CN101804052A - Liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium - Google Patents
Liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium Download PDFInfo
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- CN101804052A CN101804052A CN 201010151971 CN201010151971A CN101804052A CN 101804052 A CN101804052 A CN 101804052A CN 201010151971 CN201010151971 CN 201010151971 CN 201010151971 A CN201010151971 A CN 201010151971A CN 101804052 A CN101804052 A CN 101804052A
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- mezlocillin
- liposome
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Abstract
The invention provides a liposome injection based on a drug combination of mezlocillin sodium and sulbactam sodium. The liposome injection comprises the following components: mezlocillin sodium, sulbactam sodium, liposome carriers, frozen and dried supporting agent and optional existing antioxidant, wherein the liposome carriers are particularly hydrogenated soybean phosphatidylcholine and octadecylamine. The liposome injection of the invention has good preparation stability, prevents the liposome from being cracked under the action of dehydration, fusion and ice crystal generation in the freezing-drying process, and keeps good entrapment rate of the liposome after re-dissolution through hydration.
Description
Technical field
The present invention relates to a kind of antibiotic Liposomal formulation, relate in particular to a kind of liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium and method for making thereof, belong to medical technical field.
Background technology
The mezlocillin belongs to the penicillins broad ectrum antibiotic, and is main by disturbing the bactericidal action of having synthesized of bacteria cell wall; Sulbactam does not have antibiotic activity except that to Neisseriaceae and the acinetobacter calcoaceticus to other antibacterial, but sulbactam has the inhibitory action of irreversibility to the most important beta-lactamase that is produced by the beta-lactam antibiotic Resistant strain.Sulbactam can prevent the destruction of fastbacteria to penicillins and cephalosporins, and sulbactam and penicillins and cephalosporins have the obvious synergistic effect.
The clinical consumption of mezlocillin sodium and sulbactam sodium compound preparation is big, determined curative effect, and market prospect is good, and is the same with most of cephalosporinses, all is to be made by mezlocillin sodium and the aseptic raw material packing of sulbactam sodium or lyophilizing.There is a common defective in it is exactly that preparation stabilization is poor, the prescription that can not satisfy the prescriptive period.Patent documentation CN101322685A discloses the preparation method of a kind of mezlocillin for inj sulbactam sodium and lyophilized injectable powder thereof, and the isolation and purification method of the mezlocillin sodium of injection and sulbactam sodium, adopt high speed adverse current chromatogram, constitute the dicyandiamide solution of immobile phase, mobile phase with chloroform, the preparation of first alcohol and water, mezlocillin sodium and sulbactam sodium are carried out separation and purification, obtain the mezlocillin sodium and the sulbactam sodium of injection, lyophilization, aseptic subpackaged, make the mezlocillin for inj sulbactam sodium.This patent has improved the purity of preparation to a certain extent, but just with simple aseptic subpackaged the making of two kinds of compositions, active component mezlocillin sodium and sulbactam sodium is not carried out corresponding protection, causes product stability poor, has had a strong impact on clinical efficacy.
Summary of the invention
This injection that common process is prepared, physics and poor chemical stability, long-term storage drug quality can descend but also can generate some impurity, bring toxic and side effects, have stayed hidden danger for clinical use.If can screen some specific adjuvant and preparation technologies, increase the stability of this product, bring very big safety will for clinical use.In line with this meaning, the inventor has finally finished the present invention by consulting a large amount of documents and materials and carrying out arduous experiment sieving demonstration.
Preparation lipidosome injection membrane material commonly used is phospholipid and additives, wherein phospholipid can be selected natural phospholipid and synthetic phospholipid for use usually, and described natural phospholipid is one or more in Ovum Gallus domesticus Flavus lecithin, hydrogenation egg yolk lecithin, EPG, egg yolk lecithin acyl serine, egg yolk lecithin acyl inositol, soybean lecithin, hydrogenated soya phosphatide, soybean phospholipid acyl glycerol, soy phosphatidylserine, the soybean phospholipid acyl inositol; Described synthetic phospholipid is one or more in dioleoyl phospholipid phatidylcholine, distearyl acid phosphatidylcholine, dipalmitoyl phosphatidyl choline, dimyristoyl phosphatidyl choline, two Laurel phosphatidyl cholines, DOPG, distearyl acid phosphatidyl glycerol, two palmityl phosphatidyl glycerols, GLYCEROL,DIMYRISTOYL PHOSPHATIDYL, the two lauroyl phosphatidyl glycerols.The membrane material of additives commonly used has cholesterol, 18-amine., phosphatidic acid, sodium deoxycholate and poloxamer 188.The membrane material that is used to prepare lipidosome injection also has PHOSPHATIDYL ETHANOLAMINE, cholesterol second fat, paddy to carry alcohol, natrii tauroglycocholas, phosphatidyl silk amino acid, stearmide, single stearoyl phosphatidic acid, single stearoyl PHOSPHATIDYL ETHANOLAMINE, two cetyl phosphate (DCP), two palmityl PHOSPHATIDYL ETHANOLAMINE, single palmityl PHOSPHATIDYL ETHANOLAMINE, two myristoyl PHOSPHATIDYL ETHANOLAMINE.Additives generally are used for regulating membrane structure, change charged character, as cholesterol liposome bimolecular tunic are solidified, thereby reduce the generation of free radical, have reduced oxidation level, and liposome stability is significantly strengthened.
Bound by theory not, the inventor has found hydrogenated soy phosphatidyl choline, two kinds of materials of 18-amine. are made up unexpectedly, has beyond thought effect, thereby obtained the liposome of excellent in stability, it has good preparation stability, liposome can not break because of dehydration, fusion, ice crystal generation etc. in the freeze-drying process, and after aquation was redissolved, liposome kept good envelop rate equally.
Technical solution of the present invention is as follows:
A kind of liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium, be made up of mezlocillin sodium, sulbactam sodium, liposome vectors, frozen-dried supporting agent and the optional antioxidant that exists, wherein said liposome vectors is hydrogenated soy phosphatidyl choline and 18-amine..
Liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium of the present invention, wherein mezlocillin sodium and sulbactam sodium are 4: 1 aseptic mixtures of weight ratio.
Liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium of the present invention, each composition weight umber is:
4 parts of mezlocillin sodiums
1 part of sulbactam sodium
Hydrogenated soy phosphatidyl choline 2.5-13 part
18-amine. 0.3-5 part
Frozen-dried supporting agent 4-15 part
Antioxidant 0-3 part.
As the present invention's one preferred embodiment, each composition weight umber is:
4 parts of mezlocillin sodiums
1 part of sulbactam sodium
Hydrogenated soy phosphatidyl choline 5-9 part
18-amine. 0.6-2 part
Frozen-dried supporting agent 6-12 part
Antioxidant 0.01-0.1 part.
Above-mentioned described liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium, wherein said frozen-dried supporting agent is selected from one or more in sodium chloride, mannitol, glucose, lactose, polyvinylpyrrolidone, sucrose, glycine, sorbitol, trehalose, the dextran, is preferably 2: 1 the mixture of weight ratio of trehalose and lactose.
Above-mentioned described liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium, wherein said antioxidant is selected from one or more in sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, ascorbic acid, vitamin E, propyl gallate, ascorbyl palmitate, the butylated hydroxyarisol, preferred sodium sulfite.
The present invention also provides a kind of method for preparing liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium, and concrete steps comprise:
(1) hydrogenated soy phosphatidyl choline and 18-amine. are dissolved in the organic solvent, placing reduces pressure on the rotating thin film evaporimeter eliminates organic solvent, has obtained immobilized artificial membrane, adds the buffer salt solution stirring and dissolving, obtains blank liposome solution;
(2) mezlocillin sodium and sulbactam sodium are dissolved in the water for injection,, are incubated under the 50-70 ℃ of state supersound process 40-60 minute, add again after frozen-dried supporting agent, antioxidant fully dissolves, filter with prepared blank liposome solution mix homogeneously;
(3) above-mentioned steps (2) gained solution is carried out spray drying, carry out packing under the aseptic condition, make liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium.
In the above-mentioned described preparation method, organic solvent is selected from one or more in ethanol, isopropyl alcohol, methanol, butanone, acetone, ethyl acetate, chloroform, dichloromethane or the Ethyl formate, and being preferably volume ratio is 1: 2 the isopropyl alcohol and the mixed solvent of ethyl acetate.
In the above-mentioned described preparation method, what buffer salt solution can be in phosphate buffer, citrate buffer, carbonate buffer solution, the borate buffer solution is a kind of, is preferably pH value and is phosphoric acid-sodium hydrogen phosphate buffer of 6.0.
Liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium advantage provided by the invention is as follows:
(1) stability is high: active component mezlocillin sodium and sulbactam sodium are wrapped in the liposome, and the long-term every detection index in back of placing does not all have significant change, has greatly improved stability;
(2) envelop rate height: the envelop rate of Liposomal formulation of the present invention is generally 84%-92%, can reach 94%, is higher than other Liposomal formulations according to the conventional method preparation significantly, and long-term placement the seepage phenomenon can not take place, and has guaranteed product quality;
(3) side effect is little: liposome vectors vivo degradation, avirulence and non-immunogenicity, and can improve the Drug therapy index, reduce drug toxicity and reduce drug side effect;
(4) preparation is simple: the present invention selects mixed organic solvents for use, compares with using single organic solvent, and solubility property is better, dissolves sooner, and easier reduction vaporization is removed.
The specific embodiment
Following examples all are for further explaining that the superiority to preparation technology of the present invention and prepared sample carries out, and are unintelligible for the present invention has been done further claim limitation.
The preparation of embodiment 1 liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium
Prescription (specification 2.5g)
Mezlocillin sodium 200g
Sulbactam sodium 50g
Hydrogenated soy phosphatidyl choline 250g
18-amine. 30g
Trehalose 200g
Lactose 100g
Sodium sulfite 0.5g
Preparation process
(1) 250g hydrogenated soy phosphatidyl choline and 30g 18-amine. are dissolved in the mixed solvent that the 1500ml volume ratio is 1: 2 isopropyl alcohol and ethyl acetate, placing reduces pressure on the rotating thin film evaporimeter eliminates organic solvent, obtained immobilized artificial membrane, add pH value 6.0 phosphoric acid-disodium hydrogen phosphate buffer solution 600ml stirring and dissolving, obtain blank liposome solution;
(2) 200g mezlocillin sodium and 50g sulbactam sodium are dissolved in the 800ml water for injection, with prepared blank liposome solution mix homogeneously, be incubated under 60 ℃ of states supersound process 40 minutes, add again after 200g trehalose and 100g lactose, 0.5g sodium sulfite fully dissolve, with 0.45 μ m filtering with microporous membrane;
(3) above-mentioned steps (2) gained solution is carried out spray drying, be distributed into 100 bottles under the aseptic condition, make liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium.
The preparation of embodiment 2 liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium
Prescription (specification 3.75g)
Mezlocillin sodium 300g
Sulbactam sodium 75g
Hydrogenated soy phosphatidyl choline 675g
18-amine. 150g
Trehalose 600g
Lactose 300g
Sodium sulfite 7.5g
Preparation process
(1) 675g hydrogenated soy phosphatidyl choline and 150g 18-amine. are dissolved in the mixed solvent that the 2000ml volume ratio is 1: 2 isopropyl alcohol and ethyl acetate, placing reduces pressure on the rotating thin film evaporimeter eliminates organic solvent, obtained immobilized artificial membrane, add pH value 6.0 phosphoric acid-disodium hydrogen phosphate buffer solution 1000ml stirring and dissolving, obtain blank liposome solution;
(2) 300g mezlocillin sodium and 75g sulbactam sodium are dissolved in the 1000ml water for injection, with prepared blank liposome solution mix homogeneously, be incubated under 70 ℃ of states supersound process 60 minutes, add again after 600g trehalose and 300g lactose, 7.5g sodium sulfite fully dissolve, with 0.45 μ m filtering with microporous membrane;
(3) above-mentioned steps (2) gained solution is carried out spray drying, be distributed into 100 bottles under the aseptic condition, make liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium.
The preparation of embodiment 3 liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium
Prescription (specification 2.5g)
Mezlocillin sodium 200g
Sulbactam sodium 50g
Hydrogenated soy phosphatidyl choline 350g
18-amine. 60g
Trehalose 300g
Lactose 150g
Sodium sulfite 2g
Preparation process makes liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium with embodiment 2.Comparative example 1-3 respectively write out a prescription component and parts by weight such as table 1.
Table 1 Comparative Examples prescription is formed
Component | Comparative Examples 1 | Comparative Examples 2 | Comparative Examples 3 |
Mezlocillin sodium | ??200g | ??300g | ??200g |
Sulbactam sodium | ??50g | ??75g | ??50g |
Hydrogenated soy phosphatidyl choline | ??/ | ??675g | ??350g |
Component | Comparative Examples 1 | Comparative Examples 2 | Comparative Examples 3 |
Soy phosphatidylserine | ??250g | ??/ | ??/ |
18-amine. | ??30g | ??/ | ??60g |
Poloxamer 188 | ??/ | ??150g | ??/ |
Trehalose | ??200g | ??600g | ??/ |
Lactose | ??100g | ??300g | ??/ |
Sorbitol | ??/ | ??/ | ??450g |
Sodium sulfite | ??0.5g | ??7.5g | ??/ |
Vitamin E | ??/ | ??/ | ??2g |
Prepare liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium by above prescription component, preparation method is with embodiment 1.
The investigation of test example 1 liposome
Sample prepared among embodiment 1-3 and the Comparative Examples 1-3 is carried out quality investigation, mainly carry out liposome morphologic observation, particle size determination and liposome encapsulation and measure.
Wherein liposome form and particle size determination adopt optical microscopy and the computing of statistica 5.0 statistical softwares to observe about 2000 to average.Entrapment efficiency determination adopts column chromatography for separation in conjunction with spectrophotometry, this method operating procedure is: use column chromatography the liposome in the drug solution is separated, utilize surfactant to destroy the liposome bilayer, calculate envelop rate with ultraviolet spectrophotometry and standard control again after medicine is discharged.
Every result adds up as following table 2:
The investigation of table 2 liposome
The liposome form | Mean diameter (nm) | Envelop rate (%) | |
Embodiment 1 | Spherical or oval entity | ??220 | ??88.6 |
Embodiment 2 | Spherical or oval entity | ??230 | ??89.1 |
Embodiment 3 | Spherical or oval entity | ??220 | ??86.7 |
Comparative Examples 1 | Irregular shape | ??1000 | ??12.7 |
The liposome form | Mean diameter (nm) | Envelop rate (%) | |
Comparative Examples 2 | Irregular shape | ??1050 | ??29.1 |
Comparative Examples 3 | Oval entity | ??670 | ??52.6 |
Above result has proved absolutely that the liposome effect of embodiment of the invention 1-3 preparation is fine, the form rule, and size is suitable for injection, and envelop rate is higher, has proved practical feasibility of the present invention.
Test example 2 study on the stability
The mezlocillin for inj sulbactam sodium that the sample and the RuiYang Pharmacy Co., Ltd of embodiment of the invention 1-3, Comparative Examples 1-3 preparation produced was respectively at accelerated test under 40 ℃ of high temperature, relative humidity 75% condition 6 months, respectively the 0th, 1,2,3,6 sampling at the end of month, detect the variation of every index, the every detection index of sample of embodiment of the invention 1-3 preparation as a result has no significant change, related substance obviously increases after 6 months and Comparative Examples 1-3 and listing preparation quicken, content obviously reduces, and the back clarity of redissolving is against regulation.The superiority of the present invention aspect the increase product stability has been described.
Foregoing description of the present invention is intended to explaining, rather than restriction.Concerning the art technology people, can carry out multiple variation or modification in the embodiment described herein.Do not depart from the scope of the present invention or spirit in can obtain these variations.Each list of references that the application quoted is incorporated herein by reference in full at this.
Claims (9)
1. liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium, be made up of mezlocillin sodium, sulbactam sodium, liposome vectors, frozen-dried supporting agent and the optional antioxidant that exists, wherein said liposome vectors is hydrogenated soy phosphatidyl choline and 18-amine..
2. liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium according to claim 1 is characterized in that mezlocillin sodium and sulbactam sodium are 4: 1 aseptic mixtures of weight ratio.
3. according to the arbitrary described liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium of claim 1-2, it is characterized in that each composition weight umber is:
4 parts of mezlocillin sodiums
1 part of sulbactam sodium
Hydrogenated soy phosphatidyl choline 2.5-13 part
18-amine. 0.3-5 part
Frozen-dried supporting agent 4-15 part
Antioxidant 0-3 part.
4. liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium according to claim 3 is characterized in that each composition weight umber is:
4 parts of mezlocillin sodiums
1 part of sulbactam sodium
Hydrogenated soy phosphatidyl choline 5-9 part
18-amine. 0.6-2 part
Frozen-dried supporting agent 6-12 part
Antioxidant 0.01-0.1 part.
5. according to the arbitrary described liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium of claim 1-4, wherein said frozen-dried supporting agent is selected from one or more in sodium chloride, mannitol, glucose, lactose, polyvinylpyrrolidone, sucrose, glycine, sorbitol, trehalose, the dextran, is preferably 2: 1 the mixture of weight ratio of trehalose and lactose.
6. according to the arbitrary described liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium of claim 1-5, wherein said antioxidant is selected from one or more in sodium sulfite, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, ascorbic acid, vitamin E, propyl gallate, ascorbyl palmitate, the butylated hydroxyarisol, preferred sodium sulfite.
7. method for preparing the arbitrary described liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium of claim 1-6, concrete steps comprise:
(1) hydrogenated soy phosphatidyl choline and 18-amine. are dissolved in the organic solvent, placing reduces pressure on the rotating thin film evaporimeter eliminates organic solvent, has obtained immobilized artificial membrane, adds the buffer salt solution stirring and dissolving, obtains blank liposome solution;
(2) mezlocillin sodium and sulbactam sodium are dissolved in the water for injection,, are incubated under the 50-70 ℃ of state supersound process 40-60 minute, add again after frozen-dried supporting agent, antioxidant fully dissolves, filter with prepared blank liposome solution mix homogeneously;
(3) above-mentioned steps (2) gained solution is carried out spray drying, carry out packing under the aseptic condition, make liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium.
8. the preparation method of liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium according to claim 7, it is characterized in that described organic solvent is selected from one or more in ethanol, isopropyl alcohol, methanol, butanone, acetone, ethyl acetate, chloroform, dichloromethane or the Ethyl formate, being preferably volume ratio is 1: 2 the isopropyl alcohol and the mixed solvent of ethyl acetate.
9. the preparation method of liposome injection based on drug combination of mezlocillin sodium and sulbactam sodium according to claim 7, what it is characterized in that wherein said buffer salt solution can be in phosphate buffer, citrate buffer, carbonate buffer solution, the borate buffer solution is a kind of, is preferably pH value and is phosphoric acid-sodium hydrogen phosphate buffer of 6.0.
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102579351A (en) * | 2012-03-23 | 2012-07-18 | 浙江磐谷药源有限公司 | Injection mezlocillin sodium liposome and preparation method |
CN104887679A (en) * | 2015-04-27 | 2015-09-09 | 海南通用康力制药有限公司 | Piperacillin sodium and sulbactam sodium sterile powder-injection and preparation method thereof |
CN107496366A (en) * | 2017-09-30 | 2017-12-22 | 苏州二叶制药有限公司 | A kind of pharmaceutical composition of mezlocillin sodium and sulbactam sodium compound |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101322685A (en) * | 2008-08-01 | 2008-12-17 | 海南百那医药发展有限公司 | Mezlocillin sodium and sulbactam sodium for injection and freeze-dried injection preparation thereof |
CN101623259A (en) * | 2009-07-23 | 2010-01-13 | 海南美大制药有限公司 | Amoxicillin lipidosome solid preparation and new application thereof |
CN101669910A (en) * | 2009-08-18 | 2010-03-17 | 海南美大制药有限公司 | Preparation of cefobutazine sodium proliposome |
CN101693010A (en) * | 2009-08-18 | 2010-04-14 | 海南美大制药有限公司 | Cefathiamidine prosoma liposome preparation |
-
2010
- 2010-04-21 CN CN 201010151971 patent/CN101804052B/en not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101322685A (en) * | 2008-08-01 | 2008-12-17 | 海南百那医药发展有限公司 | Mezlocillin sodium and sulbactam sodium for injection and freeze-dried injection preparation thereof |
CN101623259A (en) * | 2009-07-23 | 2010-01-13 | 海南美大制药有限公司 | Amoxicillin lipidosome solid preparation and new application thereof |
CN101669910A (en) * | 2009-08-18 | 2010-03-17 | 海南美大制药有限公司 | Preparation of cefobutazine sodium proliposome |
CN101693010A (en) * | 2009-08-18 | 2010-04-14 | 海南美大制药有限公司 | Cefathiamidine prosoma liposome preparation |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102579351A (en) * | 2012-03-23 | 2012-07-18 | 浙江磐谷药源有限公司 | Injection mezlocillin sodium liposome and preparation method |
CN104887679A (en) * | 2015-04-27 | 2015-09-09 | 海南通用康力制药有限公司 | Piperacillin sodium and sulbactam sodium sterile powder-injection and preparation method thereof |
CN104887679B (en) * | 2015-04-27 | 2018-07-17 | 海南通用康力制药有限公司 | A kind of piperacillin-sulbactam sodium sterile powder injection and preparation method thereof |
CN107496366A (en) * | 2017-09-30 | 2017-12-22 | 苏州二叶制药有限公司 | A kind of pharmaceutical composition of mezlocillin sodium and sulbactam sodium compound |
CN107496366B (en) * | 2017-09-30 | 2020-03-17 | 苏州二叶制药有限公司 | Pharmaceutical composition of mezlocillin sodium and sulbactam sodium compound |
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