CN108042512A - A kind of hud typed alginate/polyacrylamide microsphere for loading andrographolide and its preparation method and application - Google Patents
A kind of hud typed alginate/polyacrylamide microsphere for loading andrographolide and its preparation method and application Download PDFInfo
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- 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
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- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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Abstract
The invention discloses a kind of hud typed alginate/polyacrylamide microspheres for loading andrographolide and its preparation method and application, belong to novel pharmaceutical formulation preparing technical field.The microballoon is made of following components：Sodium alginate, polyacrylamide, andrographolide.The preparation method of alginate/polyacrylamide microsphere of present invention load andrographolide is electrostatic drop generation, have many advantages, such as that microballoon preparation efficiency is high, preparation condition is mild, Microsphere Size is controllable, micro-ball load is efficient, stability is good, can be widely applied to field of medical applications.Microballoon prepared by the present invention can be used for treatment infantile pneumonia, upper respiratory tract infection, has the function of immunological regulation, antitumor etc., can be widely applied to the fields such as health products, drug and bio-medical material.
Description
Technical field
The invention belongs to novel pharmaceutical formulation preparing technical fields, are related to a kind of polymer microballoon and preparation method thereof, specifically
It is related to a kind of hud typed alginate/polyacrylamide microsphere for loading andrographolide and its preparation method and application.
Background technology
Andrographolide (C20H30O5) it is the diterpene ginkgolide extracted in acanthaceous plant Herba Andrographitis, in being
One of principle active component of medicine Herba Andrographitis, chemical structural formula is shown in Figure 1A.Andrographolide has antipyretic, anti-inflammatory, antiviral, guarantor
The effects that liver cholagogic, is clinically mainly used for treating the diseases such as the infection of the upper respiratory tract, pneumonia.Andrographolide is square prismatic or piece
Shape crystallizes, and odorless, taste is extremely bitter, is soluble in acetone, methanol, ethyl alcohol, almost insoluble in water, 230~231 DEG C of fusing point.With other
Common infection of the upper respiratory tract medicine is compared, and the antibacterial of andrographolide acts synergistically with antiviral with more preferably controlling
Therapeutic effect, but because its oral bitter pole causes Treatment Compliance poor, particularly in infection of the upper respiratory tract pediatric population occurred frequently
Curative compliance it is very poor.In order to solve the problems, such as this, the ripe dosage form developed at present includes pill, suspension, tablet etc.,
But still bitter taste cannot be sheltered well, and existing dosage form particle is larger, and single dose medicament contg is higher, is unsuitable for children (especially
It is infant) administration.
Sodium alginate (Sodium Alginate) is《Pharmacopoeia of People's Republic of China》(2015 editions) include medicinal auxiliary
Material, it is the linear anionic natural polysaccharide extracted from brown alga, sweet by α-L- guluronic acids and its stereoisomer β-D-
The unbranched linear block copolymers that dew two kinds of structural units of uronic acid are polymerized by (1-4) glycosidic bond, chemical constitution
Formula is shown in Figure 1B.Research show sodium alginate can in a mild condition with Ca2+It reacts and forms biocompatibility and mechanical strength is excellent
Good calcium alginate gel, the three-dimensional network pore structure of gel provide material base for the load of drug with release.Ca2+Cause
The mechanism that sodium alginate colloidal sol changes to gel state is：1 Ca2+4 coordinate bonds used with 2 GG segment units, which are formed, has 2
The stable chelate of six-membered ring structure, i.e. " egg lattice " structure, as shown in Figure 1 C.Fundamental reaction equation is as follows：
2n Na+-Alginate+n Ca2+→n Ca2+-Alginate↓+2n Na+
The preparation method of calcium alginate microsphere mainly has emulsion process, interfacial polymerization, spray drying process and electrostatic field drop
Method etc..Wherein, there are microspheres product grain size is uneven, monodispersity is poor, drug for emulsion process, interfacial polymerization, spray drying process
The common problems such as envelop rate is low and homogeneity is poor cause preparation of traditional Chinese medicine release behavior difference big.In addition, organic solvent residual
It is the major reason for influencing product quality.Calcium alginate microsphere is prepared using electrostatic field droplet process, have monodispersity it is excellent,
The advantages that uniform particle sizes are controllable, drug encapsulation efficiency is high and dosage is controllable, preparation condition is mild efficiently, organic solvent-free addition,
Suitable for the high-efficient carrier of the multiple compounds such as cell and protein, nucleic acid.The basic principle of electrostatic field droplet process is：In raw material
Liquid end, coagulating bath end load the positive electrode and negative electrode of electric field respectively.Under electric field force effect, the material liquid of positive terminal is said in miniflow
Mouth can overcome solution surface tension and high throughput is spouting in the form of fine drop, subsequently into coagulation bath and Ca2+Reaction
Form calcium alginate gel beads.By adjusting preparation condition parameter, gel beads grain size can be regulated and controled between 50~1000 μm.
Since the three-dimensional network pore structure of calcium alginate gel is more loose, be carried on encapsulated component therein be easy to
Surrounding medium is spread, and is unable to reach effective control releasing effect.Existing research generally use polycationic compounds (rely as poly-
Propylhomoserin, chitosan) it is reacted with calcium alginate microsphere, a layer-selective half is formed in microsphere surface by polyelectrolyte complex reaction
Permeable membrane reaches and is encapsulated component in limitation microballoon and outwardly Medium Diffusion or makes what it was outwardly discharged with controlled rate
Purpose.Although this polyelectrolyte membrane can effectively shield the leakage that cell is encapsulated in microballoon and control protein, nucleic acid, more
The rate of release of the macromolecular components such as sugar, but preferable controlled release ability is had no to small molecule component, thus, relied using traditional gathering
Propylhomoserin/calcium alginate or chitosan/calcium alginate microsphere cannot reach the taste masking effect to being encapsulated andrographolide.
The content of the invention
In order to overcome the problems of the above-mentioned prior art, it is an object of the invention to provide a kind of load andrographolides
Hud typed alginate/polyacrylamide microsphere and its preparation method and application, the hud typed alginate/polyacrylamide
Microballoon can effectively shelter andrographolide bitter taste, and drug loading is efficiently controllable, suitable for children novel form.
The present invention is realized by the following technical programs：
A kind of hud typed alginate/polyacrylamide microsphere for loading andrographolide disclosed by the invention, the core
In shell mould alginate/polyacrylamide microsphere, core is the alginate ball for loading andrographolide, and shell is polyacrylamide
Amine；
Hud typed alginate/the polyacrylamide microsphere, in terms of mass fraction, including：1~8 part of sodium alginate gathers
1~6 part of acrylamide, 3~9 parts of andrographolide.
Preferably, the weight average molecular weight of the sodium alginate is 200000~800000, and the range of viscosities of 1% aqueous solution
For 0.02~1Pas, the average molecular weight of polyacrylamide is 500000~5000000.
Preferably, a diameter of 50~2000 microns of the hud typed alginate/polyacrylamide microsphere.
Preferably, polyacrylamide can be replaced with the better polystyrene of biocompatibility and poly N-vinyl pyrrolidone
It changes.
Hud typed alginate/polyacrylamide microsphere the invention also discloses above-mentioned load andrographolide is being made
Application in the drug of the standby treatment infection of the upper respiratory tract or pneumonia.
Microballoon can effectively shelter the strong bitterness of andrographolide, expand the application range of andrographolide, particularly
There is application advantage apparent in childrens respiratory tract infection and pneumonia treatment, be the new way for developing children.
The invention also discloses a kind of preparations for the hud typed alginate/polyacrylamide microsphere for loading andrographolide
Method is prepared using electrostatic field sessile drop method, comprised the following steps：
1) sodium alginate is pressed：Andrographolide：Water=(0.5~3) g：(0.01~0.5) g：The amount ratio of 100mL, by sea
Mosanom is soluble in water to be made into sodium alginate soln, adds andrographolide, and preparation obtains material liquid；
2) CaCl is pressed2：Acrylamide monomer：Water=(1~5) g：(0.1~2) g：The amount ratio of 100mL, by CaCl2It is dissolved in
CaCl is made into water2Solution adds acrylamide monomer, and coagulation bath is made；
3) impulse electric field anode is connected with loading the syringe metal needle of material liquid, by impulse electric field cathode and gel
Wire coil connection in bath, is then sprayed material liquid into coagulation bath by syringe metal needle；In course of injection,
Sodium alginate and Ca in drop2+Crosslinking, forms calcium alginate, and drop is solidified into gel micro-ball and is wrapped in andrographolide
Wherein；During drop is formed by curing gel micro-ball, acrylamide monomer molecule in coagulation bath by physical absorption and
Molecule diffusion way is supported on the surface of calcium alginate gel bead, and using filter, washing, area load acrylamide list is made
Body and the calcium alginate gel bead for encapsulating andrographolide；
Wire coil refers to, during electrostatic drop generation prepares microballoon, contains coagulation bath solution and contains acryloyl
The container of the calcium chloride solution of amine is plastic culture dish or glass culture dish, and a wire coil ability is placed in the culture dish
Make the cathode of coagulation bath solution make pulse electric field, and electrostatic field is formed between syringe and coagulation bath solution, in electric field force
Under the action of realize gel micro-ball preparation.
4) it is micro- to the calcium alginate gel of area load acrylamide monomer made from step 3) and encapsulating andrographolide
Ball carries out polymerization crosslinking reaction, is washed out, microballoon, drying is collected by filtration, and the hud typed seaweed of load andrographolide is made
Hydrochlorate/polyacrylamide microsphere.
Preferably, in step 3), when injection, uses micro syringe that material liquid is made to pass through metal needle with the rate of 10mL/h
Head pumps out.
Preferably, in step 4), the polymerization crosslinking reaction is by area load acrylamide monomer and encapsulating Herba Andrographitis
After the calcium alginate gel bead of lactone is mixed with the solution containing crosslinking agent, initiator, catalyst, reaction 1~for 24 hours, solidifying
Glue microsphere surface forms fine and close polyacrylamide shell；
Wherein, the mass ratio of crosslinking agent, initiator and acrylamide monomer is (50~200)：(1~6)：(100~
2000)。
Preferably, the crosslinking agent is N, and N- methylene-bisacrylamides, the initiator is potassium peroxydisulfate or persulfuric acid
Ammonium.
Preferably, containing crosslinking agent, initiator solution in be additionally added catalyst tetramethylethylenediamine, catalyst adds in
It measures as the μ L of 50 μ L~400.
Preferably, in step 4), adopt and be washed with distilled water 3~5 times, then with 0.45 μm of filtering with microporous membrane, collect micro-
Ball, vacuum drying is for 24 hours.
The invention also discloses the systems of hud typed alginate/polyacrylamide microsphere of another load andrographolide
Preparation Method is prepared using gravitational field sessile drop method, comprised the following steps：
1) sodium alginate is pressed：Andrographolide：Water=(0.5~3) g：(0.01~0.5) g：The amount ratio of 100mL, by sea
Mosanom is soluble in water to be made into sodium alginate soln, adds andrographolide, and preparation obtains material liquid；
2) CaCl is pressed2：Acrylamide monomer：Water=(1~5) g：(0.1~2) g：The amount ratio of 100mL, by CaCl2It is dissolved in
CaCl is made into water2Solution adds acrylamide monomer, and coagulation bath is made；
3) material liquid is oozed into drop by syringe needle, drop is instilled into coagulation bath under the effect of gravity, drop
In sodium alginate and Ca2+Crosslinking, forms calcium alginate, and drop is solidified into gel micro-ball and andrographolide is wrapped in it
In, during drop is formed by curing gel micro-ball, the acrylamide monomer molecule in coagulation bath by physical absorption and divides
Sub- diffusion way is supported on the surface of calcium alginate gel bead, and using filter, washing, area load acrylamide monomer is made
And the calcium alginate gel bead of encapsulating andrographolide；
4) it is micro- to the calcium alginate gel of area load acrylamide monomer made from step 3) and encapsulating andrographolide
Ball carries out polymerization crosslinking reaction, is washed out, microballoon, drying is collected by filtration, and the hud typed seaweed of load andrographolide is made
Hydrochlorate/polyacrylamide microsphere.
Compared with prior art, the present invention has technique effect beneficial below：
Hud typed alginate/polyacrylamide microsphere of load andrographolide disclosed by the invention, the microballoon have
The poroid space structure of three dimensional network, core are to contain the gel micro-ball that andrographolide formed by alginate, and shell is polyacrylamide；
The microballoon can largely load andrographolide, have envelop rate high, and Microsphere Size is controllable, shelters bitter taste, increases in Herba Andrographitis
The advantages that ester clinical application range, is studied for pharmaceutical carrier and provides development space with application.
One of method disclosed by the invention utilizes electrostatic field droplet process, makes the sodium alginate raw material of load andrographolide
Drop enters in the calcium chloride coagulation bath containing acrylamide monomer molecule, during sol-gel phase transition occurs for drop, makes
Acrylamide monomer molecule is incorporated in calcium alginate gel bead surface；By monomer polymerization reactions, the acryloyl of microsphere surface
Amine monomers polymerize to form fine and close shell, achieve the purpose that control andrographolide rate of release, masking andrographolide bitter taste.
Another kind method disclosed by the invention makes sodium alginate and andrographolide mixed liquor using gravitational field droplet process
(material liquid) is oozed with given pace by front end of the syringe needle syringe needle, and drop is instilled under the effect of gravity containing acrylamide monomer
CaCl2In solution (coagulating bath).Sodium alginate and Ca in drop2+It is crosslinked and forms calcium alginate not soluble in water, drop
It is formed by curing gel micro-ball and encapsulates andrographolide wherein.During drop is formed by curing gel micro-ball, solidification
Acrylamide monomer molecule in bath is supported on calcium alginate microsphere surface by physical absorption and molecule diffusion way.By list
Body polymerisation, the acrylamide monomer of microsphere surface polymerize to form fine and close shell, reach control andrographolide rate of release,
Shelter the purpose of andrographolide bitter taste.
Microballoon disclosed by the invention can effectively shelter the strong bitterness of andrographolide, expand the application of andrographolide
Scope particularly has application advantage apparent, is the new way for developing children in childrens respiratory tract infection and pneumonia treatment.
Description of the drawings
Figure 1A is andrographolide chemical structural formula；Figure 1B is alginate chemical constitution, and G is guluronic acid list in figure
Member, M are mannuronic acid unit；Fig. 1 C are " egg lattice " structure of alginate and calcium ion gel；
Fig. 2 is the process flow chart that electrostatic drop generation prepares hud typed alginate/polyacrylamide microsphere；
Fig. 3 is alginate/polyacrylamide microsphere optical microscopic image；Wherein, (A) grain size is 450 μm -470 μm；
(B) grain size is 230 μm -240 μm；
Fig. 4 is scanning electron microscopy picture；Wherein, (A) is alginate/polyacrylamide microsphere surface；(B) it is seaweed
Hydrochlorate/polyacrylamide microsphere section；(C) calcium alginate microsphere surface；(D) it is calcium alginate microsphere section；
Fig. 5 is the infrared spectrum of alginate/polyacrylamide microsphere, N,N methylene bis acrylamide and acrylamide
Analysis chart；
Fig. 6 is that the release of andrographolide in calcium alginate microsphere and hud typed alginate/polyacrylamide microsphere is bent
Line chart；
Fig. 7 is the uv absorption spectra of acrylamide monomer and alginate/polyacrylamide microsphere leaching liquor.
Specific embodiment
With reference to specific embodiment, the present invention is described in further detail, it is described be explanation of the invention and
It is not to limit.
Embodiment 1
Calcium alginate microsphere is prepared using electrostatic field sessile drop method：
By impulse electric field anode and it is mounted with 1% sodium alginates of 10mL and 0.1g andrographolides mixed liquor (material liquid)
Syringe metal needle connection, by electric field cathode and 3%CaCl2Wire coil connection in solution (coagulation bath), thus
Electrostatic field is formed between material liquid and coagulation bath.Use micro-injection pump that material liquid is made to pass through metal needle with the rate of 10mL/h
It pumps out, under the action of electric field force, material liquid is overcome solution surface tension and is injected into the controllable drops of size solidifying
Gu bath.Sodium alginate and Ca in drop2+It is crosslinked and forms calcium alginate not soluble in water, drop is formed by curing microballoon and will wear
Heart lotus lactone wraps up wherein.By filtering, washing, the calcium alginate gel bead of encapsulating andrographolide is obtained.
Embodiment 2
Referring to Fig. 2, alginate/polyacrylamide microsphere is prepared using electrostatic drop generation：
By impulse electric field anode and it is mounted with 1% sodium alginates of 10mL and 0.1g andrographolides mixed liquor (material liquid)
The connection of syringe metal needle, by the 3%CaCl of the acrylamide monomer containing 1.4g in electric field cathode and 25mL2Solution (gel
Bath) in wire coil connection, so as to forming electrostatic field between material liquid and coagulation bath.Material liquid is made using micro-injection pump
It is pumped out with the rate of 10mL/h by metal needle, under the action of electric field force, material liquid overcomes solution surface tension and with ruler
Very little controllable drops are injected into coagulating bath.Sodium alginate and Ca in drop2+It is crosslinked and forms seaweed not soluble in water
Sour calcium, drop are formed by curing microballoon and wrap up andrographolide wherein.During drop is formed by curing gel micro-ball,
Acrylamide monomer molecule in coagulation bath is supported on calcium alginate microsphere surface by physical absorption and molecule diffusion way.Through
Filtering and washing obtain area load acrylamide monomer molecule and encapsulate the calcium alginate gel bead of andrographolide.
By area load acrylamide monomer molecule obtained above and encapsulate andrographolide calcium alginate microsphere with
25mL distilled water is added in 50mL conical flasks, is started blender, then will be contained crosslinking agent 93mg N, N- methylene-bisacrylamides
With the solution of 400 μ L 10mg/mL initiator potassium persulfates (ammonium persulfate), and 200 μ L tetramethylethylenediamines are added in simultaneously and are urged
Agent makes the acrylamide of calcium alginate microsphere area load and crosslinking agent that polymerization crosslinking, reaction occur into 50mL conical flasks
For 24 hours, fine and close polyacrylamide shell is formed in microsphere surface.It is washed with distilled water 3-5 times, with 0.45 μm of miillpore filter mistake
Microballoon is collected in filter, is freeze-dried after washing for 24 hours to get hud typed alginate/pam microemulsion of load andrographolide
Ball.
Its appearance structure is observed under an optical microscope, as a result referring to Fig. 3, wherein the grain size of (A) is 450 μm -470 μm,
(B) grain size is 230 μm -240 μm.As can be seen that microsphere features smooth surface, pattern rounding, grain size is relatively uniform, and envelop rate
It is high.Scanning electron microscope (SEM) photograph referring to Fig. 4, wherein, (A) be alginate/polyacrylamide microsphere surface；(B) it is alginate/poly- third
Acrylamide microballoon section；(C) it is calcium alginate microsphere surface；(D) calcium alginate microsphere section；Alginic acid can be gone out to the eye
Salt/polyacrylamide microsphere surface texture is continuous, and hole is less, and calcium alginate microsphere rough surface, and surface is broken
It splits, there is larger hole；Section can be seen that alginate/polyacrylamide microsphere compared with calcium alginate microsphere more structure
More fine and close, in alginate/polyacrylamide microsphere outermost layer, there are apparent shells, it was demonstrated that the alginate of preparation/poly- third
There are nucleocapsids for acrylamide microballoon.
Referring to Fig. 5, be alginate/polyacrylamide microsphere (on), N, N- methylene-bisacrylamides (in) and propylene
Amide (under) infrared spectrogram.2814cm is can be seen that from the infrared spectrogram of acrylamide-1The moderate strength absworption peak at place
=CH is belonged in acrylamide2The stretching vibration of group；1613cm-1Neighbouring strong absworption peak belongs to the flexible of C=C keys and shakes
It is dynamic.It can be seen that from the infrared spectrogram of alginate/polyacrylamide microsphere as=CH2It is changed into-CH2- when, 2814cm-1Locate the position transfer of absworption peak to 2925cm-1Near, 1613cm-1Neighbouring strong absworption peak disappears substantially, this can show
Polymerisation generation polyacrylamide microsphere has occurred in acrylamide, and polyacrylamide bag is born in calcium alginate gel.
Embodiment 3
Andrographolide in calcium alginate microsphere and alginate/polyacrylamide microsphere is measured with ultraviolet specrophotometer
Release：
Alginate/the polyacrylamide microsphere prepared in embodiment 1 and embodiment 2 and calcium alginate microsphere immersion are contained
In the beaker for having 30mL distilled water, fully shaking in 37 DEG C of shaking tables is placed on.After 5min, 3mL aqueous solutions are pipetted from beaker, and
3mL distilled water is supplemented into beaker.10min, 20min, 30min, 45min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h,
The experimental procedure is repeated for 24 hours.The two kinds of microballoons absorbance of andrographolide in distilled water at wavelength 226nm is measured respectively
Value according to absorbance of the andrographolide in distilled water and concentration relationship standard curve and calculates its corresponding concentration, draws
Release profiles of the andrographolide in two kinds of microballoons.As a result referring to Fig. 6, it can be seen that calcium alginate microsphere is in interior release for 24 hours
Speed and burst size are all higher than alginate/polyacrylamide microsphere.
The envelop rate of alginate/polyacrylamide microsphere is measured with ultraviolet specrophotometer and drugloading rate is tested：
Alginate/the polyacrylamide microsphere prepared in embodiment 2 is broken into capsule (being crushed using mechanical means), and is placed
It in 100mL methanol solutions, is sufficiently stirred with magnetic stirring apparatus, is completely dissolved andrographolide.Use ultraviolet specrophotometer
Absorbance is measured at wavelength 236nm, according to the absorbance of andrographolide in methyl alcohol and concentration relationship standard curve,
Calculate corresponding concentration.
Envelop rate=(Determination of Andrographolide in microballoon)/(andrographolide feed intake total amount)=67.2%
By the freeze-drying of the alginate prepared in embodiment 2/polyacrylamide microsphere, and precise its quality.
Drugloading rate=(Determination of Andrographolide in microballoon)/(microballoon gross mass after dry)=25.7% (g/g)
Embodiment 4
Residues detection of the acrylamide in alginate/polyacrylamide microsphere：
On the basis of embodiment 2, be added without drug andrographolide, be prepared the alginate of unsupported drug/
Polyacrylamide microsphere, and place it in distilled water, it is stirred at low speeds with magnetic stirring apparatus for 24 hours so that seaweed
The acrylamide monomer that polymerisation is had neither part nor lot in hydrochlorate/polyacrylamide microsphere is fully diffused in distilled water.
With ultraviolet specrophotometer in the absorption spectrum that wave-length coverage is 200-400nm measure microballoon leachates.By 56mg
Acrylamide is dissolved in 1mL distilled water, measures the absorption light of solution in 200-400nm wave-length coverages with ultraviolet specrophotometer
Spectrum.Fig. 7 results are as it can be seen that acrylamide monomer has a strong absorption at 236nm wavelength, and alginate/polyacrylamide microsphere
Without absworption peak at 236nm wavelength.It can draw, by way of membrane filtration washing, can remove and remain in alginate/poly- third
The Residual acrylamide monomer for having neither part nor lot in reaction in acrylamide microballoon, so as to further illustrate the alginate of preparation/poly- third
Acrylamide microballoon is not present because acrylamide monomer residual causes the neurotoxicity to human body, can prove the microballoon being prepared
There is good biocompatibility.
In conclusion a kind of hud typed sodium alginate/pam microemulsion for loading andrographolide disclosed by the invention
Ball, the microballoon are made of following components：Sodium alginate, polyacrylamide, andrographolide.Andrographolide alginic acid of the present invention
Salt/polyacrylamide microsphere, which can effectively wrap up andrographolide, can simultaneously shelter bitter taste, increase the application range of drug.The present invention
The preparation method of andrographolide alginate/polyacrylamide microsphere is electrostatic field sessile drop method, have microballoon preparation efficiency it is high,
The advantages that preparation condition is mild, Microsphere Size is controllable, drug loading efficiencies are high, microballoon stability is good, can be widely applied to give birth to
Object field of medical applications.Microballoon prepared by the present invention can be used for treatment infantile pneumonia, upper respiratory tract infection, have immune
The functions such as adjusting, antitumor, can be widely applied to the fields such as health products, drug and bio-medical material.
Claims (10)
1. a kind of hud typed alginate/polyacrylamide microsphere for loading andrographolide, which is characterized in that described hud typed
In alginate/polyacrylamide microsphere, core is the microballoon formed by alginate load andrographolide, and shell is polyacrylamide
Amine；
Hud typed alginate/the polyacrylamide microsphere, in terms of mass fraction, including：1~8 part of sodium alginate, polypropylene
1~6 part of amide, 3~9 parts of andrographolide.
2. hud typed alginate/polyacrylamide microsphere of load andrographolide according to claim 1, feature
Be, the weight average molecular weight of the sodium alginate is 200000~800000, and the range of viscosities of 1% aqueous solution for 0.02~
1Pas, the molecular weight of polyacrylamide is 500000~5000000.
3. hud typed alginate/polyacrylamide microsphere of load andrographolide according to claim 1, feature
It is, a diameter of 50~1000 microns of the hud typed alginate/polyacrylamide microsphere.
4. hud typed alginate/pam microemulsion of the load andrographolide in claims 1 to 3 described in any one
Application of the ball in the drug of the treatment infection of the upper respiratory tract or pneumonia is prepared.
5. a kind of preparation method for the hud typed alginate/polyacrylamide microsphere for loading andrographolide, which is characterized in that
It is prepared, comprised the following steps using electrostatic field sessile drop method：
1) sodium alginate is pressed：Andrographolide：Water=(0.5~3) g：(0.01~0.5) g：The amount ratio of 100mL, by alginic acid
Sodium is soluble in water to be made into sodium alginate soln, adds andrographolide, and preparation obtains material liquid；
2) calcium chloride is pressed：Acrylamide monomer：Water=(1~5) g：(0.1~2) g：The amount ratio of 100mL, calcium chloride are dissolved in water
In be made into calcium chloride solution, add acrylamide monomer, be made coagulation bath；
3) impulse electric field anode with loading the syringe metal needle of material liquid is connected, by impulse electric field cathode and is placed in gel
Wire coil connection in bath, is then sprayed material liquid with drops into coagulation bath by syringe metal needle,
In coagulation bath, sodium alginate and calcium ion crosslinking in drop form calcium alginate gel, drop are made to be solidified into gel micro-ball simultaneously
By andrographolide package wherein；During drop is formed by curing gel micro-ball, the acrylamide monomer in coagulation bath
Molecule is supported on the surface of calcium alginate gel bead by physical absorption and molecule diffusion way, using filter, washing, is made
Area load acrylamide monomer and the calcium alginate gel bead for encapsulating andrographolide；
4) to area load acrylamide monomer made from step 3) and encapsulate andrographolide calcium alginate gel bead into
Row polymerization crosslinking react, be washed out, microballoon, drying be collected by filtration, be made load andrographolide hud typed alginate/
Polyacrylamide microsphere.
6. the preparation of hud typed alginate/polyacrylamide microsphere of load andrographolide according to claim 5
Method, which is characterized in that in step 3), use micro-injection pump that material liquid is made to be pumped with the rate of 10mL/h by metal needle
Go out.
7. the preparation of hud typed alginate/polyacrylamide microsphere of load andrographolide according to claim 5
Method, which is characterized in that in step 4), the polymerization crosslinking reaction is by area load acrylamide monomer and encapsulating Herba Andrographitis
After the calcium alginate gel bead of lactone is mixed with the solution containing crosslinking agent, initiator, reaction 1~for 24 hours, in gel micro-ball table
Face forms fine and close polyacrylamide shell；
Wherein, the mass ratio of crosslinking agent, initiator and acrylamide monomer is (50~200)：(1~6)：(100~2000).
8. the preparation of hud typed alginate/polyacrylamide microsphere of load andrographolide according to claim 7
Method, which is characterized in that the crosslinking agent is N, and N- methylene-bisacrylamides, the initiator is potassium peroxydisulfate or persulfuric acid
Ammonium.
9. the preparation of hud typed alginate/polyacrylamide microsphere of load andrographolide according to claim 7
Method, which is characterized in that containing crosslinking agent, initiator solution in be additionally added catalyst, wherein, catalyst be tetramethyl second
Diamines, catalyst charge are the μ L of 50 μ L~400.
10. a kind of preparation method for the hud typed alginate/polyacrylamide microsphere for loading andrographolide, feature exist
In, using gravitational field sessile drop method prepare, comprise the following steps：
1) sodium alginate is pressed：Andrographolide：Water=(0.5~3) g：(0.01~0.5) g：The amount ratio of 100mL, by alginic acid
Sodium is soluble in water to be configured to sodium alginate soln, adds andrographolide, and preparation obtains material liquid；
2) calcium chloride is pressed：Acrylamide monomer：Water=(1~5) g：(0.1~2) g：The amount ratio of 100mL, calcium chloride is dissolved in
Calcium chloride solution is made into water, adds acrylamide monomer, preparation obtains coagulation bath；
3) material liquid is oozed into drop by syringe needle, drop is instilled in coagulation bath under the effect of gravity, the sea in drop
Mosanom and Ca2+Crosslinking forms calcium alginate gel, and drop is solidified into gel micro-ball and wraps up andrographolide wherein,
During drop is formed by curing gel micro-ball, the acrylamide monomer molecule in coagulation bath is expanded by physical absorption and molecule
Scattered mode is supported on the surface of calcium alginate gel bead, and using filter, washing, area load acrylamide monomer and bag is made
Seal the calcium alginate gel bead of andrographolide；
4) to area load acrylamide monomer made from step 3) and encapsulate andrographolide calcium alginate gel bead into
Row polymerization crosslinking react, be washed out, microballoon, drying be collected by filtration, be made load andrographolide hud typed alginate/
Polyacrylamide microsphere.
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| CN102258481A (en) * | 2011-08-19 | 2011-11-30 | 薛巍 | Method for preparing self-assembled medicine-carried microspheres by combining high-voltage electrostatic liquid droplet method and layer-by-layer self-assembly method |
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