CN107496366A - 一种美洛西林钠舒巴坦钠化合物的药物组合物 - Google Patents
一种美洛西林钠舒巴坦钠化合物的药物组合物 Download PDFInfo
- Publication number
- CN107496366A CN107496366A CN201710911609.8A CN201710911609A CN107496366A CN 107496366 A CN107496366 A CN 107496366A CN 201710911609 A CN201710911609 A CN 201710911609A CN 107496366 A CN107496366 A CN 107496366A
- Authority
- CN
- China
- Prior art keywords
- sodium
- sulbactam
- mezlocillin
- pharmaceutical composition
- parts
- 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
- A61K31/431—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems containing further heterocyclic rings, e.g. ticarcillin, azlocillin, oxacillin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及一种美洛西林钠舒巴坦钠化合物的药物组合物。本发明采用烟酰胺和甘氨酸组成稳定剂,磷酸二氢钠作为pH调节剂,海藻糖作为冻干支持剂,有效地提高了美洛西林钠和舒巴坦钠在制备和存储过程中的稳定性,保证了临床使用的疗效和安全性。
Description
技术领域
本发明涉及一种美洛西林钠舒巴坦钠化合物的药物组合物。
背景技术
美洛西林属于青霉素类广谱抗生素,主要通过干扰细菌细胞壁合成来起到杀菌作用,目前在国内外广泛应用,并且被认为是最有价值的酰脲类青霉素。它对大多数革兰氏阴性菌、大多数革兰氏阳性菌和厌氧菌都具有抗菌作用。其最大特点在于在胸腹腔液中浓度很高,甚至可穿透心脏瓣膜和前列腺组织,在脑脊液中也可以达到有效浓度,常常用于腹腔感染的治疗。然而,它对β-内酰胺酶不稳定。
舒巴坦是一种β-内酰胺酶抑制剂,它对β-内酰胺酶的亲和性远远大于其他β-内酰胺类抗生素,本身没有或只有很弱的抗菌活性,但是舒巴坦对由β-内酰胺类抗生素耐药菌株产生的多数重要的β-内酰胺酶都具有不可逆的抑制作用。舒巴坦可以防止耐药菌对青霉素类和头孢菌素类抗生素的破坏,与青霉素类和头孢菌素类抗生素具有明显的协同作用,可以增强抗菌活性和扩大抗菌谱。
现有技术中已经存在美洛西林和舒巴坦的复方制剂,但是由于其组合的稳定性受pH值、温度、 含水量等多因素影响,目前都是由美洛西林钠和舒巴坦钠无菌原料分装或冻干制得,使用时由无菌粉末混合溶解于注射溶剂中使用,造成了二次感染的可能以及药量不准的情形。
发明内容
为了解决现有的美洛西林钠舒巴坦钠稳定性差的问题,本发明提供了一种稳定的美洛西林钠舒巴坦钠复方制剂,并且提供了其制备方法。
本发明提供一种美洛西林钠舒巴坦钠组合物,其按重量份计包括如下组分:
美洛西林钠4份;
舒巴坦钠1份;
烟酰胺0.5-1份;
磷酸二氢钠 0.1-0.5份;
甘氨酸0.5-1份;
海藻糖 1-5份。
本发明采用烟酰胺和甘氨酸组成稳定剂,磷酸二氢钠作为pH调节剂,海藻糖作为冻干支持剂,有效地提高了美洛西林钠和舒巴坦钠在制备和存储过程中的稳定性,且制剂溶解快速,保证了临床使用的疗效和安全性。
本发明的制备方法如下:
在洁净度级别至少百级的区域中,采用三维运动混合机将无菌美洛西林钠和无菌舒巴坦钠以质量比4:1的比例混合,然后加入烟酰胺2-5份、磷酸二氢钠 1-3份、甘氨酸1-5份、海藻糖 5-20份,混合时间为至少60min,混合时环境温度控制在20℃~22℃,相对湿度控制在70%以下,得到无菌美洛西林钠舒巴坦钠复方(4:1)混合物;对西林瓶、丁基胶塞和铝塑盖进行清洗和灭菌,然后进行干燥;将所述中间体在洁净度至少百级的区域中分装到上述无菌西林瓶中,装量误差控制在±3%之内,环境温度控制在20-22%,相对湿度控制在45-60%,然后冷冻干燥得美洛西林钠舒巴坦钠混悬粉针剂。
具体实施方式
实施例1 美洛西林钠舒巴坦钠(4:1)混悬粉针剂的制备
处方(200瓶):
美洛西林钠 100g
舒巴坦钠 25g
烟酰胺 12.5g
磷酸二氢钠 2.5g
甘氨酸 12.5g
海藻糖 50g
制备方法
(1)在洁净度级别至少百级的区域中,采用三维运动混合机将无菌美洛西林钠和无菌舒巴坦钠以质量比4:1的比例混合,然后加入烟酰胺、磷酸二氢钠、甘氨酸和海藻糖,混合时间为至少60min,混合时环境温度控制在20℃~22℃,相对湿度控制在70%以下,得到无菌美洛西林钠舒巴坦钠复方(4:1)中间体;
(2)对西林瓶、丁基胶塞和铝塑盖进行清洗和灭菌,然后进行干燥;
(3)将所述中间体在洁净度至少百级的区域中分装到上述无菌西林瓶中,装量误差控制在±3%之内,环境温度控制在20-22%,相对湿度控制在45-60%,然后冷冻干燥得美洛西林钠舒巴坦钠混悬粉针剂。
实施例2 美洛西林钠舒巴坦钠(4:1)混悬粉针剂的制备
处方(100瓶):
美洛西林钠 50g
舒巴坦钠 12.5g
烟酰胺 6g
磷酸二氢钠 1g
甘氨酸 6g
海藻糖 25g
制备方法
(1)在洁净度级别至少百级的区域中,采用三维运动混合机将无菌美洛西林钠和无菌舒巴坦钠以质量比4:1的比例混合,然后加入烟酰胺、磷酸二氢钠、甘氨酸和海藻糖,混合时间为至少60min,混合时环境温度控制在20℃~22℃,相对湿度控制在70%以下,得到无菌美洛西林钠舒巴坦钠复方(4:1)中间体;
(2)对西林瓶、丁基胶塞和铝塑盖进行清洗和灭菌,然后进行干燥;
(3)将所述中间体在洁净度至少百级的区域中分装到上述无菌西林瓶中,装量误差控制在±3%之内,环境温度控制在20-22%,相对湿度控制在45-60%,然后冷冻干燥得美洛西林钠舒巴坦钠混悬粉针剂。
实施例3 长期稳定性试验
批号1:160101 批量:2000瓶 规格:1.25g/瓶 包装:西林瓶
考察条件:25±2℃/60±10%RH
通过长期稳定性试验可以发现,本发明的美洛西林钠和舒巴坦钠组合物在制备和存储过程中具有良好的稳定性,保证了临床使用的疗效和安全性。
Claims (2)
1.一种美洛西林钠舒巴坦钠组合物,其按重量份计包括如下组分:
美洛西林钠4份;
舒巴坦钠1份;
烟酰胺0.5-1份;
磷酸二氢钠 0.1-0.5份;
甘氨酸0.5-1份;
海藻糖 1-5份。
2.根据权利要求1所述的美洛西林钠舒巴坦钠组合物,其特征在于组成如下:
美洛西林钠 100g
舒巴坦钠 25g
烟酰胺 12.5g
磷酸二氢钠 2.5g
甘氨酸 12.5g
海藻糖 50g 。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710911609.8A CN107496366B (zh) | 2017-09-30 | 2017-09-30 | 一种美洛西林钠舒巴坦钠化合物的药物组合物 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201710911609.8A CN107496366B (zh) | 2017-09-30 | 2017-09-30 | 一种美洛西林钠舒巴坦钠化合物的药物组合物 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN107496366A true CN107496366A (zh) | 2017-12-22 |
CN107496366B CN107496366B (zh) | 2020-03-17 |
Family
ID=60699015
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201710911609.8A Active CN107496366B (zh) | 2017-09-30 | 2017-09-30 | 一种美洛西林钠舒巴坦钠化合物的药物组合物 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107496366B (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112089693A (zh) * | 2020-09-28 | 2020-12-18 | 成都倍特药业股份有限公司 | 一种注射用青霉素类组合物及其制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101703506A (zh) * | 2009-08-18 | 2010-05-12 | 海南永田药物研究院有限公司 | 一种美洛西林钠舒巴坦钠药物组合物混悬粉针剂及其新应用 |
CN101804052A (zh) * | 2010-04-21 | 2010-08-18 | 海南美兰史克制药有限公司 | 一种美洛西林钠舒巴坦钠药物组合物脂质体注射剂 |
CN105560243A (zh) * | 2016-01-10 | 2016-05-11 | 苏州二叶制药有限公司 | 一种注射用哌拉西林钠舒巴坦钠组合物的制备方法 |
CN105651887A (zh) * | 2016-01-10 | 2016-06-08 | 苏州二叶制药有限公司 | 一种注射用哌拉西林钠舒巴坦钠的检测方法 |
-
2017
- 2017-09-30 CN CN201710911609.8A patent/CN107496366B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101703506A (zh) * | 2009-08-18 | 2010-05-12 | 海南永田药物研究院有限公司 | 一种美洛西林钠舒巴坦钠药物组合物混悬粉针剂及其新应用 |
CN101804052A (zh) * | 2010-04-21 | 2010-08-18 | 海南美兰史克制药有限公司 | 一种美洛西林钠舒巴坦钠药物组合物脂质体注射剂 |
CN105560243A (zh) * | 2016-01-10 | 2016-05-11 | 苏州二叶制药有限公司 | 一种注射用哌拉西林钠舒巴坦钠组合物的制备方法 |
CN105651887A (zh) * | 2016-01-10 | 2016-06-08 | 苏州二叶制药有限公司 | 一种注射用哌拉西林钠舒巴坦钠的检测方法 |
Non-Patent Citations (1)
Title |
---|
高建青 主编: "《药剂学与工业药剂学实验指导》", 30 June 2012, 浙江大学出版社 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112089693A (zh) * | 2020-09-28 | 2020-12-18 | 成都倍特药业股份有限公司 | 一种注射用青霉素类组合物及其制备方法 |
Also Published As
Publication number | Publication date |
---|---|
CN107496366B (zh) | 2020-03-17 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101129382B (zh) | 含β-内酰胺类抗生素和缓冲组分的抗生素复方 | |
CN101648016A (zh) | 稳定性高的药物组合物 | |
CN110279698B (zh) | 头孢特咯瓒抗生素组合物 | |
CN102895181B (zh) | 注射用美洛西林钠的制备方法 | |
AU2009222020A1 (en) | Stable liquid formulations of anti-infective agents and adjusted anti-infective agent dosing regimens | |
CN101647779B (zh) | 一种注射用阿莫西林钠克拉维酸钾复方粉针剂制剂及其制备技术 | |
CN103301131A (zh) | 注射用哌拉西林钠舒巴坦钠制备方法 | |
CN102526040B (zh) | 注射用美洛西林钠舒巴坦钠4:1组合物的制备方法 | |
CN107496366A (zh) | 一种美洛西林钠舒巴坦钠化合物的药物组合物 | |
CN103920137B (zh) | 一种具有抗耐药性革兰阳性细菌作用的药物组合物 | |
CN102949390A (zh) | 注射用阿莫西林钠克拉维酸钾 | |
CN101904822B (zh) | 一种法罗培南钠冻干粉针及其制备方法 | |
CN100356921C (zh) | 一种硫酸头孢匹罗组合物及其制备方法 | |
CN101336903B (zh) | 注射用左旋奥硝唑磷酸二钠静脉制剂的制备方法 | |
CN102949397B (zh) | 注射用头孢噻肟钠和他唑巴坦钠制剂及其制备方法 | |
CN108066338A (zh) | 预防和治疗需氧菌与厌氧菌混合感染时的新型抗生素组合物及其制备方法 | |
CN109745546A (zh) | 用于提高注射用替考拉宁稳定性的等渗组合物及其制备方法 | |
SE463804B (sv) | En anvaendningsklar farmaceutisk komposition av vinkadimerasalter | |
CN103230367B (zh) | 一种头孢泊肟酯组合物干混悬剂及其制备方法 | |
CN107281187B (zh) | 一种注射用头孢哌酮钠他唑巴坦钠及其制备方法 | |
CN102716096B (zh) | 一种含有头孢替安的药物组合物 | |
CN101732264B (zh) | 一种头孢西酮钠冻干粉针剂 | |
CN107638394B (zh) | 一种哌拉西林钠舒巴坦钠化合物的药物组合物 | |
CN104887679B (zh) | 一种哌拉西林钠舒巴坦钠无菌粉针剂及其制备方法 | |
CN102198105B (zh) | 萘夫西林钠注射剂及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |