CN111821462A - 青霉素类钠盐与丙磺舒钠组成的复方冻干制剂 - Google Patents
青霉素类钠盐与丙磺舒钠组成的复方冻干制剂 Download PDFInfo
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- QCCCFHDTBTUDEA-UHFFFAOYSA-M sodium;4-(dipropylsulfamoyl)benzoate Chemical compound [Na+].CCCN(CCC)S(=O)(=O)C1=CC=C(C([O-])=O)C=C1 QCCCFHDTBTUDEA-UHFFFAOYSA-M 0.000 title claims abstract description 53
- 150000001875 compounds Chemical class 0.000 title claims abstract description 42
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- FCPVYOBCFFNJFS-LQDWTQKMSA-M benzylpenicillin sodium Chemical class [Na+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1 FCPVYOBCFFNJFS-LQDWTQKMSA-M 0.000 title claims abstract description 17
- 238000004108 freeze drying Methods 0.000 claims abstract description 62
- 229930182555 Penicillin Natural products 0.000 claims abstract description 20
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims abstract description 19
- 229940049954 penicillin Drugs 0.000 claims abstract description 19
- KCVTVKMPZQSSNU-UHFFFAOYSA-N 2-pyridin-4-ylethanethioyl chloride Chemical compound ClC(=S)CC1=CC=NC=C1 KCVTVKMPZQSSNU-UHFFFAOYSA-N 0.000 claims abstract description 13
- NRSJYUSYBNFGAK-UHFFFAOYSA-N 3-bromo-4-propan-2-yloxybenzoic acid Chemical group CC(C)OC1=CC=C(C(O)=O)C=C1Br NRSJYUSYBNFGAK-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229960003200 azlocillin sodium Drugs 0.000 claims abstract description 13
- FWRNIJIOFYDBES-ZQDFAFASSA-L disodium;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[[(2r)-2-phenyl-2-sulfonatoacetyl]amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Na+].[Na+].C1([C@H](C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C([O-])=O)(C)C)S([O-])(=O)=O)=CC=CC=C1 FWRNIJIOFYDBES-ZQDFAFASSA-L 0.000 claims abstract description 13
- 229960001994 mezlocillin sodium Drugs 0.000 claims abstract description 13
- WCMIIGXFCMNQDS-IDYPWDAWSA-M piperacillin sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 WCMIIGXFCMNQDS-IDYPWDAWSA-M 0.000 claims abstract description 13
- 229960005264 piperacillin sodium Drugs 0.000 claims abstract description 13
- 238000011049 filling Methods 0.000 claims abstract description 6
- 238000000859 sublimation Methods 0.000 claims description 42
- 230000008022 sublimation Effects 0.000 claims description 42
- 238000001035 drying Methods 0.000 claims description 28
- 238000007710 freezing Methods 0.000 claims description 28
- 230000008014 freezing Effects 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 16
- 238000001816 cooling Methods 0.000 claims description 14
- 238000010438 heat treatment Methods 0.000 claims description 14
- 238000005096 rolling process Methods 0.000 claims description 14
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 claims description 13
- 229960003081 probenecid Drugs 0.000 claims description 13
- 239000003814 drug Substances 0.000 abstract description 9
- 229940079593 drug Drugs 0.000 abstract description 5
- 239000000843 powder Substances 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 3
- 159000000000 sodium salts Chemical class 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 22
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000002156 mixing Methods 0.000 description 7
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229940088710 antibiotic agent Drugs 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 239000013078 crystal Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- JETQIUPBHQNHNZ-NJBDSQKTSA-N (2s,5r,6r)-3,3-dimethyl-7-oxo-6-[[(2r)-2-phenyl-2-sulfoacetyl]amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound C1([C@H](C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)S(O)(=O)=O)=CC=CC=C1 JETQIUPBHQNHNZ-NJBDSQKTSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- TUPFOYXHAYOHIB-YCAIQWGJSA-M sodium;(2s,5r,6r)-6-[[(2r)-2-[(4-ethyl-2,3-dioxopiperazine-1-carbonyl)amino]-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate;(2s,3s,5r)-3-methyl-4,4,7-trioxo-3-(triazol-1-ylmethyl)-4$l^{6}-thia-1-azabicyclo[3.2.0]h Chemical group [Na+].C([C@]1(C)S([C@H]2N(C(C2)=O)[C@H]1C(O)=O)(=O)=O)N1C=CN=N1.O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 TUPFOYXHAYOHIB-YCAIQWGJSA-M 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000005092 sublimation method Methods 0.000 description 1
- 229960004932 sulbenicillin Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
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Abstract
本发明涉及一种青霉素类钠盐与丙磺舒钠组成的复方冻干制剂,其特征在于按重量份数折干折纯计算含量,每一种青霉素类钠盐与丙磺舒钠组成的复方制剂处方比例分别为3.5‑4:1;其中溶液的pH值为6.0~8.0,溶液的总配制量为2,500 ml,每个西林瓶装量是5 ml;其中青霉素类钠盐为阿洛西林钠,美洛西林钠,哌拉西林钠和磺苄西林钠;其冻干时第一步就是将所有原料药分在一起配制成溶液,在溶液中,所有药粉都会绝对混合均匀,这就规避了因没有混合均匀而出现的每瓶之间的装量差过大的问题。
Description
技术领域
本发明涉及青霉素类钠盐与丙磺舒钠组成的复方冻干制剂,属于医药技术领域。
背景技术
青霉素类分别是注射用阿洛西林钠,注射用美洛西林钠,注射用哌拉西林钠和注射用磺苄西林钠,其中只有哌拉西林钠与他唑巴坦钠组成过复方制剂,而其它三种抗生素均没有复方制剂的剂型。丙磺舒钠目前在全球市场上既没有丙磺舒钠注射剂也没有丙磺舒钠原料药可供使用。因此,丙磺舒钠与上述四种青霉素类抗生素组成复方制剂更没有冻干制剂。复方制剂的制备通常采用药粉混合的方式。在口服复方制剂制备过程中,为了增加药粉的流动性以便于混合均匀,通常要加入一些辅料如硬脂酸镁和淀粉以增加药物的流动性。然而,在注射用复方制剂中,这些辅料都被禁止加入。因此,在注射用复方制剂制备过程中,如果两种药物的理化特性相差很大的话(比如流动性和粘滞性),这两种药粉就难以混合均匀,从而造成制成品的装量差超出标准范围,不合格率就会增加。如果这样不合格产品流向市场,那就会给临床抗感染治疗带来不利影响。丙磺舒钠本身就具有一个明显特征,那就是流动性非常差,吸湿性强,通过常规的原料粉混合方式很难做到混合均一,由此会造成每个药瓶之间的装量差过大,不合格率大幅增加。
发明内容
本发明的目的在于提供一种青霉素类钠盐与丙磺舒钠组成的复方冻干制剂,其冻干工艺的第一步就是将所有原料药分在一起配制成溶液,在溶液中,所有药粉都会绝对混合均匀,这就规避了因没有混合均匀而出现的每瓶之间的装量差过大的问题。
本发明的技术方案是这样实现的:一种注射用青霉素类钠盐与丙磺舒钠组成复方冻干制剂,其特征在于按重量份数折干折纯计算含量,每一种青霉素类钠盐与丙磺舒钠组成的复方制剂处方比例分别为3.5-4:1;其中溶液的pH值为6.0~8.0,溶液的总配制量为2,500 ml,每个西林瓶装量是5 ml。
具体冻干方法如下:
(1)预冻阶段开启冻干机:板层从室温以2℃/min左右的速度降温至-40℃,保温60-90分钟;
(2)升华干燥:在预冻阶段结束后,板层在15-23小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(3)解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为22小时和28小时;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
所述的青霉素类钠盐为阿洛西林钠,美洛西林钠,哌拉西林钠和磺苄西林钠。
本发明的积极效果是:首次采用冻干工艺制备青霉素类钠盐加上丙磺舒钠的复方制剂以外,丙磺舒钠的加入也体现出一些意想不到的益处。丙磺舒钠在冻干状态下呈现出树枝状针状晶型结构,形成复方制剂的骨架,相应的青霉素类抗生素能均匀地附着在丙磺舒钠的针状结晶上。这样的特性一方面可防止有些产品在升华过程中出现喷瓶现象,造成废品率增高,另一方面,丙磺舒钠使得整体复方制剂结构疏松,易于水分挥发。无论是哪一种处方比例,复方制剂和单方制剂相比都多出了丙磺舒钠这一组分,每瓶多出的丙磺舒钠从0.25到0.285 g不等,并且在总体冻干时间一样(大约22小时)的情况下,复方制剂的水分还是略低于单方制剂的水分,说明丙磺舒钠还是具有促进水分挥发的功能作用,这一优点最终能体现在可以适当地缩短冻干时间。磺苄西林产品的总冻干时间要长一些,为28小时左右,但丙磺舒钠的加入同样体现出上述优势。
具体实施方式
下面结合实施例对本发明做进一步的描述:
溶液配制:溶液总量为2500 ml。
单方制剂溶液:分别含阿洛西林钠,美洛西林钠,哌拉西林钠和磺苄西林钠500 g。
复方制剂溶液:每一个复方制剂分三个处方,每个处方复方制剂的溶液也都含有同样含量(500 g)上述四种青霉素类抗生素,只是丙磺舒钠的含量彼此不同:处方1的溶液含125 g丙磺舒钠;处方2的溶液含133.33 g丙磺舒钠以及处方3的溶液含142.86 g丙磺舒钠。在所有四种单方制剂中,每瓶青霉素类抗生素的含量都是1g,而处方1丙磺舒钠含量0.25 g,处方2丙磺舒钠含量是0.267 g,处方3丙磺舒钠含量是0.286g。
表2复方制剂产品的处方比例
产品 | 处方1 | 处方2 | 处方3 |
阿洛西林钠:丙磺舒钠 | 4:1 | 3.75:1 | 3.5:1 |
美洛西林钠:丙磺舒钠 | 4:1 | 3.75:1 | 3.5:1 |
哌拉西林钠:丙磺舒钠 | 4:1 | 3.75:1 | 3.5:1 |
磺苄西林钠:丙磺舒钠 | 4:1 | 3.75:1 | 3.5:1 |
实施例1
将阿洛西林钠:丙磺舒钠处方比例4:1的复方溶液(阿洛西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法如下:
(1)预冻阶段开启冻干机:板层从室温以2℃/min左右的速度降温至-40℃,保温60-90分钟;
(4)升华干燥:在预冻阶段结束后,板层在15-17小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(5)解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为22小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
实施例2
将美洛西林钠:丙磺舒钠处方比例4:1的复方溶液(美洛西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法如下:
(1)预冻阶段开启冻干机:板层从室温以2℃/min左右的速度降温至-40℃,保温60-90分钟;
(6)升华干燥:在预冻阶段结束后,板层在15-17小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(7)解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为22小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
实施例3
将哌拉西林钠:丙磺舒钠处方比例4:1的复方溶液(哌拉西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法如下:
(1)预冻阶段开启冻干机:板层从室温以2℃/min左右的速度降温至-40℃,保温60-90分钟;
(8)升华干燥:在预冻阶段结束后,板层在15-17小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(9)解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为22小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
实施例4
将磺苄西林钠:丙磺舒钠处方比例4:1的复方溶液(磺苄西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法:
(1)、预冻阶段开启冻干机
①、板层从室温以3℃/min左右的速度降温至-20℃,保温30-60分钟;
②、板层从-20℃以1.5℃/min左右的速度降温至-40℃,保温40-60
(2)、升华干燥:在预冻阶段结束后,板层在20-23小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(3)、解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为28小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
实施例5
将阿洛西林钠:丙磺舒钠处方比例3.75:1的复方溶液(阿洛西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法如下:
(1)预冻阶段开启冻干机:板层从室温以2℃/min左右的速度降温至-40℃,保温60-90分钟;
(2)升华干燥:在预冻阶段结束后,板层在15-17小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(3)解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为22小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
实施例6
将美洛西林钠:丙磺舒钠处方比例3.75:1的复方溶液(美洛西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法如下:
(1)预冻阶段开启冻干机:板层从室温以2℃/min左右的速度降温至-40℃,保温60-90分钟;
(4)升华干燥:在预冻阶段结束后,板层在15-17小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(5)解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为22小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
实施例7
将哌拉西林钠:丙磺舒钠处方比例3.75:1的复方溶液(哌拉西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法如下:
(1)预冻阶段开启冻干机:板层从室温以2℃/min左右的速度降温至-40℃,保温60-90分钟;
(6)升华干燥:在预冻阶段结束后,板层在15-17小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(7)解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为22小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
实施例8
将磺苄西林钠:丙磺舒钠处方比例3.75:1的复方溶液(磺苄西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法:
(1)、预冻阶段开启冻干机
①、板层从室温以3℃/min左右的速度降温至-20℃,保温30-60分钟;
②、板层从-20℃以1.5℃/min左右的速度降温至-40℃,保温40-60
(2)、升华干燥:在预冻阶段结束后,板层在20-23小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(3)、解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为28小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
实施例9
将阿洛西林钠:丙磺舒钠处方比例3.5:1的复方溶液(阿洛西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法如下:
(1)预冻阶段开启冻干机:板层从室温以2℃/min左右的速度降温至-40℃,保温60-90分钟;
(2)升华干燥:在预冻阶段结束后,板层在15-17小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(3)解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为22小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
实施例10
将美洛西林钠:丙磺舒钠处方比例3.5:1的复方溶液(美洛西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法如下:
(1)预冻阶段开启冻干机:板层从室温以2℃/min左右的速度降温至-40℃,保温60-90分钟;
(4)升华干燥:在预冻阶段结束后,板层在15-17小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(5)解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为22小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
实施例11
将哌拉西林钠:丙磺舒钠处方比例3.5:1的复方溶液(哌拉西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法如下:
(1)预冻阶段开启冻干机:板层从室温以2℃/min左右的速度降温至-40℃,保温60-90分钟;
(6)升华干燥:在预冻阶段结束后,板层在15-17小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(7)解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为22小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
实施例12
将磺苄西林钠:丙磺舒钠处方比例3.5:1的复方溶液(磺苄西林钠+丙磺舒钠)装入西林瓶(5 ml/瓶)中,半加塞,入冻干机板层进行冻干。
具体冻干方法:
(1)、预冻阶段开启冻干机
①、板层从室温以3℃/min左右的速度降温至-20℃,保温30-60分钟;
②、板层从-20℃以1.5℃/min左右的速度降温至-40℃,保温40-60
(2)、升华干燥:在预冻阶段结束后,板层在20-23小时内逐渐升温至30℃,使升华线肉眼基本看不见;
(3)、解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为28小时左右;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
Claims (5)
1.青霉素类钠盐与丙磺舒钠组成的复方冻干制剂,其特征在于按重量份数折干折纯计算含量,每一种青霉素类钠盐与丙磺舒钠组成的复方制剂处方比例分别为3.5-4:1;其中溶液的pH值为6.0~8.0,溶液的总配制量为2,500 ml,每个西林瓶装量是5 ml;其中青霉素类钠盐为阿洛西林钠,美洛西林钠,哌拉西林钠和磺苄西林钠;
具体冻干方法如下:
(1)预冻阶段开启冻干机:板层从室温以2℃/min左右的速度降温至-40℃,保温60-90分钟;
升华干燥:在预冻阶段结束后,板层在15-23小时内逐渐升温至30℃,使升华线肉眼基本看不见;
解析干燥:在升华阶段结束后板层稳定升到40℃左右保温3小时,使水分充分挥发,根据冻干箱体内压力变化情况判断,合格后出箱,冻干总时间为22小时和28小时;
轧盖:样品冻干结束后,真空下压胶塞,放掉冻干机的真空取出样品轧盖,检测外观和水分含量。
2.根据权利要求1所述的一种青霉素类钠盐与丙磺舒钠组成的复方冻干制剂,其特征在于所述的阿洛西林钠与丙磺舒钠冻干比例为3.5-4:1。
3.根据权利要求1所述的一种青霉素类钠盐与丙磺舒钠组成的复方冻干制剂,其特征在于所述的美洛西林钠与丙磺舒钠冻干比例为3.5-4:1。
4.根据权利要求1所述的一种青霉素类钠盐与丙磺舒钠组成的复方冻干制剂,其特征在于所述的哌拉西林钠与丙磺舒钠冻干比例为3.5-4:1。
5.根据权利要求1所述的一种青霉素类钠盐与丙磺舒钠组成的复方冻干制剂,其特征在于所述的磺苄西林钠与丙磺舒钠冻干比例为3.5-4:1。
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CN1698896A (zh) * | 2005-05-30 | 2005-11-23 | 西安交通大学 | 注射用复方β-内酰胺类钠盐/丙磺舒钠的制备方法 |
CN1813700A (zh) * | 2006-03-01 | 2006-08-09 | 吴晓辉 | 丙磺舒钠与青霉素类抗生素组成复方针剂 |
CN1853724A (zh) * | 2004-12-01 | 2006-11-01 | 吴晓辉 | 丙磺舒钠、钾与β-内酰胺类抗生素组成复方针剂及其用途 |
US20190374516A1 (en) * | 2018-06-07 | 2019-12-12 | Iterum Therapeutics International Limited | Combinations of beta-lactam compounds and probenecid and uses thereof |
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CN1853724A (zh) * | 2004-12-01 | 2006-11-01 | 吴晓辉 | 丙磺舒钠、钾与β-内酰胺类抗生素组成复方针剂及其用途 |
CN1698896A (zh) * | 2005-05-30 | 2005-11-23 | 西安交通大学 | 注射用复方β-内酰胺类钠盐/丙磺舒钠的制备方法 |
CN1813700A (zh) * | 2006-03-01 | 2006-08-09 | 吴晓辉 | 丙磺舒钠与青霉素类抗生素组成复方针剂 |
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