CN101601986B - Preparation method of chitosan-silicon dioxide compound hollow microballoon and application thereof - Google Patents
Preparation method of chitosan-silicon dioxide compound hollow microballoon and application thereof Download PDFInfo
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- CN101601986B CN101601986B CN2009100321459A CN200910032145A CN101601986B CN 101601986 B CN101601986 B CN 101601986B CN 2009100321459 A CN2009100321459 A CN 2009100321459A CN 200910032145 A CN200910032145 A CN 200910032145A CN 101601986 B CN101601986 B CN 101601986B
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 239000000377 silicon dioxide Substances 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title description 8
- 239000004005 microsphere Substances 0.000 claims abstract description 28
- 239000002131 composite material Substances 0.000 claims abstract description 16
- 229920001661 Chitosan Polymers 0.000 claims abstract description 14
- 230000007062 hydrolysis Effects 0.000 claims abstract description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 6
- 239000002245 particle Substances 0.000 claims abstract description 4
- 238000006068 polycondensation reaction Methods 0.000 claims abstract description 4
- 230000006196 deacetylation Effects 0.000 claims abstract description 3
- 238000003381 deacetylation reaction Methods 0.000 claims abstract description 3
- 229920002125 Sokalan® Polymers 0.000 claims abstract 4
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 claims abstract 4
- 239000004584 polyacrylic acid Substances 0.000 claims abstract 4
- 238000003756 stirring Methods 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 239000000839 emulsion Substances 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 8
- 102000004169 proteins and genes Human genes 0.000 claims description 8
- 108090000623 proteins and genes Proteins 0.000 claims description 8
- 239000002808 molecular sieve Substances 0.000 claims description 5
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 5
- 239000006228 supernatant Substances 0.000 claims description 4
- 239000011148 porous material Substances 0.000 claims description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims 1
- 102000004506 Blood Proteins Human genes 0.000 claims 1
- 108010017384 Blood Proteins Proteins 0.000 claims 1
- 241000283690 Bos taurus Species 0.000 claims 1
- 102000018832 Cytochromes Human genes 0.000 claims 1
- 108010052832 Cytochromes Proteins 0.000 claims 1
- 239000012153 distilled water Substances 0.000 claims 1
- 229960001866 silicon dioxide Drugs 0.000 description 40
- 239000003814 drug Substances 0.000 description 30
- 229940079593 drug Drugs 0.000 description 13
- 238000000034 method Methods 0.000 description 12
- MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 10
- 229960002918 doxorubicin hydrochloride Drugs 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 238000004108 freeze drying Methods 0.000 description 10
- 238000007710 freezing Methods 0.000 description 10
- 230000008014 freezing Effects 0.000 description 10
- 150000001875 compounds Chemical class 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 4
- 229940098773 bovine serum albumin Drugs 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 235000012239 silicon dioxide Nutrition 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 2
- -1 Lalgine Polymers 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000001354 calcination Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 239000011806 microball Substances 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000008177 pharmaceutical agent Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 235000012976 tarts Nutrition 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241000237502 Ostreidae Species 0.000 description 1
- 239000004159 Potassium persulphate Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000010364 biochemical engineering Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000002086 nanomaterial Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 235000020636 oyster Nutrition 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
- 235000019394 potassium persulphate Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Manufacturing Of Micro-Capsules (AREA)
Abstract
一种壳聚糖-二氧化硅的复合空心微球，正硅酸乙酯经水解、缩聚沉积在壳聚糖-聚丙烯酸微球的表面，最终得到具有大孔、介孔两种孔结构的壳聚糖-二氧化硅复合空心微球，平均粒径为50-200nm，其中壳聚糖的分子量为10000-200000，脱乙酰度为70～95％。A composite hollow microsphere of chitosan-silicon dioxide, tetraethyl orthosilicate is deposited on the surface of chitosan-polyacrylic acid microspheres through hydrolysis and polycondensation, and finally obtains a composite hollow microsphere with macropores and mesoporous structures. The chitosan-silicon dioxide composite hollow microsphere has an average particle diameter of 50-200nm, wherein the molecular weight of the chitosan is 10000-200000, and the degree of deacetylation is 70-95%.
Description
Technical field:
The present invention relates to the preparation and the drug release Application Areas of the compound nano material of organic-inorganic, be specifically related to a kind ofly have the preparation method of macropore, mesoporous chitosan-silicon dioxide composite Nano tiny balloon and as the carrier of drug release, the application of molecular sieve aspect.
Technical background:
Since the sixties in 20th century, controlled delivery of pharmaceutical agents discharges and studies in the intravital target property administration of people is a research focus of chemistry, medical science and field of pharmacology always.Compare with traditional mode of administration, controlled delivery of pharmaceutical agents discharges and has lot of advantages, such as: (1) drug release is more stable to the concentration in the environment; (2) the highly effective medicine that utilizes of ability makes it that very high utilization ratio arranged; (3) can make the release of medicine as much as possible near lesions position, improve drug effect, avoid taking place the spinoff of general; (4) can suitably reduce the medication number of times, safer to the patient.Therefore, in view of above-mentioned various advantages, the research of medicine sustained release has using value very widely to clinical medicine.
The key of medicine control release technic is processability excellent drug carrier.In numerous macromolecular materials, the natural polysaccharide material has obtained researchist's extensive concern with its better biocompatibility and cellular affinity.At present, the natural biological degradable macromolecule as pharmaceutical carrier mainly contains: chitosan, Lalgine, agar, scleroproein and collagen protein etc.Wherein, chitosan has obtained using widely in pharmacy and field of biology with its nontoxicity, biocompatibility and degradability.(Biometerial，1993，(20)，7-16；J?Control?Rel，1998，(52)，109-18)。In the present invention, utilize chitosan tiny balloon as template just, the tiny balloon of preparation composite chitosan-silicon-dioxide with good biological performance.
Lot of domestic and international seminar is devoted to the preparation and the research of chitosan microball, and up to now, the method for preparing chitosan microball mainly contains crosslinking, coacervation, emulsification-solvent evaporated method, spray-drying process etc.Above several method prepares the process relative complex, and will use harmful organic solvent unavoidably sometimes.In the present invention, our used template chitosan-polyacrylic tiny balloon, the preparation process is simple, and carries out at aqueous phase fully, therefore very environmental protection (Advanced Materials, 2004, (16), 933-936.).Further preparing in the process of chitosan-silicon dioxide complex microsphere the removal of ROHM molecule quilt nature in treating processes.
The ordered mesoporous silica dioxide microballoon has bigger specific surface area, aperture and volume adjustable size, and biologically inert and biocompatibility, so it is the inorganic materials preferably as pharmaceutical carrier.But; Unmodified silicon dioxide microsphere can not carry out controlled release to the medicine of parcel, if therefore can the advantages of chitosan and silicon-dioxide be got up, that will be the significant work of ten minutes; Because the specific surface area that mesoporous silicon oxide is big can make it have bigger drug loading; And having multiple functional group (amino, hydroxyl) on the chitosan segment, the chemical action power through between regulation and control functional group and the medicine can reach the purpose to the medicine sustained release.The present invention has embodied this characteristic just.
Summary of the invention:
The object of the present invention is to provide a kind of biodegradable, chitosan-silicon dioxide composite nano-microsphere with biocompatibility.
Another object of the present invention is to provide a kind of preparation method with macropore, mesoporous chitosan-silicon dioxide composite Nano tiny balloon.The present invention adopts template; With chitosan-ROHM hollow microsphere is template; With the tetraethoxy is the silicon-dioxide precursor; Under acetic acid or ammonia-catalyzed agent effect, tetraethoxy is deposited on the surface of chitosan-ROHM microballoon through hydrolysis, polycondensation, finally obtains having macropore, the chitosan-silicon dioxide compound hollow microballoon of mesoporous two kinds of pore structures.
Technical scheme of the present invention is following: the compound hollow microballoon of chitosan-silicon dioxide; Adopt tetraethoxy to be deposited on the method on the surface of chitosan-ROHM microballoon through hydrolysis, polycondensation; Finally obtain having macropore, the chitosan-silicon dioxide compound hollow microballoon of mesoporous two kinds of pore structures; Median size is 50-200nm, and wherein the molecular weight of chitosan is 10000-200000, and deacetylation is 70～95%.
The method of the compound hollow microballoon of preparation chitosan-silicon dioxide; Chitosan-ROHM tiny balloon is dissolved in the alkaline zero(ppm) water; It is joined under agitation condition in the ethanolic soln of tetraethoxy, promptly get the compound hollow microballoon of chitosan-silicon dioxide after the hydrolysis fully.After stirring at room 12-24 hour, under 50 ℃ of conditions, left standstill 12-24 hour filtration, the centrifugal compound hollow microballoon that promptly gets chitosan-silicon dioxide again.
Especially chitosan-ROHM emulsion is mixed with the ammoniacal liquor of isopyknic 1-2M; Left standstill 48 hours; And tetraethoxy is dissolved in the ethanol, the chitosan-ROHM emulsion of alkalescence slowly is added drop-wise in the ethanolic soln of tetraethoxy stirring at room 12-24 hour; Be placed on afterwards under 50 ℃ of conditions and left standstill 12-24 hour, through filtration, the centrifugal chitosan-silicon dioxide compound hollow microballoon that promptly gets.
Another method is that chitosan-ROHM tiny balloon is dissolved in the acid zero(ppm) water, and it is joined under agitation condition in the ethanolic soln of tetraethoxy, promptly gets the compound hollow microballoon of chitosan-silicon dioxide after the hydrolysis fully.Under the stirring at room condition; Tart chitosan-ROHM tiny balloon emulsion is joined in the ethanolic soln of tetraethoxy; After the stirring at room 24 hours, under 50 ℃ of conditions, left standstill 24 hours filtration, the centrifugal compound hollow microballoon that promptly gets chitosan-silicon dioxide again.The purposes of described Nano microsphere as medicine, proteic carrier, can also be come separating protein as molecular sieve.Load has the antitumor drug doxorubicin hydrochloride of broad spectrum.The chitosan-silicon dioxide microballoon has bigger cavity, therefore can improve its drug loading greatly, and through changing some condition of external environment, reaches the purpose to medicine controlled releasing.The corresponding pH value of acid and alkaline zero(ppm) water can be in the scope of pH4-pH10.
The chitosan-silicon dioxide composite nano-microsphere that the invention still further relates to the employing method for preparing separates the protein with different molecular weight and iso-electric point as molecular sieve.And, reach proteinic separation through changing some condition of external environment.
As the carrier of medicine, it can add in the solution of chitosan-silicon dioxide complex microsphere of the present invention wants loaded drugs, centrifugal after normal temperature stirs 24-48 hour, can obtain being enclosed with the chitosan-silicon dioxide compound hollow microballoon of medicine
As molecular sieve, it can add Lrax and bovine serum albumin in the solution of chitosan-silicon dioxide complex microsphere of the present invention, stirs more than 48 hours through normal temperature, goes out supernatant liquid through spinning.Lower floor is wrapped up in the solution that proteic complex microsphere is dissolved in certain pH value, and stirring at normal temperature is more than 48 hours, and is centrifugal, can be with two kinds of protein separation.
The invention provides a kind of median size is the chitosan-silicon dioxide composite Nano tiny balloon of 50-200nm, and it is hydrophilic, has stability preferably, biocompatibility in the pH scope widely.Experimentation carries out in aqueous phase system fully, does not use any organic solvent and tensio-active agent.Microsphere surface rule has a lot of ducts on the outer shell silica wall, and for the absorption and the release of medicine provides passage, and the physical strength of silica shell is high, not yielding.Therefore, this microballoon meets the application need in biomedical and biochemical engineering field as a kind of carrier on performance.
Description of drawings:
Fig. 1 is the model diagram of chitosan-silicon dioxide compound hollow microballoon: 1 is chitosan, and 2 is silicon-dioxide.
Fig. 2 is the transmission electron microscope picture (amplifying 50,000 times) of chitosan-silicon dioxide compound hollow microballoon
The release profiles that Fig. 3 tests under buffered soln pH4 and pH7.4 checker condition for the chitosan-silicon dioxide compound hollow microballoon of load doxorubicin hydrochloride
Fig. 4 is the release profiles of SiO 2 hollow microsphere under pH4 and pH7.4 condition of load doxorubicin hydrochloride.
Embodiment
Embodiment 1:
At first prepare chitosan-polyacrylic tiny balloon.The chitosan of 0.25g and the vinylformic acid of 0.12g are dissolved in the zero(ppm) water of 25mL, treat that it dissolves fully after, be warming up to 80 ℃, the Potassium Persulphate that adds 0.05g causes acroleic acid polymerization.When oyster white appears in system, system is cooled to room temperature, the LUTARALDEHYDE that adds 0.1mL afterwards comes optionally cross-linked chitosan, promptly obtains the emulsion of chitosan-ROHM tiny balloon, but the REFERENCE TO RELATED people in first to file.
Get freshly prepd chitosan-ROHM emulsion 2.5mL and mix, left standstill 48 hours with the ammoniacal liquor of isopyknic 2M.The tetraethoxy of 520 microlitres is dissolved in the 2mL ethanol.Chitosan-ROHM the emulsion of alkalescence slowly is added drop-wise in the ethanolic soln of tetraethoxy.Stirring at room 24 hours is placed on afterwards under 50 ℃ of conditions and left standstill 24 hours, through filtration, the centrifugal chitosan-silicon dioxide compound hollow microballoon that promptly gets.
Chitosan-silicon dioxide compound hollow microballoon in the above-mentioned system; Using the transmission electron microscope observing nanoparticle is regular globosity; And outer field silicon-dioxide and chitosan-ROHM template boundary are clearly, and median size is 120nm, can stable existence in pH value scope widely.
Embodiment 2:
Get freshly prepd chitosan-ROHM emulsion 2.5mL, emulsion is transferred to pH3, left standstill 48 hours with the acetic acid of 2M.520 microlitre tetraethoxys are dissolved in the 2mL ethanol.Tart chitosan-ROHM emulsion slowly is added drop-wise in the ethanolic soln of tetraethoxy.Stirring at room 24 hours is placed on afterwards under 50 ℃ of conditions and left standstill 24 hours, through filtration, the centrifugal chitosan-silicon dioxide compound hollow microballoon that promptly gets.
Chitosan-silicon dioxide compound hollow microballoon in the above-mentioned system, using the transmission electron microscope observing nanoparticle be regular globosity, median size is 110nm, can stable existence in pH value scope widely.
Embodiment 3:
Get freshly prepd chitosan-ROHM emulsion 2.5mL and mix, left standstill 48 hours with the ammoniacal liquor of isopyknic 2M.520 microlitre tetraethoxys are dissolved in the 2mL ethanol.Chitosan-ROHM the emulsion of alkalescence slowly is added drop-wise in the ethanolic soln of tetraethoxy.Stirring at room 24 hours is placed on afterwards under 50 ℃ of conditions and left standstill 24 hours, through filtration, the centrifugal chitosan-silicon dioxide compound hollow microballoon that promptly gets.Be dispersed in the zero(ppm) water after this product repeatedly washed, freezing freezing, afterwards in Freeze Drying Equipment with its freeze-drying.The doxorubicin hydrochloride of getting freeze dried chitosan-silicon dioxide compound hollow microballoon powder 15mg and certain mass is mixed in the zero(ppm) water; Stirring at room 48 hours; Centrifugal, the washing three times, remove the chitosan-silicon dioxide complex microsphere that supernatant liquid promptly gets the load doxorubicin hydrochloride.
In the above-mentioned complex microsphere, when the quality that adds doxorubicin hydrochloride was 1.5mg, the drug loading of particle was 8.9%, and medicine carrying efficient is 97.5%.The drug release experiment shows: when release media solution was the buffered soln checker of pH4 and 7.4, the quality of the doxorubicin hydrochloride that is discharged presented pulsed; That is to say, be 4 o'clock in the pH of extraneous solution value, and a large amount of medicines are released out, is 7.4 o'clock in the pH of extraneous solution value, has only a spot of medicine to be released out.
Get freshly prepd chitosan-ROHM emulsion 2.5mL and mix, left standstill 48 hours with the ammoniacal liquor of isopyknic 2M.520 microlitre tetraethoxys are dissolved in the 2mL ethanol.Chitosan-ROHM the emulsion of alkalescence slowly is added drop-wise in the ethanolic soln of tetraethoxy.Stirring at room 24 hours is placed on afterwards under 50 ℃ of conditions and left standstill 24 hours, through filtration, the centrifugal chitosan-silicon dioxide compound hollow microballoon that promptly gets.Be dispersed in the zero(ppm) water after this product repeatedly washed, freezing freezing, afterwards in Freeze Drying Equipment with its freeze-drying.With freeze dried powder in retort furnace under 550 ℃ the condition calcining obtained the silica nanometer tiny balloon in 4 hours.SiO 2 hollow microsphere powder 15mg and the doxorubicin hydrochloride of certain mass got after the calcining are mixed in the zero(ppm) water; Stirring at room 48 hours; Centrifugal, the washing three times, remove the chitosan-silicon dioxide compound hollow microballoon that supernatant liquid promptly gets the load doxorubicin hydrochloride.
In the above-mentioned complex microsphere, when the quality that adds doxorubicin hydrochloride was 1.5mg, the drug loading of particle was 4.2%, and medicine carrying efficient is 43.5%.The drug release experiment shows: when the pH of extraneous solution value was 4, a large amount of medicines were released out, were 7.4 o'clock in the pH of extraneous solution value, had only a spot of medicine to be released out.
Get freshly prepd chitosan-ROHM emulsion 2.5mL and mix, left standstill 48 hours with the ammoniacal liquor of isopyknic 2M.520 microlitre tetraethoxys are dissolved in the 2mL ethanol.Chitosan-ROHM the emulsion of alkalescence slowly is added drop-wise in the ethanolic soln of tetraethoxy.Stirring at room 24 hours is placed on afterwards under 50 ℃ of conditions and left standstill 24 hours, through filtration, the centrifugal chitosan-silicon dioxide compound hollow microballoon that promptly gets.Be dispersed in the zero(ppm) water after this product repeatedly washed, freezing freezing, afterwards in Freeze Drying Equipment with its freeze-drying.Get freeze dried sample 15mg, Lrax 5mg was dissolved in the PBS buffered soln of 2mLpH7.4 stirring at normal temperature 96 hours.Afterwards,, isolate upper solution and test, the quality of the Lrax that promptly obtains being wrapped this solution centrifugal.
Embodiment 6
Get freshly prepd chitosan-ROHM emulsion 2.5mL and mix, left standstill 48 hours with the ammoniacal liquor of isopyknic 2M.520 microlitre tetraethoxys are dissolved in the 2mL ethanol.Chitosan-ROHM the emulsion of alkalescence slowly is added drop-wise in the ethanolic soln of tetraethoxy.Stirring at room 24 hours is placed on afterwards under 50 ℃ of conditions and left standstill 24 hours, through filtration, the centrifugal chitosan-silicon dioxide compound hollow microballoon that promptly gets.Be dispersed in the zero(ppm) water after this product repeatedly washed, freezing freezing, afterwards in Freeze Drying Equipment with its freeze-drying.Get freeze dried sample 15mg, bovine serum albumin 5mg was dissolved in the PBS buffered soln of 2mL pH7.4 stirring at normal temperature 96 hours.Afterwards,, isolate upper solution and test, the quality of the bovine serum albumin that promptly obtains being wrapped this solution centrifugal.
Embodiment 7
Get freshly prepd chitosan-ROHM emulsion 2.5mL and mix, left standstill 48 hours with the ammoniacal liquor of isopyknic 2M.520 microlitre tetraethoxys are dissolved in the 2mL ethanol.Chitosan-ROHM the emulsion of alkalescence slowly is added drop-wise in the ethanolic soln of tetraethoxy.Stirring at room 24 hours is placed on afterwards under 50 ℃ of conditions and left standstill 24 hours, through filtration, the centrifugal chitosan-silicon dioxide compound hollow microballoon that promptly gets.Be dispersed in the zero(ppm) water after this product repeatedly washed, freezing freezing, afterwards in Freeze Drying Equipment with its freeze-drying.Get freeze dried sample 15mg, bovine serum albumin 5mg, Lrax 5mg was dissolved in the PBS buffered soln of 2mL pH7.4 stirring at normal temperature 96 hours.Afterwards, with this solution centrifugal, isolate upper solution.Lower sediment is dissolved in the buffered soln of pH10 stirring at normal temperature 48 hours.With this solution centrifugal, can two kinds of protein be separated.
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| CN101953797B (en) * | 2010-09-06 | 2012-05-23 | 中华人民共和国卫生部肝胆肠外科研究中心 | Method for preparing medicament carrying controlled-release nanometer material and application |
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| CN113875507B (en) * | 2021-10-09 | 2023-05-02 | 内蒙古自治区农牧业科学院 | Grassland ecological restoration method |
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