CN108283621A - A kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle and preparation method thereof - Google Patents
A kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle and preparation method thereof Download PDFInfo
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Abstract
The present invention discloses a kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle and preparation method thereof, including 0.06~0.09wt% of momestasone furoate, 30~50wt% of liquid crystal material, 20~30wt% of phosphatidyl choline, 5~15wt% of surfactant, 5~15wt% of solvent, 0~40wt% of deionized water.Above-mentioned gel with liquid crystal structure nanoparticle preparation method is first by the raw material mixing in addition to solvent and deionized water and solvent to be added and is disperseed, add water and further disperse to obtain finished product through high-shear homogenizing machine or ultrasonic wave.Gained momestasone furoate gel with liquid crystal structure nanoparticle grain size is small, and encapsulation rate is high, and absorptivity, slow release effect, the therapeutic effect of drug are all good to have significant curative effect to allergic rhinitis, bacillary rhinitis.
Description
Technical field
The invention belongs to gel nanometer formulation field, especially a kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure is received
Grain of rice and preparation method thereof.
Background technology
Momestasone furoate is a kind of glucocorticoid of synthesis, has the effects that anti-inflammatory, antiallergy, is widely used in nerve
In scytitis and pruitus caused by property dermatitis, eczema, atopic dermatitis, seborrhea and psoriasis etc..
Lipid liquid crystal nanoparticle refer to certain density amphipathic lipids material and surfactant-dispersed in aqueous solution
It is self-assembled into aquaporin containing co-continuous and is closed cellular or spongelike structure the nano-particle of lipid bilayer.The system
It is to have small pore passageway (5~10nm) in cubic lattice using cubic lattice as structural unit, it is not connected containing two
Co-continuous water channel, wherein water channel is logical with outer continuous phase, and another water channel is then closed, co-continuous aquaporin and is closed
Lipid bilayer spatially three-dimensional extension, ordered stacks are closed, have the characteristics that the tight of three-dimensional, cycle arrangement and minimal surface area
Close structure.Common lipid liquid crystal nanoparticle is with glyceryl monooleate (GMO) and phytantriol (PT) etc. for liquid crystal material system
Standby liquid crystal nanoparticle system.The drug finished product prepared using lipid liquid crystal nanoparticle preparation method, drug molecule are existed by package
In cubic lattice, there is slow-release function, realize the controlled release of drug, and then extend duration of efficacy, reduce and use daily
Drug number.
Currently, momestasone furoate is applied seldom in terms for the treatment of bacillary rhinitis, allergic rhinitis, such as patent application number
The momestasone furoate nasal spray and preparation method thereof with thixotropic fluid property that CN2016106682925 is provided,
Momestasone furoate content is relatively low, and the preparation process due to not using lipid liquid crystal nanoparticle so that the nasal spray developed
With certain effect, but effect is not strong, and duration of efficacy is short, needs frequent medication daily, to formed certain drug according to
Lai Xing；Selected wetting agent Tween-80 and moisturizer glycerine, moisturizing wetting effect effect are not up to best level.In another example
Brufen cubic liquid crystal precursor solution, cubic liquid crystal nanoparticle and its system that patent application CN2016111796080 is provided
Preparation Method, used fatty glyceride include unsaturated mono fatty acid glyceride, and certain density unsaturated monoester
Fatty acid glyceride can lead to haemolysis in animal body, there is certain risk when in use；Due to brufen and momestasone furoate
Physicochemical property it is different, and the preparation method of the patent add water to stir together all raw materials after carry out ultrasonic disruption and high pressure
Homogeneous, the granule size to the liquid crystal nanoparticle of formation and the not applicable and present invention, need to restudy new preparation method.
Invention content
To achieve the goals above, the present invention provides a kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticles
And preparation method thereof, it is realized especially by following technical scheme.
A kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle, including raw material group become：Momestasone furoate
0.06~0.09wt%, 30~50wt% of diacylglycerol, 20~30wt% of phosphatidyl choline, Tween-80 5~
15wt%, 5~15wt% of solvent, 0~39wt% of deionized water.
Preferably, including raw material group becomes：Momestasone furoate 0.08wt%, liquid crystal material 40wt%, phosphatidyl choline
25wt%, surfactant 10wt%, solvent 10wt%, deionized water 14.92wt%.
Preferably, the phosphatidyl choline is soybean lecithin.
Preferably, the solvent is Aqueous organic solvent.
The present invention also provides a kind of preparation methods of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle, including
Following steps：
S1, momestasone furoate, liquid crystal material, phosphatidyl choline, surfactant, 30-45 DEG C of heating stirring mixing are weighed
Obtain mixed solution；
S2, solvent will be added in mixed solution obtained by S1, carries out ultrasonic wave and disperse 3~5min, obtains the liquid crystal of clear
Gel nanoparticle precursor solution；
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer or ultrasonic probe further disperse, and obtain the nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle.
Preferably, the linear velocity of the high-shear homogenizing machine rotor is 45~60m/s, homogenization cycles 5~10 times.
It is highly preferred that the linear velocity of homogeneous machine rotor is 55m/s, homogenization cycles 8 times.
Preferably, the power of the ultrasonic probe be 30~150W, ultrasonic time 8-10min.
Compared with prior art, the invention has the beneficial effects that：
1. using momestasone furoate treatment allergic rhinitis, the bacillary rhinitis of better efficacy；
2. realizing the sustained release of drug using gel with liquid crystal structure nano particle, nano particle diameter is small, and entrapment efficiency is high, drug
Slow-release time and absorptivity significantly improve；
3. selecting diacylglycerol as liquid crystal material, avoids and dive existing for unsaturated mono fatty acid glyceride because selecting
In haemolysis risk；
4. select Tween-80 as surfactant and soak moisturizer, make gel with liquid crystal structure nanoparticle stability,
Clarity significantly improves, and generates better dispersion effect；
5. using 2 dispersing methods, the relatively small particle of nano particle is effectively ensured, and particle size is kept to stablize relatively
Property.
Specific implementation mode
Technical scheme of the present invention will be clearly and completely described below, it is clear that described embodiment is only
A part of the embodiment of the present invention, instead of all the embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art
The all other embodiment obtained under the conditions of not making creative work, shall fall within the protection scope of the present invention.
Embodiment 1
Present embodiments provide a kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle, including raw material composition
For：Momestasone furoate 0.09wt%, diacylglycerol 50wt%, soybean lecithin 20wt%, Tween-80 5wt%, nothing
Water-ethanol 5wt%, deionized water 19.91wt%.
The preparation method of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle provided in this embodiment, including it is as follows
Step：
S1, momestasone furoate, diacylglycerol, soybean lecithin, Tween-80 are weighed, 30-45 DEG C of heating stirring is mixed
It is even to obtain mixed solution；
S2, anhydrous solvent will be added in mixed solution obtained by S1, carries out ultrasonic wave and disperse 3~5min, obtains clear
Gel with liquid crystal structure nanoparticle precursor solution；
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer further disperses, and the linear velocity of high-shear homogenizing machine rotor is 55m/s, and homogenization cycles 8 times obtain the nasal cavity nanometer system
Agent momestasone furoate gel with liquid crystal structure nanoparticle.
Embodiment 2
The present embodiment is substantially the same manner as Example 1, the difference is that following aspect：
A kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle, including raw material group become：Momestasone furoate
0.06wt%, diacylglycerol 30wt%, soybean lecithin 30wt%, Tween-80 15wt%, absolute ethyl alcohol 15wt%,
Deionized water 9.94wt%.
Embodiment 3
The present embodiment is substantially the same manner as Example 1, the difference is that following aspect：
A kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle, including raw material group become：Momestasone furoate
0.08wt%, diacylglycerol 40wt%, soybean lecithin 25wt%, Tween-80 10wt%, absolute ethyl alcohol 10wt%,
Deionized water 14.92wt%.
Embodiment 4
The present embodiment is substantially the same manner as Example 3, the difference is that following aspect：
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer further disperses, and the linear velocity of homogeneous machine rotor is 45m/s, and homogenization cycles 8 times obtain the nasal cavity nanometer formulation furancarboxylic acid
Mometasone gel with liquid crystal structure nanoparticle.
Embodiment 5
The present embodiment is substantially the same manner as Example 3, the difference is that following aspect：
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer further disperses, and the linear velocity of homogeneous machine rotor is 50m/s, and homogenization cycles 8 times obtain the nasal cavity nanometer formulation furancarboxylic acid
Mometasone gel with liquid crystal structure nanoparticle.
Embodiment 6
The present embodiment is substantially the same manner as Example 3, the difference is that following aspect：
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer further disperses, and the linear velocity of homogeneous machine rotor is 60m/s, and homogenization cycles 8 times obtain the nasal cavity nanometer formulation furancarboxylic acid
Mometasone gel with liquid crystal structure nanoparticle.
Embodiment 7
The present embodiment is substantially the same manner as Example 3, the difference is that following aspect：
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer further disperses, and the linear velocity of homogeneous machine rotor is 55m/s, and homogenization cycles 5 times obtain the nasal cavity nanometer formulation furancarboxylic acid
Mometasone gel with liquid crystal structure nanoparticle.
Embodiment 8
The present embodiment is substantially the same manner as Example 3, the difference is that following aspect：
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer further disperses, and the linear velocity of homogeneous machine rotor is 55m/s, and homogenization cycles 10 times obtain the nasal cavity nanometer formulation chaff
Sour Mometasone gel with liquid crystal structure nanoparticle.
Comparative example 1
This comparative example provides a kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle, including raw material composition
For：Momestasone furoate 0.05wt%, diacylglycerol 55wt%, soybean lecithin 15wt%, Tween-80 3wt%, nothing
Water-ethanol 3wt%, deionized water 23.95wt%.
The preparation method for the nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle that this comparative example provides, including it is as follows
Step：
S1, momestasone furoate, diacylglycerol, soybean lecithin, Tween-80 are weighed, 30-45 DEG C of heating stirring is mixed
It is even to obtain mixed solution；
S2, absolute ethyl alcohol will be added in mixed solution obtained by S1, carries out ultrasonic wave and disperse 3~5min, obtains clear
Gel with liquid crystal structure nanoparticle precursor solution；
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer further disperses, and the linear velocity of high-shear homogenizing machine rotor is 55m/s, and homogenization cycles 8 times obtain the nasal cavity nanometer system
Agent momestasone furoate gel with liquid crystal structure nanoparticle.
Comparative example 2
This comparative example and comparative example 1 are essentially identical, the difference is that following aspect：
This comparative example provides a kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle, including raw material composition
For：Momestasone furoate 1.2wt%, diacylglycerol 20wt%, soybean lecithin 35wt%, Tween-80 18wt%, nothing
Water-ethanol 18wt%, deionized water.
Comparative example 3
A kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle that this comparative example provides, including raw material composition
For：Momestasone furoate 0.08wt%, diacylglycerol 40wt%, soybean lecithin 25wt%, Tween-80 10wt%, nothing
Water-ethanol 10wt%, deionized water 7.8%.
The preparation method for the nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle that this comparative example provides, including it is as follows
Step：
S1, momestasone furoate, diacylglycerol, soybean lecithin, Tween-80 are weighed, 30-45 DEG C of heating stirring is mixed
It is even to obtain mixed solution；
S2, anhydrous solvent will be added in mixed solution obtained by S1, carries out ultrasonic wave and disperse 3~5min, obtains clear
Gel with liquid crystal structure nanoparticle precursor solution；
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer further disperses, and the linear velocity of high-shear homogenizing machine rotor is 40m/s, and homogenization cycles 8 times obtain the nasal cavity nanometer system
Agent momestasone furoate gel with liquid crystal structure nanoparticle.
Comparative example 4
This comparative example and comparative example 3 are essentially identical, the difference is that following aspect：
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer further disperses, and the linear velocity of high-shear homogenizing machine rotor is 65m/s, and homogenization cycles 8 times obtain the nasal cavity nanometer system
Agent momestasone furoate gel with liquid crystal structure nanoparticle.
Comparative example 5
This comparative example and comparative example 3 are essentially identical, the difference is that following aspect：
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer further disperses, and the linear velocity of high-shear homogenizing machine rotor is 55m/s, and homogenization cycles 3 times obtain the nasal cavity nanometer system
Agent momestasone furoate gel with liquid crystal structure nanoparticle.
Comparative example 6
This comparative example and comparative example 4 are essentially identical, the difference is that following aspect：
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear
Homogenizer further disperses, and the linear velocity of high-shear homogenizing machine rotor is 55m/s, and homogenization cycles 13 times obtain the nasal cavity nanometer
Preparation momestasone furoate gel with liquid crystal structure nanoparticle.
Application examples 1：The grain size of momestasone furoate gel with liquid crystal structure nanoparticle prepared by embodiment 3~8 and comparative example 3~6 with
And encapsulation rate
1, Particle Size Determination Method.
Momestasone furoate gel with liquid crystal structure nanoparticle ultra-pure water prepared by embodiment 3~8 and comparative example 3~6 is diluted 100
After times, 1mL samples is taken to be added to sample cell, 25 DEG C of balance 1min, dispersion viscosity 0.8872cPa, with nanometer particle size current potential
Analyzer (Zetasizer Nano ZS90) measures the particle size parameters of cubic liquid crystal nanoparticle, and particle size analyzer software calculates vertical
The particle size and polydispersity coefficient (PDI) of square liquid crystal nanoparticle.PDI is the index for reflecting particle size distribution range,
The smaller expression particle sizes of PDI are more uniform, integrated distribution, and the bigger expression particle sizes of PDI are uneven, significant difference.
2, entrapment efficiency determination method
Momestasone furoate gel with liquid crystal structure nanoparticle ultra-pure water prepared by embodiment 3~8 and comparative example 3~6 is diluted 100
After times, takes 1mL gel with liquid crystal structure nanoparticle solution to be dissolved to 5mL with ultra-pure water, takes 0.5mL in the super filter tube of YM-100,
15000r/min centrifuges 30min, collects gel with liquid crystal structure nanoparticle and lower liquid, and after being washed with methanol, dimethyl sulfoxide (DMSO) is fixed molten
To 5mL, take 0.2mL methanol constant volumes to 10mL, high performance liquid chromatography measures momestasone furoate content.High performance liquid chromatography item
Part：Chromatographic column：Phenomenex luna C18 (250x4.6mm, 5 μm), mobile phase is：Acetonitrile (0.01mol/L) and phosphoric acid are slow
Fliud flushing (pH value 6.20) ratio is 40:60,35 DEG C, Detection wavelength 406nm of column temperature, flow velocity：1.0mL/min, sample size：20μL.
Encapsulation rate formula is：EE%=(Wtotal- Wfree)/Wtotal× 100%.Wherein, WtotalFor：Momestasone furoate is thrown
Dose；WfreeFor：Free momestasone furoate.
Acquired results see the table below 1.
The grain size and encapsulation rate of momestasone furoate gel with liquid crystal structure nanoparticle prepared by 1 embodiment 3~8 of table and comparative example 3~6
According to 1 result of table it is found that the grain size and encapsulation rate of momestasone furoate gel with liquid crystal structure nanoparticle are not to be cut with height always
The linear velocity and homogenization cycles for cutting the rotor of homogenizer rise and linearly improve；When the high-shear homogenizing machine for reaching embodiment 3
Rotor linear velocity and homogenization cycles when, grain size is minimum, encapsulation rate highest；When the high shear in 4~embodiment of embodiment 6
When within the scope of the linear velocity range of the rotor of homogenizer and the homogenization cycles in embodiment 7~8, grain size and encapsulation rate obtain
Preferably as a result, when more than the two range (i.e. comparative example 3~4 and comparative example 5~6), grain size significantly increases, and encapsulation rate is notable
It reduces, is unfavorable for drug absorption and medicament slow release.
Application examples 2：The stability of the momestasone furoate gel with liquid crystal structure nanoparticle of Examples 1 to 3 and comparative example 1~2
It places at room temperature 1 month, is sampled respectively 15 days, 30 days, measure grain size and the encapsulating of gel with liquid crystal structure nanoparticle
Rate, as a result such as the following table 2.
The grain size and encapsulation rate of the momestasone furoate gel with liquid crystal structure nanoparticle of 2 Examples 1 to 3 of table and comparative example 1~2
According to table 2 it is found that momestasone furoate gel with liquid crystal structure nanoparticle prepared by Examples 1 to 3, stability is preferable,
The optimal stability of middle embodiment 3；Momestasone furoate gel with liquid crystal structure nanoparticle prepared by comparative example 1 and comparative example 2, average grain
Diameter dramatically increases, and encapsulation rate is remarkably decreased, and stability is poor.
Application examples 3：Momestasone furoate gel with liquid crystal structure nano particle preparations prepared by Examples 1 to 3 and comparative example 1~2 are to TDI
Cause the influence of cavy allergic rhinitis model
(1) the momestasone furoate gel with liquid crystal structure nanoparticle prepared according to Examples 1 to 3 and comparative example 1~2, correspondingly makes
Obtain nasal cavity nanometer formulation.
(2) 273.4 ± 17.3g of weight cavys 70, half male and half female is taken to be randomly divided into 7 groups by gender, every group 10, compile
Number for implement 1~3 group, compare 1~2 group, model control group, Normal group.
(3) in addition to Normal group, 10%TDI olive oil solutions are instilled cavy bilateral by remaining each group micro sample adding appliance
Prenasal intracavitary instills 5 μ L/ times, 1 times/day, totally 7 days per side nasal cavity；The next day of being changed to after 7th day 1 time, Normal group cavy are used
Isometric olive oil solution replaces TDI processing.
(4) since the 7th day, implement 1~3 group, the cavy of comparing 1~2 group is added dropwise respectively by Examples 1 to 3 and compares
Physiological saline is added dropwise in the cavy of momestasone furoate nasal cavity nanometer formulation prepared by example 1~2, model control group and Normal group,
Twice daily, continuous 11 days.
(5) observation index
Since administration the 1st day, after TDI collunariums in 30min, each group cavy nose appearance symptom was observed respectively and is scored
(rhiocnesmus dabs nose several times, 1 point；It is more than to scratch nose, face, rubs 2 points everywhere；Sneeze 1~3,1 point；Sneeze 4~10,2
Point；Sneeze 11 or more, 3 points；Clear nasal discharge flow to anterior naris, 1 point；Clear nasal discharge be more than anterior naris, 2 points；Runny nose is had one's face covered with, 3 points).Last
To cavy is put to death after observing, bridge of the nose is opened rapidly, and mucous membrane of nasal septum, 10% formaldehyde is taken to fix, paraffin embedding, conventional section,
4 μm after piece, HE dyeing, light microscopy checking is used in combination computer to calculate inflammatory cell area, average optical density, integral optical density peace
Equal blackness.
(6) statistical analysis
All data are indicated with mean ± standard deviation (x ± S), and data processing is carried out using SPSS11.5 statistical softwares.It is more
Comparison among groups carry out one-way analysis of variance, and variance is examined when having homogeneous with LSD, is examined with Dunnett's T3 when heterogeneity of variance
It tests and carries out each comparison among groups.P ＜ 0.05 indicate that difference has conspicuousness.
(7) result
1. causing cavy allergic rhinitis to TDI according to the nasal cavity nanometer formulation prepared by Examples 1 to 3 and comparative example 1~2
The influence of model symptom
Compared with Normal group, model control group cavy before administration and to will after in 2 weeks, rhiocnesmus, sneeze and clear nasal discharge
Symptom obviously aggravates, and symptom score is at 6 points or more；Compared with model control group, the nasal cavity nanometer formulation of Examples 1 to 3 preparation
Start within the 5th day after administration, symptom is substantially reduced, and the symptom degree of alleviation of comparative example 1~2 is relatively small, with treatment time
Extend allergic symptom scoring to continuously decrease, the results are shown in Table 3.
Table 3 causes TDI the influence (x ± S, n=10) of cavy allergic rhinitis model symptom score
Compared with Normal group,##P ＜ 0.01；Compared with model control group,*P ＜ 0.05,**P ＜ 0.01.
2. according to the nasal cavity nanometer formulation prepared by Examples 1 to 3 and comparative example 1~2 to cavy nasal mucosa pathology
Morphologic influence
Under light microscopic, TDI causes the visible inflammatory cell largely infiltrated of cavy allergic rhinitis model mucous membrane of nasal septum epithelium, scorching
Property cell is infiltrated based on acidophilia, neutrocyte into mucosal epithelium.Compared with Normal group, model control group
Mucous membrane of nasal septum inflammatory cell sum, inflammatory cell area summation, inflammatory cell average optical density summation, inflammatory cell integral light
Density summation and inflammatory cell the blackness summation that is averaged have notable raising.Compared with model control group, Examples 1 to 3 and compare
Nasal cavity nanometer formulation prepared by example 1~2 can be such that These parameters reduce, but reduce degree and have nothing in common with each other.As a result 4 be see the table below.
Table 4 causes TDI the influence (x ± S, n=10) of cavy allergic rhinitis model inflammatory cell
Compared with Normal group,##P ＜ 0.01；Compared with model control group,*P ＜ 0.05,**P ＜ 0.01.
According to the result of table 3 and table 4 it is found that Examples 1 to 3 and the nasal cavity nanometer formulation of the preparation of comparative example 1~2 are to allergy
Property rhinitis is all effective.But after the nasal cavity nanometer formulation treatment of Examples 1 to 3 preparation, the symptom of allergic rhinitis mitigates more
Obviously, inflammatory cell sum, inflammatory cell area, inflammatory cell average optical density, inflammatory cell integral optical density, inflammatory cell
These data of average blackness have more obvious reduction, have better effect to allergic rhinitis；Wherein, prepared by embodiment 3
Nasal cavity nanometer formulation therapeutic effect it is best.
Application examples 4：Momestasone furoate gel with liquid crystal structure nano particle preparations prepared by Examples 1 to 3 and comparative example 1~2 are to urgency
The preventive and therapeutic effect of the bacillary rhinitis models rat of property
(1) the momestasone furoate gel with liquid crystal structure nanoparticle prepared according to Examples 1 to 3 and comparative example 1~2, correspondingly makes
Obtain nasal cavity nanometer formulation.
(2) take SD rats male 70, be randomly divided into 7 groups, every group 10, respectively Examples 1 to 3 group, comparative example 1~
2 groups, normal control, model comparison.
(3) it uses staphylococcus aureus yeast to increase venom nasal drip and prepares rat rhinitis models, staphylococcus aureus
Strain MRSAI is cultivated in microbial room, faces used time fresh configuration, 10ml bacterium solutions is taken to add 1g dry ferments, Examples 1 to 3 group, comparative example
1~2 group of this 5 groups of elder generation's prevention administration 3 days.Remaining each group rat gives staphylococcus aureus yeast increasing poison in addition to Normal group
120 μ L/ days collunariums of liquid, the modeling in 4 days of continuous collunarium, while corresponding nasal cavity nanometer formulation, Normal group, model are given respectively
Control group gives the water of equivalent respectively.Continuing administration 3 days after last collunarium modeling, femoral artery takes after last dose 0.5h
Blood simultaneously detaches serum, horizontal using CRP in immunoturbidimetry detection serum using automatic biochemistry analyzer.Animal is put to death, nose is taken
Mucous membrane and bronchial tissue, 5% formalin are fixed, and schneiderian membrance epithelium and Bronchial epithelial tissue pathology shape are observed in HE dyeing
State changes.
(4) statistical analysis
All data are indicated with mean ± standard deviation (x ± S), and data processing is carried out using SPSS11.5 statistical softwares.It is more
Comparison among groups carry out one-way analysis of variance, and variance is examined when having homogeneous with LSD, is examined with Dunnett's T3 when heterogeneity of variance
It tests and carries out each comparison among groups.P ＜ 0.05 indicate that difference has conspicuousness.
(5) result
1. the general Symptoms of rat after modeling
Rat can comparatively fast cause staphylococcus aureus sense after staphylococcus aureus yeast increases the infection of venom collunarium
Dye, from model control group it is found that infection after rat often have significantly with fore paw grab nose action, and have a running nose.It is observed that using real
The rat of 1~2 group of 1~3 group of example and comparative example is applied, symptom degree is alleviated than model control group, wherein Examples 1 to 3 group
The symptom degree of rat is substantially better than 1~2 group of comparative example.This illustrates that nasal cavity nanometer formulation prepared by Examples 1 to 3 can be effective
Link staphylococcus aureus yeast increases the inflammatory symptom after venom infringement.
2. the nasal cavity nanometer formulation of 1~2 group of preparation of Examples 1 to 3 group and comparative example is to rhinitis rat blood serum c reactive protein
(CRP) horizontal influence
CRP makes a kind of albumen in serum, polysaccharide can be sticked with the C- in staphylococcus aureus body, precipitation reflection occurs.It is several
All acute bacterial infections, pulmonary tuberculosis and all types of tissue damages, operation wound, radiation injury etc. can all be such that CRP increases.Disease
It is then rapidly decreased to normal level when becoming alleviation.If the result of the following table 5 is it is found that after model control group rat modeling, inflammatory reaction is strong
Strong, CRP is obviously increased, and the CRP of 1~2 group of the Examples 1 to 3 group of modeling and comparative example is less than model to prevention administration again after 3 days
Control group, and the CRP of Examples 1 to 3 is significantly lower than 1~2 group of comparative example, and the CRP of embodiment 3 is minimum；This illustrates embodiment 1
~3 nasal cavity nanometer formulations prepared can more effectively reduce the infringement that staphylococcus aureus yeast increases venom.Concrete outcome is shown in
The following table 5.
Influence (x ± S, n=10) of the table 5 to rhinitis rat blood serum CRP levels
Compared with model control group,*P ＜ 0.05,**P ＜ 0.01.
3. the nasal cavity nanometer formulation of 1~2 group of preparation of Examples 1 to 3 group and comparative example is to the schneiderian membrance and branch of rhinitis rat
The influence of tracheal mucosa histopathology form
The normal schneiderian membrance cladding ciliated epithelial cell of rats in normal control group schneiderian membrance structure is clear, has no congested and inflammatory
Cellular infiltration；Bronchial mucosa epithelial structure is normal, and ciliated epithelial cell is clear, has no congested.The nose of model control group rat
Mucosal epithelium falls off obviously, and mucous membrane has hyperemia, and has neutrocyte, lymphocytic infiltration；Bronchial mucosa epithelium, which has, to fall off,
There is apparent lymphocytic infiltration in mucous membrane.The rat schneiderian membrance epithelial structure of Examples 1 to 3 is normal, and cilliated epithelium is clear, not
See and fall off, without leucocyte, lymphocytic infiltration in mucous membrane；Bronchial mucosa epithelial structure is normal, and ciliated epithelial cell has no
It falls off, without lymphocytic infiltration.The rat schneiderian membrance epithelial structure of comparative example 1~2 is normal, has and falls off a little, branch gas
Pipe mucosal epithelium structure is normal, has a little ciliated epithelial cell to fall off, a small amount of lymphocytic infiltration.Therefore, Examples 1 to 3 group
1~2 group of the nasal cavity nanometer formulation and comparative example of preparation have the effect of preferably prevention bacterium infection.
Claims (8)
1. a kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle, which is characterized in that including original in parts by weight
Material group becomes：0.06~0.09wt% of momestasone furoate, 30~50wt% of diacylglycerol, 20~30wt% of phosphatidyl choline,
5~15wt% of Tween-80,5~15wt% of solvent, 0~39wt% of deionized water.
2. a kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle according to claim 1, which is characterized in that
Become including raw material group：Momestasone furoate 0.08wt%, liquid crystal material 40wt%, phosphatidyl choline 25wt%, surfactant
10wt%, solvent 10wt%, deionized water 14.92wt%.
3. according to a kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle of claims 1 or 2 any one of them,
It is characterized in that, the phosphatidyl choline is soybean lecithin.
4. according to a kind of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle of claims 1 or 2 any one of them,
It is characterized in that, the solvent is Aqueous organic solvent.
5. a kind of preparation method of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle as claimed in claim 1 or 2,
It is characterized in that, includes the following steps：
S1, momestasone furoate, liquid crystal material, phosphatidyl choline, surfactant are weighed, 30-45 DEG C of heating stirring mixing must mix
Close solution；
S2, solvent will be added in mixed solution obtained by S1, carries out ultrasonic wave and disperse 3~5min, obtains the gel with liquid crystal structure of clear
Nanoparticle precursor solution；
In S3, the liquid crystal nanoparticle gel precursors solution obtained by S2 plus deionized water is to 100wt%, then passes through high shear homogeneous
Machine or ultrasonic probe further disperse, and obtain the nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle.
6. a kind of preparation method of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle according to claim 5,
It is characterized in that, the linear velocity of the high-shear homogenizing machine rotor is 45~60m/s, homogenization cycles 5~10 times.
7. a kind of preparation method of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle according to claim 6,
It is characterized in that, the linear velocity of high-shear homogenizing machine rotor is 55m/s, homogenization cycles 8 times.
8. a kind of preparation method of nasal cavity nanometer formulation momestasone furoate gel with liquid crystal structure nanoparticle according to claim 5,
It is characterized in that, the power of the ultrasonic probe is 30~150W, ultrasonic time 8-10min.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109091451A (en) * | 2018-09-10 | 2018-12-28 | 武汉百纳礼康生物制药有限公司 | Oil phase liquid crystalline substance gel precursors preparation of hydrophilic medicament and preparation method thereof |
| CN113109488A (en) * | 2021-05-18 | 2021-07-13 | 广州白云山医药集团股份有限公司白云山何济公制药厂 | Method for extracting and detecting mometasone furoate in mometasone furoate gel |
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2018
- 2018-03-16 CN CN201810219858.5A patent/CN108283621B/en active Active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109091451A (en) * | 2018-09-10 | 2018-12-28 | 武汉百纳礼康生物制药有限公司 | Oil phase liquid crystalline substance gel precursors preparation of hydrophilic medicament and preparation method thereof |
| CN109091451B (en) * | 2018-09-10 | 2021-08-13 | 武汉百纳礼康生物制药有限公司 | Oil phase liquid crystal gel precursor preparation of hydrophilic medicine and preparation method thereof |
| CN113109488A (en) * | 2021-05-18 | 2021-07-13 | 广州白云山医药集团股份有限公司白云山何济公制药厂 | Method for extracting and detecting mometasone furoate in mometasone furoate gel |
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