CN104784117B - A kind of curcumin mixed micelle oral formulations and preparation method thereof - Google Patents
A kind of curcumin mixed micelle oral formulations and preparation method thereof Download PDFInfo
- Publication number
- CN104784117B CN104784117B CN201510194806.3A CN201510194806A CN104784117B CN 104784117 B CN104784117 B CN 104784117B CN 201510194806 A CN201510194806 A CN 201510194806A CN 104784117 B CN104784117 B CN 104784117B
- Authority
- CN
- China
- Prior art keywords
- curcumin
- pla
- tpgs
- mpeg
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Abstract
The invention discloses a kind of curcumin mixed micelle oral formulations and preparation method thereof, curcumin bulk drug is mixed with methoxy poly (ethylene glycol) PLA, TPGS, it is dissolved in absolute methanol, revolving forms uniform film, add the ultrasonic aquation of water, centrifuging and taking supernatant, obtains curcumin methoxy poly (ethylene glycol) PLA/TPGS mixed micelle.The microscopic pattern of micellar preparation of the present invention is rounded, and average grain diameter is 46nm, and zeta current potentials are+0.613mV, and drugloading rate is 16.1%, preferable dilution stability are presented, and have controlled-release function to medicine.Oral Administration in Rats pharmacokinetics shows that curcumin mixed micelle preparation can significantly improve the maximum plasma concentration of medicine, and the mean residence time of extension medicine in vivo improves the oral administration biaavailability of curcumin.
Description
Technical field
The present invention relates to a kind of curcumin mixed micelle oral formulations and preparation method thereof, and in particular to curcumin methoxyl group
Polyethylene glycol-polylactic acid/TPGS mixed micelle oral formulations and preparation method thereof, belong to micella
Preparing technical field.
Background technology
Curcumin is that a kind of acid aldehydes matter of obtained yellow is extracted from the rhizome of the plants such as turmeric, curcuma zedoary, is had
The multiple pharmacological effect such as anti-inflammatory, anti-oxidant, anti-infective, and kinds cancer such as breast cancer, liver cancer and colon cancer etc. can be suppressed.This
Outside, the toxic side effect of curcumin is small, and tolerance is preferable when dosage reaches 12g/d, and cheap, preferably should make it have
Use prospect.But due to water-soluble poor, the easy generation bioconversion during intestinal transport, into blood of curcumin
Original shape medicine is less, and oral administration biaavailability is low, limits its application clinically.To solve the oral bio profit of curcumin
Expenditure problem, the load medicine of characteristic of solubilizing well, which passs release system, turns into the focus of research, such as micro emulsion, liposome, micella nanometer skill
Art.
Although Chinese patent《A kind of curcumin nano micellar preparation and preparation method thereof》, application number：
201110231519.7 disclose a kind of turmeric being made with curcumin and MPEG-PLA di-block copolymer
Plain nano-micelle preparations, but it is prepared into single micella only with a kind of amphipathic nature material, compared with mixed micelle, contains medicine
The ability and stability of thing are weaker.
Although Chinese patent《TPGS modification curcumin chitosan hydrochloride liposome and its
Preparation method》, application number：201410291079.8 disclose a kind of turmeric modified by TPGS
Plain chitosan hydrochloride liposome, but its larger particulate that is unfavorable for of liposomal particle size prepared carries out intestinal transport, and medicine generation
Kinetic results show the blood concentration for inspection not being measured after 3.5h to curcumin.
The content of the invention
For above-mentioned problems of the prior art, the invention provides a kind of curcumin methoxy poly (ethylene glycol)-poly-
Lactic acid/polyethyleneglycol VE-succinate mixed micelle oral formulations and preparation method thereof.
A kind of curcumin mixed micelle oral formulations, are made up of following parts by weight of raw materials：1-15 parts of curcumin, methoxy
5-25 parts of base polyethylene glycol-polylactic acid (mPEG-PLA), 5-25 parts of TPGS (TPGS), moisture
2-8 parts.
It is preferred that, a kind of curcumin mixed micelle oral formulations are made up of following parts by weight of raw materials：6 parts of curcumin,
6 parts of 24 parts of mPEG-PLA, TPGS, 5 parts of moisture.
The curcumin mixed micelle oral formulations are that ultrasonic disperse is formed in water by mPEG-PLA and TPGS.
In the mPEG-PLA, the molecular weight of polyethylene glycol block is 1000~2000, preferably point of polyethylene glycol block
Son amount is 2000, and PLA block is racemic polymer, and its molecular weight 1000~2000, preferably PLA block molecule amount are
2000, it is abbreviated as mPEG2000-PLA2000。
The TPGS is the water-soluble derivative of vitamin E, wherein, polyethylene glycol block
Molecular weight is 1000~2000, preferably 1000.
The micella particle diameter formed in curcumin and mPEG-PLA, TPGS disperse water is in the range of 0~50nm.
The preparation method of the curcumin mixed micelle oral formulations, comprises the following steps：
(1) curcumin of proportioning, mPEG-PLA and TPGS mixing will be set, absolute methanol, dissolving is added.
(2) mixed solution of dissolving is evaporated, evaporation is stopped after methanol until removing, form uniform thin after evaporation
Film.
(3) film is dried, to remove remnants organic solvent.
(4) add water in film, at a set temperature ultrasonic aquation.
(5) solution after aquation is centrifuged, it is that curcumin mPEG-PLA/TPGS mixed micelles are oral to take supernatant
Preparation.
In step (1), curcumin and mPEG-PLA mass ratio are 0.04~3:1, curcumin and TPGS mass ratio is
0.04~3:1, mPEG-PLA and TPGS mass ratio is 0.2~5:1, the mass volume ratio (w/v) of curcumin and absolute methanol
For 0.1~3.75:1mg/mL.
In step (1), the method for the dissolving is ultrasonic wave dissolving, and ultrasonic time is 2~10min, during preferred ultrasound
Between be 5min.
In step (2), the method for the evaporation uses rotary evaporation, and the temperature of evaporation is 30~40 DEG C, preferably evaporates temperature
Spend for 35 DEG C.
In step (3), the method for the drying is vacuum drying, and the dry time is 12~18h, and the preferably time is 12h,
Dry temperature is room temperature (25 DEG C).
In step (4), the volume mass ratio of the water and the curcumin in step (1) is 1：0.125~4mL/mg, water is excellent
Elect distilled water as.
In step (4), the ultrasonic hydration temperature is 20~40 DEG C, and ultrasonic time is 5~15min, preferably ultrasonic time
For 10min.
In step (5), the centrifugal speed is 12000r/min, and centrifugation time is 5~10min, and preferably centrifugation time is
5min。
MPEG-PLA is a kind of with biocompatibility, biodegradable high polymer material.MPEG-PLA has amphiphilic
Property：(1) mPEG can improve the stability of micella as hydrophilic segment, it is to avoid internal reticuloendothelial system to the identification of micella and
Immuno-recuperative function；(2) PLA can form the kernel of micella as hydrophobic segment, contain fat-soluble medicine.TPGS is vitamin E
Water-soluble derivative, the VE-succinate segment in its molecular structure can increase the hydrophobicity of micelle inner core, hydrophilic
Polyethylene glycol segment accounts for the 66% of total molecular weight, can cooperate with mPEG blocks and water molecules, moisture is formed around micella
Sublayer, it is to avoid micellar aggregates, improves the stability of micella.Research shows that also there is TPGS certain suppression to make to P- glycoprotein
With contributing to carrier micelle in the transmembrane transport process of small intestine site.
In summary, using amphipathic block copolymer mPEG-PLA and TPGS as carrier material, its in aqueous from
Hair forms micellar structure, and curcumin is wrapped in the hydrophobic inner core of micella, the solubility of curcumin in aqueous is added, and promotees
Enter the drug absorption process of intestines and stomach, improve the oral administration biaavailability of curcumin, have broad application prospects.The present invention is ground
A kind of curcumin mPEG-PLA/TPGS mixed micelle oral formulations with high drug load and stability are studied carefully.The curcumin is mixed
The microscopic pattern of rubber alloy beam is rounded, and smaller average grain diameter is 46nm, and surface charge weakly acidic pH is+0.613mV, and drugloading rate is
16.1%, it is only 4% that the medicine sedimentation rate after 48h is placed at 4 DEG C, and with good dilution stability.With patent
201410291079.8 curcumin liposomes prepared are compared, and particle diameter is reduced to below 100nm, extend medicine in vivo stagnant
Stay the time.
Extracorporeal releasing experiment shows that the mixed micelle preparation is compared with curcumin raw material medicine solution, with certain slow control
Release characteristic.Pharmacokinetics results show in animal body, peak drug levels of the mixed micelle preparation in rat body, average stagnant
Time and accumulation medication amount is stayed to be above curcumin bulk drug.Curcumin mPEG-PLA prepared by the present invention/TPGS mixed micelles
Preparation improves the solubility of insoluble drug in aqueous, is expected to pass release system as the new of field of cancer treatment.
Brief description of the drawings
Fig. 1：The grain size distribution of curcumin mPEG-PLA/TPGS mixed micelles.
Fig. 2：The electromicroscopic photograph of curcumin mPEG-PLA/TPGS mixed micelles.
Fig. 3-A and Fig. 3-B：The dilution stability figure of curcumin mPEG-PLA/TPGS mixed micelles.Fig. 3-A：Curcumin is mixed
Close micellar preparation and the medicament contg change histogram after different multiples is diluted by simulated gastric fluid (pH 1.2)；Fig. 3-B：Curcumin is mixed
Close micellar preparation and the medicament contg change histogram after different multiples is diluted by simulated intestinal fluid (pH 6.8)
Fig. 4：With simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8) containing 1% Tween 80 for dissolution medium, 37
At DEG C, the release in vitro behavior of mixed micelle preparation and bulk drug.Two curves represent curcumin mPEG-PLA/TPGS and mixed respectively
Close the release in vitro behavior of micellar preparation (circle) and curcumin propylene glycol solution (triangle).
Fig. 5：The blood concentration after curcumin mPEG-PLA/TPGS mixed micelle preparations and curcumin suspension is administered orally
To the curve map of time.Rat dosage 75mg/kg, it is (real that two curves represent oral curcumin mixed micelle preparation respectively
The heart is circular) and the blood concentration of the sodium carboxymethyl cellulose suspension liquid of curcumin 0.5% (hollow circle) change.
Embodiment
With reference to case study on implementation, the present invention is further illustrated.
Be not particularly illustrated using raw material is commercially available.The curcumin is purchased from Sigma-Aldrich,
MPEG-PLA is purchased from Jinan Dai Gang bio tech ltd, and TPGS is purchased from Sigma-Aldrich.
Embodiment 1：Prepare curcumin mPEG-PLA/TPGS mixed micelle oral formulations
Step is as follows：By 3mg curcumins, 5mg mPEG-PLA and 20mg TPGS mixing add 4mL absolute methanols, ultrasound
Dissolve 5min.At 35 DEG C, mixed solution is subjected to rotary evaporation 10min, methanol is removed, uniform film is formed.By film
It is dried in vacuo, drying time 12h, drying temperature is room temperature.2mL distilled water is added in film, ultrasonic water at 30 DEG C
Change 10min.Solution after aquation is centrifuged, speed 12000r/min, centrifugation time 5min, take supernatant as curcumin
MPEG-PLA/TPGS mixed micelle solution.
Embodiment 2：Prepare curcumin mPEG-PLA/TPGS mixed micelle oral formulations
Step is as follows：By 3mg curcumins, 20mg mPEG-PLA and 10mg TPGS mixing add 4mL absolute methanols, surpassed
Sound dissolves 5min.At 35 DEG C, mixed solution is subjected to rotary evaporation 10min, methanol is removed, uniform film is formed.Will be thin
Film is dried in vacuo, and drying time 12h, drying temperature is room temperature.8mL distilled water is added in film, it is ultrasonic at 25 DEG C
Aquation 10min.Solution after aquation is centrifuged, speed 12000r/min, centrifugation time 5min, take supernatant as turmeric
Plain mPEG-PLA/TPGS mixed micelles solution.
Embodiment 3：Prepare curcumin mPEG-PLA/TPGS mixed micelle oral formulations
Step is as follows：By 3mg curcumins, 25mg mPEG-PLA and 5mg TPGS mixing add 4mL absolute methanols, ultrasound
Dissolve 5min.At 35 DEG C, mixed solution is subjected to rotary evaporation 10min, methanol is removed, uniform film is formed.By film
It is dried in vacuo, drying time 12h, drying temperature is room temperature.5mL distilled water is added in film, ultrasonic water at 25 DEG C
Change 10min.Solution after aquation is centrifuged, speed 12000r/min, centrifugation time 5min, take supernatant as curcumin
MPEG-PLA/TPGS mixed micelle solution.
Embodiment 4：Prepare curcumin mPEG-PLA/TPGS mixed micelle oral formulations
Step is as follows：By 7mg curcumins, 25mg mPEG-PLA and 5mg TPGS mixing add 5mL absolute methanols, ultrasound
Dissolve 5min.At 35 DEG C, mixed solution is subjected to rotary evaporation 10min, methanol is removed, uniform film is formed.By film
It is dried in vacuo, drying time 12h, drying temperature is room temperature.6mL distilled water is added in film, ultrasonic water at 35 DEG C
Change 10min.Solution after aquation is centrifuged, speed 12000r/min, centrifugation time 5min, take supernatant as curcumin
MPEG-PLA/TPGS mixed micelle solution.
Embodiment 5：Prepare curcumin mPEG-PLA/TPGS mixed micelle oral formulations
Step is as follows：By 7mg curcumins, 22mg mPEG-PLA and 8mg TPGS mixing add 5mL absolute methanols, ultrasound
Dissolve 5min.At 35 DEG C, mixed solution is subjected to rotary evaporation 10min, methanol is removed, uniform film is formed.By film
It is dried in vacuo, drying time 12h, drying temperature is room temperature.5mL distilled water is added in film, ultrasonic water at 20 DEG C
Change 10min.Solution after aquation is centrifuged, speed 12000r/min, centrifugation time 5min, take supernatant as curcumin
MPEG-PLA/TPGS mixed micelle solution.
Embodiment 6：Prepare curcumin mPEG-PLA/TPGS mixed micelle oral formulations
Step is as follows：By 8mg curcumins, 25mg mPEG-PLA and 5mg TPGS mixing add 6mL absolute methanols, ultrasound
Dissolve 5min.At 35 DEG C, mixed solution is subjected to rotary evaporation 10min, methanol is removed, uniform film is formed.By film
It is dried in vacuo, drying time 12h, drying temperature is room temperature.2mL distilled water is added in film, ultrasonic water at 20 DEG C
Change 10min.Solution after aquation is centrifuged, speed 12000r/min, centrifugation time 5min, take supernatant as curcumin
MPEG-PLA/TPGS mixed micelle solution.
Embodiment 7：Prepare curcumin mPEG-PLA/TPGS mixed micelle oral formulations
Step is as follows：By 6mg curcumins, 25mg mPEG-PLA and 5mg TPGS mixing add 4mL absolute methanols, ultrasound
Dissolve 5min.At 35 DEG C, mixed solution is subjected to rotary evaporation 10min, methanol is removed, uniform film is formed.By film
It is dried in vacuo, drying time 12h, drying temperature is room temperature.5mL distilled water is added in film, ultrasonic water at 25 DEG C
Change 10min.Solution after aquation is centrifuged, speed 12000r/min, centrifugation time 5min, take supernatant as curcumin
MPEG-PLA/TPGS mixed micelle solution.
Embodiment 8：Prepare curcumin mPEG-PLA/TPGS mixed micelle oral formulations
Method and step such as embodiment 6, is distinguished as the ultrasonic dissolution time for 10min, drying time is 18h, during ultrasonic aquation
Between be 15min, centrifugation time is 10min.
Embodiment 9：Prepare curcumin mPEG-PLA/TPGS mixed micelle oral formulations
Method and step such as embodiment 7, is distinguished as the ultrasonic dissolution time for 2min, drying time is 15h, ultrasonic hydration time
For 5min, centrifugation time is 10min.
The curcumin mixed micelle preparation of appropriate above-mentioned preparation is taken, dynamic light scattering determination average grain diameter, zeta electricity is used
Position-finding instrument investigates the surface electrical behavior of micella, and the microscopic pattern of transmission electron microscope observation micella, ultraviolet specrophotometer is surveyed
Determine drug delivery amount.As a result it is that average grain diameter 46nm, zeta current potential are+0.613mV, Fig. 1 is mixed for curcumin mPEG-PLA/TPGS
The grain size distribution of rubber alloy beam.As shown in Fig. 2 the microscopic morphology of micella is rounded, size is homogeneous without adhesion.Ultraviolet spectrometry light
The drugloading rate that degree meter determines curcumin is 16.1% (w/w).
In embodiment 1-9, in the mPEG-PLA, the molecular weight of polyethylene glycol block is 2000, PLA block molecule
Measure as 2000；The molecular weight of polyethylene glycol block is 1000 in TPGS, and molecular weight unit is g/mol.
Test example 1：
Curcumin mPEG-PLA/TPGS mixed micelle preparations are prepared according to embodiment 7, manually gastric juice (pH 1.2) is distinguished
200 times, 500 times and 1000 times are diluted with simulated intestinal fluid (pH 6.8), room temperature places 2h, 4h and 6h, uses ultraviolet specrophotometer
Determine the changes of contents of curcumin in dilution.
As a result：As shown in figure 3, ordinate is the content of curcumin in 5mL dilutions, curcumin mPEG-PLA/TPGS is mixed
Close micellar preparation to be diluted after different multiples by simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 6.8), medicament contg is in 0h to 6h
It is interior without significant change, illustrate that curcumin mixed micelle preparation has preferable dilution stability.
Test example 2：
Curcumin mPEG-PLA/TPGS mixed micelle preparations are prepared according to embodiment 3,1mL micellar solutions are taken in pre-swollen
Bag filter in, bag filter two ends are sealed.Bag filter is first placed in the simulated gastric fluid (pH1.2) that 100mL contains 1% Tween 80
In, (120r/min) is vibrated in 37 DEG C of water-baths.Discharge after 2h, bag filter is transferred to the simulated intestinal fluid that 100mL contains 1% Tween 80
In (pH 6.8), (120r/min) is vibrated in 37 DEG C of water-baths.In default point in time sampling 1mL, and add isometric synthermal
Blank dissolution medium.The release sample of taking-up is crossed into 0.22 μm of filter membrane, the curcumin concentration in dissolution medium is determined with HPLC methods,
And calculate preparation.Using curcumin propylene glycol solution as control, extracorporeal releasing experiment is carried out according to identical step.
As a result：As shown in figure 4, in 48h curcumin mPEG-PLA/TPGS mixed micelle preparations release amount of medicine and medicine
Rate of release is below curcumin propylene glycol solution, shows that curcumin mixed micelle solution shows preferable sustained release feature.
Test example 3：
Curcumin mPEG-PLA/TPGS mixed micelle preparations are prepared according to embodiment 6, model is used as using Wista rats
Animal studies oral drugs dynamics.Wsita rats are randomly divided into two groups, every group five, entered according to 75mg/kg dosage
Row gastric infusion, gives curcumin mPEG-PLA/TPGS mixed micelle preparations and the sodium carboxymethylcellulose of curcumin 0.5% respectively
Suspension.At default time point, rat jugular vein blood is taken, is placed in the test tube of anticoagulant heparin, 4000rpm centrifugation 15min are received
Collect blood plasma and in -20 DEG C of storages.Rat plasma is mixed with pH 4.0 citric acid solution, ethyl acetate is used:Methanol=9:1 carries
Curcumin is taken, vortex 3min, 4000rpm centrifugation 10min merges supernatant and dried up in nitrogen under 37 DEG C of water-baths, 100ul methanol
After redissolution, vortex 3min, 10000rpm centrifugation 10min takes the μ l of supernatant 20 to carry out HPLC measure.Draw blood concentration-time
Curve, and calculate pharmacokinetic parameter such as TG-AUC (AUC), mean residence time (MTR), up to (T during peakmax) and blood
Peak concentration of drug (Cmax)。
Pharmacokinetic parameters after the Oral Administration in Rats curcumin preparation of table 1
As a result：After Oral Administration in Rats curcumin mPEG-PLA/TPGS mixed micelle preparations, curcumin can be detected in 24h
Blood concentration, and curcumin suspension, after oral 12h, the curcumin concentration in blood is reduced to below detection line.In table 1
Statistical moment parameter show that (MRT is h) the three of curcumin suspension to the mean residence time of curcumin mixed micelle in vivo
Times, illustrate curcumin mixed micelle can long lasting for release curcumin.In addition, curcumin mixed micelle reaches maximum peak
Time (the T of concentrationmax, h) 1h faster than curcumin suspension, and maximum plasma concentration (Cmax, ng/mL) and it is curcumin suspension
7 times of group, illustrate that carrier material mPEG-PLA and TPGS promote absorption of the curcumin in intestines and stomach.Meanwhile, curcumin mixing
Area under the drug-time curve (the AUC of micella group0-∞, μ g/mL*h) and it is 9 times of curcumin suspension, it was demonstrated that curcumin mPEG-PLA/
TPGS mixed micelle preparations significantly improve the oral administration biaavailability of curcumin.
Claims (9)
1. a kind of curcumin mixed micelle oral formulations, it is characterized in that, it is made up of following parts by weight of raw materials：Curcumin 1-15
Part, 5-25 parts of MPEG-PLA, 5-25 parts of TPGS, 2-8 parts of moisture；
The micella oral formulations, which are prepared by the following method, to be obtained：
（1）The curcumin, MPEG-PLA and TPGS that set proportioning are mixed,
Add absolute methanol, dissolving；
The mass ratio of curcumin and MPEG-PLA is 0.04 ~ 3:1, curcumin and polyethylene glycol vitamin E amber
The mass ratio of amber acid esters is 0.04 ~ 3:1, the quality of MPEG-PLA and TPGS
Than for 0.2 ~ 5:1, the mass volume ratio of curcumin and absolute methanol is 0.1 ~ 3.75:1 mg/mL；
（2）The mixed solution of dissolving is evaporated, stops evaporation after methanol until removing, uniform film is formed after evaporation；
（3）Film is dried, to remove remnants organic solvent；
（4）Add water in film, at a set temperature ultrasonic aquation；
The ultrasonic hydration temperature is 20 ~ 40 DEG C, and ultrasonic time is 5 ~ 15min；
The water and step（1）In curcumin volume mass ratio be 1：0.125~4mL/mg；
（5）Solution after aquation is centrifuged, it is curcumin MPEG-PLA/poly- second two to take supernatant
Alcohol VE-succinate mixed micelle oral formulations；
Step（3）In, the method for the drying is vacuum drying, and the dry time is 12 ~ 18h, and dry temperature is room temperature.
2. the preparation method of curcumin mixed micelle oral formulations as claimed in claim 1, it is characterized in that, comprise the following steps：
（1）The curcumin, MPEG-PLA and TPGS that set proportioning are mixed,
Add absolute methanol, dissolving；
（2）The mixed solution of dissolving is evaporated, stops evaporation after methanol until removing, uniform film is formed after evaporation；
（3）Film is dried, to remove remnants organic solvent；
（4）Add water in film, at a set temperature ultrasonic aquation；
（5）Solution after aquation is centrifuged, it is curcumin MPEG-PLA/poly- second two to take supernatant
Alcohol VE-succinate mixed micelle oral formulations.
3. preparation method as claimed in claim 2, it is characterized in that：Step（1）In, curcumin and methoxy poly (ethylene glycol)-poly-
The mass ratio of lactic acid is 0.04 ~ 3:1, the mass ratio of curcumin and TPGS is 0.04 ~ 3:1, methoxy
The mass ratio of base polyethylene glycol-polylactic acid and TPGS is 0.2 ~ 5:1, curcumin and absolute methanol
Mass volume ratio be 0.1 ~ 3.75:1 mg/mL.
4. preparation method as claimed in claim 2, it is characterized in that：Step（1）In, the method for the dissolving is ultrasonic dissolved
Solution, ultrasonic time is 2 ~ 10min.
5. preparation method as claimed in claim 2, it is characterized in that：Step（2）In, the method for the evaporation is steamed using rotation
Hair, the temperature of evaporation is 30 ~ 40 DEG C.
6. preparation method as claimed in claim 2, it is characterized in that：Step（3）In, the method for the drying is vacuum drying,
The dry time is 12 ~ 18h, and dry temperature is room temperature.
7. preparation method as claimed in claim 2, it is characterized in that：Step（4）In, the water and step（1）In curcumin
Volume mass ratio be 1：0.125~4mL/mg.
8. preparation method as claimed in claim 2, it is characterized in that：Step（4）In, the ultrasonic hydration temperature is 20 ~ 40 DEG C,
Ultrasonic time is 5 ~ 15min.
9. preparation method as claimed in claim 2, it is characterized in that：Step（5）In, the centrifugal speed is 12000r/min,
Centrifugation time is 5 ~ 10min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510194806.3A CN104784117B (en) | 2015-04-22 | 2015-04-22 | A kind of curcumin mixed micelle oral formulations and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510194806.3A CN104784117B (en) | 2015-04-22 | 2015-04-22 | A kind of curcumin mixed micelle oral formulations and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN104784117A CN104784117A (en) | 2015-07-22 |
| CN104784117B true CN104784117B (en) | 2017-08-08 |
Family
ID=53549625
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510194806.3A Expired - Fee Related CN104784117B (en) | 2015-04-22 | 2015-04-22 | A kind of curcumin mixed micelle oral formulations and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104784117B (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108956816B (en) * | 2018-07-12 | 2021-12-24 | 西南医科大学 | HPLC analysis method for simultaneously determining curcumin and 5-fluorouracil concentration in plasma |
| CN110840838A (en) * | 2018-08-03 | 2020-02-28 | 山东大学 | Galactose receptor mediated mixed micelle oral preparation and preparation method thereof |
| CN109125294A (en) * | 2018-10-16 | 2019-01-04 | 中山大学惠州研究院 | A kind of packaging method of curcumin |
| US20220387383A1 (en) * | 2019-11-12 | 2022-12-08 | University Of South Africa | Ezetimibe and curcumin for use in cancer treatment |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102274163A (en) * | 2011-08-12 | 2011-12-14 | 山东大学 | Curcumin nano micelle preparation and preparation method thereof |
| CN104042569A (en) * | 2014-06-18 | 2014-09-17 | 重庆医科大学 | D-alpha-tocopheryl polyethylene glycol succinate modified curcumin chloride chitosan lipidosome and preparation method thereof |
-
2015
- 2015-04-22 CN CN201510194806.3A patent/CN104784117B/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102274163A (en) * | 2011-08-12 | 2011-12-14 | 山东大学 | Curcumin nano micelle preparation and preparation method thereof |
| CN104042569A (en) * | 2014-06-18 | 2014-09-17 | 重庆医科大学 | D-alpha-tocopheryl polyethylene glycol succinate modified curcumin chloride chitosan lipidosome and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 聚乙二醇1000维生素E琥珀酸酯在纳米制剂中的应用进展;杜广盛等;《沈阳药科大学学报》;20121231;第29卷(第12期);第981-987页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN104784117A (en) | 2015-07-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Siew et al. | Enhanced oral absorption of hydrophobic and hydrophilic drugs using quaternary ammonium palmitoyl glycol chitosan nanoparticles | |
| Liang et al. | α-Tocopherol succinate-modified chitosan as a micellar delivery system for paclitaxel: Preparation, characterization and in vitro/in vivo evaluations | |
| Liu et al. | Antitumor drug effect of betulinic acid mediated by polyethylene glycol modified liposomes | |
| CN104784117B (en) | A kind of curcumin mixed micelle oral formulations and preparation method thereof | |
| Bonde et al. | Assessing the viability of Soluplus® self-assembled nanocolloids for sustained delivery of highly hydrophobic lapatinib (anticancer agent): Optimisation and in-vitro characterisation | |
| Zhang et al. | Cyclosporin A-loaded poly (ethylene glycol)-b-poly (d, l-lactic acid) micelles: preparation, in vitro and in vivo characterization and transport mechanism across the intestinal barrier | |
| CN106727336B (en) | Oridonin cubic liquid crystal nanoparticles and preparation method thereof | |
| Lu et al. | Preparation and in vitro and in vivo evaluation of quercetin-loaded mixed micelles for oral delivery | |
| Nguyen et al. | Reverse micelles prepared from amphiphilic polylactide-b-poly (ethylene glycol) block copolymers for controlled release of hydrophilic drugs | |
| WO2019137005A1 (en) | Drug-loaded nanoparticle based on tannic acid and preparation method therefor and use thereof | |
| Kapare et al. | Micellar drug delivery system: a review | |
| CN102885772B (en) | Docetaxel-loading mixed micelle preparation and preparation method thereof | |
| CN102302447B (en) | Novel taxol lipid microsphere injection and preparation method thereof | |
| CN108619094A (en) | A kind of nanometer formulation and preparation method thereof of anticancer natural product gambogicacid | |
| CN107638388B (en) | Asiatic acid chitosan deoxycholic acid graft micelle and preparation method thereof | |
| Li et al. | Critical determinant of intestinal permeability and oral bioavailability of pegylated all trans-retinoic acid prodrug-based nanomicelles: Chain length of poly (ethylene glycol) corona | |
| Zhang et al. | The enhancing effect of N-acetylcysteine modified hyaluronic acid-octadecylamine micelles on the oral absorption of paclitaxel | |
| Kahraman et al. | Polyethylenimine modified and non-modified polymeric micelles used for nasal administration of carvedilol | |
| Chen et al. | Pursuing for the better lung cancer therapy effect: comparison of two different kinds of hyaluronic acid and nitroimidazole co-decorated nanomedicines | |
| WO2018196819A1 (en) | Protein particle wrapped with medicine insoluble in water and preparation method therefor | |
| Luo et al. | Fabrication of pH/Redox dual-responsive mixed polyprodrug micelles for improving cancer chemotherapy | |
| CN103933016A (en) | Capsaicin ternary nanomicelle as well as preparation method and application thereof | |
| CN112545988A (en) | Hydrobromic acid halofuginone-TPGS polymer micelle and preparation method thereof | |
| Yin et al. | Preparation and characterization of long-circulating PELMD/mPEG–PLGA-mixed micelles for 10-hydroxycamptothecin | |
| CN102008454A (en) | Daidzein-entrapped PLGA nanoparticles and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20170808 Termination date: 20200422 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |