CN109481403A - A kind of chitosan-modified triamcinolone acetonide acetate liposome and preparation method - Google Patents
A kind of chitosan-modified triamcinolone acetonide acetate liposome and preparation method Download PDFInfo
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Abstract
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of chitosan-modified triamcinolone acetonide acetate liposome eye drops and preparation method.The present invention provides a kind of chitosan-modified triamcinolone acetonide acetate liposomes of Calcium acetate gradient preparation, soybean lecithin, cholesterol are prepared into adipose membrane, calcium acetate solution is added and prepares blank liposome, a kind of triamcinolone acetonide acetate liposome is obtained after triamcinolone acetonide acetate is added, obtains chitosan-modified triamcinolone acetonide acetate liposome through Chitosan-coated.The liposome has good pharmaceutical properties, and surface of liposome is presented positive charge, it is formulated as eye drops with sodium hyaluronate solution, the water solubility that triamcinolone acetonide acetate can be improved to the adsorptivity of cornea, and can reduce its drug toxicity, compared with injection type, use is more easy, safe.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of chitosan-modified triamcinolone acetonide acetate liposome and system
Preparation Method.
Background technique
Triamcinolone acetonide acetate is a kind of Glucocorticoid, which has strong and lasting anti-inflammatory and antiallergic action
Effect is mainly used for treating the diseases such as uveitis, macular edema, age-related macular degeneration in field of ophthalmology.Acetic acid is bent
The administration mode of An Naide is mainly local administration, including subconjunctival injection, retrobulbar injection and intravitreal injection, need it is long-term,
Multiple dosing, complication include intraocular hypertension, entophthamia, intraocular hemorrhage, cataract, retinal toxicity etc..In clinical ophthalmology medication
In practice, eye drops is easy to use, tolerance is good, is the preferred dosage form of ophthalmic remedy.But since triamcinolone acetonide acetate is liposoluble
Property drug, stability and poor permeability, be directly dissolved in eye drops made of water cannot effectively by eye barrier structure reach eye
Deutomerite can not treat ocular posterior segment eye disease.Moreover, existing document proves that triamcinolone acetonide acetate concentration is positively correlated with drug toxicity,
By improving its concentration, both increases toxicity, be also unable to reach intraocular effective dose.
Liposome has biodegradability and biocompatibility, and containing transport drug can be improved drug solubility, promotes
Polarity macromolecular penetrating cell film；With slow release, the half-life period of drug within the eye can be extended；Drug molecule can be protected from generation
Thank to the attack of enzyme；Reduce the toxic side effect of drug.But clinically used feminine gender liposome and the absorption of neutral liposome anterior corneal surface
Power is poor；And the problems such as that there are stability is poor, easily flocculation occurs, partial size becomes larger, and is unable to long-term preservation, and encapsulation rate is low.Liposome
The eye drops for containing medicine preparation can not be applied to clinic.
Chitosan has good biomembrane adhesiveness, biocompatibility and antibacterial activity as a kind of positivity polysaccharide, can
Promote drug absorption, is remarkably improved pharmaceutical properties applied to eye drops, previously in research, chitosan was also not disclosed in this field
The triamcinolone acetonide acetate liposome eye drops of modification.
Summary of the invention
In view of the above technical problems, present invention combination chitosan and the advantages of liposome, provides a kind of chitosan-modified
Triamcinolone acetonide acetate liposome improves solubility, stability, adsorptivity and the permeability of triamcinolone acetonide acetate, has sustained release
Characteristic, toxic side effect is small, effectively treatment ocular posterior segment eye disease, reduces complication, increases patient's compliance.
In order to realize above-mentioned technical effect, the application the following technical schemes are provided:
The application is in a first aspect, provide a kind of chitosan-modified triamcinolone acetonide acetate liposome, the triamcinolone acetonide acetate
Liposome is prepared using lecithin, cholesterol as raw material by Calcium acetate gradient, after the completion of triamcinolone acetonide acetate liposome preparation
Package chitosan obtains the chitosan-modified triamcinolone acetonide acetate liposome.
It is known in the art that cholesterol is a kind of neutral lipid, the liposome for using lecithin and cholesterol to prepare is neutrality
Liposome, percutaneous abilities are fine, but stability is bad.The application modifies the liposome by chitosan, and sun is added
Ionic surface active agent generates the effect of collaborative combination transformation: liposome is in electropositive after modification, and there is surface charge to repel and make
With can prevent from assembling；Transdermal effect is good, easily with negative electrical charge cornea abundant and conjunctiva Glycoprotein binding.The application passes through shell
The modification of glycan obtains a kind of liposome in positive charge, and through potentiometric detection, surface of liposome current potential is (+13.2 in the application
±0.7)mV。
The application second aspect provides the preparation method of above-mentioned chitosan-modified triamcinolone acetonide acetate liposome, the system
Steps are as follows for Preparation Method:
(1) soybean lecithin and cholesterol are dissolved in chloroform, rotary evaporation removes organic solvent into adipose membrane；
(2) it is added calcium acetate solution, ultrasonic aquation obtains blue-opalescent liposome turbid liquor, multigelation and through micropore device
Transparent Liposomal suspensions are obtained after filtering；
(3) transparent Liposomal suspensions obtained in step (2) are put into bag filter, using physiological saline as dialyzate into
Row is incubated for, and obtains blank liposome suspension；
(4) triamcinolone acetonide acetate is added in blank liposome suspension with certain medicine rouge ratio, water bath with thermostatic control is incubated for one section
Time obtains triamcinolone acetonide acetate liposome after crushing by high pressure homogenizer；
(5) it weighs a certain amount of chitosan and is dissolved in glacial acetic acid aqueous solution, obtain chitosan solution；
(6) mode that the chitosan solution in step (5) is stirred when being added dropwise is added in step (4) and persistently stirs one section
Time obtains chitosan-modified triamcinolone acetonide acetate liposome.
A kind of method for preparing lipidosome of the Calcium acetate gradient as Active loading type is produced by the transmembrane movement of calcium acetate
Raw concentration gradient so that a large amount of protons from liposome interior be transported to it is external generate pH gradient, make drug it is spontaneous to lipid
Internal portion's aggregation, so that the encapsulating effect of drug is greatly improved, under usual condition, since the film infiltration coefficient of calcium ion is smaller,
Play the role of storage cavern, when concentration is too low, tends not to form effective calcium acetate gradient.It is found in the application research process,
For the liposome preparation of triamcinolone acetonide acetate, certain density calcium acetate solution is added, by dialyse by solution dissociate
Calcium ion removing is conducive to triamcinolone acetonide acetate and actively enters lipid layer.
Preferably, the molar ratio of soybean lecithin and cholesterol is 7~9:0.5~1.5 in step (1).
Preferably, revolving condition is 30~40 DEG C in step (1), and 150~250 revs/min of rotations remove chloroform.
Preferably, further include being placed in adipose membrane in vacuum environment overnight in step (1), thoroughly remove residual organic solvent.
Preferably, calcium acetate solution concentration is 110~130mM, 40~50 DEG C of 2.5~3.5h of ultrasound in step (2).
Preferably, by 0.22 μm of micropore device, the step 8~12 time will be recycled after suspension multigelation in step (2).
Preferably, it is incubated at normal temperature in step (3) using physiological saline as dialyzate, it is saturating every replacement in 1.5~2.5 hours
Liquid is analysed, free calcium ion is thoroughly removed.
Preferably, the mass ratio of triamcinolone acetonide acetate and adipose membrane is 0.8~1.2:18~22 in step (4).
Preferably, the blank liposome suspension that triamcinolone acetonide acetate is added is placed in 48~52 DEG C in step (4) and is incubated for 13
~17min.
Preferably, the liposome after the completion of being incubated in step (4) is added in high pressure homogenizer, under 400~600bar pressure
4~6 crushing are recycled, recycles 12~17 times and is crushed under 1400~1600bar pressure.
Preferably, the concentration of chitosan solution is 0.45~0.65% (w/v) in step (5).
Preferably, after Liposomal suspensions are added in step (6) chitosan solution, 0.8~1.2h is persistently stirred, and 4
DEG C be incubated overnight.
The application third aspect, provides a kind of triamcinolone acetonide acetate eye drops, which passes through above-mentioned chitosan-modified
Triamcinolone acetonide acetate liposome be mixed with sodium hyaluronate eye drops.
Preferably, in above-mentioned eye drops, triamcinolone acetonide acetate concentration is 1.4~1.6mg/mL.
Fourth aspect present invention, triamcinolone acetonide acetate liposome is provided or above-mentioned preparation method obtain it is chitosan-modified
Application of the triamcinolone acetonide acetate liposome in terms of preparing anti-inflammatory or antiallergic action preparation.
Fifth aspect present invention provides above-mentioned chitosan-modified triamcinolone acetonide acetate eye drops in treatment ocular posterior segment eye disease
The application of aspect.
Beneficial effects of the present invention
1. the application provides a kind of chitosan-modified triamcinolone acetonide acetate liposome, which passes through calcium acetate gradient
Method preparation.It had not been reported in the prior art and triamcinolone acetonide acetate liposome, the application research is prepared by Calcium acetate gradient
Find in the process, certain density calcium acetate be added, remove free calcium ion during the preparation process, be conducive to drug actively into
Enter lipid layer, improve the encapsulation rate of drug, through measuring, liposome is averaged DL% (carrying drug ratio) >=80% in the application, average
EE% (encapsulation rate) >=90%.
2. the chitosan-modified triamcinolone acetonide acetate liposome in the application can be used as ophthalmic administration, repaired by chitosan
Decorations improve surface of liposome electrical property, make a kind of liposome particles with positive charge, preventing lipid granule from assembling,
While increasing stability, be conducive to the combination of drug and cornea, conjunctiva, improve drug bioavailability.Primary stability is examined
Examine the experimental results showed that, in the liposome 45d in the application encapsulation rate stabilization does not change.Applied to rat retina oedema
Model shows good therapeutic effect.
3. it is known in the art that the liposome medicament of high concentration, which acts on eye, has certain toxicity, the rouge in the application
Plastid is proved through cell toxicity test, under same concentrations, the cell activity of chitosan-modified triamcinolone acetonide acetate liposome group
Higher than triamcinolone acetonide acetate group, with increasing for concentration, cell activity gap is bigger, it was demonstrated that the chitosan liposome in the application
Play the role of reducing drug toxicity.
Detailed description of the invention
The accompanying drawings constituting a part of this application is used to provide further understanding of the present application, and the application's shows
Meaning property embodiment and its explanation are not constituted an undue limitation on the present application for explaining the application.
Fig. 1 is chitosan-modified triamcinolone acetonide acetate liposome eye drops transmission electron microscope picture
Fig. 2 is triamcinolone acetonide acetate In-vitro release curves
Fig. 3 is chitosan-modified triamcinolone acetonide acetate liposome eye drops cytotoxicity experiment
Fig. 4 is chitosan-modified triamcinolone acetonide acetate liposome eye drops effect experiment result
Specific embodiment
It is noted that following detailed description is all embodiment, it is intended to provide further instruction to the application.Unless otherwise
It indicates, all technical and scientific terms used herein has usually manages with the application person of an ordinary skill in the technical field
The identical meanings of solution.
It should be noted that term used herein above is merely to describe specific embodiment, and be not intended to restricted root
According to the illustrative embodiments of the application.As used herein, unless the context clearly indicates otherwise, otherwise singular
Also it is intended to include plural form, additionally, it should be understood that, when in the present specification using term "comprising" and/or " packet
Include " when, indicate existing characteristics, step, operation, device, component and/or their combination.
As background technique is introduced, there are many disadvantages for the ophthalmic administration of triamcinolone acetonide acetate in the prior art
End, triamcinolone acetonide acetate is fat-soluble medicine, and dosage is difficult to be promoted, and osmosis is poor.Traditional triamcinolone acetonide acetate
Liposome is low with cornea and conjunctiva affinity, and it is undesirable to carry drug effect fruit.For the technical problem more than solving, the application proposes one kind
Chitosan-modified triamcinolone acetonide acetate liposome, the liposome are prepared by Calcium acetate gradient, have good load drug effect
Fruit and encapsulation rate.
In order to enable those skilled in the art can clearly understand the technical solution of the application, below with reference to tool
The technical solution of the application is described in detail in the embodiment and comparative example of body.
The chitosan-modified triamcinolone acetonide acetate liposome preparation of embodiment 1
Soybean lecithin and cholesterol are dissolved in chloroform according to 8:1 molar ratio, with 35 DEG C of Rotary Evaporators, revolving speed
200 revs/min, 15min, rotary evaporation film forming.It is placed in vacuum environment overnight, thoroughly removes residual organic solvent.
It is added calcium acetate solution (120mM), 45 DEG C, ultrasonic aquation 3h, is made the blank liposomes for having blue-opalescent under normal pressure
Body suspension.
By suspension multigelation, and in the case where nitrogen pressure≤200psi, filtered with 0.22 micron Millipore Filter,
The step cycle 10 times, obtains transparent Liposomal suspensions.
Suspension is put into bag filter, using 0.9% sodium chloride solution as dialyzate, is incubated overnight at room temperature, every
Every the dialyzate of replacement in 2 hours, free calcium ions are thoroughly removed.
By triamcinolone acetonide acetate with 1:20 medicine rouge than being added in blank liposome suspension, the thermostatted water on magnetic stirring apparatus
50 DEG C of incubation 15min in bath carry out whole grain by high pressure homogenizer, are first crushed for the first time with 500bar pressures cycle 5 times, after
Refinement crushing is carried out with 1500bar pressures cycle 15 times.
The chitosan of certain mass is dissolved in the dissolution of glacial acetic acid water, obtains the chitosan solution of 0.5% (w/v).
At room temperature, triamcinolone acetonide acetate made from above-mentioned steps is added in a manner of stirring when being added dropwise in chitosan solution
In Liposomal suspensions, after persistently stirring 1 hour, 4 DEG C of overnight incubations obtain the triamcinolone acetonide acetate liposome of chitosan package.
The preparation of the chitosan-modified triamcinolone acetonide acetate liposome eye drops of embodiment 2
The triamcinolone acetonide acetate Liposomal suspensions of chitosan package in embodiment 1 and sodium hyaluronate eye drops are mixed,
Drug concentration is adjusted, control triamcinolone acetonide acetate concentration is 1.5mg/mL, and chitosan-modified triamcinolone acetonide acetate lipid is made
Body eye drops.4 DEG C of preservations.
3 carrying drug ratio of embodiment and entrapment efficiency determination
Chromatographic condition: chromatographic column is Hypersil ODS column (250mm × 4.6mm, 5 μm), methanol-water-ether (volume ratio
68: 32: 4) it is mobile phase, ultraviolet detection wavelength 240nm, 30 DEG C of column temperature, flow velocity 1.0mLmin-1, sample volume is 20 μ L, internal standard
Standard measure.
Chitosan-modified triamcinolone acetonide acetate liposome eye drops 1ml is drawn in the volumetric flask of 10mL, methanol is added
Dispersing and dissolving is complete, and 0.22 μm of filtering with microporous membrane is transferred in 10mL volumetric flask and is settled to scale with mobile phase, shakes up i.e.
Sample solution is obtained, 20 μ L of sample introduction carries out chromatography, measures triamcinolone acetonide acetate drug gross mass mMedicine。
The chitosan-modified triamcinolone acetonide acetate liposome eye drops 1ml of another draws equal amounts, with 0.1molL-1Hydrochloric acid
Solution adjusts the pH ≈ 2.5 of aqueous dispersions, agglomerates liposome nano granule, is centrifugated nanoparticle (centrifugal condition: 4 DEG C, 12
000r/min, 15min, purifying distillation water washing nanoparticle 2 times, centrifuge separation, supernatant merges constant volume, 0.22 μm of miillpore filter
Filtering, 20 μ L of subsequent filtrate sample introduction carry out chromatography, measure the quality m of free drugMedicine。
Carrying drug ratio (DL%) and encapsulation rate (EE%) are calculated as follows after converting:
DL% (carrying drug ratio)=(mMedicine-mTrip)/mAlways× 100%
EE% (encapsulation rate)=(mMedicine-mTrip)/mMedicine× 100%；
mAlways: the gross mass of triamcinolone acetonide acetate.
Above step in triplicate measures average DL% (carrying drug ratio) >=80%, average EE% (encapsulation rate) >=90%.
The investigation of 4 physicochemical property of embodiment
1. the measurement of partial size and current potential
Suitable chitosan-modified triamcinolone acetonide acetate liposome is taken, is diluted to debita spissitudo with PBS, is used
Mastersizer-2000 measures its particle diameter distribution and surface potential.Obtaining its average grain diameter is 100nm, is Unimodal Distribution；
Surface potential is (+13.2 ± 0.7) mV.
2. mode of appearance is investigated
Take chitosan-modified triamcinolone acetonide acetate liposome appropriate, pure water dilution is added dropwise on copper mesh, with 2% phosphorus tungsten
Sour sodium negative staining, observes its form under transmission electron microscope.It can be seen that its is spherical in shape from electromicroscopic photograph, there is preferable pattern, point
It is good to dissipate property, it is consistent (Fig. 1) uniform in size.
5 extracorporeal releasing experiment of embodiment
Chitosan-modified triamcinolone acetonide acetate liposome 3.5mL is taken to be packed into bag filter (retention relative molecular mass
14000) in, bag filter is placed in the dissolution medium (6.2 phosphate buffers of pH/ethyl alcohol=80/20) of 200mL, in 37.0 DEG C
Mix slowly lower carry out extracorporeal releasing experiment.Dialysis medium 1.0mL is taken every 30min, while it is molten to add 1.0mL dissolution medium
Liquid.Using high performance liquid chromatography, the Assaying of triamcinolone acetonide acetate released is measured under 240nm wavelength.Preparation: medicine
Object release rate=(m/m0In the formula of) × 100%., m is the quality of triamcinolone acetonide acetate in dissolution medium, m0For acetic acid in eye drops
The quality of Triamcinolone acetonide.In-vitro release curves (Fig. 2) is drawn according to release rate in different time periods.It can be with by In-vitro release curves
Find out in 5h, there can be 80% triamcinolone acetonide acetate to discharge from chitosan liposome, 10-12h substantially completely discharges.
6 stability experiment of embodiment
Chitosan-modified triamcinolone acetonide acetate liposome 5ml is taken, is placed in 4 DEG C of environment, respectively at 0,1,15,30,45d
Its encapsulation rate and partial size are measured, its encapsulation rate in 45d is measured and stablizes, drug is without leakage, and partial size is constant, it is evenly distributed, nothing
Aggregation occurs.
7 cytotoxicity experiment of embodiment
The cytotoxicity of chitosan-modified triamcinolone acetonide acetate liposome eye drops is evaluated using CCK-8 method.It takes respectively
Human glioma cell (HCEC) and Human RPE Cells in Vitro (ARPE-19) (1 × 104A/hole) it is inoculated in 96
Well culture plate is incubated overnight, until cell is completely adherent, degrees of fusion is 60%~80%.It is added after PBS washing and contains different amounts of vinegar
Sour Triamcinolone acetonide or chitosan-modified 100 hole μ l/ of triamcinolone acetonide acetate liposome serum-free medium, blank control group add
100 μ l serum-free mediums, 5 multiple holes of every group of setting.Continue to cultivate 4h.Culture solution is removed later, is changed into containing 10% small ox blood
Clear complete medium continues culture for 24 hours.Every hole shakes 1min after 20 μ l CCK-8,4h are added, in microplate reader, in 570nm
Measure A value.Cells survival rate is calculated as follows.
Cells survival rate (%)=(Asample/Acontrol) × 100%
Histogram (Fig. 3) is drawn according to result, as shown, under same concentrations, chitosan-modified triamcinolone acetonide acetate
The cell activity of liposome group is higher than triamcinolone acetonide acetate group, and with increasing for concentration, cell activity gap is bigger, it was demonstrated that shell is poly-
Glycolipid plastid plays the role of reducing drug toxicity.
8 effect experiment of embodiment
The BN rat animal model that macular edema is established using 577nm induced with laser, uses optical coherence tomography
(OCT) variation of technology observation macular edema situation.
Experimental group is set: chitosan-modified triamcinolone acetonide acetate liposome eye drops group, by chitosan-modified acetic acid
Triamcinolone acetonide liposome dilutes the eye drops of 1.5mg/mL with sodium hyaluronate, 3 times a day, puts 20 μ l of perceptiveness every time, continues 1w.
Control group: triamcinolone acetonide acetate suspension intravitreal injection group is set, using sterile micro sample injector, to model
2 μ l suspension of intravitreal injection, 1 times a week.
The OCT image of every rat eye ground oedema is recorded in 0,3,7,10d.As a result as shown in figure 4, normal rat
Retina layering is obvious, clear in structure；3d after macular edema model foundation still can be observed retina and thicken, and oedema is obvious.
The macular edema of 7d after treatment, experimental group and control group has apparent alleviation, and retinal thickness has been restored to after 10d
Normal condition, and two groups and indifference.And in no intervention group, after macular edema model foundation, oedema in observation in 10 days
It is lasting to exist, have no alleviation.Should the result shows that, chitosan-modified triamcinolone acetonide acetate liposome eye drops have good medicine
Effect, is administered by eye droppings approach, effect identical with intravitreal injection can be obtained.
The foregoing is merely preferred embodiment of the present application, are not intended to limit this application, for the skill of this field
For art personnel, various changes and changes are possible in this application.Within the spirit and principles of this application, made any to repair
Change, equivalent replacement, improvement etc., should be included within the scope of protection of this application.
Claims (10)
1. a kind of chitosan-modified triamcinolone acetonide acetate liposome, which is characterized in that the triamcinolone acetonide acetate liposome with
Lecithin, cholesterol are that raw material is prepared by Calcium acetate gradient, and it is poly- that shell is wrapped up after the completion of triamcinolone acetonide acetate liposome preparation
Sugar obtains the chitosan-modified triamcinolone acetonide acetate liposome.
2. the preparation method of chitosan-modified triamcinolone acetonide acetate liposome described in claim 1, which is characterized in that the system
Steps are as follows for Preparation Method:
(1) soybean lecithin and cholesterol are dissolved in chloroform, rotary evaporation removes organic solvent into adipose membrane；
(2) calcium acetate solution is added, ultrasonic aquation obtains blue-opalescent liposome turbid liquor, and multigelation is simultaneously filtered through micropore device
After obtain transparent Liposomal suspensions；
(3) transparent Liposomal suspensions obtained in step (2) are put into bag filter, are incubated using physiological saline as dialyzate
It educates, obtains blank liposome suspension；
(4) triamcinolone acetonide acetate being added in blank liposome suspension with certain medicine rouge ratio, water bath with thermostatic control is incubated for a period of time,
Triamcinolone acetonide acetate liposome is obtained after crushing by high pressure homogenizer；
(5) it weighs a certain amount of chitosan and is dissolved in glacial acetic acid aqueous solution, obtain chitosan solution；
(6) persistently stirring a period of time is added in step (4) in the mode that the chitosan solution in step (5) is stirred when being added dropwise
Obtain chitosan-modified triamcinolone acetonide acetate liposome.
3. preparation method as claimed in claim 2, which is characterized in that soybean lecithin described in step (1) and cholesterol
Molar ratio is 7~9:0.5~1.5；Preferably, the revolving condition is 30~40 DEG C, and 150~250 revs/min of rotations remove dechlorination
It is imitative；Preferably, further include being placed in adipose membrane in vacuum environment overnight, thoroughly remove residual organic solvent.
4. preparation method as claimed in claim 2, which is characterized in that calcium acetate solution concentration described in step (2) be 110~
130mM, 40~50 DEG C of 2.5~3.5h of ultrasound；Preferably, 0.22 μm of micropore device is crossed after suspension multigelation, recycles the step 8
~12 times.
5. preparation method as claimed in claim 2, which is characterized in that using physiological saline be dialyzate in room temperature in step (3)
Lower incubation thoroughly removes free calcium ion every 1.5~2.5 hours replacement dialyzates.
6. preparation method as claimed in claim 2, which is characterized in that triamcinolone acetonide acetate described in step (4) and adipose membrane
Mass ratio is 0.8~1.2:18~22；Preferably, the blank liposome suspension that triamcinolone acetonide acetate is added is placed in 48~52 DEG C and incubates
Educate 13~17min；Preferably, the liposome after the completion of the incubation is added in high pressure homogenizer, follows under 400~600bar pressure
Ring 4~6 times crushing, recycle 12~17 times under 1400~1600bar pressure and are crushed.
7. preparation method as claimed in claim 2, which is characterized in that the concentration of chitosan solution described in step (5) is
0.45~0.65% (w/v)；Preferably, after Liposomal suspensions are added in chitosan solution described in step (6), 0.8 is persistently stirred
~1.2h, and be incubated overnight at 4 DEG C.
8. a kind of triamcinolone acetonide acetate eye drops, which is characterized in that the triamcinolone acetonide acetate eye drops passes through in claim 1
The triamcinolone acetonide acetate liposome is mixed with sodium hyaluronate eye drops；Preferably, in the eye drops, how is acetic acid Qu An
The concentration of moral is 1.4~1.6mg/mL.
9. the chitosan that any one of triamcinolone acetonide acetate liposome or claim 2-7 preparation method obtain described in claim 1
Application of the triamcinolone acetonide acetate liposome of modification in terms of preparing anti-inflammatory or antiallergic action preparation.
10. application of the triamcinolone acetonide acetate eye drops in terms of preparing anti-ocular posterior segment eye disease described in claim 8.
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| CN110575437A (en) * | 2019-10-24 | 2019-12-17 | 上海交通大学 | Tigecycline liposome preparation |
| CN113730601A (en) * | 2021-09-08 | 2021-12-03 | 浙江科技学院 | Preparation method of gardenia yellow liposome |
| CN117643573A (en) * | 2024-01-29 | 2024-03-05 | 天津医科大学眼科医院 | Nanometer eye drop capable of delivering medicine to posterior segment of eye, preparation method and application thereof |
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| CN113730601A (en) * | 2021-09-08 | 2021-12-03 | 浙江科技学院 | Preparation method of gardenia yellow liposome |
| CN117643573A (en) * | 2024-01-29 | 2024-03-05 | 天津医科大学眼科医院 | Nanometer eye drop capable of delivering medicine to posterior segment of eye, preparation method and application thereof |
| CN117643573B (en) * | 2024-01-29 | 2024-05-03 | 天津医科大学眼科医院 | Nanometer eye drop capable of delivering medicine to posterior segment of eye, preparation method and application thereof |
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| CN109481403B (en) | 2020-10-20 |
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