CN102626381A - Vesicular phospholipid gel injection of latamoxef sodium - Google Patents
Vesicular phospholipid gel injection of latamoxef sodium Download PDFInfo
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- CN102626381A CN102626381A CN2012101180981A CN201210118098A CN102626381A CN 102626381 A CN102626381 A CN 102626381A CN 2012101180981 A CN2012101180981 A CN 2012101180981A CN 201210118098 A CN201210118098 A CN 201210118098A CN 102626381 A CN102626381 A CN 102626381A
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Abstract
The invention discloses a vesicular phospholipid gel injection of latamoxef sodium and a preparation method thereof. The vesicular phospholipid gel injection is prepared from latamoxef sodium, lecithin high potency, cholesterol, trehalose, and dextran according to a specific weight ratio. The vesicular phospholipid gel injection of the invention has good preparation stability and still maintains a fine entrapment rate after long term storage. The vesicular phospholipid gel injection of the invention improves the quality of preparation products, increases the bioavailability of drugs, and reduces toxic side effect. Besides, the preparation method is simple, which is suitable for industrial production.
Description
Technical field
The present invention relates to novel injection of a kind of Latamoxef Sodium and method for making thereof, be specifically related to a kind of vesicle type phospholipid gel injection and method for making thereof of Latamoxef Sodium, belonged to technical field of medicine.
Background technology
Latamoxef Sodium (Latamoxef Sodium) (6R; 7R)-7-[2-carboxyl-2-(4-hydroxyphenyl) acetylamino]-7-methoxyl group-3-[(1-methyl isophthalic acid H-tetrazolium-5-yl) sulphomethyl]-8-oxo-5-oxa--1-azabicyclo [4.2.0] oct-2-ene-2-formic acid disodium salt; Relative molecular mass: 564.44, molecular formula: C
20H
18N
6Na
2O
9S; Structural formula is following:
Latamoxef Sodium is semisynthetic oxacephem (oxacephem) type new antibiotic.Its anti-microbial property and third generation cephalosporin are close, and antimicrobial spectrum and cefotaxime are approximate, and multiple gram-negative bacteria is had good antibacterial action.
The mechanism of action of latamoxef is to suppress the biosynthesis of bacteria cell wall and play bactericidal action.With first and second in generation cephalosporin compare, its antimicrobial spectrum further enlarges, and is highly stable to beta-lactamase, thus to the bacterial strain of the enzyme of anti-the penicillium sp or anti-first and second in generation cephalosporin some gram-negative bacterias antibacterial action is arranged.Latamoxef is a kind of 1-benzene azoles-beta-Lactam antibiotic, and its structure is unique in beta-lactam compound.Its basic structure and cephamycin-type are approaching, but an oxygen molecule is got the sulphur atom that has replaced the beta-lactam core, and this is relevant with its enhanced antibacterial activity.Latamoxef also has half tetramethyl penta ethylmercapto group, and in antibacterial activity in vitro, reaches to greatest extent, and its 7-α-methoxyl group has strengthened the beta-lactam enzyme stability of medicine simultaneously.It has strengthened beta-lactam enzyme stability and antibacterial action to the hydroxyl malonyl, has influenced the pharmacodynamics of medicine, makes it have the long half-life and protein binding rate is not high.
Latamoxef Sodium has good antibacterial action to escherichia coli, hemophilus influenza, klebsiella bacillus, various Bacillus proteus, Enterobacter, citrobacter, serratia marcecens, bacteroid etc.Relatively poor to Pseudomonas aeruginosa and acinetobacter calcoaceticus effect; To the effect of gram positive bacterias such as staphylococcus aureus, streptococcus pneumoniae than cefalotin, cefazolin sodium and penicillin a little less than.
Be used to treat pneumonia due to the sensitive organism, tracheitis, pleuritis, peritonitis clinically, and the infection at position such as skin and soft tissue, bone and joint, ear,nose & throat, wound surface, also can be used for septicemia and meningitis.
Latamoxef Sodium is oral not to be absorbed; Vein or these article of intramuscular injection artifact availability are higher; Can extensively be distributed in viscera tissue, skin, muscle, bone, joint, sputum, ascites, hydrothorax, amniotic fluid, Cord blood, bile, uterus adnexa, cardiac muscle, the cerebrospinal fluid after the drug absorption, but divide a word with a hyphen at the end of a line to Placenta Hominis hardly.Biological metabolism does not take place in latamoxef in vivo, mainly with the original shape medicine that is high activity with urine and bile excretion, plasma half-life and intravenously administrable amount, drip velocity are relevant, and the good clinical using value is arranged.
Mostly the Latamoxef Sodium of listing is aseptic freeze-dried powder at present, and poor stability to the instability of temperature and light, turbid phenomenon etc. occurs after the redissolution.
Patent documentation CN101332188A discloses a kind of method that adopts superfine communication technique to prepare the Latamoxef Sodium sterilized powder; With Latamoxef Sodium through super micron mill; Through the comminution by gas stream technology; Being ground into particle diameter is 1250-2500 purpose micropowders, carries out aseptic subpackagedly again, makes injectable sterile powder.This method has just changed flowability difference and the slow shortcoming of redissolving of dividing in the process of assembling, equally can very fast hydrolysis oxidation in aqueous solution, do not change the problem of poor stability.
Patent documentation CN101642432A discloses a kind of method for preparing latamoxef sodium lipidosome aseptic powder; Comparatively speaking than the Latamoxef Sodium aseptic powder of other prepared; Stability, bioavailability all have lifting, but the space that has greatly improved is as improving envelop rate, type steady in a long-term, control drug release etc.
In the pharmaceutical carrier induction system, the research of submicrons such as microemulsion, microsphere, nanoparticle, liposome, vesicle type phospholipid gel, pharmacosomes has become field very active in the novel pharmaceutical formulation research.Drug encapsulation can be changed medicine distribution in vivo in these submicrons, increase the abundance of medicine, thereby improve curative effect, alleviate toxic and side effects at target organ.
In targeting drug delivery system, vesicle type phospholipid gel shows special advantages as a kind of novel drug-supplying system at aspects such as control drug release, raising anti-tumor activity, increase medicine stabilities.
(vesicular phospholipid gels VPG) is a kind of semisolid phospholipid disperse system to vesicle type phospholipid gel.Similar vesicle on the form, and be different from traditional lipidosome gel and conventional liposome cell structure.Because formed unique three-dimensional netted stereochemical structure, VPG can be used as " the storage storehouse " of medicine, thereby control drug release.The phospholipid denseness that increases is dwindled the interval between adjacent vesicle, and final result is the water that all contains certain volume in the vesicle and between vesicle, is suitable for loaded with water-soluble, fat-soluble and amphipathic medicine.Especially as far as water soluble drug; The inside and outside water volume that equates that is close to of vesicle not only makes its envelop rate improve; And inside and outside drug level reaches unanimity, and weakened the influence to stability such as drug leakage that gradient causes to a certain extent, for it has opened up prospective application prospect.
In recent years; Continuous progress along with biotechnology; Preparation technology is progressively perfect for vesicle type phospholipid gel, and vesicle type phospholipid gel mechanism of action is further illustrated, and vesicle type phospholipid gel is fit to vivo degradation, avirulence and non-immunogenicity in addition; Particularly great number tested data proof vesicle type phospholipid gel can improve the Drug therapy index, reduces drug toxicity and reduce drug side effect as pharmaceutical carrier, and reduces advantage such as drug dose.
But, the challenge of preparation vesicle type phospholipid gel is to select suitable liposome constituent and method for making.Because the character of vesicle type phospholipid gel is directly closely related with its composition like stability, envelop rate, onset time, in vivo circulation time, bioavailability and toxic and side effects etc.; And used component with the pharmaceutical properties that will seal directly closely related; Therefore, selecting which type of composition to form the vesicle type phospholipid gel with better quality is the problem that needs to be resolved hurrily.
Summary of the invention
The inventor is through discover in a large number; Can process the Latamoxef Sodium vesicle type phospholipid gel injection of excellent quality through Latamoxef Sodium, soybean lecithin, cholesterol, trehalose and the dextran of selecting the specified weight proportioning for use, thereby accomplish the present invention.
To achieve these goals, big quantity research and realization that the inventor carries out find that Latamoxef Sodium, soybean lecithin, cholesterol, trehalose and the dextran of specified weight proportioning can be processed Latamoxef Sodium vesicle type phospholipid gel injection; Wherein, Envelop rate as the Latamoxef Sodium of active constituents of medicine is high, and vesicle type phospholipid gel particle diameter is little and be evenly distributed, and compares with latamoxef sodium injection of the prior art; The retention time significant prolongation of the active constituents of medicine of preparation of the present invention in the body circulation; The biocompatibility of medicine is high, and bioavailability obviously improves, and curative effect obviously improves.
The purpose of this invention is to provide a kind of Latamoxef Sodium vesicle type phospholipid gel injection, it is mainly processed by the composition of following weight proportion:
Preferably: the weight ratio between cholesterol and the soybean lecithin is 1: 3-2: 5.
As the preferred embodiments of the invention, described Latamoxef Sodium vesicle type phospholipid gel injection, mainly process by the composition of following weight proportion:
Preferably: the weight ratio between cholesterol and the soybean lecithin is 1: 2-2: 5.
As the phospholipid that is used to form vesicle type phospholipid gel, can use natural phospholipid and synthetic phospholipid.In the present invention, as the Latamoxef Sodium of active constituents of medicine, its good water solubility.To the characteristics of Latamoxef Sodium, the inventor is particularly suitable for the material as basic vesicle type phospholipid gel through discovering soybean lecithin.
Soybean lecithin (Lecithin High Potency) is a kind of natural phospholipid, sells manyly on the market, and the content high price is cheap.Soybean lecithin forms stable vesicle type phospholipid gel film easily.
In Latamoxef Sodium vesicle type phospholipid gel injection of the present invention, for the Latamoxef Sodium of 1 weight portion, the consumption of soybean lecithin is the 4-5 weight portion.If the consumption of soybean lecithin is lower than 4 weight portions, the stability of the vesicle type phospholipid gel that then forms can reduce significantly; Otherwise if the consumption of soybean lecithin is higher than 5 weight portions, then the envelop rate as the Latamoxef Sodium of active constituents of medicine also can descend thereupon, and the quality of injection and curative effect reduce.
In Latamoxef Sodium vesicle type phospholipid gel injection of the present invention, cholesterol is used to regulate the stability of vesicle type phospholipid gel.
(cholesterol Ch) is a kind of amphiphilic to cholesterol, combines with soybean lecithin, stops it to be condensed into crystal structure.Cholesterol mixes the soybean lecithin bilayer, is similar to " buffer agent " and equally plays the effect of regulating membrane structure " flowability ".When being lower than phase transition temperature, cholesterol can make film reduce ordered arrangement, increases mobile; When being higher than phase transition temperature, cholesterol can increase the ordered arrangement of film, thereby reduces the flowability of film.Cholesterol can make liposome bimolecular tunic solidify, thereby reduces the generation of free radical, reduces oxidation level, and liposome stability is significantly strengthened.As a kind of synthetic product, the cholesterol source is abundant, low price.
The inventor is through discovering that cholesterol and soybean lecithin weight ratio are 1: 2-2:, can form stable Latamoxef Sodium vesicle type phospholipid gel at 5 o'clock.When with cholesterol and soybean lecithin weight ratio during less than 1: 2, membrane stability reduces, and Latamoxef Sodium is easy to seepage; When with the weight sum of cholesterol and soybean lecithin weight ratio greater than in 2: 5 the time, Latamoxef Sodium vesicle type phospholipid gel membrane fluidity is too high, the Latamoxef Sodium that is wrapped in the vesicle type phospholipid gel is easy to discharge.In addition, discover, when cholesterol and weight sum and soybean lecithin weight ratio be 1: 2-2: in the time of 5, formed vesicle type phospholipid gel toxicity is minimum.
Discover that the size of vesicle type phospholipid gel is to influence the vesicle type phospholipid gel principal element with the time of staying that distributes in vivo, the particle diameter of vesicle type phospholipid gel is more little, in the body time of staying long more, bioavailability is high more.
On the other hand; The inventor discovers, in Latamoxef Sodium vesicle type phospholipid gel injection of the present invention, for the Latamoxef Sodium of 1 weight portion; The consumption of soybean lecithin is the 4-5 weight portion; Cholesterol is 2 weight portions, and cholesterol soybean lecithin weight ratio is 1: 2-2: 5 o'clock, the envelop rate of formed Latamoxef Sodium vesicle type phospholipid gel injection was high.
Discover that when the Latamoxef Sodium that uses above-mentioned specified quantitative, soybean lecithin, cholesterol, can obtain colory Latamoxef Sodium vesicle type phospholipid gel, its envelop rate and stability are all very high, toxicity is low, and bioavailability is high.
In Latamoxef Sodium vesicle type phospholipid gel injection of the present invention, use trehalose and dextran as excipient, be used to form stable injection.
Trehalose be by two glucose molecules with α, α, 1; The nonreducing sugar that the 1-glycosidic bond constitutes; Self property is highly stable, and its most tangible character is that the biomembranous ability of protection is arranged under anhydrous condition, even make vesicle type phospholipid gel under the situation of dehydration, also keep complete form.So in Latamoxef Sodium vesicle type phospholipid gel injection of the present invention, trehalose can effectively be protected particulate form of vesicle type phospholipid gel and stability, further improves the stability of vesicle type phospholipid gel injection.
Dextran mainly is α-1 by the extracellular polysaccharide that antibacterial (like leuconostoc mesenteroide (Leuconostoc mesenteroides)) produces, and the glucose that the 6-glycosidic bond connects also has α-1,2, α-1,3, α-1,4 branched structure sometimes.Main in this preparation as the lyophilized powder excipient.
Latamoxef Sodium vesicle type phospholipid gel injection of the present invention, its specification is 0.25g, 0.5g, 1.0g/ bottle.
The present invention also provides a kind of method for making of Latamoxef Sodium vesicle type phospholipid gel injection, specifically comprises being prepared as follows step:
(1) Latamoxef Sodium is dissolved in the water for injection;
(2) soybean lecithin and cholesterol are dissolved in the latamoxef sodium solution, stirred ultrasonic 20 minutes, do the gradient homogenizing 5～6 times at 100bar to 800bar then, promptly get Latamoxef Sodium vesicle type phospholipid gel solution;
(3), add in the Latamoxef Sodium vesicle type phospholipid gel solution of above-mentioned preparation and dissolve with trehalose and dextran;
(4) 0.22 μ m filtering with microporous membranes, packing, directly lyophilization obtains Latamoxef Sodium vesicle type phospholipid gel injection lyophilized injectable powder.
As one of concrete embodiment, the temperature of the quick freezing described in the step (4) is-40 ℃.
Concerning drug holding theca alveolitoid phospholipid gel, vesicle type phospholipid gel size evenly suitably, not spill active component etc. all be a challenge for the envelop rate plastid high, that material forms of structural material.
The inventor screens suitable material composition, adopts suitable preparation technology, and it is little to have obtained vesicle type phospholipid gel particle diameter, and particle size distribution is even, and envelop rate is high, the colory Latamoxef Sodium vesicle type phospholipid gel injection that stability is high.
The Latamoxef Sodium vesicle type phospholipid gel injection that makes through the inventive method; Increase the retention time of medicine in the body circulation, improved bioavailability of medicament, reduced toxic and side effects; Curative effect obviously improves; Improved the long-time stability of preparation, and method for making is simple, is suitable for industrialized great production.
Description of drawings
Below, specify embodiment of the present invention in conjunction with accompanying drawing, wherein:
Fig. 1 is the stripping curve figure of Latamoxef Sodium vesicle type phospholipid gel injection.
Wherein:
The specific embodiment
Following examples are to further specify of the present invention, but never limit the scope of the present invention.Further set forth the present invention in detail with reference to embodiment below, but it will be appreciated by those skilled in the art that the present invention is not limited to the method for preparing of these embodiment and use.And those skilled in the art can be equal to replacement, combination, improvement or modification to the present invention according to description of the invention, but these all will comprise within the scope of the invention.
Embodiment 1The preparation of Latamoxef Sodium vesicle type phospholipid gel injection
Prescription: (1000 bottles)
Preparation technology
(1) the 250g Latamoxef Sodium is dissolved among the water for injection 1000ml;
(2) soybean lecithin 1000g and cholesterol 500g are dissolved in the latamoxef sodium solution, stirred ultrasonic 20 minutes, do the gradient homogenizing 6～7 times at 200bar to 1000bar then, promptly get Latamoxef Sodium vesicle type phospholipid gel solution;
(3), add in the Latamoxef Sodium vesicle type phospholipid gel solution of above-mentioned preparation and dissolve with trehalose 250g and dextran 500g;
(4) 0.22 μ m filtering with microporous membranes, packing (1ml/ bottle), directly lyophilization obtains Latamoxef Sodium vesicle type phospholipid gel injection lyophilized injectable powder.
Embodiment 2The preparation of Latamoxef Sodium vesicle type phospholipid gel injection
Prescription: (1000 bottles)
Preparation technology
(1) the 500g Latamoxef Sodium is dissolved among the water for injection 2000ml;
(2) soybean lecithin 2000g and cholesterol 1000g are dissolved in the latamoxef sodium solution, stirred ultrasonic 20 minutes, do the gradient homogenizing 6～7 times at 200bar to 1000bar then, promptly get Latamoxef Sodium vesicle type phospholipid gel solution;
(3), add in the Latamoxef Sodium vesicle type phospholipid gel solution of above-mentioned preparation and dissolve with trehalose 500g and Dextran 10 00g;
(4) 0.22 μ m filtering with microporous membranes, packing (2ml/ bottle), directly lyophilization obtains Latamoxef Sodium vesicle type phospholipid gel injection lyophilized injectable powder.
Embodiment 3The preparation of Latamoxef Sodium vesicle type phospholipid gel injection
Prescription: (1000 bottles)
Preparation technology
(1) the 1000g Latamoxef Sodium is dissolved among the water for injection 3000ml;
(2) soybean lecithin 4000g and cholesterol 2000g are dissolved in the latamoxef sodium solution, stirred ultrasonic 20 minutes, do the gradient homogenizing 6～7 times at 200bar to 1000bar then, promptly get Latamoxef Sodium vesicle type phospholipid gel solution;
(3), add in the Latamoxef Sodium vesicle type phospholipid gel solution of above-mentioned preparation and dissolve with trehalose 1000g and Dextran 10 00g;
(4) 0.22 μ m filtering with microporous membranes, packing (3ml/ bottle), directly lyophilization obtains Latamoxef Sodium vesicle type phospholipid gel injection lyophilized injectable powder.
Comparative Examples 1-3The preparation of Latamoxef Sodium vesicle type phospholipid gel injection
Adopt respectively with embodiment 1-3 in identical production technology, the composition in will the Comparative Examples 1-3 shown in following table 1 is processed Latamoxef Sodium vesicle type phospholipid gel injection respectively:
Used composition among the table 1 Comparative Examples 1-3
Wherein, "/" expression is not used.
Adopt the technology of CN101642432A embodiment 1, prepare a collection of, as a comparison routine 4.
Test Example 1The mensuration of vesicle type phospholipid gel particle diameter
Under the room temperature condition, get the Latamoxef Sodium vesicle type phospholipid gel injection among embodiment 1-3 and the Comparative Examples 1-3, place the sample cell of Submicron Particle Sizer Model 370 particle diameter detectors, measure particle size distribution and mean diameter; Observe particle shape with projection electron microscope.The result is shown in the following table 2.
Table 2 vesicle type phospholipid gel particle diameter testing result
Can know that from table 2 the vesicle type phospholipid gel particle diameter that embodiment 1-3 makes is even, show spherical, big or small homogeneous; The vesicle type phospholipid gel particle diameter that Comparative Examples 1-3 makes is inhomogeneous, and shape is indefinite, and is not of uniform size.
Particularly, even when adopting same production technology, the Latamoxef Sodium vesicle type phospholipid gel that the particle appearance of gained Latamoxef Sodium vesicle type phospholipid gel and mean diameter thereof obviously are superior to gained among the Comparative Examples 1-3 among the embodiment 1-3.When the composition beyond using the used composition of the present invention was described, perhaps when the composition consumption was outside the composition amount ranges that the present invention limits, the outward appearance of gained Latamoxef Sodium vesicle type phospholipid gel was inferior to the present invention, and mean diameter goes out greatly a lot.
Test Example 2The mensuration of envelop rate
With the rotating speed high speed centrifugation of the Latamoxef Sodium vesicle type phospholipid gel injection for preparing among embodiment 1-3 and the Comparative Examples 1-3, centrifugal 20 minutes, get supernatant with 5000r/min; Use the methanol ultrasonic dissolution; The HPLC method is surveyed the latamoxef sodium content, and computational envelope rate, result are shown in the following table 3.
Table 3 entrapment efficiency determination result
Can know that by table 3 envelop rate of the vesicle type phospholipid gel preparation of embodiment 1-3 preparation is higher than the envelop rate of the vesicle type phospholipid gel preparation of Comparative Examples 1-3 significantly.When the composition beyond using the used composition of the present invention was described, perhaps when the composition consumption was outside the composition amount ranges that the present invention limits, the vesicle type phospholipid gel envelop rate of gained vesicle type phospholipid gel was lower than the present invention.
Test Example 3Study on the stability
With the sample of embodiment of the invention 1-3 preparation and the latamoxef sodium for injection (lot number: 20111003 of listing; Zhejiang Hui Disen pharmaceutcal corporation, Ltd) places following 6 months of the condition of 40 ℃ of high temperature, relative humidity 75% respectively; Carry out accelerated test and investigate, experimental result is shown in the following table 4.
Table 4 accelerated test result
Can be known that by table 4 when quickening June, the content of listing preparation and Comparative Examples preparation reduces, related substance raises; And sample character of the present invention, content and related substance variation are all not obvious, explain that product stability of the present invention is good.
Test Example 4The percolation ratio test
Get the sample of Test Example 1-3 and Comparative Examples 1-3 preparation, at ambient temperature,, make regular check on, measure envelop rate respectively at 0 day, 30 days, 60 days, 90 days and 180 days, with the dose of sealing in 0 day relatively, calculate percolation ratio, the result is shown in the following table 5.
Table 5 percolation ratio result of the test
Can know by table 5; During long term storage; The Latamoxef Sodium vesicle type phospholipid gel injection percolation ratio for preparing among the embodiment of the invention 1-3 changes little; And the injection percolation ratio for preparing among the Comparative Examples 1-3 increases gradually, and vesicle type phospholipid gel seepage is serious, and the Latamoxef Sodium vesicle type phospholipid gel injection of this explanation the present invention preparation has higher stability.
Test Example 5The mensuration of blood drug level
28 rats are divided into 4 groups at random, every group of injection of distinguishing preparation in drug administration by injection embodiment 1-2 and Comparative Examples 1-2 and 4, and commercially available (lot number: 20111003, Zhejiang Hui Disen pharmaceutcal corporation, Ltd), specification is a 0.5g latamoxef sodium injection.Respectively at 0.5h, 1h, 1.5h, 2h, 3h, 6h, 8h, 12h and 24h, take a blood sample after the administration, blood sample is measured blood drug level with the HPLC-MS method after treatment.The Latamoxef Sodium vesicle type phospholipid gel injection of preparation and the blood drug level and the time relation curve of commercially available latamoxef sodium for injection are shown in the accompanying drawing 1 among the Latamoxef Sodium vesicle type phospholipid gel injection for preparing among the drafting embodiment 1-2, the Comparative Examples 1-2 and 4.
Can know by Fig. 1; The Latamoxef Sodium vesicle type phospholipid gel injection of preparation is compared with commercially available latamoxef sodium injection in embodiment 1-2 and Comparative Examples 1-2 and 4; The Latamoxef Sodium vesicle type phospholipid gel injection for preparing among the embodiment of the invention 1-2 has the slow release slow release effect, has improved bioavailability.
Industrial applicibility
More than through the specific embodiment the present invention is further specified: the result according to embodiment and experimental example can know that Latamoxef Sodium vesicle type phospholipid gel of the present invention has good surface appearance, and granule is little; Particle diameter is even, and envelop rate is high, and stability is high; Percolation ratio is low; The time of staying in vivo is long, and bioavailability is high, has the favorable industrial using value.
More than through the specific embodiment and embodiment the present invention is specified; But should understand; These explanations do not constitute any restriction to scope of the present invention; Under the situation that does not depart from spirit of the present invention and protection domain, can carry out multiple modification, improvement and replacement to technical scheme of the present invention and embodiment thereof, because of these all fall in protection scope of the present invention.
Claims (6)
1. Latamoxef Sodium vesicle type phospholipid gel injection is characterized in that mainly being processed by the composition of following weight proportion:
Preferably: the weight ratio between cholesterol and the soybean lecithin is 1: 3-2: 5.
2. Latamoxef Sodium vesicle type phospholipid gel injection according to claim 1 is characterized in that mainly being processed by the composition of following weight proportion:
Preferably: the weight ratio between cholesterol and the soybean lecithin is 1: 2-2: 5.
3. according to each described Latamoxef Sodium vesicle type phospholipid gel injection among the claim 1-2, it is characterized in that specification is 0.25g, 0.5g, 1.0g/ bottle.
4. a method for preparing Latamoxef Sodium vesicle type phospholipid gel injection is characterized in that comprising the steps:
(1) Latamoxef Sodium is dissolved in the water for injection;
(2) soybean lecithin and cholesterol are dissolved in the latamoxef sodium solution, stirred ultrasonic 20 minutes, do the gradient homogenizing 6～7 times at 200bar to 1000bar then, promptly get Latamoxef Sodium vesicle type phospholipid gel solution;
(3), add in the Latamoxef Sodium vesicle type phospholipid gel solution of above-mentioned preparation and dissolve with trehalose and dextran;
(4) 0.22 μ m filtering with microporous membranes, packing, directly lyophilization obtains Latamoxef Sodium vesicle type phospholipid gel injection lyophilized injectable powder.
5. method according to claim 4 is characterized in that the temperature of the quick freezing described in the step (4) is-40 ℃.
6. the described Latamoxef Sodium vesicle of claim 1 type phospholipid gel injection pneumonia, tracheitis, pleuritis, peritonitis due to preparation treatment sensitive organism; And the infection at position such as skin and soft tissue, bone and joint, ear,nose & throat, wound surface, and the application in septicemia and the meningitic medicine.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015143217A (en) * | 2013-12-25 | 2015-08-06 | 参天製薬株式会社 | Injectable agent and depot formation method |
| CN106176625A (en) * | 2015-04-29 | 2016-12-07 | 重庆福安药业(集团)股份有限公司 | The pharmaceutical composition of latamoxef sodium for injection |
| CN111840232A (en) * | 2020-07-24 | 2020-10-30 | 广东金城金素制药有限公司 | Ceftazidime combined powder injection and preparation method and product specification thereof |
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| CN101642432A (en) * | 2009-08-26 | 2010-02-10 | 海南美大制药有限公司 | Latamoxef sodium proliposome preparation |
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- 2012-04-19 CN CN 201210118098 patent/CN102626381B/en not_active Expired - Fee Related
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| CN101332188A (en) * | 2008-07-11 | 2008-12-31 | 海南数尔药物研究有限公司 | Method for preparing powder injection using superfine communication technique and prepared products |
| CN101642432A (en) * | 2009-08-26 | 2010-02-10 | 海南美大制药有限公司 | Latamoxef sodium proliposome preparation |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015143217A (en) * | 2013-12-25 | 2015-08-06 | 参天製薬株式会社 | Injectable agent and depot formation method |
| CN106176625A (en) * | 2015-04-29 | 2016-12-07 | 重庆福安药业(集团)股份有限公司 | The pharmaceutical composition of latamoxef sodium for injection |
| CN106176625B (en) * | 2015-04-29 | 2019-05-31 | 重庆福安药业(集团)股份有限公司 | The pharmaceutical composition of latamoxef sodium for injection |
| CN111840232A (en) * | 2020-07-24 | 2020-10-30 | 广东金城金素制药有限公司 | Ceftazidime combined powder injection and preparation method and product specification thereof |
| CN111840232B (en) * | 2020-07-24 | 2021-06-18 | 广东金城金素制药有限公司 | Ceftazidime combined powder injection and preparation method and product specification thereof |
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