CN109589367A - A kind of vine tea general flavone solid lipid nano granule and preparation method - Google Patents
A kind of vine tea general flavone solid lipid nano granule and preparation method Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/87—Vitaceae or Ampelidaceae (Vine or Grape family), e.g. wine grapes, muscadine or peppervine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
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- A—HUMAN NECESSITIES
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5123—Organic compounds, e.g. fats, sugars
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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- A61P3/06—Antihyperlipidemics
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- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
- A61P39/06—Free radical scavengers or antioxidants
Abstract
The invention belongs to field of pharmaceutical preparations, it is related to a kind of vine tea general flavone solid lipid nano granule and preparation method.Using solid natural or synthetic lipoid as carrier, raw material proportioning score by weight are as follows: vine tea general flavone 0.3%~0.7%；Medicine rouge ratio: 1:3~1:12；Surfactant: 4%~12%；Excess water.Preparation method uses melting-ultrasonic method or high pressure homogenization method.By selecting suitable solid lipid and emulsifier, optimizing raw material proportion can be improved the encapsulation rate and drugloading rate of vine tea general flavone, reduces partial size, to improve its stability, bioavilability and targeting the present invention.Present invention selection is simple and easy to do, operates controllable sonication, prepares small partial size, encapsulation rate and the higher vine tea general flavone solid lipid nano granule of encapsulation rate, and embody slow release characteristic, provide a kind of novel form for the exploitation and clinical application of vine tea general flavone.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, it is related to a kind of vine tea general flavone solid lipid nano granule and preparation method thereof.
Background technique
Vine tea system Vitaceae Ampelopsis ampelopsis grossdentata Ampelopsis grossedentata (Hand.-Mazz.)
W.T.Wang. cauline leaf is the class tea plant resource of dual-purpose of drug and food, is Fujian Taining, by the rare of the Hakkas, the counties and districts such as pleasure, Youxi
It is precious.It cures mainly icteric hepatitis, cold anemopyretic, the diseases such as throat, red eye, swell pain with the effect of clearing heat and detoxicating, inducing diuresis and reducing edema.Closely
Year studies have shown that vine tea is a kind of natural plants rich in flavones ingredient, general flavone content is up to 40% or more, be flavones it
King, wherein dihydromyricetin (also known as Ampelopstin), is its characteristic chemical constituent.Modern pharmacological research shows that vine tea general flavone has
Have good anti-tumor activity, liver protecting, hypoglycemic lipid-loweringing, it is anti-oxidant, anti-inflammatory it is antibacterial, adjust immunity the effects of.Thus may be used
See, vine tea general flavone has very high Development volue and application prospect.
However, vine tea general flavone is eliminated fastly in vivo, oral absorption is poor, and bioavilability is low, has seriously affected clinic and has answered
With with internal drug effect.To solve the above-mentioned problems, by developing suitable pharmaceutical carrier, change drug distribution in vivo and will
Drug is transported to target organ.Preparation containing carrier, with that can discharge drug in time, maintains higher blood concentration than General Medicine
Or the drug concentration of target organ, and have many advantages, such as longer action time.Common pharmaceutical carrier have O/W emulsion, liposome,
Particle and milimicron particle etc..But the long-circulating nanoliposome of currently reported vine tea general flavone principal component dihydromyricetin,
Liposome, micro-capsule, self-emulsifying drug delivery systems, inclusion compound etc. have that larger partial size, encapsulation rate, drugloading rate be not high to ask in various degree
Topic, it is to be improved.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of vine tea general flavone solid lipid nano granule and preparation side
Vine tea general flavone is made solid lipid nano granule to improve its clinical application defect, and improves encapsulation rate and drugloading rate by method.
The present invention is implemented as follows:
Present invention firstly provides a kind of vine tea general flavone solid lipid nano granules, with solid natural or synthetic lipoid
For carrier, raw material proportioning score by weight are as follows: vine tea general flavone 0.3%~0.7%；Medicine rouge ratio: 1:3~1:12；Surface-active
Agent: 4%~12%；Excess water.
Further, the carrier includes at room temperature in solid Compritol 888 ATO, stearic acid, glycerol monostearate
Ester, glyceryl tristearate.Wherein preferred water-in-oil type glycerin monostearate, the vine tea total flavones nano grain partial size of preparation
Small, encapsulation rate, drugloading rate are high.
Further, the surfactant preferably has preferable emulsifying capacity and the non-ionic surface of safety living
Property agent PLURONICS F87, in addition it has preferable dissolubility to vine tea general flavone itself.
Preferably, raw material proportioning of the invention score by weight are as follows: vine tea general flavone 0.48%, glycerin monostearate
2.4%, PLURONICS F87 6.6%, excess water.
The present invention also provides a kind of preparation methods of vine tea general flavone solid lipid nano granule, i.e. melting ultrasound
Method specifically comprises the following steps:
(1) surfactant and ultrapure water are mixed, dissolution, and is heated to temperature T, as water phase；
(2) vine tea general flavone powder, carrier are mixed, ethyl alcohol is added to stir melting at temperature T, as oily phase；
(3) water phase and oil are mutually mixed at identical temperature T, and are sufficiently stirred, liquid to be mixed evaporates into no alcohol taste, uses
Ultrasonic cell disruptor carries out Probe Ultrasonic Searching, obtains vine tea general flavone solid lipid nano granule suspension；
Temperature T described above is the melting temperature of the carrier.
The condition of the ultrasonic cell disruptor are as follows: amplitude transformer is adjusted to 6, power 200w, the every ultrasound interval 1s 2s surpass
Sound 5 minutes.
Vine tea general flavone solid lipid nano granule suspension prepared by the present invention is uniform, the visible apparent pale blue at light transmission
Color opalescence.Obtained solid lipid nano granule suspension can further be freeze-dried to obtain freeze-dried powder, as solid lipid nano
Grain.
The ethyl alcohol that the present invention uses is the effect for playing hydrotropy, and additional amount is according to ethyl alcohol volume: nanoparticle suspension is overall
Product is that 1:10 is added.
It is the present invention also provides the preparation method of another vine tea general flavone solid lipid nano granule, i.e., high-pressure homogeneous
Method specifically comprises the following steps:
(1) surfactant and ultrapure water are mixed, dissolution, and is heated to temperature T, as water phase；
(2) vine tea general flavone powder, carrier are mixed, ethyl alcohol is added to stir melting at temperature T, as oily phase；
(3) water phase and oil are mutually mixed at identical temperature T, and are sufficiently stirred, liquid to be mixed evaporates into no alcohol taste, uses
High-shear homogenizer homogenous disperse obtains colostric fluid, and colostric fluid is then obtained vine tea general flavone solid lipid with high pressure homogenizer homogeneous and is received
Grain of rice suspension.
Further, the processing condition of step (3) described high-shear homogenizer are as follows: the homogenous disperse 1min at 8000r/min；
The processing condition of the high pressure homogenizer are as follows: recycled homogeneous 3 times at 800bar.
It is good with physiological compatibility, can drop in vivo the present invention has the advantage that solid lipid nano granule of the invention
Solution, no biotoxicity, physical stability are high, it is excellent to promote to absorb, improve bioavilability, controlled release and good targeting etc.
Gesture.For the present invention by selecting suitable solid lipid and emulsifier, the encapsulation rate of vine tea general flavone is can be improved in optimizing raw material proportion
And drugloading rate, reduce partial size, to improve its stability, bioavilability and targeting.The present invention selects simple and easy to do, operation
Controllable sonication prepares small partial size, encapsulation rate and the higher vine tea general flavone solid lipid nano granule of encapsulation rate, and
Slow release characteristic is embodied, provides a kind of novel form for the exploitation and clinical application of vine tea general flavone.
Detailed description of the invention
The present invention is further illustrated in conjunction with the embodiments with reference to the accompanying drawings.
Fig. 1 is vine tea general flavone solid lipid nano granule transmission electron microscope picture (× 100000) of the invention.
Fig. 2 is vine tea general flavone solid lipid nano granule tablets in vitro curve (n=3) of the invention.
Specific embodiment
The present invention is specific by 8.0 software optimization prescription of design-expert: factor is dosage, medicine rouge ratio, surface
The quality of activating agent；Evaluation index is partial size, encapsulation rate, drugloading rate.When investigating carrier and surfactant material, Zeng Xuanyong
Compritol 888 ATO makees matrix material, and partial size is bigger than normal, and in 220nm or so, encapsulation rate is up to 83%；And it selects single stearic
When acid glyceride, partial size becomes smaller, encapsulation rate and drugloading rate are improved.Dissolution of the emulsifier to drug is done with PLURONICS F87
Property is good and highly-safe.Therefore it using PLURONICS F87 as surfactant, using glycerin monostearate as carrier material, carries out
Following preliminary experiment:
(1) PLURONICS F87 is weighed, and measures a certain amount of ultrapure water for its ultrasonic dissolution, is placed in constant temperature blender with magnetic force
It is heated to 75~80 DEG C, as water phase.
(2) vine tea general flavone material medicine, glycerin monostearate separately are weighed, adds a small amount of ethyl alcohol, with water phase in same temperature state
Lower stirring melting, as oily phase.
(3) when water phase is mutually completely dissolved with oil and temperature is identical, water phase, which is poured into oily mutually and quickly stir, makes it sufficiently
Mixing.Liquid to be mixed is waved to no alcohol taste, is carried out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor and (amplitude transformer is adjusted to 6, power
200w, every ultrasound 1s interval 2s) to get vine tea general flavone solid lipid nano granule suspension.
Free drug of the present invention using ultrafiltration separation vine tea general flavone solid lipid nano granule, the measurement encapsulating of HPLC method
Rate and drugloading rate.
The specific steps of the present invention measurement encapsulation rate and drugloading rate are as follows:
(1) chromatographic condition chromatographic column: TOP ODS-AQ column (4.6 × 250mm, 5 μm)；Mobile phase: -0.1% phosphorus of methanol (A)
Aqueous acid (D), gradient elution (0~10min, 35%A；10~20min, 35%A → 80%A；20~30min, 80%A)；
Detection wavelength: dihydromyricetin 291nm, myricetrin and myricetin are 252nm；Flow velocity 1.0ml/min；30 DEG C of column temperature；Sample introduction
Measure 10 μ L.
(2) mix reference substance preparation: respectively precision weigh a certain amount of dihydromyricetin, myricetrin, myricetin in
10mL volumetric flask, methanol dissolve constant volume, and concentration is respectively 505.68 μ g/mL, 6.29 μ g/mL, 13.42 μ g/mL, and 4 DEG C of preservations are standby
With.According to above-mentioned chromatographic condition, sample introduction is analyzed, draws standard curve using external standard method.
(2) free Flavonoids assay: precision draws 500 μ L of vine tea general flavone solid lipid nano granule suspension in ultrafiltration
Centrifuge tube, 8000r/min are centrifuged 10min, 100 μ L of extracting centrifugal liquid, with methanol constant volume to 1mL, measure by above-mentioned chromatographic condition.
(3) flavones total content measures: the another accurate 500 μ L of vine tea general flavone solid lipid nano granule suspension that draws is in 10mL
In measuring bottle, methanol heating for dissolving, is shaken up constant volume, is filtered with 0.45 μm of filter, is measured by above-mentioned chromatographic condition.
(4) W of the present inventionGeneral flavone=WDihydromyricetin+WMyricetrin+WMyricetin；Encapsulation rate and drugloading rate are according to calculation formula: encapsulation rate=(W
Always-W is free)/W is total；Drugloading rate=(total-W of W is free)/(total-W of W lipid+W is free) (wherein W always indicates the total of general flavone
Amount, W is free to indicate that free general flavone amount, W lipid indicate the quality of glycerin monostearate).
For the present invention on the basis of preliminary experiment, determining influences the aobvious of vine tea general flavone solid lipid nano-particle preparation property
Work factor is quality, the dosage of lipid and surfactant of drug.Then using partial size, encapsulation rate, drugloading rate as index, application
Star point design-response phase method optimizes its prescription proportion.It is formulated and is designed with 8.0 software optimization of design-expert, drawn up optimal
The conditions of mixture ratios of change: dosage 0.48%, medicine rouge ratio are 1:5, PLURONICS F87 quality is 6.6%.Prediction obtain partial size,
Encapsulation rate, drugloading rate value be respectively 158.4nm, 86.13%, 12.15%.Observed simultaneously by potential measurement, micromorphology,
Release behaviour in vitro investigation has carried out preliminary quality evaluation to vine tea general flavone solid lipid nano granule obtained.
The result that the present invention makes: the nanoparticle suspension of preparation is uniform and stable, has apparent opalescence, particle size distribution range
It is 20~500nm, according to the conditions of mixture ratios of optimization, progress 3 times or more confirmatory experiments obtain average grain diameter, encapsulation rate, load
Dose is respectively (148.2 ± 7.1) nm, (87.27 ± 0.96) %, (12.43 ± 0.49) %.If Fig. 1 transmission electron microscope is shown, receive
The grain of rice is rounded or spherical.Tablets in vitro behavior shows that solid lipid nano granule discharges comparatively fast before 4h, preparation
Up to 79.64%, sustained release is presented in the later period, and drug release is substantially completely (preparation 98.81%), always yellow with free vine tea for 24 hours
Ketone is compared, and has good slow release characteristic.As shown in table 1, vine tea general flavone solid lipid nano granule prepared by the present invention and total
The existing dosage form of principal component dihydromyricetin contained by flavones is compared, and partial size is small, and encapsulation rate, drugloading rate are higher.
1 this law of table has prepared principal component dihydromyricetin contained by vine tea general flavone solid lipid nano granule and general flavone
There is dosage form data comparison
[1] Zhang Wenjuan, Chen Yizhen, Tang Lanru are waited in preparation and the rat body of vine tea general flavone long-circulating nanoliposome
Pharmacokinetic studies [J] Chinese herbal medicine, 2018,49 (4): 806-812.
[2] Qi Na, Huang Fengxiang, Liao Ying wait the formulation optimization of vine tea general flavone liposome and property to investigate section, the world [J]
Technology-TCM Modernization ★ technical application research, 2014,16 (6): 1427-1433.
Treasure's traditional Chinese medical science when preparation process [J] of the preferred vine tea general flavone micro-capsule of [3] Ye Yong, Ou Xianhong, Huang Qiujie Orthogonal Method
Traditional Chinese medicines, 2012,23 (9): 2251-2252.
[4] Qi Na, Liu Guang, Liu Chunyan wait the design of vine tea general flavone self-emulsifying drug delivery systems to lead with quality evaluation [J] medicine
Report, 2014,33 (7): 940-944.
[5] Liang Xiaolan, Li Yunyao, He Guixia wait vine tea general flavone Benexate Hydrochloride Study on Preparation in vine tea
[J] Hunan University of Traditional Chinese Medicine journal, 2011,31 (1): 43-45.
Embodiment 1
Claim 0.6g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.06g, glycerin monostearate 0.6g separately are weighed, adds a small amount of ethyl alcohol.With water phase in equality of temperature
Melting is stirred under state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and quickly stirred and is filled
Divide mixing.Liquid to be mixed is waved to no alcohol taste, and it is solid to get vine tea general flavone to carry out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor
Body lipid nano particle suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 2
Claim 0.8g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.05g, glycerin monostearate 0.17g separately are weighed, adds a small amount of ethyl alcohol.With water phase same
Melting is stirred under temperature state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and is quickly stirred
It is sufficiently mixed.Liquid to be mixed is waved to no alcohol taste, carries out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor to get vine tea general flavone
Solid lipid nano granule suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 3
Claim 1.0g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.04g, glycerin monostearate 0.2g separately are weighed, adds a small amount of ethyl alcohol.With water phase in equality of temperature
Melting is stirred under state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and quickly stirred and is filled
Divide mixing.Liquid to be mixed is waved to no alcohol taste, and it is solid to get vine tea general flavone to carry out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor
Body lipid nano particle suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 4
Claim 1.14g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.05g, glycerin monostearate 0.375g separately are weighed, adds a small amount of ethyl alcohol.With water phase same
Melting is stirred under temperature state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and is quickly stirred
It is sufficiently mixed.Liquid to be mixed is waved to no alcohol taste, carries out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor to get vine tea general flavone
Solid lipid nano granule suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 5
Claim 0.8g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.067g, glycerin monostearate 0.50g separately are weighed, adds a small amount of ethyl alcohol.With water phase same
Melting is stirred under temperature state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and is quickly stirred
It is sufficiently mixed.Liquid to be mixed is waved to no alcohol taste, carries out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor to get vine tea general flavone
Solid lipid nano granule suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 6
Claim 0.46g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.05g, glycerin monostearate 0.38g separately are weighed, adds a small amount of ethyl alcohol.With water phase same
Melting is stirred under temperature state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and is quickly stirred
It is sufficiently mixed.Liquid to be mixed is waved to no alcohol taste, carries out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor to get vine tea general flavone
Solid lipid nano granule suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 7
Claim 0.66g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.048g, glycerin monostearate 0.24g separately are weighed, adds a small amount of ethyl alcohol.With water phase same
Melting is stirred under temperature state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and is quickly stirred
It is sufficiently mixed.Liquid to be mixed is waved to no alcohol taste, carries out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor to get vine tea general flavone
Solid lipid nano granule suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 8
Claim 1.0g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.06g, glycerin monostearate 0.60g separately are weighed, adds a small amount of ethyl alcohol.With water phase same
Melting is stirred under temperature state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and is quickly stirred
It is sufficiently mixed.Liquid to be mixed is waved to no alcohol taste, carries out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor to get vine tea general flavone
Solid lipid nano granule suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 9
Claim 0.8g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.033g, glycerin monostearate 0.249g separately are weighed, adds a small amount of ethyl alcohol.Exist with water phase
With melting is stirred under temperature state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and is quickly stirred
It mixes and is sufficiently mixed.Liquid to be mixed is waved to no alcohol taste, and it is always yellow to get vine tea to carry out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor
Ketone solid lipid nano granule suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 10
Claim 0.6g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.06g, glycerin monostearate 0.3g separately are weighed, adds a small amount of ethyl alcohol.With water phase in equality of temperature
Melting is stirred under state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and quickly stirred and is filled
Divide mixing.Liquid to be mixed is waved to no alcohol taste, and it is solid to get vine tea general flavone to carry out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor
Body lipid nano particle suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 11
Claim 0.8g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.05g, glycerin monostearate 0.58g separately are weighed, adds a small amount of ethyl alcohol.With water phase same
Melting is stirred under temperature state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and is quickly stirred
It is sufficiently mixed.Liquid to be mixed is waved to no alcohol taste, carries out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor to get vine tea general flavone
Solid lipid nano granule suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 12
Claim 0.6g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.04g, glycerin monostearate 0.4g separately are weighed, adds a small amount of ethyl alcohol.With water phase in equality of temperature
Melting is stirred under state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and quickly stirred and is filled
Divide mixing.Liquid to be mixed is waved to no alcohol taste, carries out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor.It is solid up to vine tea general flavone
Body lipid nano particle suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 13
Claim 1.0g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.04g, glycerin monostearate 0.4g separately are weighed, adds a small amount of ethyl alcohol.With water phase in equality of temperature
Melting is stirred under state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and quickly stirred and is filled
Divide mixing.Liquid to be mixed is waved to no alcohol taste, carries out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor.It is solid up to vine tea general flavone
Body lipid nano particle suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 14
Claim 1.0g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.06g, glycerin monostearate 0.3g separately are weighed, adds a small amount of ethyl alcohol.With water phase in equality of temperature
Melting is stirred under state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and quickly stirred and is filled
Divide mixing.Liquid to be mixed is waved to no alcohol taste, carries out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor.It is solid up to vine tea general flavone
Body lipid nano particle suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Embodiment 15
Claim 0.6g PLURONICS F87, and measure appropriate ultrapure water for its ultrasonic dissolution, is heated to 75~80 DEG C of constant temperature, makees
For water phase.Vine tea general flavone material medicine 0.04g, glycerin monostearate 0.2g separately are weighed, adds a small amount of ethyl alcohol.With water phase in equality of temperature
Melting is stirred under state, as oily phase.When two-phase is completely dissolved and temperature is identical, water phase is poured into oily phase and quickly stirred and is filled
Divide mixing.Liquid to be mixed is waved to no alcohol taste, carries out Probe Ultrasonic Searching 5min with ultrasonic cell disruptor.It is solid up to vine tea general flavone
Body lipid nano particle suspension.It is saved after room temperature is cooling in 4 DEG C of refrigerators.
Below by the description of the various physical and chemical property determinings of the nanoparticle prepared to 1-15 of the embodiment of the present invention, furtherly
The advantages of bright result of the present invention.
1 partial size of experimental example and potential measurement
The 100 μ L of nanoparticle suspension of accurate extraction embodiment 1-15 preparation, ultrapure water are diluted to 10mL measuring bottle, shake up,
Using NICOMPTM 380ZLS Zeta potential/particle sizer nano particle size instrument measure its particle size and
Zeta potential.It the results are shown in Table 2.
2 embodiment 1-15 partial size of table, Zeta potential, encapsulation rate and drugloading rate measurement result
2 vine tea general flavone solid lipid nano granule extracorporeal releasing test of experimental example
Vitro release is an important indicator for evaluating medicine-carried system, and it is solid to investigate vine tea general flavone using equilibrium dialysis
The external release behavior of body lipid nano particle.Dissolution medium is 5.8 phosphate buffer of pH (containing 2% Tween 80), medium volume
For 100mL, medium temperature is (37 ± 0.5) DEG C, revolving speed 100r/min.Precision pipettes 2.0mL vine tea general flavone solid lipid
Nanoparticle suspension is placed in through clamping two with bag filter folder in pretreated bag filter (molecular cut off 8000~14000)
End bag mouth is placed in dissolution medium, respectively 0.5,1,2,4,8,12, replaced for 24 hours with 100mL isothermal fresh dissolution medium, inhale
Take 1mL dissolution medium through 0.45 μm of filtering with microporous membrane, discard primary filtrate, using HPLC method measurement dihydromyricetin, myricetrin,
Red bayberry cellulose content.It is appropriate that another precision weighs vine tea general flavone material medicine, is dissolved by heating, is prepared into 5.8 phosphate buffer of pH
With solid lipid nano granule with the solution of concentration.Same precision pipettes 2.0mL vine tea general flavone solution (free general flavone) and is placed in
In bag filter, release test is ibid carried out, the preparation (Q of general flavone is calculated as followsi)。Qi=(C1+C2+……+Ci)
V/C0V0(V0And C0The sample volume and mass concentration being respectively added in bag filter, V are dialysis medium volume, CiWhen being each
Between put the general flavone mass concentration measured)
The In-vitro release curves of vine tea general flavone solid lipid nano granule prepared by free general flavone and embodiment 7 are shown in Fig. 2.
The result shows that: free preparation of the general flavone in 4h is 97.59%, and basic release is complete；Nanoparticle is released before 4h
Put very fast, preparation is up to 79.64%, thus it is speculated that be that the drug of free drug and solid lipid nano granule adsorption is released jointly
It puts.Sustained release is presented in later period, may spread from carrier framework with drug, or degrades and discharge related with carrier material.Drug for 24 hours
Release substantially completely (preparation 98.81%), illustrates that solid lipid nano granule of the invention has and delays drug release
Effect.
Although specific embodiments of the present invention have been described above, those familiar with the art should be managed
Solution, we are merely exemplary described specific embodiment, rather than for the restriction to the scope of the present invention, it is familiar with this
The technical staff in field should be covered of the invention according to modification and variation equivalent made by spirit of the invention
In scope of the claimed protection.
Claims (9)
1. a kind of vine tea general flavone solid lipid nano granule, it is characterised in that: using solid natural or synthetic lipoid as carrier,
Raw material proportioning score by weight are as follows: vine tea general flavone 0.3%~0.7%；Medicine rouge ratio: 1:3~1:12；Surfactant: 4%~
12%；Excess water.
2. vine tea general flavone solid lipid nano granule according to claim 1, it is characterised in that: the carrier includes behenyl
Acid glyceride, stearic acid, glycerin monostearate or glyceryl tristearate.
3. vine tea general flavone solid lipid nano granule according to claim 1, it is characterised in that: the surfactant packet
Include PLURONICS F87.
4. vine tea general flavone solid lipid nano granule according to claim 1, it is characterised in that: raw material proportioning parts by weights
Number are as follows: vine tea general flavone 0.48%, glycerin monostearate 2.4%, PLURONICS F87 6.6%, excess water.
5. the preparation method of the vine tea general flavone solid lipid nano granule as described in Arbitrary Term in claim 1-4, feature exist
In: specifically comprise the following steps:
(1) surfactant and ultrapure water are mixed, dissolution, and is heated to temperature T, as water phase；
(2) vine tea general flavone powder, carrier are mixed, ethyl alcohol is added to stir melting at temperature T, as oily phase；
(3) water phase and oil are mutually mixed at identical temperature T, and are sufficiently stirred, liquid to be mixed evaporates into no alcohol taste, with ultrasound
Wave cell disruptor carries out Probe Ultrasonic Searching, obtains vine tea general flavone solid lipid nano granule suspension；
Temperature T described above is the melting temperature of the carrier.
6. the preparation method of vine tea general flavone solid lipid nano granule according to claim 5, it is characterised in that: described super
The condition of sound wave cell disruptor are as follows: amplitude transformer is adjusted to 6, power 200w, the every ultrasound interval 1s 2s are 5 minutes ultrasonic.
7. the preparation method of vine tea general flavone solid lipid nano granule according to claim 5, it is characterised in that: step
(2) additional amount of the ethyl alcohol is according to ethyl alcohol volume: nanoparticle suspension total volume is 1:10 addition.
8. the preparation method of the vine tea general flavone solid lipid nano granule as described in Arbitrary Term in claim 1-4, feature exist
In: specifically comprise the following steps:
(1) surfactant and ultrapure water are mixed, dissolution, and is heated to temperature T, as water phase；
(2) vine tea general flavone powder, carrier are mixed, ethyl alcohol is added to stir melting at temperature T, as oily phase；
(3) water phase and oil are mutually mixed at identical temperature T, and are sufficiently stirred, liquid to be mixed evaporates into no alcohol taste, with high speed
Homogenizer homogenous disperse obtains colostric fluid, and colostric fluid is then obtained vine tea general flavone solid lipid nano granule with high pressure homogenizer homogeneous
Suspension；
Temperature T described above is the melting temperature of the carrier.
9. the preparation method of vine tea general flavone solid lipid nano granule according to claim 8, it is characterised in that: step
(3) processing condition of the high-shear homogenizer are as follows: the homogenous disperse 1min at 8000r/min；The homogeneous of the high pressure homogenizer
Condition are as follows: recycled homogeneous 3 times at 800bar.
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