CN102727439A - Tigecycline liposome injection - Google Patents
Tigecycline liposome injection Download PDFInfo
- Publication number
- CN102727439A CN102727439A CN2012102239910A CN201210223991A CN102727439A CN 102727439 A CN102727439 A CN 102727439A CN 2012102239910 A CN2012102239910 A CN 2012102239910A CN 201210223991 A CN201210223991 A CN 201210223991A CN 102727439 A CN102727439 A CN 102727439A
- Authority
- CN
- China
- Prior art keywords
- tigecycline
- liposome
- lipidosome injection
- injection
- buffer solution
- 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
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a tigecycline liposome injection, which is mainly prepared from tigecycline, hydrogenated ovolecithin, cholesterol, polyoxyethylene alkyl amine, sodium metabisulphite, and dextran. The liposome injection provided by the invention has good preparation stability. During a lyophilization process, the liposome is prevented from rupture caused by dehydration and fusion. After hydration and reconstitution, good entrapment efficiency and stability of the liposome are maintained. With the liposome injection provided by the invention, the quality of preparation product is improved, and the toxic and side effects of tigecycline are reduced. Therefore, the injection is suitable for large-scale productions.
Description
Technical field
The present invention relates to a kind of novel formulation of tigecycline, be specifically related to a kind of tigecycline lipidosome injection and method for making thereof, belong to medical technical field.
Background technology
Tigecycline is first glycylcycline class antibiotic, and English name Tigecycline obtained drugs approved by FDA and goes on the market in 2005.Chemical name be (4S, 4aS, 5aR, 12aS)-9-[2-(uncle-Ding amino) ethylamino] 4,7bis (dimethylamino)-1,4,4a; 5,5a, 6,11,12a-octahydro-3; 10,12,12a-tetrahydroxy-1,11-dioxy-2-aphthacene carboxylic amine is new class antibiotic-glycyl tetracycline.Molecular formula is C
19H
39N
5O
8, molecular weight is 585.65, structural formula is:
The mechanism of action of tigecycline is similar with TCs, all is through combining with antibacterial 30S ribosome, stop the entering of transfer RNA, make aminoacid can't be combined into peptide chain, finally playing the blocking-up bacterioprotein and synthesize, the effect of restricting bacterial growth.But, tigecycline is stronger 5 times than tetracycline or minocycline with ribosomal binding ability.Tigecycline is very similar on molecular structure with minocycline, and its main distinction is that the former has increased a glycyl amino on 9.Up to the present, it is exclusive that the glycyl amino on this 9 is substituted by tigecycline institute.In other natural or semi-synthetic TCses, all do not occur; It makes tigecycline can overcome by effluxing and the drug resistance (the two kind main resistance mechanisms relevant with TCs) of ribosome protection mediation, thereby can be used to treat the infection due to the tetracycline resistant bacterial strain.Known at present, some other resistance mechanism can not influence the activity of tigecycline like change (like helicase/topoisomerase) of the modification of beta-lactamase (comprising the wide spectrum beta-lactamase), target site, macrolide efflux pump, enzyme target position etc.Tigecycline is approved for complicated skin and the perhaps treatment of the interior infected patient of complicated abdomen of skin texture infection more than 18 years old and 18 years old.Comprise that complicated appendicitis, burn infection, intraabdominal abscesses, deep soft tissue infect and ulcer infects.
Because the oral bioavailability of tigecycline is very limited, only can be used for drug administration by injection.Because the phenolic hydroxyl group in its molecule is prone to oxidative degradation takes place, solution colour is deepened, extremely unstable in aqueous solution, so tigecycline mainly is prepared into lyophilized injectable powder, to increase its stability.
Patent documentation CN101167732A, CN1985835A, CN102258476A, CN101401812A all disclose the method for preparing of tigecycline freeze-dried injection; Patent documentation CN101919816A discloses a kind of tigecycline sterilized powder that adopts solvent crystallization to be prepared from.The tigecycline preparation of list marketing at present is the lyophilized injectable powder that Wyeth produces, and also is to adopt the method for preparing of common lyophilized injectable powder to be prepared from.But use the tigecycline injection of method for preparing, the stability of phenolic hydroxyl group is still not ideal enough in its molecule, causes medicament contg to reduce, and related substance increases, and affects the treatment.
Because there is described shortcoming in above-mentioned prior art, tigecycline still has improved space as active medicine at aspects such as dissolubility, stability, bioavailability, toxic and side effects.
People are through discovering, liposome can be controlled the release of medicine as the carrier of medicine, improves drug targeting property, reduces drug toxicity and side effect, improves curative effect of medication.If can tigecycline be processed lipidosome injection, then be expected to overcome a series of problems that existing tigecycline injection exists, improve the dissolubility and the stability of medicine; Prolong drug retention time in vivo; Permanent performance drug effect improves bioavailability, reduces toxic and side effects; Reduce incidence rate of adverse reaction, improve treatment speed and therapeutic effect.
Liposome is to be used for various purpose sealing lipid microcapsules.Exactly, through the whole body administration of liposome, liposome can be used for transporting therapeutic agent and arrive target site or cell.Confirmed that liposome is particularly useful for cushioning drug toxicity and the pharmacokinetic parameters that changes some treatment chemical compound.The stability of drug liposome preparation is the importance of liposome product with effectively storing.Specifically, importantly Liposomal formulation long term store and the undue loss of the medicine do not sealed or the change of liposome size under proper condition.But, it is when liposome is dehydrated or freezing when melting subsequently that kind of a worry is arranged, and possibly take place that microcapsule merges and/or the seepage of container.
Protection microcapsule complete usual method between dehydration and pool period is in Liposomal formulation, to comprise a kind of cryoprotector, for example sugar (" chemistry of lipid and physics " 52:139-149 such as Harrigan (1990)).Cryoprotector keeps the complete of lipid, prevents that microcapsule from merging and the loss of microcapsule content.For example, United States Patent(USP) No. 4,927,571 relate to liposome composition regenerated from lyophilized form, that contain amycin, and it comprises a kind of cryoprotector of 1% to 10%, and for example trehalose or lactose are used to protect freezing infringement.
But, the challenge of preparation liposome is to select suitable liposome constituent and method for making.Because the character of liposome is directly closely related with the composition of liposome like stability, envelop rate, onset time, in vivo circulation time, bioavailability and toxic and side effects etc.; And the composition of liposome with the pharmaceutical properties that will seal directly closely related; Therefore, selecting which type of composition to form the tigecycline liposome with better quality is the problem that needs to be resolved hurrily.
Summary of the invention
The inventor is through studying discovery for a long period of time; Through tigecycline, hydrogenated yolk lecithin, cholesterol, polyoxyethylene alkyl amine, sodium pyrosulfite and the dextran of selecting the specified weight proportioning for use; Can form the tigecycline lipidosome injection of excellent quality, thereby accomplish the present invention.
As the phospholipid that is used to form liposome, can use natural phospholipid and synthetic phospholipid.Natural phospholipid comprises PHOSPHATIDYL ETHANOLAMINE, Ovum Gallus domesticus Flavus lecithin, hydrogenated yolk lecithin, EPG, egg yolk lecithin acyl serine, egg yolk lecithin acyl inositol, soybean lecithin, hydrogenated soy phosphatidyl choline, soybean phospholipid acyl glycerol, soy phosphatidylserine and soybean phospholipid acyl inositol etc.Synthetic phospholipid is dioleoyl phospholipid phatidylcholine (DOPC), DSPC (DSPC), dipalmitoyl phosphatidyl choline (DPPC), two myristoyl phosphatidylcholines (DMPC), two Laurel phosphatidyl cholines (DLPC), DOPG, distearyl phosphatidyl glycerol, two palmityl phosphatidyl glycerols, GLYCEROL,DIMYRISTOYL PHOSPHATIDYL, two lauroyl phosphatidyl glycerols etc.
In the present invention; Have phenolic hydroxyl group to be prone to oxidative degradation takes place in the tigecycline molecular structure as active constituents of medicine, to the tigecycline characteristics, the inventor is when a large amount of screening experiment; Find when using phospholipid and cholesterol simple combination to be difficult to form its colory liposome; The gained liposome is under the accelerated test of 40 ℃ of high temperature, relative humidity 75% ± 5%, and character such as envelop rate, stability and percolation ratio are relatively poor, must modify its membrane material.
In tigecycline lipidosome injection of the present invention; Use hydrogenated yolk lecithin and cholesterol basis as liposome membrane; Use polyoxyethylene alkyl amine that its membrane material is modified, with the stability of further improvement liposome membrane and the envelop rate of medicine.Polyoxyethylene alkyl amine is a kind of non-ionic surface active agent; When being used for the tigecycline liposome membrane; Can improve the character of membrane material and the dissolubility of tigecycline, thereby improve envelop rate, and can improve the chemical energy between this duplicature; Thereby improve the chemical stability of liposome in waterborne liquid, and then improve the stability of tigecycline lipidosome injection.
In tigecycline lipidosome injection of the present invention, for the tigecycline of 1 weight portion, the consumption of hydrogenated yolk lecithin is 1-4 part, and the consumption of cholesterol is 0.5-4 part, and the consumption of polyoxyethylene alkyl amine is 0.1-2 part.If the consumption of polyoxyethylene alkyl amine is lower than 0.1 weight portion; Then cause the stability improvement of tigecycline lipidosome injection not enough owing to its consumption is low excessively; Otherwise; If the consumption of polyoxyethylene alkyl amine is higher than 2 weight portions, it is too high and cause liposome membrane to be easy to tigecycline revealing then to be used for its consumption.
In tigecycline lipidosome injection of the present invention, sodium pyrosulfite not only has the antioxidative effect, can also be used for further regulating the membrane stability of liposome.Bound by theory not, the inventor is surprisingly found out that, adds sodium pyrosulfite and can change membrane stability, improves the pharmaceutical properties of tigecycline liposome.After deliberation, the inventor finds that sodium pyrosulfite is superior to sodium sulfite, sodium sulfite, sodium thiosulfate, thiourea, vitamin C and propyl gallate, and for the tigecycline of 1 weight portion, most preferred consumption is 0.01-0.1 part.
Discover; When the tigecycline that uses above-mentioned specified quantitative, hydrogenated yolk lecithin, cholesterol, polyoxyethylene alkyl amine and sodium pyrosulfite, can obtain colory tigecycline liposome, its envelop rate and stability are all very high; Toxicity is low, and bioavailability is high.
In tigecycline lipidosome injection of the present invention, use dextran as excipient, the tigecycline liposome is had protective effect, especially when lyophilizing, can be used for forming stable injection.
The object of the present invention is to provide a kind of stable tigecycline lipidosome injection, mainly process by tigecycline, hydrogenated yolk lecithin, cholesterol, polyoxyethylene alkyl amine, sodium pyrosulfite and dextran.
Lipidosome injection of the present invention has good preparation stability; Liposome can be because of dehydration, fusion, ice crystal etc. break in the freeze-drying process, and after hydration was redissolved, outward appearance was even; Not aggregation crystallization of liposome; Good envelop rate and the stability of the same maintenance of liposome has reduced toxic and side effects, has improved the formulation products quality.
The technical scheme that the present invention solves is following:
The present invention provides a kind of tigecycline lipidosome injection, and it is mainly processed by tigecycline, hydrogenated yolk lecithin, cholesterol, polyoxyethylene alkyl amine, sodium pyrosulfite and dextran.
Tigecycline lipidosome injection provided by the invention, wherein the specification of the tigecycline of UD is 50mg.
Tigecycline lipidosome injection provided by the invention, mainly process by the composition of following ratio of weight and number:
Tigecycline lipidosome injection provided by the invention, preferred components by weight percent is:
The present invention also provides a kind of method for preparing of tigecycline lipidosome injection, comprises the steps:
(1) component takes by weighing tigecycline, hydrogenated yolk lecithin, cholesterol, polyoxyethylene alkyl amine and sodium pyrosulfite and places the pyriform bottle by weight; Add organic solvent; Heated and stirred makes its dissolving; Organic solvent is removed in decompression on rotary evaporator then, on the bottle wall, forms the homogeneous transparent immobilized artificial membrane;
(2) under nitrogen protection, in bottle, add the buffer solution of pH6.0～6.6, jog; Make the immobilized artificial membrane eluting and be distributed to swelling hydration in the medium; Do the gradient homogenizing 4～6 times at 100bar to 600bar then, 0.22 μ m filtering with microporous membrane makes the tigecycline liposome;
(3) dextran is joined in the above-mentioned liposome, ultrafilter membrane removes and degerms and thermal source, fill under the aseptic condition, and lyophilization makes the tigecycline lipidosome injection.
Above-mentioned method for preparing, wherein said organic solvent is selected from one or more in benzyl alcohol, methanol, n-butyl alcohol, isopropyl alcohol, acetone, acetonitrile, normal hexane and the dichloromethane, and being preferably volume ratio is the methanol of 1:1 and the mixed solution of acetone.
Above-mentioned method for preparing, wherein said buffer solution are selected from a kind of in citrate buffer solution, carbonate buffer solution, the PBS, are preferably pH and are 6.2 citrate buffer solution.
The tigecycline lipidosome injection that the present invention makes has not only improved the quality of formulation products, has reduced toxic and side effects, has increased the retention time of medicine in the body circulation, has improved bioavailability of medicament, and curative effect obviously improves; And method for preparing is simple, is suitable for industrialized great production.
Description of drawings
Fig. 1 is the blood drug level-time graph of tigecycline lipidosome injection.
Wherein:
The specific embodiment
Below further explain and explanation the present invention through embodiment; But the invention is not restricted to following examples; And, can carry out various modifications, and these modifications are also included within the technical scope of the present invention not departing under this paper situation above-mentioned and intention hereinafter described.
Embodiment 1 tigecycline lipidosome injection
Prescription (1000 bottles)
Preparation technology:
(1) component takes by weighing 50g tigecycline, 120g hydrogenated yolk lecithin, 40g cholesterol, 50g polyoxyethylene alkyl amine and 3g sodium pyrosulfite and places the pyriform bottle by weight; Adding the 5000ml volume ratio is the methanol of 1:1 and the mixed solution of acetone; 50 ℃ of heated and stirred make its dissolving; Organic solvent is removed in decompression on rotary evaporator then, on the bottle wall, forms the homogeneous transparent immobilized artificial membrane;
(2) under nitrogen protection, the pH that in bottle, adds 5000ml is 6.2 citrate buffer solution, jog; Make the immobilized artificial membrane eluting and be distributed to swelling hydration in the medium; Do the gradient homogenizing 4～6 times at 100bar to 600bar then, 0.22 μ m filtering with microporous membrane makes the tigecycline liposome;
(3) the 120g dextran is joined in the above-mentioned liposome, ultrafilter membrane removes and degerms and thermal source, fill under the aseptic condition, and lyophilization makes the tigecycline lipidosome injection.
Embodiment 2 tigecycline lipidosome injections
Prescription (1000 bottles)
Preparation technology:
(1) component takes by weighing 50g tigecycline, 200g hydrogenated yolk lecithin, 90g cholesterol, 20g polyoxyethylene alkyl amine and 4g sodium pyrosulfite and places the pyriform bottle by weight; Adding the 5000ml volume ratio is the methanol of 1:1 and the mixed solution of acetone; 50 ℃ of heated and stirred make its dissolving; Organic solvent is removed in decompression on rotary evaporator then, on the bottle wall, forms the homogeneous transparent immobilized artificial membrane;
(2) under nitrogen protection, the pH that in bottle, adds 5000ml is 6.2 citrate buffer solution, jog; Make the immobilized artificial membrane eluting and be distributed to swelling hydration in the medium; Do the gradient homogenizing 4～6 times at 100bar to 600bar then, 0.22 μ m filtering with microporous membrane makes the tigecycline liposome;
(3) the 200g dextran is joined in the above-mentioned liposome, ultrafilter membrane removes and degerms and thermal source, fill under the aseptic condition, and lyophilization makes the tigecycline lipidosome injection.
Embodiment 3 tigecycline lipidosome injections
Prescription (1000 bottles)
Preparation technology:
(1) component takes by weighing 50g tigecycline, 80g hydrogenated yolk lecithin, 150g cholesterol, 80g polyoxyethylene alkyl amine and 1g sodium pyrosulfite and places the pyriform bottle by weight; Adding the 5000ml volume ratio is the methanol of 1:1 and the mixed solution of acetone; 50 ℃ of heated and stirred make its dissolving; Organic solvent is removed in decompression on rotary evaporator then, on the bottle wall, forms the homogeneous transparent immobilized artificial membrane;
(2) under nitrogen protection, the pH that in bottle, adds 5000ml is 6.2 citrate buffer solution, jog; Make the immobilized artificial membrane eluting and be distributed to swelling hydration in the medium; Do the gradient homogenizing 4～6 times at 100bar to 600bar then, 0.22 μ m filtering with microporous membrane makes the tigecycline liposome;
(3) the 70g dextran is joined in the above-mentioned liposome, ultrafilter membrane removes and degerms and thermal source, fill under the aseptic condition, and lyophilization makes the tigecycline lipidosome injection.
The preparation of Comparative Examples 1-3 tigecycline lipidosome injection
Adopt respectively with embodiment 1-3 in production technology, the composition in will the Comparative Examples 1-3 shown in following table 1 is processed the tigecycline lipidosome injection respectively:
Used supplementary material composition among the table 1 Comparative Examples 1-3
Wherein, "/" expression is not used.
The mensuration of Test Example 1 liposome particle diameter
Under the room temperature condition, get the tigecycline lipidosome 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 liposome particle diameter testing result
Can know that from table 2 the liposome particle diameter that embodiment 1-3 makes is even, show spherical, big or small homogeneous; The liposome 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 particle appearance of gained tigecycline liposome and mean diameter thereof obviously are superior to the tigecycline liposome of 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 tigecycline liposome was inferior to the present invention, and mean diameter obviously goes out greatly a lot.
The mensuration of Test Example 2 envelop rates
With the rotating speed high speed centrifugation of the tigecycline lipidosome injection for preparing among embodiment 1-3 and the Comparative Examples 1-3 with 10000r/min, centrifugal 5 minutes, get supernatant, use dissolve with methanol, the HPLC method is surveyed tigecycline 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 Liposomal formulation of embodiment 1-3 preparation is higher than the envelop rate of the Liposomal formulation 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 liposome encapsulation of gained liposome was lower than the present invention.
Test Example 3 study on the stability
Sample and listing injection tigecycline (lot number: 20110601 with embodiment of the invention 1-3 and Comparative Examples 1-3 preparation; Wyeth Pharmaceuticals Inc.) places following 6 months of the condition of 40 ℃ of high temperature, relative humidity 75% respectively; Carry out accelerated test and investigate, result of the test is shown in the following table 4.
Table 4 accelerated test result
Can be known that by table 4 when quickening June, Comparative Examples reduces with the listing formulation content, 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.
The test of Test Example 4 percolation ratios
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 tigecycline lipidosome 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 the liposome seepage is serious, and the tigecycline lipidosome injection of this explanation the present invention preparation has higher stability.
The mensuration of Test Example 5 blood drug level
42 rats are divided into 7 groups at random; Every group of injection for preparing among intravenous administration embodiment 1-3 and the Comparative Examples 1-3 respectively; And commercially available injection tigecycline (lot number: 20110601, Wyeth Pharmaceuticals Inc.), injection volume is the 1mg tigecycline.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 tigecycline lipidosome injection for preparing among the tigecycline lipidosome injection for preparing among the drafting embodiment 1-3, the Comparative Examples 1-3 and the blood drug level and the time relation curve of commercially available tigecycline injection are shown in the accompanying drawing 1.
Can know by Fig. 1; Compare with commercially available tigecycline injection with the tigecycline lipidosome injection for preparing among the Comparative Examples 1-3; The tigecycline lipidosome injection for preparing among the embodiment of the invention 1-3 has the following advantages: elimination speed is in vivo slowed down; Distribution time prolongs in the body circulation, has reached improved slow release effect, and bioavailability increases.
Industrial applicibility
Result by the foregoing description and experimental example can know that tigecycline liposome of the present invention has good surface appearance, and granule is little, and particle diameter is even; Envelop rate is high, and stability is high, and 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, these are all because of falling in protection scope of the present invention.
Each list of references of mentioning among the application or quoting is incorporated herein by reference at this in full.
Claims (8)
1. a tigecycline lipidosome injection is characterized in that mainly being processed by tigecycline, hydrogenated yolk lecithin, cholesterol, polyoxyethylene alkyl amine, sodium pyrosulfite and dextran.
2. tigecycline lipidosome injection according to claim 1, the specification that it is characterized in that the tigecycline of UD is 50mg.
3. according to claim 1 or 2 arbitrary described tigecycline lipidosome injections, it is characterized in that processing by the composition of following ratio of weight and number:
4. tigecycline lipidosome injection according to claim 3 is characterized in that mainly being processed by the composition of following ratio of weight and number:
5. a method for preparing the tigecycline lipidosome injection is characterized in that comprising the steps:
(1) component takes by weighing tigecycline, hydrogenated yolk lecithin, cholesterol, polyoxyethylene alkyl amine and sodium pyrosulfite and places the pyriform bottle by weight; Add organic solvent; Heated and stirred makes its dissolving; Organic solvent is removed in decompression on rotary evaporator then, on the bottle wall, forms the homogeneous transparent immobilized artificial membrane;
(2) under nitrogen protection, in bottle, add the buffer solution of pH6.0～6.6, jog; Make the immobilized artificial membrane eluting and be distributed to swelling hydration in the medium; Do the gradient homogenizing 4～6 times at 100bar to 600bar then, 0.22 μ m filtering with microporous membrane makes the tigecycline liposome;
(3) dextran is joined in the above-mentioned liposome, ultrafilter membrane removes and degerms and thermal source, fill under the aseptic condition, and randomly lyophilization makes the tigecycline lipidosome injection.
6. method for preparing according to claim 5; It is characterized in that described organic solvent is selected from one or more in benzyl alcohol, methanol, n-butyl alcohol, isopropyl alcohol, acetone, acetonitrile, normal hexane and the dichloromethane, being preferably volume ratio is 1: 1 the methanol and the mixed solution of acetone.
7. method for preparing according to claim 6 is characterized in that described buffer solution is selected from a kind of in citrate buffer solution, carbonate buffer solution, the PBS, is preferably pH and is 6.2 citrate buffer solution.
8. the application in the medicine of each described tigecycline lipidosome injection of claim 1-7 treatment of infected patient in the complicated skin of preparation and skin texture infection or complicated abdomen, said disease comprises that complicated appendicitis, burn infection, intraabdominal abscesses, deep soft tissue infect and ulcer infects.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210223991 CN102727439B (en) | 2012-06-29 | 2012-06-29 | Tigecycline liposome injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210223991 CN102727439B (en) | 2012-06-29 | 2012-06-29 | Tigecycline liposome injection |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102727439A true CN102727439A (en) | 2012-10-17 |
| CN102727439B CN102727439B (en) | 2013-09-25 |
Family
ID=46984213
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201210223991 Expired - Fee Related CN102727439B (en) | 2012-06-29 | 2012-06-29 | Tigecycline liposome injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102727439B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103040752A (en) * | 2012-12-20 | 2013-04-17 | 海南百思特医药科技有限公司 | Shuxuening lipidosome injection |
| CN110575437A (en) * | 2019-10-24 | 2019-12-17 | 上海交通大学 | Tigecycline liposome preparation |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101152152A (en) * | 2006-09-28 | 2008-04-02 | 南京华威医药科技开发有限公司 | Lgecycline composition for injection and processes for producing same |
| CN101401812A (en) * | 2008-11-14 | 2009-04-08 | 江苏奥赛康药业有限公司 | Tigecycline freeze-dried injection |
-
2012
- 2012-06-29 CN CN 201210223991 patent/CN102727439B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101152152A (en) * | 2006-09-28 | 2008-04-02 | 南京华威医药科技开发有限公司 | Lgecycline composition for injection and processes for producing same |
| CN101401812A (en) * | 2008-11-14 | 2009-04-08 | 江苏奥赛康药业有限公司 | Tigecycline freeze-dried injection |
Non-Patent Citations (1)
| Title |
|---|
| 谢安云等: "梯度洗脱高效液相色谱法检测注射用替加环素的有关物质", 《实用药物与临床》, vol. 14, no. 4, 31 December 2011 (2011-12-31), pages 306 - 308 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103040752A (en) * | 2012-12-20 | 2013-04-17 | 海南百思特医药科技有限公司 | Shuxuening lipidosome injection |
| CN103040752B (en) * | 2012-12-20 | 2015-01-07 | 海南圣欣医药科技有限公司 | Shuxuening lipidosome injection |
| CN110575437A (en) * | 2019-10-24 | 2019-12-17 | 上海交通大学 | Tigecycline liposome preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102727439B (en) | 2013-09-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102188377B (en) | Method for preparing medicine encapsulating liposome | |
| CN103040748B (en) | Pemetrexed disodium liposome injection | |
| JPS60502205A (en) | Lipid vesicles prepared in a single phase | |
| CN102805730A (en) | Ceramide liposome and preparation method and application thereof | |
| US8298573B2 (en) | Stable sterile filterable liposomal encapsulated taxane and other antineoplastic drugs | |
| CN101822669B (en) | Liposome injection of amoxicillin sodium sulbactam sodium medicinal composition | |
| CN101530393A (en) | Clindamycin phosphate lipidosome freeze-dried preparation and preparation method thereof | |
| CN102727439B (en) | Tigecycline liposome injection | |
| CN102366410B (en) | Argatroban liposome injection | |
| CN102716089B (en) | Gemcitabine hydrochloride liposome injection | |
| CN102188379B (en) | Preparation method of drug-carrying liposome | |
| CN101810610B (en) | Amoxicillin sodium flucloxacillin sodium medicine compound liposome injection | |
| CN102579347B (en) | Thymalfasin liposome preparation for injecting | |
| WO2019023873A1 (en) | Nano-lipid microparticle composition and pharmaceutical composition for treating hematopoietic system proliferative diseases | |
| CN102309450B (en) | Doxycycline hydrochloride liposome injection | |
| CN101732232B (en) | Docetaxel nano-particle composition | |
| CN102626392B (en) | Solid preparation of doxycycline ambroxol medicine compound | |
| CN102579349B (en) | Torasemide liposome injection | |
| CN102716085B (en) | Topotecan hydrochloride liposome injection | |
| CN102440959B (en) | Pidotimod liposome solid preparation | |
| CN103040722B (en) | Hydrochloride thiamphenicol glycinate lipidosome injection | |
| CN102406607B (en) | Tiopronin liposome injection | |
| CN102366407B (en) | Clindamycin palmitate hydrochloride liposome solid preparation | |
| CN102366409B (en) | Nizatidine liposome solid preparation | |
| CN102327236B (en) | Esomeprazole sodium liposome injection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130925 Termination date: 20160629 |