CN104940146A - Compound polyurethane medicine carrying microsphere as well as preparation method and application thereof - Google Patents
Compound polyurethane medicine carrying microsphere as well as preparation method and application thereof Download PDFInfo
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- CN104940146A CN104940146A CN201510319858.9A CN201510319858A CN104940146A CN 104940146 A CN104940146 A CN 104940146A CN 201510319858 A CN201510319858 A CN 201510319858A CN 104940146 A CN104940146 A CN 104940146A
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Abstract
The invention belongs to the technical field of composites and medicines, and particularly relates to a compound polyurethane medicine carrying microsphere as well as a preparation method and application thereof. The preparation method adopts antibiotic medicines as capsule-core materials, adopts castor oil, nano-hydroxyapatite, diisocyanate and polylactic acid as raw materials, and adopts an in-situ polymerization-emulsion polymerization method so as to prepare the compound polyurethane medicine carrying microsphere. According to the prepared compound polyurethane medicine carrying microsphere, the mole content of nano-hydroxyapatite is 1-5%, the mole content of polylactic acid is 0-1%, the average particle diameter of the microsphere is 0.8-1.2 mm, the medicine entrapment rate reaches 80% or higher, the medicine carrying amount reaches 6% or higher, the medicine slow release half-life period is 12-24 h, and the medicine slow release behavior conforms to the Higuchi dynamics. The compound polyurethane medicine carrying microsphere has practical application values on the fields of environmental protection, and medicine and health, particularly on application to a veterinary medicine slow release system.
Description
Technical field
The invention belongs to composite and medical art, be specifically related to a kind of polyurethane composite drug carried microsphere and preparation method thereof and application.
Background technology
Along with the development of biotechnology, degradable biological material oneself become the focus of research and development.Polyurethane has good biocompatibility and excellent physical and mechanical properties, has good physiological acceptability to human body, and polyaminoester microball can be applied to multi-field huge prospect as excellent sustained-release and controlled release material with having.
Polylactic acid is synthesis and degradation polymer drug carrier material, advantages such as there is avirulence, biodegradation can be controlled, biocompatibility is better, application in medicament slow release is one of biomedical sector of extremely paying close attention to of current people, especially its microball preparation, can Different Organs and tissue in targeting body, make medicine target controlling and releasing effectively; Patent documentation CN104083340A discloses a kind of preparation method embedding the polylactic acid medicine carrying microballoons of tretinoin, by o/w emulsification-evaporation method, obtains uniform particle sizes and the polylactic acid medicine carrying microgranule high to tretinoin envelop rate.But polylactic acid also has intensity not enough, and the material after degraded is unfavorable for bone cell growth, does not have the shortcomings such as bone conductibility.
Hydroxyapatite is as the nano meter biomaterial in a kind of modern times, it is the main inorganic composition of animal and human's body skeleton and tooth, there is good biocompatibility, therefore be commonly used for bone renovating material and pharmaceutical carrier, but the shortcoming such as have that fragility is large, mechanical performance and poor processability, degradation speed are slow, limits its application clinically.
Therefore, how effectively by the advantages of multiple material together, to reach prepared compound polyurethane material microsphere, there is the application of excellent real value, becoming research emphasis in recent years as having good biological degradability and the compatibility.
By polyurethane and nanometer hydroxyapatite compound, to a certain degree strengthening the mechanical property of nanometer hydroxyapatite, also strengthening the biocompatibility of polyurethane, bi-material compound had both played the superiority of bi-material, overcame again the deficiency of often kind of single material.The mechanical property of composite is made moderate progress, and degradation speed more meets the service time maintaining active drug concentration in body, and biocompatibility increases, and the medical domain of medicinal slow release agent has the prospect developing into practical application.Patent documentation CN103755919A discloses a kind of preparation method of organic silicon modified polyurethane microsphere, in hydroxy silicon oil, the reactivity of hydroxyl is moderate, building-up process reacting balance, be easy to control, can react under the condition of not adding solvent, decrease the pollution of environment, meet the trend to ep-type material developmental research, this reference also for utilizing the reactivity of hydroxyl in nanometer hydroxyapatite and polyurethane compound to provide actual.
Hydroxyapatite/polylactic acid/compound polyurethane material also compensate for the deficiency that three class materials are applied separately, possessed good biological degradability, biocompatibility and mechanical performance simultaneously, and it is easy as the synthesis of the composite of matrix using polyurethane, price is cheaper, can apply to medical field better.Patent documentation CN103319696A discloses a kind of hydroxyapatite/biodegradable polyester composite material and preparation method thereof, the composite material surface enrichment that this invention provides has bioactive hydroxyapatite layer, possesses excellent biocompatibility and biological activity; But this method needs under the condition of anhydrous and oxygen-free and argon shield, use stannous octoate as catalyst, complicated condition, cost is high, is unfavorable for large-scale application in practice.
Summary of the invention
In order to overcome the deficiencies in the prior art and shortcoming, primary and foremost purpose of the present invention is to provide a kind of polyurethane composite drug carried microsphere.
Another object of the present invention is to the preparation method that above-mentioned polyurethane composite drug carried microsphere is provided.
Another object of the present invention be to provide above-mentioned polyurethane composite drug carried microsphere application.
Object of the present invention is achieved by the following technical programs:
A preparation method for polyurethane composite drug carried microsphere, comprises following steps:
(1) under the condition of reaction temperature 80 DEG C ~ 90 DEG C, pre-polymerization in early stage is carried out in the mixing of Oleum Ricini, nanometer hydroxyapatite, vulcabond and organic solvent, obtain composite prepolymer in early stage;
(2) under the condition of reaction temperature 80 DEG C ~ 90 DEG C, add polylactic acid and polyhydric alcohol in the early stage that step (1) prepares in composite prepolymer, reaction 30 ~ 40min, obtains composite prepolymer; Molal quantity total moles 0 ~ 1% shared by Oleum Ricini and vulcabond of described polylactic acid;
(3) under nitrogen atmosphere, reaction temperature are the condition of 50 DEG C ~ 60 DEG C, prepolymer, firming agent and the drug solution mixing that step (2) is prepared, be cured reaction 2h ~ 3h, obtain composite aqueous emulsion, then dewater, drying, obtains polyurethane composite drug carried microsphere;
The mol ratio that Oleum Ricini described in step (1) and vulcabond add is-NCO:-OH=(1:1) ~ (4:1) preferably;
The molal quantity of the nanometer hydroxyapatite described in step (1) shared by Oleum Ricini and vulcabond total moles 1% ~ 5%;
Vulcabond described in step (1) is preferably toluene di-isocyanate(TDI), diphenyl methane-4, one in 4 '-vulcabond, 1,5-naphthalene diisocyanate, isoflurane chalcone diisocyanate, XDI, hexamethylene diisocyanate, PPDI, lysinediisocyanate and dicyclohexyl methyl hydride diisocyanate;
Organic solvent described in step (1) is preferably acetone;
Prepolymerization reaction condition in early stage described in step (1) is: reaction 2h ~ 4h;
Described in step (1) early stage prepolymerization reaction condition be preferably: under stirring, reaction 2h ~ 4h;
The rotating speed of described stirring is preferably 400 ~ 600r/min;
Polyhydric alcohol described in step (2) is preferably the one in BDO, ethylene glycol, propylene glycol, hexanediol and diglycol;
The molal quantity of the polyhydric alcohol described in step (2) is 10% ~ 50% of Oleum Ricini and vulcabond total moles;
Firming agent described in step (3) is preferably the one in polyvinylpyrrolidone and calcium chloride;
Medicine described in step (3) is preferably antibiotic;
Antibiotic described in step (3) is preferably the one in amoxicillin, streptomycin, gentamycin, Roxithromycin and azithromycin;
The mass fraction of the drug solution described in step (3) is 0.1% ~ 0.5%;
The quality of the prepolymer described in step (3) is 5% ~ 10% of drug solution quality;
The quality of the firming agent described in step (3) is 10% ~ 50% of prepolymer quality;
Polyurethane composite drug carried microsphere described in step (3) is nanometer hydroxyapatite/polyurethane composite drug carried microsphere or nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere;
A kind of polyurethane composite drug carried microsphere, is prepared by said method;
Described polyurethane composite drug carried microsphere mean diameter is 0.8 ~ 1.2mm, complex microsphere to the envelop rate more than 80% of medicine, drug loading more than 6%, the medicament slow release half-life is 12h ~ 24h;
The described application of polyurethane composite drug carried microsphere in environmental conservation and pharmaceutical sanitary field, the application particularly on veterinary drug slow-released system;
The present invention has following advantage and effect relative to prior art:
(1) the present invention adopts the method for suspension polymerisation-emulsion polymerisation, prepares a kind of nanometer hydroxyapatite/polyurethane composite drug carried microsphere and a kind of nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere.Prepared microsphere average grain diameter is 0.8 ~ 1.2mm, and complex microsphere is to the envelop rate more than 80% of antibiotic medicine, and drug loading more than 6%, the antibiotic medicine slow release half-life is 12h ~ 24h, and drug release behavior meets Higuchi kinetics.Synthesized microsphere all has higher drug loading, envelop rate, good sustained drug release effect and biocompatibility.
(2) instant invention overcomes the deficiencies in the prior art part, as the response time is tediously long, complicated operation and severe reaction conditions, by Optimization Technology, provide a kind of reaction condition easily to realize and gained complex microsphere has the preparation method of biodegradable, good release mechanism.Adopt commercially available common raw material to realize the present invention, but the present invention devises the reaction process more optimized, optimize the ratio of raw material simultaneously further, under same response procedures, particularly achieve the synthesis of two kinds of composite microspheres.The present invention is through experiments a large amount of for a long time and creatively analyze, and sums up the technical scheme be optimized, and adopt situ aggregation method one-step synthesis prepolymer, technological reaction step is simple, without the need to complex operations, with low cost, has important commercial introduction meaning.
(3) the present invention develops and thisly has better biocompatibility; the medical functions of the composite microsphere of biological degradability and mechanical performance; explore its application in environmental conservation and pharmaceutical sanitary field; especially the applied research of micro-sphere material on medicament slow release field, the application particularly on veterinary drug slow-released system.
Accompanying drawing explanation
Fig. 1 is nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere scanning electron microscope (SEM) photograph, wherein, and A: the surface of nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere, 80 times; B: the section of the nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere of unentrapped medicine, 160 times; C: the nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere surface of unentrapped medicine, 1600 times; D: the surface of nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere, 1600 times.
Detailed description of the invention
Below in conjunction with embodiment and accompanying drawing, the present invention is described in further detail, but embodiments of the present invention are not limited thereto.
Use reagent unless stated otherwise, be all commercial conventional reagent or raw material, the test method that embodiment uses unless stated otherwise, is all this area conventional method.
Embodiment 1
(1) in the there-necked flask that agitator, reflux condensing tube and thermometer are housed, add 0.01mol Oleum Ricini, at warming while stirring to 50 DEG C, add 0.25mmol nanometer hydroxyapatite; When temperature constant is at 80 DEG C, dropping 0.015mol isophorone diisocyanate and 4mL acetone carry out prepolymerization reaction 3h in early stage, obtain composite prepolymer in early stage; Wherein, mixing speed is 500r/min;
(2) under the condition of reaction temperature 80 DEG C, add 2.5mmol BDO in composite prepolymer, high-speed stirred 30mim in the early stage that step (1) prepares, prepare composite prepolymer;
(3) nitrogen atmosphere, reaction temperature be 60 DEG C, under the condition of high-speed stirred, it is in the amoxicillin solution of 0.2% that the 14.21g composite prepolymer slowly step (2) prepared, 1.42g firming agent add mass fraction, wherein, the quality of prepolymer is 5% of drug solution quality; Be cured reaction 2h, then steam acetone, obtain composite aqueous emulsion, filtration under diminished pressure, with distilled water wash repeatedly, be placed in frozen vacuum dryer inner drying 8h, obtain polyurethane composite drug carried microsphere, namely obtain nanometer hydroxyapatite/polyurethane composite drug carried microsphere.
The drug loading of the polyurethane composite drug carried microsphere adopting ultraviolet spectrophotometry detecting step (3) to prepare and envelop rate: the nanometer hydroxyapatite/polyurethane composite drug carried microsphere taking 50mg at random, join in 100mL conical flask, add phosphate buffer solution 50mL, after ultrasonic 30min, isothermal vibration 8h in 37.2 DEG C of constant temperature oscillation casees, mixing speed is 100r/min.Get the supernatant after leaving standstill and survey absorbance at 272nm place.According to the content of contained drug in standard curve Equation for Calculating medicine carrying microballoons.The formula calculating drug loading and envelop rate is as follows:
The drug loading of the polyurethane composite drug carried microsphere that step (3) prepares and envelop rate result as shown in table 1:
The drug loading of the polyurethane composite drug carried microsphere that table 1 embodiment 1 prepares and envelop rate
Embodiment 2
(1) in the there-necked flask that agitator, reflux condensing tube and thermometer are housed, add 0.01mol Oleum Ricini, at warming while stirring to 50 DEG C, add 1.2mmol nanometer hydroxyapatite; When temperature constant is at 90 DEG C, dropping 0.03mol isophorone diisocyanate and 4mL acetone carry out prepolymerization reaction 2h in early stage, obtain composite prepolymer in early stage; Wherein, mixing speed is 500r/min;
(2) under the condition of reaction temperature 90 DEG C, add 0.4mmol polylactic acid in the early stage that step (1) prepares in composite prepolymer, stir 10min, add 0.012mol 1 again, 4-butanediol, high-speed stirred 30mim, prepares composite prepolymer;
(3) nitrogen atmosphere, reaction temperature be 55 DEG C, under the condition of high-speed stirred, it is in the amoxicillin solution of 0.3% that the 26.94g composite prepolymer slowly step (2) prepared, 4.59g firming agent add mass fraction, wherein, the quality of prepolymer is 7% of drug solution quality; Be cured reaction 2.5h, then acetone is steamed, obtain composite aqueous emulsion, filtration under diminished pressure, with distilled water wash repeatedly, be placed in frozen vacuum dryer inner drying 8h, obtain polyurethane composite drug carried microsphere, namely obtain nano hydroxyapatite/polylactic acid/compound polyurethane material medicine carrying microballoons, drug loading and entrapment efficiency determination are with embodiment 1.
Drug loading and the envelop rate result of the nano hydroxyapatite/polylactic acid that step (3) prepares/compound polyurethane material medicine carrying microballoons are as shown in table 2:
The drug loading of the polyurethane composite drug carried microsphere that table 2 embodiment 2 prepares and envelop rate
Embodiment 3
(1) in the there-necked flask that agitator, reflux condensing tube and thermometer are housed, add 0.01mol Oleum Ricini, at warming while stirring to 50 DEG C, add 3.5mmol nanometer hydroxyapatite.When temperature constant is at 85 DEG C, dropping 0.06mol isophorone diisocyanate and 6mL acetone carry out prepolymerization reaction 2.5h in early stage, obtain composite prepolymer in early stage; Wherein, mixing speed is 500r/min.
(2) under the condition of reaction temperature 85 DEG C, add 0.35mmol polylactic acid in the early stage that step (1) prepares in composite prepolymer, stir 10min, add 0.035mol 1,4-butanediol, high-speed stirred 30mim, prepares composite prepolymer;
(3) nitrogen atmosphere, reaction temperature be 50 DEG C, under the condition of high-speed stirred, it is in the amoxicillin solution of 0.5% that the 36.98g composite prepolymer slowly step (2) prepared, 18.49g firming agent add mass fraction, wherein, the quality of prepolymer is 10% of drug solution quality; Be cured reaction 3h, then acetone is steamed, obtain composite aqueous emulsion, filtration under diminished pressure, with distilled water wash repeatedly, be placed in frozen vacuum dryer inner drying 8h, obtain polyurethane composite drug carried microsphere, namely obtain nano hydroxyapatite/polylactic acid/compound polyurethane material medicine carrying microballoons, drug loading and entrapment efficiency determination are with embodiment 1.
Fig. 1 is the scanning electron microscope (SEM) photograph of nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere, Figure 1A can find out, the size uniformity of nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere, diameter is about 0.9mm, rough, there is small duct, hole and the inner porosity communication on surface, this stripping being medicine provides path, can realize the dissolving release of medicine.There is many holes in the nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere inside of Figure 1B unentrapped medicine, these holes are connected with microsphere surface, and form tubulose tract, medicine through tract, can discharge from the hole of microsphere surface.Fig. 1 C finds out that the nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere surface distributed of unentrapped medicine a large amount of holes, and hole is evenly distributed on the surface of microsphere.The diameter of hole is 1 ~ 6 μm, is conducive to attachment and the stripping of medicine, and complex microsphere, in pharmaceutical carrier, has suitable structure.Clearly can find out in Fig. 1 D that white granule in nano hydroxyapatite/polylactic acid/polyurethane composite drug carried microsphere surface distributed is about 0.8 ~ 1.0 μm, be the antibiolics composition granule being attached to microsphere surface.
Drug loading and the envelop rate result of the nano hydroxyapatite/polylactic acid that step (3) prepares/compound polyurethane material medicine carrying microballoons are as shown in table 3:
The drug loading of the polyurethane composite drug carried microsphere that table 3 embodiment 3 prepares and envelop rate
Above-described embodiment is the present invention's preferably embodiment; but embodiments of the present invention are not restricted to the described embodiments; change, the modification done under other any does not deviate from spirit of the present invention and principle, substitute, combine, simplify; all should be the substitute mode of equivalence, be included within protection scope of the present invention.
Claims (10)
1. a preparation method for polyurethane composite drug carried microsphere, is characterized in that comprising following steps:
(1) under the condition of reaction temperature 80 DEG C ~ 90 DEG C, pre-polymerization in early stage is carried out in the mixing of Oleum Ricini, nanometer hydroxyapatite, vulcabond and organic solvent, obtain composite prepolymer in early stage;
(2) under the condition of reaction temperature 80 DEG C ~ 90 DEG C, add polylactic acid and polyhydric alcohol in the early stage that step (1) prepares in composite prepolymer, reaction 30 ~ 40min, obtains composite prepolymer; Molal quantity total moles 0 ~ 1% shared by Oleum Ricini and vulcabond of described polylactic acid;
(3) under nitrogen atmosphere, reaction temperature are the condition of 50 DEG C ~ 60 DEG C, prepolymer, firming agent and the drug solution mixing that step (2) is prepared, be cured reaction 2h ~ 3h, obtain composite aqueous emulsion, then dewater, drying, obtains polyurethane composite drug carried microsphere.
2. the preparation method of polyurethane composite drug carried microsphere according to claim 1, is characterized in that:
Mol ratio-NCO:-OH=(1:1) ~ (4:1) that Oleum Ricini described in step (1) and vulcabond add.
3. the preparation method of polyurethane composite drug carried microsphere according to claim 1, is characterized in that:
The molal quantity of the nanometer hydroxyapatite described in step (1) shared by Oleum Ricini and vulcabond total moles 1% ~ 5%.
4. the preparation method of polyurethane composite drug carried microsphere according to claim 1, is characterized in that:
Described in step (1) early stage prepolymerization reaction condition be: reaction 2h ~ 4h.
5. the preparation method of polyurethane composite drug carried microsphere according to claim 1, is characterized in that:
The molal quantity of the polyhydric alcohol described in step (2) is 10% ~ 50% of Oleum Ricini and vulcabond total moles.
6. the preparation method of polyurethane composite drug carried microsphere according to claim 1, is characterized in that:
Vulcabond described in step (1) is toluene di-isocyanate(TDI), diphenyl methane-4, one in 4 '-vulcabond, 1,5-naphthalene diisocyanate, isoflurane chalcone diisocyanate, XDI, hexamethylene diisocyanate, PPDI, lysinediisocyanate and dicyclohexyl methyl hydride diisocyanate;
Polyhydric alcohol described in step (2) is the one in BDO, ethylene glycol, propylene glycol, hexanediol and diglycol;
Firming agent described in step (3) is the one in polyvinylpyrrolidone and calcium chloride;
Medicine described in step (3) is antibiotic.
7. the preparation method of polyurethane composite drug carried microsphere according to claim 1, is characterized in that:
The mass fraction of the drug solution described in step (3) is 0.1% ~ 0.5%;
The quality of the prepolymer described in step (3) is 5% ~ 10% of drug solution quality;
The quality of the firming agent described in step (3) is 10% ~ 50% of prepolymer quality.
8. a polyurethane composite drug carried microsphere, is characterized in that: prepared by the preparation method described in any one of claim 1 ~ 7.
9. polyurethane composite drug carried microsphere according to claim 9, is characterized in that: described polyurethane composite drug carried microsphere mean diameter is 0.8 ~ 1.2mm, to the envelop rate more than 80% of medicine, and drug loading more than 6%.
10. the application of polyurethane composite drug carried microsphere in environmental conservation or pharmaceutical sanitary field described in claim 8 or 9.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060002980A1 (en) * | 2003-06-20 | 2006-01-05 | Ringeisen Timothy A | High density fibrous polymers suitable for implant |
| CN102489231A (en) * | 2011-12-26 | 2012-06-13 | 重庆科技学院 | Preparation method of hydroxy apatite / polylactic acid / chitosan composite microballoon |
| CN103319696A (en) * | 2012-03-23 | 2013-09-25 | 中国科学院化学研究所 | Hydroxyapatite/biodegradable polyester composite material and preparation method thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060002980A1 (en) * | 2003-06-20 | 2006-01-05 | Ringeisen Timothy A | High density fibrous polymers suitable for implant |
| CN102489231A (en) * | 2011-12-26 | 2012-06-13 | 重庆科技学院 | Preparation method of hydroxy apatite / polylactic acid / chitosan composite microballoon |
| CN103319696A (en) * | 2012-03-23 | 2013-09-25 | 中国科学院化学研究所 | Hydroxyapatite/biodegradable polyester composite material and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 叶心亮等: "羟基磷灰石/聚乳酸/聚氨酯生物材料的降解性能", 《高分子材料科学与工程》 * |
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