CN1919186A - 他克莫司口服制剂 - Google Patents

他克莫司口服制剂 Download PDF

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Publication number
CN1919186A
CN1919186A CNA2006100218596A CN200610021859A CN1919186A CN 1919186 A CN1919186 A CN 1919186A CN A2006100218596 A CNA2006100218596 A CN A2006100218596A CN 200610021859 A CN200610021859 A CN 200610021859A CN 1919186 A CN1919186 A CN 1919186A
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tacrolimus
polyvidone
polyvinylpolypyrrolidone
ethanol
lactose
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CN100515413C (zh
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张为群
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Qu Jingping Ankang medical and health care Co., Ltd.
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Liuyang Pinghe Ankang Medicine Science & Technology Co Ltd
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Abstract

本发明为他克莫司口服制剂，解决已有他克莫司口服制剂使用有毒有机溶剂制备中间体，制备工艺复杂，成品质量差的问题。包括如下重量份的原料制成：他克莫司0.5、表面活性剂0.5－4.5、乙醇3.2－6、聚维酮0.5－4.5、交联聚维酮17.6－35，所说的表面活性剂为聚乙醇－6甘油单油酸酯，泊洛萨沙姆、十二烷基硫酸钠、聚氧乙篦麻油中的一种或二种，如用两种为任意重量比，其制备方法为将他克莫司与表面活性剂一个或二个混合使他克莫司完全浸润，加入乙醇使他克莫司溶解得澄明溶液，立即加入聚维酮迅速搅拌均匀，得澄明溶液，迅速加入交联聚维酮混合均匀得成品。

Description

他克莫司口服制剂
技术领域：
本发明与他克莫司作为主药的制剂有关。
背景技术：
他克莫司为白色晶体或结晶性粉末，不溶于水，易溶于乙醇。已有的他克莫司胶囊是先将他克莫司制成固体分散体，再将固体分散体制成胶囊，其制法如下：
固体分散体(SDF)处方：
他克莫司                        1.0g
羟丙基甲基纤微素2910(TC-5R)     1.0g
乙醇                            适量
二氯甲烷                        适量
乳糖                            2.0g
交联羧甲基纤微素钠(AC-Di-Sol)   1.0g
固体分散体(SDF)的制备工艺：
精密称取处方量他克莫司溶解在一定量的乙醇中得澄明溶液；再加入处方量的羟丙基甲基纤微素混合均匀，得类白色混悬液；立即加入一定量的二氯甲烷迅速搅拌均匀，得澄明溶液；迅速加入处方量的交联羧甲基纤微素钠和乳糖混合均匀，得白色乳液。约50℃水浴加热干燥，挥干溶媒，室温真空干燥20小时。将干燥物粉碎，过100目筛，得他克莫司固体分散体。
他克莫司胶囊处方：
(1)规格：每粒含他克莫司(C44H69NO2.H2O)1mg
SDF                                         5.0g
乳糖                                        59.15g
硬脂酸镁                                    0.65g
                                            共制成1000粒
(2)规格：每粒含他克莫司(C44H69NO2.H2O)5mg
SDF                                         5.0g
乳糖                                        113.6g
硬脂酸镁                                    1.4g
                                            共制成1000粒
制备工艺：
称取上述他克莫司固体分散体与硬脂酸镁充分混合均匀，以等量多次加入乳糖充分混合均匀。装入5号(规格：1mg)和4号(规格：5mg)空胶囊，经检验合格，包装即得成品。
已有的他克莫司胶囊的缺点：
1.使用有害原料有机溶剂二氯甲烷。
2.固体分散体制备工艺复杂。
3.固体分散体与乳糖混合均匀难度大，含量均匀度不易合格。
4.固体分散体久贮产生老化现象，造成溶出度降低，成品稳定性差。
发明的内容：
本发明的目的是提供一种制备工艺简单，不使用有机溶剂二氯甲烷，工艺稳定性好，溶出度好，成品稳定性好的他克莫司口服制剂。
本发明是这样实现的：
本发明他克莫司口服制剂，由包括如下重量份的原料制成：
他克莫司                        0.5
表面活性剂                      0.5-4.5
乙醇                            3.2-6
聚维酮                          0.5-4.5
交联聚维酮                      17.6-35，
所说的表面活性剂为聚乙醇-6甘油单油酸酯，泊洛萨沙姆、十二烷基硫酸钠、聚氧乙篦麻油中的一种或二种，如用两种为任意重量比，其制备方法为将他克莫司与表面活性剂一个或二个混合使他克莫司完全浸润，加入乙醇使他克莫司溶解得澄明溶液，立即加入聚维酮迅速搅拌均匀，得澄明溶液，迅速加入交联聚维酮混合均匀得成品。
为胶囊剂。
为片剂，原料中有乳糖15-27重量份、交联羧甲基纤维素钠1.75-3重量份、硬脂酸镁0.125-0.3重量份，将成品干燥，整粒后与乳糖、交联羧甲基纤维素钠和硬脂酸混合、用冲膜压片制得。
为干混悬剂，辅料中还含有乳糖15-27重量份、矫味剂2-20量份和增稠剂1.2-10重量份，将成品制粒后干燥、整粒、与乳糖、矫味剂和增稠剂混合均匀即得。
聚维酮为Plasdone(R)K系列，交联聚维酮为Polplasdone XL(R)系列。
本发明有如下优点：
1.不使用有机溶剂二氯甲烷.
2.制备工艺简单。
3.原料混合易均匀，制剂各组分含量均匀度容易合格。
4.各组分在工艺制备过程中稳定不易老化，溶出度合格，制剂稳定性好。
具体实施方式：
实施例1：
1.胶囊剂处方：
(1)规格：胶囊每粒含他克莫司(C44H69NO2.H2O)0.5mg
处方1：
他克莫司                                    0.5g
乙醇                                        4.0g
泊洛萨沙姆(Lutorl F 68(R)                   1.5g
聚维酮(Plasdone_K25)                      4.5g
交联聚维酮(Polplasdone_XL)                22.0g
                                            共制成1000粒
处方2：
他克莫司                                    0.5g
乙醇                                        5.0g
十二烷基硫酸钠                              2.0g
聚维酮(Plasdone_K90)                      1.0g
交联聚维酮(Polplasdone_XL-10)             25.0g
                                            共制成1000粒
处方3：
他克莫司                                    0.5g
乙醇                                        6.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)   0.5g
聚维酮(Plasdone_K31/29)                   1.5g
交联聚维酮(Polplasdone_XL)                26.0g
                                            共制成1000粒
处方4：
他克莫司                                    0.5g
乙醇                                        6.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)        0.5g
聚维酮(Plasdone_K90D)                     0.5g
交联聚维酮(Polplasdone_XL)                27.0g
                                            共制成1000粒
处方5：
他克莫司                                    0.5g
乙醇                                        6.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)   0.5g
聚维酮(Plasdone_K31/29)                   1.5g
交联聚维酮(Polplasdone_XL)                22.0g
十二烷基硫酸钠                              2.0g
                                            共制成1000粒
处方6：
他克莫司                                    0.5g
乙醇                                        6.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)        0.5g
聚维酮(Plasdone_K31/29)                   2.5g
交联聚维酮(Polplasdone_XL)                22.0g
十二烷基硫酸钠                              2.0g
                                            共制成1000粒
(2)规格：胶囊每粒含他克莫司(C44H69NO2.H2O)1mg
处方1：
他克莫司                                    1.0g
乙醇                                        8.0g
泊洛萨沙姆(Lutorl F 68(R)                   3.0g
聚维酮(Plasdone_K25)                      9.0g
交联聚维酮(Polplasdone_XL)                44.0g
                                            共制成1000粒
处方2：
他克莫司                                    1.0g
乙醇                                        10.0g
十二烷基硫酸钠                              4.0g
聚维酮(Plasdone_K90)                      2.0g
交联聚维酮(Polplasdone_XL-10)             50.0g
                                            共制成1000粒
处方3：
他克莫司                                    1.0g
乙醇                                        12.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)   1.0g
聚维酮(Plasdone_K31/29)                   3.0g
交联聚维酮(Polplasdone_XL)                52.0g
                                            共制成1000粒
处方4：
他克莫司                                    1.0g
乙醇                                        12.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)        1.0g
聚维酮(Plasdone_K90D)                     1.0g
交联聚维酮(Polplasdone_XL)                54.0g
                                            共制成1000粒
处方5：
他克莫司                                    1.0g
乙醇                                        8.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)   1.0g
聚维酮(Plasdone_K31/29)                   3.0g
交联聚维酮(Polplasdone_XL)                44.0g
十二烷基硫酸钠                              4.0g
                                            共制成1000粒
处方6：
他克莫司                                    1.0g
乙醇                                        8.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)        1.0g
聚维酮(Plasdone_K31/29)                   5.0g
交联聚维酮(Polplasdone_XL-10)             44.0g
十二烷基硫酸钠                              4.0g
                                            共制成1000粒
(3)规格：胶囊每粒含他克莫司(C44H69NO2.H2O)  5mg
处方1：
他克莫司                                    5.0g
乙醇                                        32.0g
泊洛萨沙姆(Lutorl F 68(R)                   15.0g
聚维酮(Plasdone_K25)                      45.0g
交联聚维酮(Polplasdone_XL)                176.0g
                                            共制成1000粒
其中他克莫司与聚维酮(Plasdone_K25)的用量比为：1∶1～9。
处方2：
他克莫司                                    5.0g
乙醇                                        40.0g
十二烷基硫酸钠                              10.0g
聚维酮(Plasdone_K90)                      10.0g
交联聚维酮(Polplasdone_XL-10)             200.0g
                                            共制成1000粒
处方3：
他克莫司                                    5.0g
乙醇                                        48.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)   5.0g
聚维酮(Plasdone_K31/29)                   15.0g
交联聚维酮(Polplasdone_XL)                208.0g
                                            共制成1000粒
处方4：
他克莫司                                    5.0g
乙醇                                        48.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)        5.0g
聚维酮(Plasdone_K90D)                     5.0g
交联聚维酮(Polplasdone_XL)                216.0g
                                            共制成1000粒
处方5：
他克莫司                                    5.0g
乙醇                                        32.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)   5.0g
聚维酮(Plasdone_K31/29)                   15.0g
交联聚维酮(Polplasdone_XL)                176.0g
十二烷基硫酸钠                              10.0g
                                            共制成1000粒
处方6：
他克莫司                                    5.0g
乙醇                                        35.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)        5.0g
聚维酮(Plasdone_K31/29)                   25.0g
交联聚维酮(Polplasdone_XL-10)             176.0g
十二烷基硫酸钠                              10g
                                            共制成1000粒
制备工艺：
精密称取处方量他克莫司加入处方量的表面活性剂使其主药完全浸润，再加入一定量的乙醇使其溶解得澄明溶液，；立即加入处方量的聚维酮迅速搅拌均匀，得澄明溶液；迅速加入处方量的交联聚维酮混合均匀，制粒。将其放入50℃鼓风干燥箱干燥，整粒，装入5号(规格：0.5mg)、4号(规格：1mg)和0号(规格：5mg)空胶囊即得。
2.片剂处方：
(1)规格：每片含他克莫司(C44H69NO2.H2O)0.5mg
处方1：
他克莫司                                0.5g
乙醇                                    4.0g
泊洛萨沙姆(Lutorl F 68(R)               1.5g
聚维酮(Plasdone_K25)                  4.5g
交联聚维酮(Polplasdone_XL)            22.0g
乳糖                                    27.0g
交联羧甲基纤微素钠                      3.0g
硬脂酸镁                                0.3g
                                        共制成1000片
处方2：
他克莫司                                0.5g
乙醇                                    5.0g
十二烷基硫酸钠                          2.0g
聚维酮(Plasdone_K90)                  1.0g
交联聚维酮(Polplasdone_XL-10)         25.0g
乳糖                                    25.0g
交联羧甲基纤微素钠                      3.0g
硬脂酸镁                                0.3g
                                        共制成1000片
处方3：
他克莫司                                 0.5g
乙醇                                     6.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)0.5g
聚维酮(Plasdone_K31/29)                1.5g
交联聚维酮(Polplasdone_XL)             30.0g
乳糖                                    25.0g
交联羧甲基纤微素钠                      3.0g
硬脂酸镁                                0.3g
                                        共制成1000片
处方4：
他克莫司                                0.5g
乙醇                                    6.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)    0.5g
聚维酮(Plasdone_K90D)                 0.5g
交联聚维酮(Polplasdone_XL)            35.5g
乳糖                                    27.0g
交联羧甲基纤微素钠                      3.0g
硬脂酸镁                                0.3g
                                        共制成1000片
处方5：
他克莫司                                 0.5g
乙醇                                     6.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)0.5g
聚维酮(Plasdone_K31/29)                1.5g
交联聚维酮(Polplasdone_XL)             35.0g
十二烷基硫酸钠                           4g
乳糖                                     22.0g
交联羧甲基纤微素钠                       3.0g
硬脂酸镁                                 0.3g
                                         共制成1000片
处方6：
他克莫司                                0.5g
乙醇                                    6.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)    0.5g
聚维酮(Plasdone_K31/29)               2.5g
交联聚维酮(Polplasdone_XL)            22.0g
十二烷基硫酸钠                          4g
乳糖                                        25.0g
交联羧甲基纤微素钠                          3.0g
硬脂酸镁                                    0.3g
                                            共制成1000片
(2)规格：每片含他克莫司(C44H69NO2.H2O)1mg
处方1：
他克莫司                                    1.0g
乙醇                                        8.0g
泊洛萨沙姆(Lutorl F 68(R)                   3.0g
聚维酮(Plasdone_K25)                      9.0g
交联聚维酮(Polplasdone_XL)                44.0g
乳糖                                        45.0g
交联羧甲基纤微素钠                          5.0g
硬脂酸镁                                    0.5g
                                            共制成1000片
处方2：
他克莫司                                    1.0g
乙醇                                        10.0g
十二烷基硫酸钠                              4.0g
聚维酮(Plasdone_K90)                      2.0g
交联聚维酮(Polplasdone_XL-10)             50.0g
乳糖                                        45.0g
交联羧甲基纤微素钠                          5.0g
硬脂酸镁                                    0.5g
                                            共制成1000片
处方3：
他克莫司                                    1.0g
乙醇                                        12.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)   1.0g
聚维酮(Plasdone_K31/29)                   3.0g
交联聚维酮(Polplasdone_XL)                52.0g
乳糖                                        45.0g
交联羧甲基纤微素钠                            5.0g
硬脂酸镁                                      0.5g
                                              共制成1000片
处方4：
他克莫司                                      1.0g
乙醇                                          12.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)          1.0g
聚维酮(Plasdone_K90D)                       1.0g
交联聚维酮(Polplasdone_XL)                  54.0g
乳糖                                          45.0g
交联羧甲基纤微素钠                            5.0g
硬脂酸镁                                      0.5g
                                              共制成1000片
处方5：
他克莫司                                      1.0g
乙醇                                          8.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)     1.0g
聚维酮(Plasdone_K31/29)                     3.0g
交联聚维酮(Polplasdone_XL)                  44.0g
十二烷基硫酸钠                                4g
乳糖                                          45.0g
交联羧甲基纤微素钠                            5.0g
硬脂酸镁                                      0.5g
                                              共制成1000片
处方6：
他克莫司                                      1.0g
乙醇                                          8.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)          1.0g
聚维酮(Plasdone_K31/29)                     5.0g
交联聚维酮(Polplasdone_XL-10)               44.0g
十二烷基硫酸钠                                4g
乳糖                                          45.0g
交联羧甲基纤微素钠                               5.0g
硬脂酸镁                                         0.5g
                                                 共制成1000片
(3)规格：每片含他克莫司(C44H69NO2.H2O)5mg
处方1：
他克莫司                                         5.0g
乙醇                                             32.0g
泊洛萨沙姆(Lutorl F 68(R)                        15.0g
聚维酮(Plasdone_K25)                           45.0g
交联聚维酮(Polplasdone_XL)                     176.0g
乳糖                                             150.0
交联羧甲基纤微素钠                               17.5g
硬脂酸镁                                         1.25g
                                                 共制成1000片
处方2：
他克莫司                                         5.0g
乙醇                                             40.0g
十二烷基硫酸钠                                   10.0g
聚维酮(Plasdone_K90)                           10.0g
交联聚维酮(Polplasdone_XL-10)                  200.0g
乳糖                                             150.0
交联羧甲基纤微素钠                               17.5g
硬脂酸镁                                         1.25g
                                                 共制成1000片
处方3：
他克莫司                                         5.0g
乙醇                                             48.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)        5.0g
聚维酮(Plasdone_K31/29)                        15.0g
交联聚维酮(Polplasdone_XL)                     208.0g
乳糖                                             150.0
交联羧甲基纤微素钠                            17.5g
硬脂酸镁                                      1.25g
                                              共制成1000片
处方4：
他克莫司                                      5.0g
乙醇                                          48.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)          5.0g
聚维酮(Plasdone_K90D)                       5.0g
交联聚维酮(Polplasdone_XL)                  216.0g
乳糖                                          150.0
交联羧甲基纤微素钠                            17.5g
硬脂酸镁                                      1.25g
                                              共制成1000片
处方5：
他克莫司                                      5.0g
乙醇                                          32.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)     5.0g
聚维酮(Plasdone_K31/29)                     15.0g
交联聚维酮(Polplasdone_XL)                  176.0g
十二烷基硫酸钠                                10.0g
乳糖                                          150.0
交联羧甲基纤微素钠                            17.5g
硬脂酸镁                                      1.25g
                                              共制成1000片
处方6：
他克莫司                                      5.0g
乙醇                                          32.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)          5.0g
聚维酮(Plasdone_K31/29)                     25.0g
交联聚维酮(Polplasdone_XL-10)               176.0g
十二烷基硫酸钠                                10g
乳糖                                          150.0
交联羧甲基纤微素钠                    17.5g
硬脂酸镁                              1.25g
                                      共制成1000片
制备工艺：
精密称取处方量他克莫司加入处方量的表面活性剂使其主药完全浸润，再加入一定量的乙醇使其溶解得澄明溶液，；立即加入处方量的聚维酮迅速搅拌均匀，得澄明溶液；迅速加入处方量的交联聚维酮混合均匀，制粒。将其放入50℃鼓风干燥箱干燥，整粒，与乳糖和交联羧甲基纤微素钠和硬脂酸镁混合均匀，不同规格选择相应冲模压片即得。
3.干混悬剂处方：
(1)规格：每袋含他克莫司(C44H69NO2.H2O)0.5mg
处方1：
他克莫司                              0.5g
乙醇                                  4.0g
泊洛萨沙姆(Lutorl F 68(R)             1.5g
聚维酮(Plasdone_K25)                4.5g
交联聚维酮(Polplasdone_XL)          22.5g
乳糖                                  27.0g
矫味剂                                5g
增稠剂                                3g
                                      共制成1000袋
处方2：
他克莫司                              0.5g
乙醇                                  5.0g
十二烷基硫酸钠                        2.0g
聚维酮(Plasdone_K90)                1.0g
交联聚维酮(Polplasdone_XL-10)       25.0g
乳糖                                  27.0g
矫味剂                                20g
增稠剂                                10g
                                      共制成1000袋
处方3：
他克莫司                                 0.5g
乙醇                                     6.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)0.5g
聚维酮(Plasdone_K31/29)                1.5g
交联聚维酮(Polplasdone_XL)             26.0g
乳糖                                     27.0g
矫味剂                                   15g
增稠剂                                   8g
                                         共制成1000袋
处方4：
他克莫司                                 0.5g
乙醇                                     6.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)     0.5g
聚维酮(Plasdone_K90D)                  0.5g
交联聚维酮(Polplasdone_XL)             27.0g
乳糖                                     27.0g
矫味剂                                   12g
增稠剂                                   20g
                                         共制成1000袋
处方5：
他克莫司                                 0.5g
乙醇                                     4.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)0.5g
聚维酮(Plasdone_K31/29)                1.5g
交联聚维酮(Polplasdone_XL)             22.0g
十二烷基硫酸钠                           4g
乳糖                                     27.0g
矫味剂                                   10g
增稠剂                                   8g
                                         共制成1000袋
处方6：
他克莫司                            0.5g
乙醇                                4.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)0.5g
聚维酮(Plasdone_K31/29)           2.5g
交联聚维酮(Polplasdone_XL)        22.0g
十二烷基硫酸钠                      4g
乳糖                                27.0g
矫味剂                              15g
增稠剂                              10g
                                    共制成1000袋
(2)规格：每袋含他克莫司(C44H69NO2.H2O)1mg
处方1：他克莫司                     1.0g
乙醇                                4.0g
泊洛萨沙姆(Lutorl F 68(R)           3.0g
聚维酮(Plasdone_K25)              9.0g
交联聚维酮(Polplasdone_XL)        44.0g
乳糖                                45.0g
矫味剂                              10g
增稠剂                              5g
                                    共制成1000袋
处方2：
他克莫司                            1.0g
乙醇                                10.0g
十二烷基硫酸钠                      4.0g
聚维酮(Plasdone_K90)              2.0g
交联聚维酮(Polplasdone_XL-10)     50.0g
乳糖                                45.0g
矫味剂                              15g
增稠剂                              10g
                                    共制成1000袋
处方3：
他克莫司                                 1.0g
乙醇                                     12.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)1.0g
聚维酮(Plasdone_K31/29)                3.0g
交联聚维酮(Polplasdone_XL)             52.0g
乳糖                                     45.0g
矫味剂                                   15g
增稠剂                                   10g
                                         共制成1000袋
处方4：
他克莫司                                1.0g
乙醇                                    12.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)    1.0g
聚维酮(Plasdone_K90D)                 1.0g
交联聚维酮(Polplasdone_XL)            54.0g
乳糖                                    45.0g
矫味剂                                  20g
增稠剂                                  12g
                                        共制成1000袋
处方5：
他克莫司                                 1.0g
乙醇                                     12.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)1.0g
聚维酮(Plasdone_K31/29)                3.0g
交联聚维酮(Polplasdone_XL)             44.0g
十二烷基硫酸钠                           4g
乳糖                                     45.0g
矫味剂                                   18g
增稠剂                                   15g
                                         共制成1000袋
处方6：
他克莫司                              1.0g
乙醇                                  12.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)  1.0g
聚维酮(Plasdone_K31/29)             5.0g
交联聚维酮(Polplasdone_XL-10)       44.0g
十二烷基硫酸钠                        4g
乳糖                                  45.0g
矫味剂                                20g
增稠剂                                12g
                                      共制成1000袋
(3)规格：每袋含他克莫司(C44H69NO2.H2O)5mg
处方1：
他克莫司                              5.0g
乙醇                                  32.0g
泊洛萨沙姆(Lutorl F 68(R)             15.0g
聚维酮(Plasdone_K25)                45.0g
交联聚维酮(Polplasdone_XL)          176.0g
乳糖                                  150.0
矫味剂                                20g
增稠剂                                15g
                                      共制成1000袋
处方2：
他克莫司                              5.0g
乙醇                                  40.0g
十二烷基硫酸钠                        10.0g
聚维酮(Plasdone_K90)                10.0g
交联聚维酮(Polplasdone_XL-10)       200.0g
乳糖                                  150.0
矫味剂                                25g
增稠剂                                20g
                                      共制成1000袋
处方3：
他克莫司                                    5.0g
乙醇                                        48.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)   5.0g
聚维酮(Plasdone_K31/29)                   15.0g
交联聚维酮(Polplasdone_XL)                208.0g
乳糖                                        150.0
矫味剂                                      20g
增稠剂                                      18g
                                            共制成1000袋
处方4：
他克莫司                                    5.0g
乙醇                                        48.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)        5.0g
聚维酮(Plasdone_K90D)                     5.0g
交联聚维酮(Polplasdone_XL)                216.0g
乳糖                                        150.0
矫味剂                                      30g
增稠剂                                      15g
                                            共制成1000袋
处方5：
他克莫司                                    5.0g
乙醇                                        32.0g
聚乙二醇-6甘油单油酸酯(labrafil_M 1944)   5.0g
聚维酮(Plasdone_K31/29)                   15.0g
交联聚维酮(Polplasdone_XL)                176.0g
十二烷基硫酸钠                              10.0g
乳糖                                        150.0
矫味剂                                      28g
增稠剂                                      18g
                                            共制成1000袋
处方6：
他克莫司                                    5.0g
乙醇                                        32.0g
聚氧乙烯篦麻油商品名：(Cremophor EL)        5.0g
聚维酮(Plasdone_K31/29)                   25.0g
交联聚维酮(Polplasdone_XL-10)             176.0g
十二烷基硫酸钠                              10g
乳糖                                        150.0
矫味剂                                      30g
增稠剂                                      20g
                                            共制成1000袋
制备工艺：
精密称取处方量他克莫司加入处方量的表面活性剂使其主药完全浸润，再加入一定量的乙醇使其溶解得澄明溶液，；立即加入处方量的聚维酮迅速搅拌均匀，得澄明溶液；迅速加入处方量的交联聚维酮混合均匀，制粒。将其放入50℃鼓风干燥箱干燥，整粒，与矫味剂和增稠剂混合均匀，装袋、密封，即得。

Claims (5)

1、他克莫司口服制剂，其特征在于由包括如下重量份的原料制成：
他克莫司                       0.5
表面活性剂                     0.5-4.5
乙醇                           3.2-6
聚维酮                         0.5-4.5
交联聚维酮                     17.6-35，
所说的表面活性剂为聚乙醇-6甘油单油酸酯，泊洛萨沙姆、十二烷基硫酸钠、聚氧乙篦麻油中的一种或二种，如用两种为任意重量比，其制备方法为将他克莫司与表面活性剂一个或二个混合使他克莫司完全浸润，加入乙醇使他克莫司溶解得澄明溶液，立即加入聚维酮迅速搅拌均匀，得澄明溶液，迅速加入交联聚维酮混合均匀得成品。
2、根据权利要求1所述的制剂，其特征在于为胶囊剂。
3、根据权利要求1所述的制剂，其特征在于为片剂原料中有乳糖15-27重量份、交联羧甲基纤维素钠1.75-3重量份、硬脂酸镁0.125-0.3重量份，将成品干燥，整粒后与乳糖、交联羧甲基纤维素钠和硬脂酸混合、用冲膜压片制得。
4、根据权利要求1所述的制剂，其特征在于为干混悬剂，原料中还含有乳糖15-27重量份、矫味剂2-20重量份和增稠剂1.2-10重量份，将成品制粒后干燥、整粒、与乳糖、矫味剂和增稠剂混合均匀即得。
5、根据权利要求1所述的制剂，其特征在于聚维酮为Plasdone(R)K系列，交联聚维酮为Polplasdone XL(R)系列。
CNB2006100218596A 2006-09-15 2006-09-15 他克莫司口服制剂 Expired - Fee Related CN100515413C (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009098649A1 (es) 2008-02-05 2009-08-13 Igloo Zone Chile S.A. Polvo para suspensión oral de un macrólido inmunosupresor

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104840446B (zh) * 2015-05-27 2017-08-11 福建科瑞药业有限公司 一种他克莫司药物组合物及其制备方法

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2009098649A1 (es) 2008-02-05 2009-08-13 Igloo Zone Chile S.A. Polvo para suspensión oral de un macrólido inmunosupresor

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