description 6
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 claims description 6
- 239000011648 beta-carotene Substances 0.000 claims description 6
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- 239000001913 cellulose Substances 0.000 claims description 6
- 229920002678 cellulose Polymers 0.000 claims description 6
- 239000004615 ingredient Substances 0.000 claims description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 6
- 108010059642 isinglass Proteins 0.000 claims description 6
- 239000011707 mineral Substances 0.000 claims description 6
- 235000010755 mineral Nutrition 0.000 claims description 6
- 229910052627 muscovite Inorganic materials 0.000 claims description 6
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 claims description 6
- 235000010980 cellulose Nutrition 0.000 claims description 5
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 239000007909 solid dosage form Substances 0.000 claims description 5
- 229940042585 tocopherol acetate Drugs 0.000 claims description 5
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 4
- 108010010803 Gelatin Proteins 0.000 claims description 4
- 239000005913 Maltodextrin Substances 0.000 claims description 4
- 229920002774 Maltodextrin Polymers 0.000 claims description 4
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 claims description 4
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims description 4
- 229930003316 Vitamin D Natural products 0.000 claims description 4
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 claims description 4
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 4
- 235000021466 carotenoid Nutrition 0.000 claims description 4
- 150000001747 carotenoids Chemical class 0.000 claims description 4
- 239000008273 gelatin Substances 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 235000011852 gelatine desserts Nutrition 0.000 claims description 4
- 229940035034 maltodextrin Drugs 0.000 claims description 4
- QGNJRVVDBSJHIZ-QHLGVNSISA-N retinyl acetate Chemical compound CC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C QGNJRVVDBSJHIZ-QHLGVNSISA-N 0.000 claims description 4
- 235000019155 vitamin A Nutrition 0.000 claims description 4
- 239000011719 vitamin A Substances 0.000 claims description 4
- 235000019166 vitamin D Nutrition 0.000 claims description 4
- 239000011710 vitamin D Substances 0.000 claims description 4
- 150000003710 vitamin D derivatives Chemical class 0.000 claims description 4
- 229940045997 vitamin a Drugs 0.000 claims description 4
- 229940046008 vitamin d Drugs 0.000 claims description 4
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 claims description 3
- 241001597008 Nomeidae Species 0.000 claims description 3
- 229930003448 Vitamin K Natural products 0.000 claims description 3
- 235000013339 cereals Nutrition 0.000 claims description 3
- 235000013305 food Nutrition 0.000 claims description 3
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 claims description 3
- 239000011573 trace mineral Substances 0.000 claims description 3
- 235000013619 trace mineral Nutrition 0.000 claims description 3
- 235000019168 vitamin K Nutrition 0.000 claims description 3
- 239000011712 vitamin K Substances 0.000 claims description 3
- 150000003721 vitamin K derivatives Chemical class 0.000 claims description 3
- 229940046010 vitamin k Drugs 0.000 claims description 3
- 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
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical class O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims description 2
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- 239000004368 Modified starch Substances 0.000 claims description 2
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- 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 claims description 2
- VYGQUTWHTHXGQB-UHFFFAOYSA-N Retinol hexadecanoate Natural products CCCCCCCCCCCCCCCC(=O)OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-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
- 238000004220 aggregation Methods 0.000 claims description 2
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- 235000010410 calcium alginate Nutrition 0.000 claims description 2
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- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 claims description 2
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- 229960002401 calcium lactate Drugs 0.000 claims description 2
- 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 claims description 2
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 abstract description 7
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- 229910052918 calcium silicate Inorganic materials 0.000 abstract description 4
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 abstract description 4
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Abstract
本发明涉及一种可流动的干燥颗粒,所述颗粒含有存在于至少一种载体材料基质中的作为活性成分的至少一种亲油物质和包衣。包衣含有硅酸钙或硅酸钙与一种或多种混合物成分的混合物,所述混合物成分是微晶纤维素、硅酸镁、氧化镁、硬脂酸、硬脂酸钙、硬脂酸镁、亲水性硅酸、高岭土和/或Sterotex。
Description
本发明涉及可流动的干燥颗粒,所述颗粒含有存在于至少一种载体材料基质中的、作为活性成分的至少一种亲油物质和包衣。
含有存在于至少一种载体材料基质中的、作为活性成分的至少一种亲油物质和包衣的可流动干燥颗粒是已知的。作为活性成分的亲油物质的最高含量为50%(重量)。
这样的颗粒的生产方法记载于,例如德国专利1035319及相应的美国专利2756177,其中,将作为活性成分的油状维生素的分散液喷雾到大大过量的、含水量低于8%的淀粉粉末上,从而干燥的淀粉粉末捕集喷雾颗粒,喷雾颗粒失去一定量的水而固化并同时用淀粉粉末包衣。这些颗粒具有的严重缺陷是约15%量的淀粉粘附在其表面,因此颗粒仅含有相对较低含量的活性成分。
按照记载于美国专利3445563的类似方法,用吸水和不吸水的无机物质的混合物代替淀粉以消除源于细淀粉颗粒的爆裂危险。为获得理想结果,需使用20倍过量的捕集粉末。特别提及的可作为捕集粉末的吸水成分是硅酸钙,尤其是硅酸铝钙,作为油溶性活性成分的是维生素A和维生素D。在活性成分的活性为245000-532000 I.U./g的情况下,所得颗粒包含高达19%的捕集粉末作为包衣。
另外,从欧洲专利申请0074050可获知用于制备易氧化物质如维生素或类胡萝卜素的干燥的、自由流动粉末的方法,所述粉末用胶质包衣。该方法包括将这些物质分散到成膜胶质的水溶液中,所述胶质是均相的。加入一种或多种单、二或多糖物质,借助喷雾助剂将该分散液喷淋到喷雾塔中并在流化床中收集喷雾颗粒。由此,将基于分散液0.02-2.5倍重量的疏水性硅酸或者高级脂肪酸金属盐或与硅酸的混合物作为喷雾助剂引入流化床上方从而在喷雾颗粒的胶质还未发生固化的温度下均匀分布于喷雾范围内。颗粒中含有助剂,颗粒中的胶质物质基本上未凝固,在流化床中收集并用已知方法干燥。
在该方法中,虽然仅制备了疏水性喷雾助剂薄膜,但喷雾期间所形成的颗粒足够稳定,它们以非固态在一起时可避免颗粒的集聚,这样随后就可在流化床干燥器上直接干燥,该方法的主要缺点是使用了疏水性硅酸为喷雾助剂。在进一步加工的药品和食品工业中使用游离硅酸至少是有争议的,因为它危害健康,因而在许多国家禁用于该目的。
因此,上述方法和由此制造的可流动干燥颗粒并不能令人满意,尤其在用于药品和食品工业时。
本发明的目的是克服上述缺点。具体地说,提供了活性成分含量为50重量%和以上,尤其是为约70重量%的上面述及的可流动干燥颗粒,即活性成分含量高的颗粒以及制备这种颗粒的方法。本发明的具体目的还有为在给药形式中结合尽可能高含量的活性成分而用这类可流动干燥颗粒制备的固体给药形式。
可流动的颗粒由存在于至少一种载体基质中的、作为活性成分的至少一种亲油物质和包衣组成,所获得的颗粒由硅酸钙包衣而成。
包衣可仅由硅酸钙组成或者由硅酸钙和一种下列的混合物成分组成:微晶纤维素、硅酸镁、氧化镁、硬脂酸、硬脂酸钙、硬脂酸镁、亲水性硅酸、高岭土和/或润湿剂(Sterotex)。仅由硅酸钙组成的包衣是优选的。
本发明的颗粒含有50重量%或以上的亲油物质,颗粒平均粒径为约80μm-约1000μm,尤其是为约100μm-约800μm。
当仅由硅酸钙组成包衣时,亲油物质的量可高达70重量%也不会有上面所提到的缺点,甚至不会有微乎其微的缺点。依照本发明,甚至可以制备亲油物质含量高达74.0-78.0重量%的颗粒。
依照本发明,在其中包衣仅由硅酸钙组成的颗粒中,硅酸钙的含量为2-12重量%,优选为约≤7重量%。与现有技术相比,包衣物质含量低的主要原因在于活性成分含量高,即可将高含量的亲油物质掺入基质中而不会影响颗粒的加工。包衣物质含量之低至今仍令人出乎意料,推测考虑用于此目的并具有化学惰性的物质会以大约相同量完全粘附于基质载体材料。
在包衣由硅酸钙与一种或多种前述混合物成分的混合物组成的颗粒中,硅酸钙混合物的含量为5-25重量%。
然而,发现不论是硅酸钙的化学性质还是物理性质都具有重要意义。由此,出人意料地发现当粒径≤0.2μm,尤其是≤0.1μm时和比表面积为至少约80m2/g-约180m2/g,优选为约95m2/g-约120m2/g时,硅酸钙颗粒特别合适并聚成平均粒径为约5-20μm,优选5-10μm的聚集体。SiO2/CaO比例在1.65-2.65。
另外,当硅酸钙完全或部分以水合物形式存在时,是有益的。硅酸钙几乎不含结晶硅酸。因此,许多从市场上购得的作为包衣物质的硅酸钙不能用于根据本发明的颗粒,因为它们用结晶硅酸处理过。
亲油物质至少是一种下列物质:亲脂性维生素或它们的衍生物、类胡萝卜素,尤其是β-胡萝卜素和多不饱和脂肪酸如花生酸、二十碳五烯酸和二十二碳六烯酸以及至少一种选自维生素A、D、E和K或其衍生物的维生素,尤其是维生素A乙酸酯、维生素A棕榈酸酯和/或维生素E乙酸酯,优选维生素E或维生素E乙酸酯。
维生素E包括人工合成的生育酚或天然生育酚混合物。
载体材料是纤维素,水溶性纤维素衍生物,尤其是甲基纤维素或羟丙甲基纤维素,麦芽糖糊精,尤其是右旋糖当量值为约18的麦芽糖糊精,藻酸衍生物,尤其是藻酸钠、藻酸钙或藻酸丙二醇酯,乳酸钙,阿拉伯胶,明胶,尤其是鱼明胶,糖,糖醇,甘油,改性淀粉或预明胶化谷物淀粉,优选明胶,尤其是鱼明胶。已证明起霜号(Bloom number)为0-220的明胶尤其好。载体材料或包含载体材料的基质还可含有至少一种水溶性维生素。
可流动的干燥颗粒特别适于制造固体剂型,尤其是片剂,它们具有出色的流动性和压缩性质,不需加入常规量的压缩助剂。
考虑到本发明的颗粒中可掺入70重量%或更高含量(可毫无问题地分别掺入74重量%和78重量%的量)的活性成分,它们尤其适于制备多种维生素和多种矿物质的片剂,因为在这种情况下,活性成分的量应尽可能地高,而体积和重量却试图降到最低。在此,术语“多种维生素和多种矿物质片剂”还应理解为泡腾或可咀嚼片剂。
制备本发明颗粒的优选方法包括按照捕集方法,尤其是粉末捕集方法,将一种或多种亲油物质和一种或多种载体材料的水性乳液喷雾到硅酸钙或硅酸钙与特征如上所述的一种或多种混合物成分的混合物介质中,然后以常规方法干燥所得颗粒。
固体剂型,尤其是多种维生素片剂除含有作为活性成分的至少一种水溶性物质外,还优选含有作为活性成分的至少一种亲油物质,选自类胡萝卜素,尤其是β-胡萝卜素和维生素A、D、E和K或其衍生物。维生素E的含量优选为约4-50重量%,尤其是约5-19重量%。除常规辅剂外,该剂型还可含有至少一种通常以矿物形式掺入的微量元素,和/或至少一种水溶性维生素。
作为微量元素,尤其可使用锰、碘、钾、镁、钙、磷、锌、铜和铁,本发明颗粒的包衣至少在一定程度上提供了钙。其次可使用硒、铬、氯(以氯化物形式)、钼、镊、锡、硅(结合形式的)、钒和硼,同钙一样,本发明颗粒至少是部分地掺入了硅(结合形式的)。至少一种选自下组的物质可作为前述目的的水溶性物质:维生素C、B1、B2、B6和B12、泛酸、泛酸钙、叶酸、生物素和烟酰胺。
从以下实施例可清楚地看出其它特点和优点。
实施例1-3描述仅用硅酸钙包衣的颗粒。
实施例4描述用硅酸钙和微晶纤维素的混合物进行包衣。
实施例5-8描述多种维生素片。
实施例1
将38g干燥的鱼明胶(起霜号0)放在500ml容器中,然后加入95ml去离子水,在40-50℃下以1000转/分(rpm)用粉碎机盘搅拌使该混合物形成溶液,得到基质。然后在该基质中乳化154g生育酚乙酸酯并搅拌15分钟。乳化和搅拌期间粉碎机盘以4800rpm旋转。之后,乳液内相的平均粒径为约250nm。然后用130ml去离子水稀释该乳液并加热到65℃。随后,将225g硅酸钙(购自Celite Corp.,USA的Micro-Cel E,SiO2/CaO比例为1.65)放在冷却到0℃以下的实验室用喷雾罐中。使用旋转喷嘴将乳液喷雾到喷雾罐中。将如此得到的以硅酸钙包衣的颗粒过筛(筛级100-800μm)除去过量硅酸钙,并用空气流在室温干燥。由此获得190g具有出色的流动特性的硅酸钙包衣颗粒,使其充分干燥,它们十分易于加工。硅酸钙含量为7重量%。
实施例2
在类似实施例1的实验中,用购自英国Croda的起霜号为220的药用明胶代替鱼明胶。收率为195g。该产物具有与实施例1产物同样好的工业实用性。
实施例3
类似地重复实施例1,但使用SiO2/CaO比例为2.65的硅酸钙。形成了硅酸钙包衣颗粒,其中生育酚乙酸酯的含量仅为44.3重量%。硅酸钙的重量百分含量增加到大于7重量%。可见SiO2/Ca0比例大于2.65是不适宜的。
实施例4
将36g高分子的、干燥的鱼明胶(起霜号0;Norland ProductsIncorporated)放在500ml容器中,然后加入95ml去离子水,在40-50℃下以1000转/分(rpm)用粉碎机盘搅拌使该混合物形成溶液,得到基质。然后在该基质中乳化156g生育酚乙酸酯并搅拌15分钟。乳化和搅拌期间粉碎机盘以4800rpm旋转。之后,乳液内相的平均粒径为约300nm。然后用135ml去离子水稀释该乳液并加热到65℃。随后,将410g硅酸钙(购自Celite Corp.,USA的硅酸盐Micro-Cel E,SiO2/CaO比例为1.65)和微晶纤维素(VIVAPUE Type 105)的混合物放在实验室用喷雾罐中。VIVAPUE Type105与Micro-Cel E的比例为5.66∶1。将该混合物冷却到0℃以下。使用旋转喷嘴将乳液喷雾到喷雾罐中。将如此得到的以硅酸钙-纤维素包衣的颗粒过筛(筛级100-800μm)除去过量硅酸钙-纤维素混合物,并用空气流在室温干燥。由此获得222.1g具有出色的流动特性的硅酸钙-纤维素包衣颗粒,使其充分干燥,它们十分易于加工。硅酸钙含量为21重量%。
实施例5
在5-50KN压力下,由下列成分在Comprex II压片机上制备多种维生素片剂,冲头16×7.42mm。
实施例1的粉末产物 147.0mg
β-Tab7.5(购自ROCHE的
7.5%可压片β-胡萝卜素) 96.0mg
抗坏血酸90%gr. 244.5mg
微晶纤维素PH 102 130.0mg
乳糖DCL 21 50.0mg
总片重 668.0mg
所得片的硬度为20-140N。将片干燥。
实施例6
类似于实施例4,使用活性成分维生素E含量为75重量%的本发明颗粒制备多种维生素片剂(E 75%配方,含75重量%维生素E颗粒)并与相同组成的常规维生素片剂(E50%配方,含有50重量%维生素E颗粒)相比较。
E75%配方 E50%配方
片重 808.3mg 948.3mg
β-胡萝卜素* 34.5mg 34.5mg
维生素E 280.0mg 420.0mg
维生素C 90 291.7mg 291.7mg
微晶纤维素 161.6mg 161.6mg
Microcel C 24.3mg 24.3mg
PVP XL 16.2mg 16.2mg
*β-Tab 20(购自ROCHE的20%可压片的β-胡萝卜素)
由此可明显看出与使用常规制备的含维生素E颗粒相比,使用本发明的颗粒可制备出较小重量(或相应较小体积)的片剂。
实施例7
类似于实施例5,使用活性成分维生素E含量为75重量%的本发明颗粒制备多种维生素片剂(E 75%配方,含75重量%维生素E颗粒)并与相同组成的常规维生素片剂(E50%配方,含有50重量%维生素E颗粒)相比较。
E75%配方 E50%配方
维生素/矿物质混1294.8mg 1294.8mg
合物
维生素E 70.0mg 106.0mg
微纤维素 57.2mg 0.0mg
PVP XL 6.6mg 30.0mg
硬脂酸 2.0mg 2.0mg
硬脂酸镁 4.2mg 4.2mg
所得片剂的硬度为210N。在E 75%的配方中,可减少崩解剂PVP XL的量而不会改变片剂的溶出时间(不足5分钟)。
实施例8
类似于实施例5,使用活性成分维生素E含量为75重量%的本发明颗粒制备多种维生素片剂(E 75%配方,含75重量%维生素E颗粒)。该片剂不含崩解剂,具有如下组成。
E75%配方
维生素/矿物质混合物 1294.8mg
维生素E 70.7mg
微纤维素 58.0mg
淀粉 15.0mg
硬脂酸 2.0mg
硬脂酸镁 4.2mg
所得片剂硬度为210N。该片剂的溶出时间不足5分钟。
Claims (13)
1.可流动的干燥颗粒,含有存在于至少一种载体材料的基质中作为活性成分的至少一种亲油物质和包衣,其中包衣含有硅酸钙或硅酸钙与下列混合物成分之一的混合物:微晶纤维素、硅酸镁、氧化镁、硬脂酸、硬脂酸钙、硬脂酸镁、亲水性硅酸、高岭土和/或Sterotex。
2.权利要求1的可流动的干燥颗粒,其中包衣含有硅酸钙。
3.权利要求1或2的可自由流动的干燥颗粒,其中亲油物质的含量到50重量%或以上,优选高于70重量%,尤其是74.0-78.0重量%,平均粒径为约80μm-约1000μm,尤其是约100μm-约800μm。
4.权利要求2或3的可流动的干燥颗粒,其中硅酸钙的含量为2-12重量%,尤其是≤约7重量%。
5.权利要求1-4任一项的可流动的干燥颗粒,其中的硅酸钙
a)SiO2/CaO比例为1.65-2.65;
b)颗粒粒径为≤0.2μm,尤其是≤0.1μm,其聚成平均粒径为约5-20μm,特别是5-10μm的聚集体,比表面积为至少约80m2/g-约180m2/g,优选为约95m2/g-约120m2/g;并且
c)任意地全部或部分为水合硅酸钙形式。
6.权利要求1-5任一项的可流动的干燥颗粒,其中亲油物质是至少一种亲脂性维生素或它们的衍生物,优选是维生素A、D、E和K或它们的衍生物,尤其是维生素A乙酸酯、维生素A棕榈酸酯、维生素E和/或维生素E乙酸酯;类胡萝卜素,尤其是β-胡萝卜素;和/或一种多不饱和脂肪酸物质。
7.权利要求1-6任一项的可流动的干燥颗粒,其中载体材料是至少一种选自下列纤维素的物质:水溶性纤维素衍生物,尤其是甲基纤维素或羟丙甲基纤维素,麦芽糖糊精,尤其是右旋糖当量值为约18的麦芽糖糊精,藻酸衍生物,尤其是藻酸钠、藻酸钙或藻酸丙二醇酯,乳酸钙,阿拉伯胶,明胶,尤其是鱼明胶,糖,糖醇,甘油,改性淀粉或预明胶化谷物淀粉。
8.权利要求1-7任一项的可流动的干燥颗粒,其中基质中还存在至少一种水溶性维生素。
9.一种权利要求1-8任一项的可流动的干燥颗粒的制备方法,包括按照捕集方法,尤其是粉末捕集方法,将一种或多种亲油物质和一种或多种载体材料的水性乳液喷雾到硅酸钙或硅酸钙与一种或多种混合物成分的混合物的捕集介质中,然后以常规方法干燥所得颗粒。
10.由至少权利要求1-8之一的可流动干燥颗粒制备的固体剂型,尤其是多种维生素片剂。
11.权利要求10的固体剂型,尤其是多种维生素片剂,其中片剂中的维生素E含量为约4重量%-50重量%。
12.权利要求1-8任一项的可流动的干燥颗粒用于制备固体剂型,尤其是片剂的用途,特别是用于制备多种维生素片剂的用途,该片剂还任意地含有至少一种通常以矿物质形式掺入的微量元素。
13.权利要求1-8任一项的可流动干燥颗粒在药物或食品工业中的用途。
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- 1998-02-27 TW TW087102882A patent/TW505528B/zh not_active IP Right Cessation
- 1998-02-27 KR KR1019980006371A patent/KR19980071798A/ko active Search and Examination
- 1998-02-27 NO NO19980840A patent/NO320488B1/no unknown
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1326517C (zh) * | 2001-11-07 | 2007-07-18 | 芬泽尔伯格股份有限两合公司 | 制备干提取物的方法 |
CN101448408B (zh) * | 2006-05-19 | 2013-02-13 | 弗门尼舍有限公司 | 一步喷雾干燥法 |
CN103534343A (zh) * | 2011-02-14 | 2014-01-22 | 诺丁汉大学 | 油体的提取及用途 |
CN110087481A (zh) * | 2016-12-15 | 2019-08-02 | 帝斯曼知识产权资产管理有限公司 | 包含硅酸盐和含具有至少20个碳原子的多不饱和脂肪酸(lc-pufa)的微生物细胞和/或植物细胞的共混物制剂 |
CN111315241A (zh) * | 2017-10-05 | 2020-06-19 | 普拉克生化公司 | 乳酸盐粉末及其制备方法 |
CN109221869A (zh) * | 2018-10-25 | 2019-01-18 | 广州市炜鑫生物科技有限公司 | 一种复合酵素纤维素固体饮料及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
DK0867177T3 (da) | 2004-01-26 |
CN1146405C (zh) | 2004-04-21 |
EP0867177A1 (de) | 1998-09-30 |
NO980840D0 (no) | 1998-02-27 |
BR9800788A (pt) | 2000-04-04 |
US6030645A (en) | 2000-02-29 |
ID19841A (id) | 1998-08-06 |
EP0867177B1 (de) | 2003-10-08 |
CA2229351A1 (en) | 1998-08-28 |
JP4494539B2 (ja) | 2010-06-30 |
JPH10245348A (ja) | 1998-09-14 |
NO980840L (no) | 1998-08-31 |
NO320488B1 (no) | 2005-12-12 |
KR19980071798A (ko) | 1998-10-26 |
DE59809832D1 (de) | 2003-11-13 |
MX9801512A (zh) | 1999-04-01 |
CA2229351C (en) | 2009-04-14 |
ES2206770T3 (es) | 2004-05-16 |
AU5638498A (en) | 1998-09-03 |
MX205481B (zh) | 2001-12-13 |
TW505528B (en) | 2002-10-11 |
PH11998000410B1 (zh) | 2002-07-05 |
AU734530B2 (en) | 2001-06-14 |
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