CN106540264A - A kind of Graphene/anion polysaccharide complex microsphere carrier and preparation method thereof - Google Patents
A kind of Graphene/anion polysaccharide complex microsphere carrier and preparation method thereof Download PDFInfo
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- CN106540264A CN106540264A CN201610890454.XA CN201610890454A CN106540264A CN 106540264 A CN106540264 A CN 106540264A CN 201610890454 A CN201610890454 A CN 201610890454A CN 106540264 A CN106540264 A CN 106540264A
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- graphene
- complex microsphere
- anion polysaccharide
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- polysaccharide complex
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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
- A61K9/48—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
- A61K9/5115—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene
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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
- A61K9/48—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
- A61K9/5161—Polysaccharides, e.g. alginate, chitosan, cellulose derivatives; Cyclodextrin
Abstract
The present invention discloses a kind of Graphene/anion polysaccharide complex microsphere carrier and preparation method thereof.The present invention originally in anion polysaccharide microsphere internal build Graphene supporting structure, realizes the finely regulating of particle diameter to product microsphere and composite construction with high-pressure injection condition by regulating and controlling rate of charge；Process conditions are simple and convenient, cost of material is low.The method of the present invention：Avoid using the surfactant and chemical cross-linking agent that there are toxicity and difficulty or ease to remove；Using high-valence cationic cross-linking agent, the physical action of graphene molecules and polysaccharide interchain, one-step solidification shaping is coordinated to obtain stable spherical structure.The structural stability of microsphere can be significantly increased so as to more tolerant to Human Physiology salt environment；Carrier can be prepared and drug loading is separated, realize rear bearing medicine in a mild condition, protect medicines structure complete with function to greatest extent；Drug loading is remarkably improved, and realizes slow release.Therefore the present invention has extensive application value.
Description
Technical field
The invention belongs to control/slow releasing pharmaceutical microcarrier field, and in particular to a kind of Graphene/anion polysaccharide is combined micro-
Balloon borne body and preparation method thereof.
Background technology
(1) the microsphere supported technology of preparing of anion poly carbohydrates and their derivative
Anion polysaccharide (carboxymethyl chitosan, sodium alginate, heparin, hyaluronic acid etc.) is with good bio-compatible
Property, biodegradability, are the outstanding medicinal carrier materials of a class.Its method for preparing microsphere mainly includes emulsion method, spray dried
Dry method etc..In order to avoid emulsifying agent, the poison of cross-linking agent residual, negatively influencing, first-selected gentle efficiently dispersion pelletize and physical crosslinking
Method.For different applied environments, it is technological difficulties to match polysaccharide vector degradation with drug release.
(2) blending technology of Graphene and its derivant and polysaccharide
Graphene is a kind of two-dimension nano materials with monoatomic thickness, as which possesses excellent physical chemistry
Can, initially it is widely used in chemical industry, energy field.In recent years, Jing researchs have shown that the Graphene and its derivant of purification have
Low cell, tissue toxicity, and its active surface energy efficient absorption protein, polypeptide, DNA (deoxyribonucleic acid) etc..By Graphene
And its derivant is blended with anion polysaccharide, Jing chemistry, physical crosslinking reaction can obtain composite aquogel, or Jing emulsifyings, original
The various sizes of microsphere that position cross-linking method can be prepared.And under conditions of surfactant is not used, prepare particle size dispersion equal
The technology of the controllable Graphene of even, size/anion polysaccharide microsphere has no report.
The content of the invention
It is an object of the invention to overcome the shortcoming and deficiency of prior art, there is provided a kind of Graphene/anion polysaccharide
The preparation method of complex microsphere carrier.The present invention is for single polyanion polysaccharide microsphere carrier drug loading is low, control release
Difficulty, and when being applied to human physiological environment, it is understood that there may be the rapid disintegrate of carrier structure, medicine quick release, cause biology
The shortcomings of utilization rate is low, side effect is obvious, there is provided a kind of size is controllable, Stability Analysis of Structures, is resistant to human electrolyte's ring
Border, is provided simultaneously with high drug load, and realizes the preparation side of the Graphene/anion polysaccharide complex microsphere carrier of slow release
Method.
Another object of the present invention is to provide the Graphene/anion polysaccharide prepared by above-mentioned preparation method
Complex microsphere carrier.The present invention has that process conditions are simple and convenient, the low advantage of cost of material, the Graphene/anion of preparation
Polysaccharide complex microsphere carrier, possesses broad-spectrum high efficacy and carries the property of medicine, and rate of release controllability, can be obviously improved the biology of medicine
Utilization rate；Reduction is released due to dashing forward, the poison that frequent drug administration is brought, negative interaction；While therapeutic effect is guaranteed, mitigate the Jing of sufferer
Ji pressure.
The purpose of the present invention is achieved through the following technical solutions：
A kind of preparation method of Graphene/anion polysaccharide complex microsphere carrier, comprises the following steps：
(1) modified graphene and the homogeneous mixed liquor of anion polysaccharide are configured；
(2) coordinate micro-injection pump, the controllable microlayer model of grain size is ejected off field in high-pressure electrostatic；
(3) using the solidification of high-valence cationic solution crosslinking, Jing centrifugations, purification cleaning, dry, collection product, as graphite
Alkene/anion polysaccharide complex microsphere.
Preferably, described anion polysaccharide is carboxymethyl chitosan, sodium alginate, heparin or hyaluronic acid；
Preferably, described modified graphene is graphene oxide.
Concentration of the described modified graphene in mixed liquor is 2～20mg/mL；More preferably 5mg/mL；
Described modified graphene is 1 with the mass ratio of anion polysaccharide：(5～20)；More preferably 1：(8～10).
Preferably, the sample introduction speed of described micro-injection pump is 2～10mL/h；More preferably 3mL/h；
Preferably, described high-valence cationic solution is calcium chloride water.
Preferably, described injection apparatus are the plastic injector for being furnished with metal needle.
Preferably, described electrostatic field is produced by high tension generator.
The voltage of described electrostatic field is 5～25kV；More preferably 10kV.
Preferably, described centrifugal condition is different according to microsphere preparation condition, more than can isolate the minimum of product microsphere
Rotating speed；
The condition of described purification is cleaned for deionized water；
The condition of the drying is lyophilization.
As a example by preparing graphene oxide/carboxymethyl modified chitosan microball：(25 DEG C), will aoxidize stone at ambient temperature
Black alkene (GO), during carboxymethyl chitosan (CMCS) adds deionized water, ultrasound blending is uniform, and feed intake CMCS：50mg/mL, GO：
5mg/mL；Under the driving of micro-injection pump (3mL/h), mixed solution Jing metallic nozzles (Φ=250 μm) is into electrostatic field (electricity
Field voltage 10kV, pole plate is apart from 20cm), it is dispersed into droplet；There is physical crosslinking, solidified forming in calcium chloride solution.Jing
Be collected by centrifugation, purification, particle diameter can be obtained better than 200 μm of microsphere.Product microspherulite diameter size and distribution, by CMCS and GO rate of charges
Regulate and control with proportioning, sample introduction speed and its electrostatic field force.
As a kind of preferred version, in above-mentioned preparation method, the electrostatic field is produced by high tension generator.
As a kind of preferred version, in above-mentioned preparation method, the injection apparatus are the plastic injection for being furnished with metal needle
Device.
As a kind of preferred version, in above-mentioned preparation method, the sample introduction speed is by micro-injection pump control.
A kind of Graphene/anion polysaccharide complex microsphere carrier, is prepared by above-mentioned preparation method.Resulting
The particle diameter of complex microsphere is better than 200 μm.
Application of the described Graphene/anion polysaccharide complex microsphere carrier in medicine is carried.
Described Graphene/various the macromolecular drugs of anion polysaccharide microsphere energy efficient absorption is (protein, polypeptide, anti-
Raw element)；And in simulated body fluid environment, maintain Stability Analysis of Structures, drug release rate slowly controllable.
The present invention is had the following advantages and effect relative to prior art：
The present invention originally in anion polysaccharide microsphere internal build Graphene supporting structure, by regulating and controlling rate of charge
The finely regulating of the particle diameter to product microsphere and composite construction is realized with high-pressure injection condition.With existing emulsifying, chemical crosslinking side
Graphene/polysaccharide complex microsphere prepared by method is compared, and accompanying method (1) of the present invention avoids using with toxicity and difficulty or ease are clear
The surfactant for removing and chemical cross-linking agent；(2) using high-valence cationic cross-linking agent, graphene molecules and polysaccharide interchain are coordinated
Physical action, one-step solidification shaping obtains stable spherical structure.With the pure anion polysaccharide microsphere carrier phase of ionomer
Than accompanying method (1) of the present invention can significantly increase the structural stability of microsphere so as to more tolerant to Human Physiology salt environment；(2) may be used
Separated with drug loading with prepared by carrier, realize rear bearing medicine in a mild condition, protect medicines structure to greatest extent
It is complete with function；(3) drug loading is remarkably improved, and realizes slow release.Therefore the present invention has extensive popularization and application
Value.
Description of the drawings
Fig. 1 is the morphology characterization of graphene oxide/carboxymethyl chitosan (GO/CMCS) complex microsphere；Wherein, (A) physiology
Saline soak GO/CMCS outside drawings；(B) normal saline immersion GO/CMCS optical microscopes；(C, D) lyophilization GO/CMCS
Scanning electron microscope diagram.
Specific embodiment
With reference to embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are not limited
In this.
Embodiment 1
At ambient temperature (25 DEG C), by graphene oxide (GO), during carboxymethyl chitosan (CMCS) adds deionized water,
Ultrasound blending is uniform, and feed intake CMCS：50mg/mL, GO：5mg/mL；Under the driving of micro-injection pump (3mL/h), CMCS/GO is mixed
Solution Jing metallic nozzles (Φ=250 μm) is closed into electrostatic field (voltage of electric field 10kV, pole plate is apart from 20cm), little liquid is dispersed into
Drop；There is physical crosslinking, solidified forming in calcium chloride solution.Jing is collected by centrifugation, purification, can obtain particle diameter micro- better than 200 μm
Ball.As graphene oxide/carboxymethyl chitosan complex microsphere.Product microspherulite diameter size and distribution, are fed intake with GO by CMCS
Than regulating and controlling with proportioning, sample introduction speed and its electrostatic field force.As a result it is as shown in Figure 1.
Fig. 1 is graphene oxide/carboxymethyl chitosan (GO/CMCS) complex microsphere morphology characterization：(A) normal saline immersion
GO/CMCS outside drawings；(B) normal saline immersion GO/CMCS optical microscopes；(C, D) lyophilization GO/CMCS scanning electrons
Microscope figure.
As shown in Figure 1, even particle size distribution, size can successfully be prepared using said method black better than 200 μm
Color microsphere；Its micro-sphere structure can be stable in the presence of in normal saline；Microsphere top layer after Microstructure characterization result lyophilization
Densification, loose and porous inner surface.
Carry in medicine and extracorporeal releasing experiment, product microsphere energy active adsorption model drug --- Gatifloxacin (GFLX) is carried
Dose is up to 0.45mg/mg, and the pure Crosslinked Carboxymethyl Chitosan Resin of the same particle size size than preparing under similar conditions has
Nearly 350% lifting；The complex carrier can maintain good structural stability in simulated body fluid environment simultaneously, hence it is evident that better than 1
Quickly disintegrated pure Crosslinked Carboxymethyl Chitosan Resin in hour, in 24 hours, the complex microsphere can be discharged more with slower speed
Many medicines.
Embodiment 2
At ambient temperature (25 DEG C), by graphene oxide (GO), during sodium alginate (ALG) adds deionized water, ultrasound
Blending is uniform, and feed intake ALG：40mg/mL, GO：5mg/mL；Under the driving of micro-injection pump (3mL/h), ALG/GO mixed solutions
Jing metallic nozzles (Φ=250 μm) are dispersed into droplet into electrostatic field (voltage of electric field 10kV, pole plate is apart from 20cm)；In chlorine
There is physical crosslinking, solidified forming in changing calcium solution.Jing is collected by centrifugation, purification, can obtain microsphere of the particle diameter better than 200 μm.As
Graphene oxide/sodium alginate composite microsphere.Product microspherulite diameter size and distribution, by ALG and GO rate of charges and proportioning, sample introduction
Speed and its electrostatic field force regulation and control.
Carry in medicine and extracorporeal releasing experiment, product microsphere energy active adsorption model drug --- Gatifloxacin (GFLX) is carried
Dose is up to 0.28mg/mg, and the pure sodium alginate microsphere of the same particle size size than preparing under similar conditions has closely
235% lifting；The complex carrier can maintain good structural stability in simulated body fluid environment simultaneously, hence it is evident that better than 1.5
Quickly disintegrated pure sodium alginate microsphere in hour, in 24 hours, the complex microsphere can be discharged more with slower speed
Medicine.
Above-described embodiment is the present invention preferably embodiment, but embodiments of the present invention not by above-described embodiment
Limit, other any spirit without departing from the present invention and the change, modification, replacement made under principle, combine, simplification,
Equivalent substitute mode is should be, is included within protection scope of the present invention.
Claims (10)
1. the preparation method of a kind of Graphene/anion polysaccharide complex microsphere carrier, it is characterised in that comprise the following steps：
(1) modified graphene and the homogeneous mixed liquor of anion polysaccharide are configured；
(2) coordinate micro-injection pump, the controllable microlayer model of grain size is ejected off field in high-pressure electrostatic；
(3) using the solidification of high-valence cationic solution crosslinking, Jing centrifugations, purification cleaning, dry, collection product, as Graphene/the moon
Ion polysaccharide complex microsphere.
2. the preparation method of Graphene according to claim 1/anion polysaccharide complex microsphere carrier, its feature exist
In：
Described anion polysaccharide is carboxymethyl chitosan, sodium alginate, heparin or hyaluronic acid.
3. the preparation method of Graphene according to claim 1/anion polysaccharide complex microsphere carrier, its feature exist
In：Described modified graphene is graphene oxide.
4. the preparation method of the Graphene according to any one of claims 1 to 3/anion polysaccharide complex microsphere carrier,
It is characterized in that：Concentration of the described modified graphene in mixed liquor is 2～20mg/mL.
5. the preparation method of the Graphene according to any one of claims 1 to 3/anion polysaccharide complex microsphere carrier,
It is characterized in that：
Described modified graphene is 1 with the mass ratio of anion polysaccharide：(5～20).
6. the preparation method of the Graphene according to any one of claims 1 to 3/anion polysaccharide complex microsphere carrier,
It is characterized in that：The sample introduction speed of described micro-injection pump is 2～10mL/h.
7. the preparation method of the Graphene according to any one of claims 1 to 3/anion polysaccharide complex microsphere carrier,
It is characterized in that：Described high-valence cationic solution is calcium chloride water；
The voltage of described electrostatic field is 5～25kV.
8. a kind of Graphene/anion polysaccharide complex microsphere carrier, it is characterised in that by any one of claim 1～7 institute
The preparation method stated is prepared.
9. application of the Graphene described in the claim 8/anion polysaccharide complex microsphere carrier in medicine is carried.
10. application according to claim 9, it is characterised in that：Described medicine is protein, polypeptide, antibiotic.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107115269A (en) * | 2017-04-19 | 2017-09-01 | 常州大学 | A kind of alginic acid/calcium ion/graphene oxide plural gel is applied to pH and electric regulating medicine release |
| CN109646713A (en) * | 2018-12-07 | 2019-04-19 | 四川大学 | A kind of compound microcarrier of alginates/nano clay and preparation method and device |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105344329A (en) * | 2015-11-30 | 2016-02-24 | 武汉科技大学 | Graphene oxide and chitosan microsphere and preparation method thereof |
| CN105498724A (en) * | 2015-12-03 | 2016-04-20 | 陕西科技大学 | Oxidized graphene/carboxymethyl chitosan magnetic microsphere adsorbent for adsorbing methyl orange dye and preparation method of adsorbent |
-
2016
- 2016-10-12 CN CN201610890454.XA patent/CN106540264A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105344329A (en) * | 2015-11-30 | 2016-02-24 | 武汉科技大学 | Graphene oxide and chitosan microsphere and preparation method thereof |
| CN105498724A (en) * | 2015-12-03 | 2016-04-20 | 陕西科技大学 | Oxidized graphene/carboxymethyl chitosan magnetic microsphere adsorbent for adsorbing methyl orange dye and preparation method of adsorbent |
Non-Patent Citations (2)
| Title |
|---|
| YUNFENG SHI等: "Novel carboxymethyl chitosan-graphene oxide hybrid particles for drug delivery", 《J MATER SCI: MATER MED》 * |
| 陆雪飞: "聚合物微球新颖载体结构的构建及其对加替沙星缓释性能研究", 《中国优秀硕士学位论文全文数据库.工程科技I辑》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107115269A (en) * | 2017-04-19 | 2017-09-01 | 常州大学 | A kind of alginic acid/calcium ion/graphene oxide plural gel is applied to pH and electric regulating medicine release |
| CN107115269B (en) * | 2017-04-19 | 2020-08-14 | 常州大学 | Alginic acid/calcium ion/graphene oxide composite gel applied to pH and electric regulation of drug release |
| CN109646713A (en) * | 2018-12-07 | 2019-04-19 | 四川大学 | A kind of compound microcarrier of alginates/nano clay and preparation method and device |
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