CN106176620A - A kind of Graphene medicament slow-release microsphere and preparation method thereof - Google Patents
A kind of Graphene medicament slow-release microsphere and preparation method thereof Download PDFInfo
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- CN106176620A CN106176620A CN201610638299.2A CN201610638299A CN106176620A CN 106176620 A CN106176620 A CN 106176620A CN 201610638299 A CN201610638299 A CN 201610638299A CN 106176620 A CN106176620 A CN 106176620A
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1611—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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
Abstract
The present invention relates to a kind of Graphene medicament slow-release microsphere and preparation method thereof, sustained-release micro-spheres is medicine and the complex microsphere of graphene oxide GO.Preparation: graphene oxide, medicine are dissolved in PBS solution, ultrasonic, lucifuge stirring under room temperature, centrifugal, lyophilization, obtain graphene oxide medicine carrying complex；By soluble in water for graphene oxide medicine carrying complex, ultrasonic atomizatio, then by tube furnace, and collect with polytetrafluoroethylene PTFE filter membrane, be dried, to obtain final product.The medicament slow-release microsphere that the present invention prepares has the feature of pH responsive type release, may be used for antitumor research, has good practical value.
Description
Technical field
The invention belongs to slow-release material and preparation field thereof, particularly to a kind of Graphene medicament slow-release microsphere and preparation thereof
Method.
Background technology
Doxorubicin hydrochloride (Doxorubicin, DOX) is a kind of antitumor antibiotics, is a kind of suppression DNA and RNA synthesis
Anthracene ring antitumor medicinal, its mechanism of action is mainly Ah mould's molecule intercalation of DNA and suppresses the synthesis of nucleic acid.Amycin is to many
Plant tumor and all have effect, belong to cell cycle nonspecific agent (CCNSA), the tumor cell of various growth cycles is had killing action, to entity
The effective percentage of tumor about reaches 70%, is primarily adapted for use in acute leukemia, acute lymphoblastic leukemia, granulocyte leukemia, mammary gland
Cancer, pulmonary carcinoma, ovarian cancer, soft tissue sarcoma, osteogenic sarcoma, rhabdomyosarcoma, nephroblastoma, neuroblastoma, gastric cancer, liver
Cancer etc..But the toxic and side effects of doxorubicin hydrochloride is big, can kill substantial amounts of normal cell, there is also Amplatzer duct occluder in administration process
Property and bone marrow depression toxicity, clinical signs is leukopenia and myocardial necrosis, and this just greatly limit doxorubicin hydrochloride
Clinical practice.
The structure of graphene oxide (Graphene Oxide) contains substantial amounts of carboxyl, hydroxyl and epoxide group etc. hydrophilic
Group so that it is possess excellent bioaffinity, hydrophilic and be prone to the characteristics such as chemical modification.Utilize oxygen-content active base in GO
Group's chemical reactivity, can have specified chemical and biological property functional molecular to carry out covalent reaction with multiple.Research shows, oxidation
Combination between Graphene and doxorubicin hydrochloride is non-covalent pi-pi accumulation, this be one be the dependent combination of pH, in acidity
Under the conditions of, medicine, because proton abstraction is left away from surface of graphene oxide, reaches the release of pH sensitivity.But graphene oxide carries
The volume of doxorubicin hydrochloride complex is big, easily reunites so that it is be not easily accessible cell interior, and graphene oxide is lamella knot
Structure, its sharp edge can puncture cell, has certain side effect to normal cell.
Summary of the invention
The technical problem to be solved is to provide a kind of Graphene medicament slow-release microsphere and preparation method thereof, this
Bright simple to operate, the drug loading efficiency of Graphene medicament slow-release microsphere is high, and has the characteristic of pH responsive type release.
A kind of Graphene medicament slow-release microsphere of the present invention, described sustained-release micro-spheres is the compound of medicine and graphene oxide GO
Microsphere；
Wherein graphene oxide GO, the mass ratio of medicine are 1:0.5-1:5.
Described medicine is doxorubicin hydrochloride DOX.
A kind of preparation method of the Graphene medicament slow-release microsphere of the present invention, including:
(1) graphene oxide, medicine are dissolved in PBS solution, ultrasonic, lucifuge stirring under room temperature, it is centrifuged and (is repeatedly centrifuged and goes
Doxorubicin hydrochloride except unsupported), then centrifugal sediment is carried out lyophilization, obtain graphene oxide medicine carrying complex；
(2) by soluble in water for graphene oxide medicine carrying complex, ultrasonic atomizatio, then by tube furnace, and use polytetrafluoro
Ethylene PTFE filter membrane is collected, and is dried, obtains Graphene medicament slow-release microsphere.
In step (1), the pH of the PBS solution that graphene oxide, medicine are dissolved in is 7.0-7.4.
In described step (1), ultrasonic time is 0.5-1.5h, and lucifuge mixing time is 12-16h.
In described step (1), centrifugal rotational speed is 12000-14000rpm, and centrifugation time is 10-30min；Lyophilization is :-
45 DEG C～-42 DEG C, lyophilization 2-3 days.
In described step (2), graphene oxide medicine carrying complex concentration soluble in water is 0.5-3mg/mL.
In described step (2), ultrasonic atomizatio is that ultrasound atomizer is atomized, and in ultrasonic atomization process, ultrasonic frequency is
1.0MHz～2.0MHz.
In described step (2), the temperature of tube furnace is 180 DEG C～280 DEG C；The aperture of PTFE filter membrane is 0.20 μm～0.45 μ
m。
Being dried in described step (2) as room temperature lower drying time is 8-15h.
Graphene medicine carrying complex in step (1) and the Graphene medicament slow-release microsphere in step (2) are buffered at PBS
Liquid and HAc buffer carry out drug release, the extinction of the solution then taken out with ultraviolet-visible spectrophotometer test 0-72h
Degree, and calculate drug release rate according to absorbance.
The pH value of described PBS be the pH value of 7.0-7.4, HAc buffer be 5.2-6.0.
Beneficial effect
(1) present invention utilizes ultrasonic atomizatio method to be prepared for a kind of novel Graphene medicament slow-release microsphere, overcomes lamella
The shortcoming of Graphene medicine carrying complex, good dispersion, simple to operate, it is easy to industry is amplified；
(2) drug loading of the Graphene medicament slow-release microsphere containing amycin of the present invention is high, has slow-release function, point
Dissipating functional, and have the characteristic of pH sensitivity release, under lower ph environment, release rate is high, meets the micro-loop of tumor tissues
Border, it does the potentiality that follow-up related experiment is analyzed to have application.
Accompanying drawing explanation
Fig. 1 is the carrying drug ratio curve of the Graphene medicine carrying complex of embodiment 1 gained；
Fig. 2 is the Graphene medicament slow-release microsphere containing amycin, graphene oxide and pure hydrochloric acid Ah mould of embodiment 2 gained
The infrared spectrum of element；
Fig. 3 is in embodiment 3, Graphene medicine carrying complex and Graphene medicament slow-release microsphere releasing under different pH environment
Put curve.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is expanded on further.Should be understood that these embodiments are merely to illustrate the present invention
Rather than restriction the scope of the present invention.In addition, it is to be understood that after having read the content that the present invention lectures, people in the art
The present invention can be made various changes or modifications by member, and these equivalent form of values fall within the application appended claims equally and limited
Scope.
Embodiment 1
The preparation of Graphene medicine carrying complex.
Weigh graphene oxide and the 20mg doxorubicin hydrochloride of 10mg, be dissolved in 20mlPBS buffer solution, ultrasonic
0.5h, under room temperature, lucifuge stirring 12h, the doxorubicin hydrochloride that repeatedly centrifugal segregation is unsupported, then that centrifugal sediment is freezing
It is dried, obtains Graphene medicine carrying complex, be saved in 4 DEG C of refrigerators stand-by.
Embodiment 2
The preparation of Graphene medicament slow-release microsphere.
In Graphene medicine carrying complex, add ultra-pure water, be configured to the Graphene medicine carrying complex that concentration is 1mg/mL molten
Liquid, is placed in solution and connects in the ultrasound atomizer having tube furnace, and ultrasonic frequency is 1.5MHz.It is made to be atomized into aerosol liquid
Drip, at N2Slow transitting through the tube furnace being heated to 280 DEG C with sucking filtration vacuum pump under driving, end PTFE filter membrane is collected.Room temperature
Under be dried 8h, obtain Graphene medicament slow-release microsphere, its infrared spectrum is as shown in Figure 2.
Embodiment 3
Drug release experiment.
(1) weigh 2mg Graphene medicine carrying complex (embodiment 1) to be dissolved in 2mLPBS and rush in liquid (pH=7.2), the most molten
Solve, put in two bag filters (MW=1000), and be placed in digestion instrument, add the PBS solution (pH=7.2) of 20ml respectively
And HAc solution (pH=5.8).Digestion instrument temperature is set to 37 degree, rotating speed 100 revs/min, respectively at 2h, 4h, 6h, 8h, 10h, 24h,
36h, 72h take out 1mL dialysis solution, and cover 1mL corresponding PBS buffer solution and HAc buffer solution.The dialysis solution collected is existed
Absorbing wavelength is set under 481nm carry out ultraviolet detection, tests its absorbance, records corresponding absorbance data and calculates drug release
Rate.Drug release rate formula:
In formula: DRnDrug release rate
The concentration of Cn n-th sampling sample
M gross mass
(2) weigh 2mg Graphene medicament slow-release microsphere (embodiment 2) to be dissolved in 2mLPBS and rush in liquid (pH=7.2), fully
Dissolve, put in two bag filters (MW=1000), and be placed in digestion instrument, add the PBS solution (pH=of 20ml respectively
7.2) and HAc solution (pH=5.8).Digestion instrument temperature is set to 37 degree, rotating speed 100 revs/min, respectively at 2h, 4h, 6h, 8h, 10h,
24h, 36h, 72h take out 1mL dialysis solution, and cover 1mL corresponding PBS buffer solution and HAc buffer solution.To the dialysis collected
Liquid carries out ultraviolet detection under absorbing wavelength is set to 481nm, tests its absorbance, records corresponding absorbance data and calculates medicine
Release rate.
The DOX of two kinds of materials load release profiles under two kinds of pH environment is as it is shown on figure 3, Graphene as seen from the figure
DOX in medicine carrying complex and Graphene medicament slow-release microsphere about release rate in the HAc sustained-release liquid of pH=5.8 is significantly larger than it
Release rate in the PBS environment of pH=7.2, and Graphene medicament slow-release microsphere has more preferable slow release effect.
Claims (10)
1. a Graphene medicament slow-release microsphere, it is characterised in that: described sustained-release micro-spheres is answering of medicine and graphene oxide GO
Close microsphere；Wherein graphene oxide GO, the mass ratio of medicine are 1:0.5-1:5.
A kind of Graphene medicament slow-release microsphere the most according to claim 1, it is characterised in that: described medicine is hydrochloric acid Ah mould
Element DOX.
3. a preparation method for the Graphene medicament slow-release microsphere as described in claim 1-2 is arbitrary, including:
(1) graphene oxide, medicine are dissolved in PBS solution, ultrasonic, lucifuge stirring under room temperature, centrifugal, lyophilization, obtain
Graphene oxide medicine carrying complex；
(2) by soluble in water for graphene oxide medicine carrying complex, ultrasonic atomizatio, then by tube furnace, and use politef
PTFE filter membrane is collected, and is dried, obtains Graphene medicament slow-release microsphere.
The preparation method of a kind of Graphene medicament slow-release microsphere the most according to claim 3, it is characterised in that: step (1)
The pH of the PBS solution that middle graphene oxide, medicine are dissolved in is 7.0-7.4.
The preparation method of a kind of Graphene medicament slow-release microsphere the most according to claim 3, it is characterised in that: described step
(1) in, ultrasonic time is 0.5-1.5h, and lucifuge mixing time is 12-16h.
The preparation method of a kind of Graphene medicament slow-release microsphere the most according to claim 3, it is characterised in that: described step
(1) in, centrifugal rotational speed is 12000-14000rpm, and centrifugation time is 10-30min；Lyophilization is :-45 DEG C～-42 DEG C, freezing
It is dried 2-3 days.
The preparation method of a kind of Graphene medicament slow-release microsphere the most according to claim 3, it is characterised in that: described step
(2) in, ultrasonic atomizatio is that ultrasound atomizer is atomized, and in ultrasonic atomization process, ultrasonic frequency is 1.0MHz～2.0MHz.
The preparation method of a kind of Graphene medicament slow-release microsphere the most according to claim 3, it is characterised in that: described step
(2) in, the temperature of tube furnace is 180 DEG C～280 DEG C；The aperture of PTFE filter membrane is 0.20 μm～0.45 μm.
The preparation method of a kind of Graphene medicament slow-release microsphere the most according to claim 3, it is characterised in that: by step
(1) the Graphene medicine carrying complex in and the Graphene medicament slow-release microsphere in step (2) are at PBS and HAc buffer
Carry out drug release, then with the absorbance of the solution of ultraviolet-visible spectrophotometer test 0-72h taking-up, and according to extinction
Degree calculates drug release rate.
The preparation method of a kind of Graphene medicament slow-release microsphere the most according to claim 9, it is characterised in that: described PBS
The pH value of buffer be the pH value of 7.0-7.4, HAc buffer be 5.2-6.0.
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| CN106924188A (en) * | 2017-03-29 | 2017-07-07 | 东华大学 | A kind of preparation method of the Graphene drug bearing microsphere with pH sensitiveness and sustained release performance |
| CN107007836A (en) * | 2017-06-02 | 2017-08-04 | 苏州佰锐生物科技有限公司 | A kind of application of gauffer graphene microballoon in photo-thermal therapy |
| CN107080844A (en) * | 2017-04-12 | 2017-08-22 | 东华大学 | One kind carries medicine gauffer graphite nodule photo-thermal preparation and its preparation and application |
| CN112957537A (en) * | 2021-02-07 | 2021-06-15 | 西南交通大学 | Preparation method of drug-loaded sustained-release stent, product and application thereof |
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Cited By (4)
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| CN112957537A (en) * | 2021-02-07 | 2021-06-15 | 西南交通大学 | Preparation method of drug-loaded sustained-release stent, product and application thereof |
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