CN104784158B - The PLGA Electrospuns and preparation method of Daidzein nano structured lipid carrier - Google Patents
The PLGA Electrospuns and preparation method of Daidzein nano structured lipid carrier Download PDFInfo
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- CN104784158B CN104784158B CN201510158451.2A CN201510158451A CN104784158B CN 104784158 B CN104784158 B CN 104784158B CN 201510158451 A CN201510158451 A CN 201510158451A CN 104784158 B CN104784158 B CN 104784158B
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Abstract
The invention discloses a kind of PLGA Electrospuns of Daidzein nano structured lipid carrier and preparation method；The preparation method includes：Step one, PLGA is dissolved in spin solvent, be well mixed；Step 2, Daidzein nano structured lipid carrier, water-solubleazone are added into step one resulting solution, are well mixed；Step 3, Electrospun is prepared into by step 2 products therefrom.The characteristics of PLGA Electrospuns of the loading Daidzein nano structured lipid carrier of the present invention take into account nano structured lipid carrier drug carrying ability and Electrospun medicine-releasing system, the Electrospun formability that is formed is good, envelop rate is high, drug release is steady, it is a kind of efficiently to facilitate easily operated novel dosage forms, the Transdermal absorption of Daidzein can be promoted, bioavilability is improved, the compliance and therapeutic effect of patient is also improved.
Description
Technical field
The present invention relates to a kind of preparation method of the preparation capable of permeating skin of field of medicine preparing technology, and in particular to a kind of daidzin
The PLGA Electrospuns and preparation method of first nano structured lipid carrier.
Background technology
Daidzein (daidzein) is one of active ingredient of Chinese medicament kudzu-vine root, and cardiovascular protective effect curative effect is more dashed forward
Go out, be mainly used in treatment hypertension, coronary heart disease and cranial nerve disease, in view of its good therapeutic action, Daidzein is oral
Tablet and capsule all approved list.Fat-soluble also poor but Daidzein water solubility is poor, body absorption is slow, biological
Availability is low, so that the curative effect that have impact on Daidzein is played, limits it and widely uses.
Therefore consider Daidzein percutaneous dosing, first have to solve the problem of Daidzein bioavilability is low.Nanometer
Structured lipid carrier (NLC) is a kind of new submicron delivery system of excellent performance, use mixing lipid for carrier, have including
Improve drugloading rate and the envelop rate of medicine, increase the stability of system, it is excellent that drug bioavailability is high, physiological compatibility is good etc.
Point.Nano structured lipid carrier is made in Daidzein, its nanoparticle particle diameter<100nm, can effectively pass through skin, and and skin
Skin compatibility is good, and its high drug load has higher advantage with envelop rate as drug depot.Daidzein nanostructured lipid is carried
Body is implemented in combination with percutaneous dosing with electrostatic spinning for next step and laid the first stone.
Transdermal delivery system or Transcutaneous Therapeutic System are a kind of methods that medicine is absorbed by skin, and medicine is via skin
It is absorbed into blood circulation of human body and reaches effective blood drug concentration, realizes disease treatment or a class preparation of prevention.Percutaneous dosing
Improve the compliance of patient and avoid " first pass effect " of the liver to medicine, and the continual and steady release medicine of energy.Percutaneously
Drug delivery system has been developed as an important developing direction of modern medicines preparation.
Electrostatic spinning technique causes the wide of scholars in recent years as a kind of preparation method of micro/nano-fibre
General concern, micro/nano-fibre not only good mechanical properties, and there is preferable biocompatibility and biodegradability, because
And the release characteristics of medicine can be effectively controlled, electrostatic spinning turns into Recent study focus in the application of field of medicaments.It is quiet
Electrospun is as the carrier of percutaneous dosing, and its amount of containing is high, specific surface area is big, bioavilability is high, sustained release is all prominent
Advantage.Because Daidzein is water-soluble, fat-soluble all poor, it is impossible to directly carry out electrostatic spinning.So this patent is first by Huang
Nano structured lipid carrier is made in beans aglycon, then carries out Electrospun, combines both advantages.
Daidzein nano structured lipid carrier has been studied for percutaneous dosing, but nano structured lipid carrier can not be straight
Administration is connect, it is necessary to make the ability percutaneous dosing such as hydrogel adhesive.
The content of the invention
To overcome the deficiencies in the prior art, it is an object of the invention to provide a kind of Daidzein nano structured lipid carrier
PLGA Electrospuns and preparation method.This patent combines Daidzein nano structured lipid carrier and electrostatic spinning, formation
Electrospun can be done directly on skin, both solve the carrier problem of drug percutaneous release, while adding penetrating agent water-soluble nitrogen
Ketone, further increases drug percutaneous transit dose, promotes the Transdermal absorption of medicine.This new formulation takes into account nanostructured lipid
The characteristics of carrier drug carrying ability and Electrospun medicine-releasing system, with innovative and practical value.The loading Daidzein of the present invention
The PLGA Electrospuns of nano structured lipid carrier take into account the spy of nano structured lipid carrier drug carrying ability and Electrospun medicine-releasing system
Point, the Electrospun formability that is formed is good, envelop rate is high, drug release is steady.
The present invention is achieved by the following technical solutions：
The present invention provides a kind of preparation method of the PLGA Electrospuns of Daidzein nano structured lipid carrier, the preparation
Method comprises the following steps：
Step one, PLGA is dissolved in spin solvent, is well mixed, obtains mixed solution A；
Step 2, Daidzein nano structured lipid carrier, water-soluble nitrogen are added into step one gained mixed solution A
Ketone, is well mixed, obtains mixed solution B；
Step 3, Electrospun is prepared into by mixed solution B obtained by step 2.
Preferably, in step one, the spin solvent is tetrahydrofuran, the mixture of dimethylformamide.
It is highly preferred that the volume ratio of the tetrahydrofuran, dimethylformamide is 1:1.
Preferably, in step one, the PLGA is long chain macromolecule PLA-poly- second that relative molecular mass is 10000
The mol ratio of lactic acid and hydroxyacetic acid is 50 in alkyd copolymers, its structure:50.
Preferably, in step one, in the mixed solution A, PLGA mass contents are 27~33%.
Preferably, in step 2, in the mixed solution B, Daidzein nano structured lipid carrier, water-solubleazone
Mass content is respectively 5~8%, 1.5~3%.
Preferably, in step 2, the preparation of the Daidzein nano structured lipid carrier comprises the following steps：
(1) lecithin, Tween-80 are separately added into absolute ethyl alcohol and prepare organic phase 1, organic phase 2；By Daidzein, list
Tristerin, Miglyol 812N are dissolved in methanol, prepare organic phase 3；
(2) organic phase 1, organic phase 2 are quickly mixed into organic phase 3, are well mixed, be injected into aqueous phase, heating is removed
Organic solvent constituent, then rapid dispersion is in frozen water, and solidification obtains mixed emulsion；
(3) mannitol is added into the mixed emulsion, mixed, low temperature is freezed, and produces Daidzein nanostructured lipid
Carrier.
Preferably, in step (1), 70~90mg of lecithin, absolute ethyl alcohol 5mL are contained in the organic phase 1；The organic phase
In 2, containing 100~140mg of Tween-80, absolute ethyl alcohol 5mL；Member containing soya bean 30~50% (w/v), single tristearin in the organic phase 3
Acid glyceride, Miglyol 812N, methanol 10mL；Wherein, Daidzein, glycerin monostearate and Caprylic Capric
The mass ratio of three esters is 2：50：15.
Preferably, in step (2), quick be mixed into refers specifically to that organic phase 1, organic phase 2 are poured into organic phase 3 in 10s
In.
Preferably, in step (2), the cumulative volume of the organic phase 1,2,3 and the volume ratio of aqueous phase are 2:7.
Preferably, in step (2), the time of the heating is 2h, and the time of the solidification is 0.5h.
Preferably, in step (3), the mass concentration that the mannitol is added is 4% (w/v), and the mannitol is protection
Agent.
Preferably, in step 3, the Electrospun for preparing specifically uses SS-2535H type Electrospun machines, and setting receives distance
15cm, spinning voltage is -2kV~+(10-12) kV, and fltting speed is 0.25~0.27mm/min, passes through No. 9 stainless steel syringe needles
Spray.
Compared with prior art, the present invention has following beneficial effect：The loading Daidzein nanostructured of the present invention
The characteristics of PLGA Electrospuns of lipid carrier take into account nano structured lipid carrier drug carrying ability and Electrospun medicine-releasing system, is formed
Electrospun formability it is good, envelop rate is high, drug release is steady, be it is a kind of efficiently facilitate easily operated novel dosage forms, Huang can be promoted
The Transdermal absorption of beans aglycon, improves bioavilability, also improves the compliance and therapeutic effect of patient.
Brief description of the drawings
By reading the detailed description made with reference to the following drawings to non-limiting example, further feature of the invention,
Objects and advantages will become more apparent upon：
Fig. 1 is the grain size distribution for the loading Daidzein nano structured lipid carrier that embodiment 1 is obtained；
Fig. 2 is the transmission electron microscope picture for the loading Daidzein nano structured lipid carrier that embodiment 1 is obtained；
Fig. 3 is the ESEM of the PLGA Electrospuns for the loading Daidzein nano structured lipid carrier that embodiment 2 is obtained
Figure；
Fig. 4 adds up to pass through spirogram to load the transdermal test in vitro of the PLGA Electrospuns of Daidzein nano structured lipid carrier.
Embodiment
With reference to specific embodiment, the present invention is described in detail.Following examples will be helpful to the technology of this area
Personnel further understand the present invention, but the invention is not limited in any way.It should be pointed out that to the ordinary skill of this area
For personnel, without departing from the inventive concept of the premise, various modifications and improvements can be made.These belong to the present invention
Protection domain.
Raw material sources：Daidzein is purchased from Nanjing Qing Ze medical sci-teches development company, PLGA (LA/GA=50:50) Mn=
10000 are purchased from Jinan, Shandong Province Dai Gang biotechnologies Co., Ltd, and water-solubleazone is purchased from Xinxiang Gao Jin pharmaceutcal corporation, Ltds,
Other raw materials are common commercial goods.
Embodiment 1
The present embodiment is related to a kind of preparation method of Daidzein nano structured lipid carrier, specifically includes following steps：
(1) by lecithin 70mg and Tween-80 100mg, 5mL absolute ethyl alcohols are separately added into, organic phase 1 and organic phase is used as
2；Daidzein 4mg, glycerin monostearate 100mg, Miglyol 812N 30mg are dissolved in 10mL methanol, made
For organic phase 3；
(2) organic phase 1 and organic phase 2 are quickly mixed into organic phase 3, after 650r/min is uniformly mixed, at the uniform velocity noted
In the 70mL waters bath with thermostatic control for entering 60 DEG C, 2h is heated, rapid dispersion after organic solvent is removed and in 20ml frozen water, stirs 30min and consolidate
Change completely, obtain mixed emulsion；
(3) mixed emulsion adds 4% (w/v) mannitol, and low temperature freezes to obtain Daidzein nano structured lipid carrier.
The nano structured lipid carrier that embodiment 1 is obtained, is detected with particle instrument, its droplet measurement result as shown in figure 1, its
Particle diameter is (55.91 ± 4.35) nm, and effect is more excellent；Detected with transmission electron microscope, its transmission electron microscope results is as shown in Figure 2；With efficient
Liquid chromatogram (HPLC) is determined, and its drugloading rate is (1.04 ± 0.16) %, and envelop rate is (80.82 ± 3.32) %.
During the present embodiment is implemented, 70~90mg of lecithin, 100~140mg of Tween-80, soya bean in step (1)
Aglycon, glycerin monostearate and Miglyol 812N mass ratio are 2：50：15th, Daidzein content is 30~50%
(w/v) condition can be achieved.
Embodiment 2
The present embodiment is related to a kind of PLGA method for manufacturing electric spinning for loading Daidzein nano structured lipid carrier, specifically
Comprise the following steps：
(1) 30% PLGA is weighed as spinning material, accurately measures tetrahydrofuran：Dimethylformamide (1:1) spin
Wire material solvent；
(2) the Daidzein nano structured lipid carrier and water-solubleazone concentration added is respectively 8%, 2%, and mixing is equal
It is even that Electrospun is obtained by electrospinning wire feed mechanism；The Electrospun specifically uses SS-2535H type Electrospun machines, and setting receives apart from 15cm,
Spinning voltage is -2kV~+(10-12) kV, and fltting speed is 0.25~0.27mm/min, is sprayed by No. 9 stainless steel syringe needles.
The Electrospun that embodiment 2 is obtained, is detected with ESEM, and its ESEM result is as shown in figure 3, the smooth light of structure
Sliding, high performance liquid chromatography (HPLC) is determined, and its envelop rate is (98.71 ± 1.02) %.
In the present embodiment implementation process, PLGA consumptions are 27~33% in step (1), Daidzein is received in step (2)
Rice structured lipid carrier and water-solubleazone concentration are respectively that can be achieved under conditions of 5~8%, 1.5~3%.
Embodiment 3
The PLGA Electrospuns for the loading Daidzein nano structured lipid carrier that the present embodiment is prepared with embodiment 2 do rat
Percutaneous penetration：
The stand-by skin of rat is fixed on by experiment using RYJ-12B type diffusions device (RYJ-12B, the Huanghai Sea, China)
Between the supply pool and acceptance pool of diffusion cell.It is respectively that the oversaturated Daidzein solution of 2mg, content of dispersion are by 2mL content of dispersion
The PLGA Electrospuns (without hydration azone) and Daidzein nanostructured lipid of 2mg Daidzein nano structured lipid carrier
The PLGA Electrospuns (azone containing hydration) of carrier add supply pool.Reception liquid is 20% ethanol-PBS solution (pH=7.4).Regularly
Sampling is handled, and corresponding drug concentration is calculated with high performance liquid chromatography detection.Transdermal diffusion profile such as Fig. 4.
As can be seen that remaining two groups accumulative transit doses are all molten higher than active compound under same concentrations in the transdermal diffusion profiles of Fig. 4
Liquid, PLGA Electrospuns (azone containing hydration) the group 72h of Daidzein nano structured lipid carrier adds up transit dose highest.Understand Huang
The PLGA Electrospuns (azone containing hydration) of beans aglycon nano structured lipid carrier have reached good transdermal effect.
The specific embodiment of the present invention is described above.It is to be appreciated that the invention is not limited in above-mentioned
Particular implementation, those skilled in the art can make various deformations or amendments within the scope of the claims, this not shadow
Ring the substantive content of the present invention.
Claims (8)
1. a kind of preparation method of the PLGA Electrospuns of Daidzein nano structured lipid carrier, it is characterised in that the preparation
Method comprises the following steps：
Step one, PLGA is dissolved in spin solvent, is well mixed, obtains mixed solution A；
Step 2, Daidzein nano structured lipid carrier, water-solubleazone are added into step one gained mixed solution A, are mixed
Close uniform, obtain mixed solution B；
Step 3, Electrospun is prepared into by mixed solution B obtained by step 2；
Wherein, in step one, the spin solvent is tetrahydrofuran, the mixture of dimethylformamide；
In step one, in the mixed solution A, PLGA mass content is 27~33%；
In step 2, in the mixed solution B, Daidzein nano structured lipid carrier, the mass content point of water-solubleazone
Wei 5~8%, 1.5~3%.
2. the preparation method of the PLGA Electrospuns of Daidzein nano structured lipid carrier according to claim 1, it is special
Levy and be, tetrahydrofuran, the volume ratio of dimethylformamide are 1 in the spin solvent:1.
3. the preparation method of the PLGA Electrospuns of Daidzein nano structured lipid carrier according to claim 1, it is special
Levy and be, in step one, the PLGA is the long chain macromolecule polylactic acid-polyglycolic acid copolymerization that relative molecular mass is 10000
The mol ratio of lactic acid and hydroxyacetic acid is 50 in thing, its structure:50.
4. the preparation method of the PLGA Electrospuns of Daidzein nano structured lipid carrier according to claim 1, it is special
Levy and be, in step 2, the preparation of the Daidzein nano structured lipid carrier comprises the following steps：
(1) lecithin, Tween-80 are separately added into absolute ethyl alcohol and prepare organic phase 1, organic phase 2；By Daidzein, single tristearin
Acid glyceride, Miglyol 812N are dissolved in methanol, prepare organic phase 3；
(2) organic phase 1,2 is quickly mixed into organic phase 3, be well mixed, be injected into aqueous phase, heating removes organic solvent group
Point, then rapid dispersion is in frozen water, and solidification obtains mixed emulsion；
(3) mannitol is added into the mixed emulsion, mixed, low temperature is freezed, and produces Daidzein nano structured lipid carrier.
5. the preparation method of the PLGA Electrospuns of Daidzein nano structured lipid carrier according to claim 4, it is special
Levy and be, in step (1), 70~90mg of lecithin, absolute ethyl alcohol 5mL are contained in the organic phase 1；In the organic phase 2, containing telling
Temperature -80 100~140mg, absolute ethyl alcohol 5mL；It is sweet containing Daidzein 30~50% (w/v), monostearate in the organic phase 3
Grease, Miglyol 812N, methanol 10mL；Wherein, Daidzein, glycerin monostearate and Miglyol 812N
Mass ratio be 2：50：15.
6. the preparation method of the PLGA Electrospuns of Daidzein nano structured lipid carrier according to claim 4, it is special
Levy and be, in step (2), the cumulative volume of the organic phase 1,2,3 and the volume ratio of aqueous phase are 2:7；The time of the heating is
2h, the time of the solidification is 0.5h.
7. the preparation method of the PLGA Electrospuns of Daidzein nano structured lipid carrier according to claim 4, it is special
Levy and be, in step (3), the concentration 4% (w/v) that the mannitol is added.
8. the preparation method of the PLGA Electrospuns of Daidzein nano structured lipid carrier according to claim 1, it is special
Levy and be, in step 3, the Electrospun for preparing specifically uses SS-2535H type Electrospun machines, and setting receives, apart from 15cm, to spin
Filament voltage is -2kV~+(10-12) kV, and fltting speed is 0.25~0.27mm/min, is sprayed by No. 9 stainless steel syringe needles.
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| US20130149667A1 (en) * | 2011-12-13 | 2013-06-13 | The Trustees Of Columbia University In The City Of New York | Multiphase tissue complex scaffolds |
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