CN1891212B - Oral preparation and its preparing method - Google Patents

Oral preparation and its preparing method Download PDF

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CN1891212B
CN1891212B CN 200510082716 CN200510082716A CN1891212B CN 1891212 B CN1891212 B CN 1891212B CN 200510082716 CN200510082716 CN 200510082716 CN 200510082716 A CN200510082716 A CN 200510082716A CN 1891212 B CN1891212 B CN 1891212B
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formulation
fty720
pharmaceutically acceptable
octyl
oral formulation
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CN1891212A (en
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张瑜
王琼
马启明
黄宗玉
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马启明
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Abstract

The present invention relates to an immunosuppressant preparation and its preparation method. In the concrete, it is an oral preparation, including 2-p-octylphenethyl-2-aminopropanediol hydrochloride as immunosuppressant, inorganic salt and/or other medicinal auxiliary material or carrier.

Description

一种口服制剂及其制备方法 An oral preparation and preparation method

[0001] 发明领域 [0001] Field of the Invention

[0002] 本发明涉及一种免疫抑制剂制剂及其制备方法。 [0002] The present invention relates to an immunosuppressive agent and preparation method thereof. 具体讲,本发明涉及一种口服制剂,其包括作为免疫抑制剂的2-对辛基苯乙基2-氨基丙二醇盐酸盐(简称为FTY720),无机盐,和/或其它药用辅料或载体。 In particular, the present invention relates to an oral formulation comprising as an immunosuppressant for 2-octyl-2-phenethyl-propanediol hydrochloride (abbreviated as of FTY720), inorganic salts, and / or other pharmaceutically acceptable adjuvant or carrier.

背景技术 Background technique

[0003] 2-对辛基苯乙基2-氨基丙二醇盐酸盐简称为FTY720,其是近几年新开发的一种免疫抑制剂,作用机制独特,免疫抑制效果强大,毒副作用小。 [0003] 2-p-phenethyl-2-octyl-propanediol hydrochloride of FTY720 for short, which is newly developed in recent years, an immunosuppressant, a unique mechanism of action, strong immunosuppressive effect, toxic side effects. 该药选择性减少外周循环淋巴细胞数,显著延长实验动物移植器官的生存,同时并不损害对病毒的免疫应答及免疫记忆功能,毒副作用低,并且与CsA、FK506, RAD等临床一线免疫抑制药物显示出良好的协同作用,在肾移植病人的一期临床试用效果良好,临床应用前景广阔。 The drug selectively reducing the number of lymphocytes in the peripheral circulation, significantly prolong survival of transplanted organs in experimental animals, but does not impair the immune response to the virus and immune memory function, low-toxicity, and inhibition with CsA, FK506, RAD and other front-line clinical immunity the drug showed good synergy, good kidney transplant patients in a clinical trial results, the clinical application prospect. 但FTY720若与常用药用辅料如乳糖、甘露醇、HPMC、淀粉、糖粉、糊精、微晶纤维素、硬脂酸镁、微粉硅胶等单独使用或合用配成口服固体制剂时,会造成制成的固体制剂中的杂质增加或活性成分含量降低,即制剂中活性成份不稳定。 However, if using FTY720 oral solid preparations or formulated in combination with conventional pharmaceutically acceptable excipients such as lactose, mannitol, HPMC, starch, powdered sugar, dextrin, microcrystalline cellulose, magnesium stearate, aerosil, alone, can cause the solid formulations made in increasing or decreasing the impurity content of the active ingredient, i.e. the active ingredient in the formulation unstable.

发明内容 SUMMARY

[0004] 本发明的目的是提供一种能使2-对辛基苯乙基2-氨基丙二醇盐酸盐在口服制剂中稳定的制剂及其制备方法。 [0004] The object of the present invention is to provide a method for its preparation 2- phenethyl 2-octyl-propanediol hydrochloride stable oral formulations can.

[0005] 本发明人经研究现已出人意料地发现将作为免疫抑制剂的FTY720与药用无机盐混合得到的固体口服制剂能使含FTY720的制剂无论是在制备中还是贮存中都能保持良好的稳定性。 [0005] The present invention has now been surprisingly found by the study as FTY720 obtained by mixing an inorganic salt with a pharmaceutically acceptable solid oral formulations of immunosuppressant FTY720 render the formulation containing either stored or in the preparation can maintain good stability.

[0006] 因此,本发明涉及一种口服制剂,其包括作为免疫抑制剂的2-对辛基苯乙基2-氨基丙二醇盐酸盐,药用无机盐,或选择性的其它药用辅料或载体。 [0006] Accordingly, the present invention relates to an oral formulation comprising as an immunosuppressant for 2-octyl-2-phenethyl-propanediol hydrochloride, pharmaceutically acceptable inorganic salt, or other pharmaceutically acceptable adjuvant or selective carrier.

[0007] 本发明还涉及一种制备口服制剂的方法,其包括将2-对辛基苯乙基2-氨基丙二醇盐酸盐与药用无机盐混合。 [0007] The present invention further relates to a method of preparing an oral preparation, which comprises 2-p-octyl-2-phenethyl-propanediol hydrochloride mixed with a pharmaceutically acceptable inorganic salt.

[0008] 根据本发明,以制剂总重计,本发明制剂中FTY720含量优选为0. 01重量% -20重 [0008] According to the present invention, the total weight of the formulation, the content of FTY720 formulations of the invention is preferably 0.01 wt% to about 20 weight

量%。 the amount%. 药用无机盐含量优选为80重量% -99. 99重量%。 Pharmaceutically acceptable inorganic salt content is preferably 80 wt% -99 99% by weight. 药用无机盐举例有:氯化钠、氯化钾、硫酸钙、硫酸钠、硫酸钾、磷酸二氢钾、磷酸二氢钠、磷酸氢二钾、磷酸氢二钠、磷酸氢钙等、或它们的两种或两种以上的混合物。 Examples pharmaceutically acceptable salts include: sodium chloride, potassium chloride, calcium sulfate, sodium sulfate, potassium sulfate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, disodium hydrogen phosphate, calcium hydrogen phosphate, or of two or more of a mixture of two.

[0009] 进一步讲,本发明制剂的形式举例讲为:片剂、胶囊或颗粒剂。 [0009] Further, the present invention is illustrated in the form of the formulation to say: tablets, capsules or granules.

[0010] 更进一步讲,本发明的制剂也可为单位剂型(量)形式,如每片,每粒或每包,且在单位剂型中,2-对辛基苯乙基2-氨基丙二醇盐酸盐的规格或含量为0. lmg-5mg。 [0010] Still further, the formulation of the present invention may also be a unit dosage (amount) in the form, e.g., tablet, or each and every packet, and in a unit dosage form, 2-phenylethyl 2-octyl-propanediol salt specifications or salt content of 0. lmg-5mg.

[0011] 本发明制剂的制备方法更具体讲包括:将FTY720与药用无机盐分别于50〜80°C 干燥,控制水分在2%以下,过60〜180目筛,混勻后制粒,制粒后压片或充填入胶囊或直接分装即可;或混勻后用滚压法压成小块状,然后粉碎成20〜60目大小的颗粒,压片或充填入胶囊或直接分装即可。 [0011] The formulations are prepared according to the invention more particularly comprises: FTY720 and pharmaceutically acceptable salts are dried at 50~80 ° C, controlling moisture below 2%, over 60~180 mesh sieve, mix granulated, after granulation tableting or filling into capsules, or can be directly dispensed; or after mixing method using a roller press into small pieces, and then crushed into granules of 20~60 mesh size, tableted or filled into capsules or direct distribution can be installed. 具体实施方式 Detailed ways

[0012] 下面的实施例用来进一步说明本发明,但其不意味着对本发明的任何限制。 [0012] The following examples serve to further illustrate the invention, but it does not imply any limitation of the invention.

[0013] 实施例: [0013] Example:

[0014] 为了便于考察,在本实施例中各个处方制成的制剂片剂或胶囊含活性物质为1毫克/每片或每粒。 [0014] For ease of study, a tablet or capsule formulation prepared in various formulation embodiments of the present embodiment containing active substance 1 mg / or each and every piece. 每一处方均制成1000片或粒。 Each formulation was made 1,000 or granules.

[0015] 实施例1(处方1) [0015] Example 1 (Formulation 1)

[0016] FTY720 lg,氯化钠20g,分别于60°C干燥4小时,控制水分在2%以下,过80目筛, 等量递增法混勻,加适量水制软材,过30目筛制粒,60°C干燥30分钟,24目整粒,按所需剂量压片或充填入胶囊即可。 [0016] FTY720 lg, NaCl 20g, respectively, at 60 ° C for 4 hours to control the water content below 2%, over 80 mesh sieve, the method of increasing mixing equal amounts, add water system of soft material through a 30 mesh sieve granulation, 60 ° C dry for 30 minutes, and 24 mesh granulated, tableted or the desired dosage can be filled into capsules. 60°C加热4小时和五天考察,检查杂质和FTY720含量变化,结果无明显变化(见表7)。 60 ° C for 4 hours study, and five days to check and change FTY720 impurities content was no significant change (see Table 7).

[0017] 实施例2 (处方2) [0017] Example 2 (Formulation 2)

[0018] FTY720 lg,氯化钾20g,分别于60°C干燥4小时,控制水分在2%以下,过80目筛, 等量递增法混勻,加适量水制软材,过30目筛制粒,60°C干燥30分钟,24目整粒,按所需剂量压片或充填入胶囊即可。 [0018] FTY720 lg, potassium chloride 20g, respectively, at 60 ° C for 4 hours to control the water content below 2%, over 80 mesh sieve, the method of increasing mixing equal amounts, add water system of soft material through a 30 mesh sieve granulation, 60 ° C dry for 30 minutes, and 24 mesh granulated, tableted or the desired dosage can be filled into capsules. 60°C加热4小时和五天考察,检查杂质和FTY720含量变化,结果无明显变化(见表7)。 60 ° C for 4 hours study, and five days to check and change FTY720 impurities content was no significant change (see Table 7).

[0019] 实施例3 (处方3) [0019] Example 3 (Formulation 3)

[0020] FTY720 lg,氯化钠10g,氯化钾10g,分别于60°C干燥4小时,控制水分在2%以下,过80目筛,等量递增法混勻,加适量水制软材,过30目筛制粒,60°C干燥30分钟,24目整粒,按所需剂量压片或充填入胶囊即可。 [0020] FTY720 lg, NaCl 10g, potassium chloride 10g, were dried at 60 ° C 4 hours to control the moisture below 2%, over 80 mesh sieve, the method of increasing mixing equal amounts, add water system soft material , granulated through a 30 mesh sieve, 60 ° C drying for 30 minutes, sieved 24 mesh, the desired dose tableted or filled into capsules to. 60°C加热4小时和五天考察,检查杂质和FTY720 含量变化,结果无明显变化(见表7)。 60 ° C for 4 hours study, and five days to check and change FTY720 impurities content was no significant change (see Table 7).

[0021] 实施例4 (处方4) [0021] Example 4 (Formulation 4)

[0022] FTY720 lg,硫酸钙20g,分别于60°C干燥4小时,控制水分在2%以下,过80目筛, 等量递增法混勻,加适量5%聚维酮K30的水溶液制软材,过30目筛制粒,60°C干燥30分钟,24目整粒,按所需剂量压片或充填入胶囊即可。 [0022] FTY720 lg, calcium sulfate 20g, were dried at 60 ° C 4 hours to control the moisture below 2%, over 80 mesh sieve, mix equal amounts incremental method, add appropriate amount of a 5% aqueous solution of povidone K30 manufactured soft material, granulated through a 30 mesh sieve, 60 ° C drying for 30 minutes, sieved 24 mesh, the desired dose tableted or filled into capsules to. 60°C加热4小时和五天考察,检查杂质和FTY720含量变化,结果含量明显变化(见表7)。 60 ° C for 4 hours study, five days and checked impurities FTY720 and content changes, changes in the results were significantly (Table 7).

[0023] 实施例5 (处方5) [0023] Example 5 (Formulation 5)

[0024] FTY720 lg,硫酸钾18g,微粉硅胶2g,分别于60°C干燥4小时,控制水分在2%以下,过80目筛,等量递增法混勻,按所需剂量压片或充填入胶囊即可。 [0024] FTY720 lg, potassium 18g, silica powder 2g, were dried at 60 ° C 4 hours to control the moisture below 2%, over 80 mesh sieve, mix equal amounts incremental method, the desired dose filling or tabletting the capsule can be. 60°C加热4小时和五天考察,检查杂质和FTY720含量变化,结果FTY720含量明显变化。 60 ° C for 4 hours study, and five days to check and change the impurity content FTY720, FTY720 results were significantly changed.

[0025] 实施例6 (处方6) [0025] Example 6 (Formulation 6)

[0026] FTY720 lg,磷酸二氢钾18g,微晶纤维素2g,分别于60°C干燥4小时,控制水分在2%以下,过80目筛,等量递增法混勻,用滚压法压成小块状,然后粉碎成20〜60目大小的颗粒,按所需剂量压片或充填入胶囊即可。 [0026] FTY720 lg, potassium phosphate monobasic 18g, microcrystalline cellulose 2g, were dried at 60 ° C 4 hours to control the moisture below 2%, over 80 mesh sieve, mix equal amounts incremental method, using a roller method pressed into small pieces, and then crushed into 20~60 mesh size particles, according to the desired dose tableted or filled into capsules to. 60°C加热4小时和五天考察,检查杂质和FTY720 含量变化,结果FTY720含量有变化(见表7)。 60 ° C for 4 hours study, and five days to check and change the impurity content FTY720, FTY720 results of the content of change (see Table 7).

[0027] 实施例7 (处方7) [0027] Example 7 (Formulation 7)

[0028] FTY720 lg,磷酸氢钙18g,微粉硅胶2g,分别于60°C干燥4小时,控制水分在2% 以下,过80目筛,等量递增法混勻,按所需剂量压片或充填入胶囊即可。 [0028] FTY720 lg, calcium hydrogen phosphate 18g, silica powder 2g, were dried at 60 ° C 4 hours to control the moisture below 2%, over 80 mesh sieve, mix equal amounts incremental method, the desired dose tableted or can be filled into capsules. 60°C加热4小时和五天考察,检查杂质和FTY720含量变化,结果FTY720含量有变化(见表7)。 60 ° C for 4 hours study, and five days to check and change the impurity content FTY720, FTY720 results of the content of change (see Table 7). [0029] 实施例8 (处方8) [0029] Example 8 (Formulation 8)

[0030] FTY720 lg,乳糖20g,混勻,于60°C干燥4小时,控制水分在2%以下,过80目筛, 等量递增法混勻,按所需剂量压片或充填入胶囊即可。 [0030] FTY720 lg, lactose 20g, mixed and dried at 60 ° C 4 hours to control the moisture below 2%, over 80 mesh sieve, mix equal amounts incremental method, the desired dose tableted or filled into capsules i.e. can. 60°C加热4小时和五天考察,检查杂质和FTY720含量变化,结果FTY720含量和杂质明显变化(见表7)。 60 ° C for 4 hours study, and five days to check and change the impurity content FTY720, FTY720 results significantly change the content of impurities (see Table 7).

[0031] 实施例9 (处方9) [0031] Example 9 (Formulation 9)

[0032] FTY720 lmg,甘露醇20g,混勻,于60°C干燥4小时,控制水分在2%以下,过80目筛,等量递增法混勻,按所需剂量压片或充填入胶囊即可。 [0032] FTY720 lmg, mannitol 20g, mixed and dried at 60 ° C 4 hours to control the moisture below 2%, over 80 mesh sieve, mix equal amounts incremental method, the desired dose tableted or filled into capsules It can be. 60°C加热4小时和五天考察,检查杂质和FTY720含量变化,结果FTY720含量和杂质明显变化(见表7)。 60 ° C for 4 hours study, and five days to check and change the impurity content FTY720, FTY720 results significantly change the content of impurities (see Table 7).

[0033] 实施例10 (处方10) [0033] Example 10 (Formulation 10)

[0034] FTY720 lg,乳糖19. 8g,HPMC 0. 2g,分别于60°C干燥,控制水分在2%以下,过80 目筛,等量递增法混勻,用滚压法压成小块状,然后粉碎成20〜60目大小的颗粒,按所需剂量压片或充填入胶囊即可。 [0034] FTY720 lg, lactose 19. 8g, HPMC 0. 2g, were dried at 60 ° C, controlling moisture below 2%, over 80 mesh sieve, mix equal amounts incremental method, method using a roller press into small pieces shape, and then pulverized into 20~60 mesh size particles, according to the desired dose tableted or filled into capsules to. 60°C加热4小时和五天考察,检查杂质和FTY720含量变化,结果FTY720含量和杂质明显变化(见表7)。 60 ° C for 4 hours study, and five days to check and change the impurity content FTY720, FTY720 results significantly change the content of impurities (see Table 7).

[0035] 实施例11 (处方11) [0035] Example 11 (Formulation 11)

[0036] FTY720 lg,甘露醇19. 8g,HPMC 0. 2g,分别于60°C干燥,控制水分在2%以下,过80目筛,等量递增法混勻,用滚压法压成小块状,然后粉碎成20〜60目大小的颗粒,按所需剂量压片或充填入胶囊即可。 [0036] FTY720 lg, mannitol 19. 8g, HPMC 0. 2g, were dried at 60 ° C, controlling moisture below 2%, over 80 mesh sieve, mix equal amounts incremental method, using a roller press into small Method block, and then crushed into 20~60 mesh size particles, according to the desired dose tableted or filled into capsules to. 60°C加热4小时和五天考察,检查杂质和FTY720含量变化, 结果FTY720含量和杂质明显变化(见表7)。 60 ° C for 4 hours study, and five days to check and change the impurity content FTY720, FTY720 results significantly change the content of impurities (see Table 7).

[0037] 实施例12 (处方12) [0037] Example 12 (Formulation 12)

[0038] FTY720 lg,乳糖17g,甘露醇2. 8g,HPMCO. 2g,分别于60°C干燥,控制水分在2%以下,过80目筛,等量递增法混勻,用滚压法压成小块状,然后粉碎成20〜60目大小的颗粒, 按所需剂量压片或充填入胶囊即可。 [0038] FTY720 lg, 17g lactose, mannitol 2. 8g, HPMCO. 2g, were dried at 60 ° C, controlling moisture below 2%, over 80 mesh sieve, mix equal amounts incremental method, press roll method with down into smaller pieces, and then crushed into 20~60 mesh size particles, according to the desired dose tableted or filled into capsules to. 60°C加热4小时和五天考察,检查杂质和FTY720含量变化,结果FTY720含量和杂质明显变化(见表7)。 60 ° C for 4 hours study, and five days to check and change the impurity content FTY720, FTY720 results significantly change the content of impurities (see Table 7).

[0039] 实施例13 (处方13) [0039] Example 13 (Formulation 13)

[0040] FTY720 lg,可压性淀粉19. 8g,HPMC0. 2g,分别于60°C干燥,控制水分在2%以下, 过80目筛,等量递增法混勻,用滚压法压成小块状,然后粉碎成20〜60目大小的颗粒,按所需剂量压片或充填入胶囊即可。 [0040] FTY720 lg, compressible starch 19. 8g, HPMC0. 2g, were dried at 60 ° C, controlling moisture below 2%, over 80 mesh sieve, mix equal amounts incremental method, method using a roller press into small block, and then crushed into 20~60 mesh size particles, according to the desired dose tableted or filled into capsules to. 60°C加热4小时和五天考察,检查杂质和FTY720含量变化,结果FTY720含量和杂质明显变化(见表7)。 60 ° C for 4 hours study, and five days to check and change the impurity content FTY720, FTY720 results significantly change the content of impurities (see Table 7).

[0041] 实施例14 (处方14) [0041] Example 14 (Formulation 14)

[0042] FTY720 lg,酒石酸钠19g,微晶纤维素lg,分别于60°C干燥4小时,控制水分在2%以下,过80目筛,等量递增法混勻,用滚压法压成小块状,然后粉碎成20〜60目大小的颗粒,按所需剂量压片或充填入胶囊即可。 [0042] FTY720 lg, 19g sodium tartrate, microcrystalline cellulose lg, respectively, and dried 60 ° C 4 hours to control the moisture below 2%, over 80 mesh sieve, mix equal amounts incremental method, method using a roller press into small block, and then crushed into 20~60 mesh size particles, according to the desired dose tableted or filled into capsules to. 60°C加热4小时和五天考察,检查杂质和FTY720 含量变化,结果FTY720含量和杂质明显变化(见表7)。 60 ° C for 4 hours study, and five days to check and change the impurity content FTY720, FTY720 results significantly change the content of impurities (see Table 7).

[0043] 实施例15 [0043] Example 15

[0044] 本发明实施例1-3任一FTY720片剂、胶囊和颗粒剂进行了影响因素试验及加速试验考察,结果如下: Example 1-3 according to any one FTY720 tablets, capsules and granules Embodiment [0044] The present invention has been accelerated test and impact test factors investigated, the following results:

[0045] 以下用于考察实验的片剂、胶囊和颗粒剂的活性物质的含量均为1毫克/每片、 粒、包。 [0045] The following active level for tablets, capsules and granules experimental investigation was 1 mg / per tablet, tablets, packets.

[0046] 影响因素试验[0047] 取本发明实施例1-3任一FTY720片剂、胶囊和颗粒剂在高温(60°C )、高湿(RH = 92.5%)、光照(4500LX)条件下放置,于0天、5天、10天分别取样,考察外观、杂质、溶出度、 含量。 [0046] Impact Factors [0047] Take any one of embodiments 1-3 FTY720 a tablets, capsules, and granules embodiment of the present invention at a high temperature (60 ° C), humidity (RH = 92.5%), light (4500LX) Condition placed at 0 days, 5 days, 10 days were sampled, appearance inspection, impurities, dissolution, content. 结果见表1〜表3。 The results are shown in Table 1 ~ Table 3.

[0048] 表1 FTY720片影响因素试验结果 [0048] Table 1 FTY720 results of stress testing sheet

[0049] 表2 FTY720胶囊影响因素试验结果 [0049] Table 2 FTY720 capsules factors results

[0050] 表3 FTY720颗粒剂影响因素试验结果 [0050] Table 3 FTY720 results granules factors

[0051] 结论:本发明实施例1-3任一制剂经高温(60°C )、高湿(RH = 92.5% )及光照(4500LX)影响因素试验。 [0051] Conclusion: The formulation of any one of embodiments 1-3 embodiment of the present invention, a high temperature (60 ° C), humidity (RH = 92.5%) and light (4500LX) stress testing. 结果本发明制剂在高温(60°C )、高湿(RH = 92.5% )、光照(4500LX)条件下放置10天,各考察项目均无明显变化,质量稳定。 Formulations of the invention results in a high temperature (60 ° C), humidity (RH = 92.5%), light (4500LX) is placed a 10-day, no significant change in each inspection item, quality and stability.

[0052] 加速试验 [0052] The accelerated test

[0053] 本发明实施例1-3任一FTY720片剂、胶囊和颗粒剂模拟上市包装的样品置40°C、 RH= 75%的恒温培养箱中,分别于0、1、2、3、6个月取样,考察外观、杂质、溶出度、含量,结果见表4〜表6。 FTY720 embodiment a tablet, capsule, and granules according to any analog Embodiment 1-3 [0053] the present invention commercial packaging sample counter 40 ° C, RH = 75% of the incubator, 0,1,2,3, respectively, 6 months samples, study the appearance, impurities, dissolution, content and results are shown in table 4 ~ 6.

[0054] 表4 FTY720片加速试验结果 [0054] Table 4 FTY720 sheet accelerated testing

[0055] 表5 FTY720胶囊加速试验结果 [0055] Table 5 FTY720 capsule accelerated testing

[0056] 表6 FTY720颗粒剂加速试验结果 [0056] Table 6 FTY720 granules accelerated testing

[0057] 结论:本发明实施例1-3任一制剂在温度为40°C、相对湿度75%的条件下保存6 个月,除杂质略有增加,其他各项考察项目均无明显变化,质量稳定。 [0057] Conclusion: The embodiments of the present invention a formulation of any of claims 1-3 at a temperature of 40 ° C, stored for 6 months at a relative humidity of 75%, a slight increase in impurity removal, various other inspection items were no significant changes, stable quality.

[0058] 表7 FTY720不同处方制剂考察比较试验结果 [0058] Comparative formulation TABLE different formulations investigated test results 7 FTY720

[0059]结论: [0059] Conclusion:

[0060] 本发明实施例1〜3的制剂不但使制剂中活性物质含量测定不受干扰,活性物质的降解也不明显;在各种考察条件下制剂产品的质量均处于稳定,并且处方简单、制备工艺简便、成本低廉等优点。 [0060] Formulation Example 1 ~ 3 of the embodiment of the present invention is not only that the active substance content in the formulation undisturbed assay, degradation of the active substance is not obvious; under a variety of conditions investigated are in the quality of the product formulation stable and simple prescription, easy preparation and low cost.

Claims (6)

  1. 一种口服制剂,其包括式I的2-对辛基苯乙基-2-氨基丙二醇盐酸盐及药用无机盐;其中以制剂总重计,含有0.01重量%-20重量%的2-对辛基苯乙基-2-氨基丙二醇盐酸盐和80重量%-99.99重量%的药用无机盐;所述的药用无机盐选自氯化钠、氯化钾、硫酸钙、硫酸钠、硫酸钾、磷酸二氢钾、磷酸二氢钠、磷酸氢二钾、磷酸氢二钠、磷酸氢钙、或它们的两种以上的混合物。 An oral formulation comprising a Formula I 2-phenylethyl p-octyl-2-amino-propanediol hydrochloride and a pharmaceutically acceptable inorganic salts; wherein the total weight of the formulation, containing 0.01 wt% to 20 wt.% 2 p-octyl-2-phenethyl-amino-propanediol hydrochloride and 80 wt% to 99.99 wt% of a pharmaceutically acceptable inorganic salt; the pharmaceutically acceptable inorganic salt selected from sodium chloride, potassium chloride, calcium sulfate, sodium sulfate , potassium sulfate, potassium dihydrogen phosphate, sodium dihydrogen phosphate, dipotassium hydrogen phosphate, disodium hydrogen phosphate, calcium hydrogen phosphate, or a mixture of two or more thereof. FSB00000113632000011.tif FSB00000113632000011.tif
  2. 2.权利要求1的口服制剂,其还包括其它药用辅料或载体。 The oral formulation of claim 1, further comprising other pharmaceutical excipients or carriers.
  3. 3.权利要求1或2的口服制剂,其中所述制剂为片剂,胶囊或颗粒剂。 The oral formulation of claim 1 or claim 2, wherein said formulation is a tablet, capsule or granules.
  4. 4.权利要求3的口服制剂,其中所述制剂为单位剂型或单位剂量。 The oral formulation of claim 3, wherein said formulation is a unit dose or unit dosage form.
  5. 5.权利要求4的口服制剂,其中单位剂型或剂量含0. l-5mg 2-对辛基苯乙基-2-氨基丙二醇盐酸盐。 The oral formulation of claim 4, wherein the dosage form or dosage unit containing 0. l-5mg 2- phenylethyl p-octyl-2-amino-propanediol hydrochloride.
  6. 6.权利要求1至5任一项所述口服制剂的制备方法,其包括:将2-对辛基苯乙基-2-氨基丙二醇盐酸盐和药用无机盐分别于50〜80°C干燥,控制水分在2%以下,经60〜180目筛选,混勻后的粉末制粒,制粒后压片或充填入胶囊或直接分装成颗粒剂即可。 1-1 for manufacturing an oral formulation according to any claim 5, comprising: octyl-2-p-phenethyl-2-amino-propanediol hydrochloride and a pharmaceutically acceptable inorganic 50~80 ° C, respectively drying, controlling moisture below 2% by 60~180 mesh screening, granulated powder after kneading, tableting after granulation or directly filled into capsules or granules can be dispensed into.
CN 200510082716 2005-07-07 2005-07-07 Oral preparation and its preparing method CN1891212B (en)

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CN1528738A (en) 2003-10-14 2004-09-15 马启明 Method for preparing 2-para octylphenyl ehtyl-2-amino propanediol
WO2004089341A1 (en) 2003-04-08 2004-10-21 Novartis Ag Organic compounds

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