CN103585132B - Preparation method of paclitaxel silicon plastid microcapsule - Google Patents
Preparation method of paclitaxel silicon plastid microcapsule Download PDFInfo
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- 239000003094 microcapsule Substances 0.000 title claims abstract description 45
- 210000002706 plastid Anatomy 0.000 title claims abstract description 39
- 229910052710 silicon Inorganic materials 0.000 title claims abstract description 38
- 239000010703 silicon Substances 0.000 title claims abstract description 38
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 title claims abstract description 35
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 229930012538 Paclitaxel Natural products 0.000 title claims abstract description 11
- 229960001592 paclitaxel Drugs 0.000 title claims abstract description 11
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 title claims abstract description 11
- 229910010272 inorganic material Inorganic materials 0.000 claims abstract description 17
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims abstract description 12
- 239000004005 microsphere Substances 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims abstract description 10
- 229910000019 calcium carbonate Inorganic materials 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 26
- 239000002245 particle Substances 0.000 claims description 14
- 239000000377 silicon dioxide Substances 0.000 claims description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 12
- 150000002632 lipids Chemical class 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 239000012528 membrane Substances 0.000 claims description 7
- 238000006243 chemical reaction Methods 0.000 claims description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 3
- 229920001467 poly(styrenesulfonates) Polymers 0.000 claims description 3
- 238000002390 rotary evaporation Methods 0.000 claims description 3
- 239000006228 supernatant Substances 0.000 claims description 3
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 230000007159 enucleation Effects 0.000 claims description 2
- 229940059939 kayexalate Drugs 0.000 claims description 2
- 239000011859 microparticle Substances 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims 2
- 239000002246 antineoplastic agent Substances 0.000 abstract description 7
- 229940041181 antineoplastic drug Drugs 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 4
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- 239000000232 Lipid Bilayer Substances 0.000 abstract 1
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- 229940079593 drug Drugs 0.000 description 13
- 239000000243 solution Substances 0.000 description 11
- 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
- 239000002502 liposome Substances 0.000 description 9
- 238000011275 oncology therapy Methods 0.000 description 8
- 230000001093 anti-cancer Effects 0.000 description 7
- 230000002209 hydrophobic effect Effects 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
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- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229910018540 Si C Inorganic materials 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 2
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 2
- 235000011130 ammonium sulphate Nutrition 0.000 description 2
- 239000008366 buffered solution Substances 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- VBVAVBCYMYWNOU-UHFFFAOYSA-N coumarin 6 Chemical compound C1=CC=C2SC(C3=CC4=CC=C(C=C4OC3=O)N(CC)CC)=NC2=C1 VBVAVBCYMYWNOU-UHFFFAOYSA-N 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 229910052909 inorganic silicate Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 229910010271 silicon carbide Inorganic materials 0.000 description 2
- 238000005287 template synthesis Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical compound C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 description 1
- KBIWNQVZKHSHTI-UHFFFAOYSA-N 4-n,4-n-dimethylbenzene-1,4-diamine;oxalic acid Chemical compound OC(=O)C(O)=O.CN(C)C1=CC=C(N)C=C1 KBIWNQVZKHSHTI-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229920005654 Sephadex Polymers 0.000 description 1
- 239000012507 Sephadex™ Substances 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound 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(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
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- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
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- 201000002364 leukopenia Diseases 0.000 description 1
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- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a preparation method of a paclitaxel silicon plastid microcapsule. The method comprises the following steps: taking calcium carbonate microspheres as a template; according to sol-gel and self-assembly methods, mounting organic-inorganic compound lipids to the surfaces of the colloid microspheres; at the same time, loading a lipid-soluble anticancer drug on a lipid bilayer; according to a chemical method, removing the template calcium carbonate microspheres to obtain the silicon plastid microcapsule with uniform and controllable grain size, stable properties and monodisperse performance; jointly hatching the silicon plastid microcapsule and a water-soluble anticancer drug, so as to embed the water-soluble anticancer drug into the silicon plastid microcapsule. The organic-inorganic compound lipids for preparing the microcapsule are non-toxic, and have excellent biocompatibility. The preparation method is simple in process, mild in operation conditions, high in repeatability, good in slow-release effect, and meanwhile suitable for embedding and controllably releasing the lipid-soluble anticancer drug and the water-soluble anticancer drug, and has an excellent application prospect.
Description
Technical field
The present invention relates to field of biomedical materials, specifically, relate to a kind of anti-cancer medicament silicon plastid microcapsule and preparation method thereof.
Background technology
Malignant tumor is one of disease of serious harm human health, and chemotherapy is current requisite Therapeutic Method.But current chemotherapeutics not only has killing action to tumor cell after entering human body in free mode, also has lethal effect to normal cell, thus causes serious toxic and side effects simultaneously.The side reaction of cancer therapy drug is mainly manifested in clinically: suppress hemopoietic function of bone marrow, platelet and leukopenia, gastrointestinal reaction etc.Some medicine has obvious toxicity to heart, liver, and these toxic actions add the misery of patient in chemotherapy process, limits the application of cancer therapy drug in clinical to a great extent.Liposome has obtained paying close attention to more and more widely as the carrier of Diagnosis and Treat medicine.Especially to be used to parcel various hydrophilic with hydrophobic cancer therapy drug for liposome.But the maximum shortcoming of liposome is the unstability of chemistry and physics, and liposome vesicle easily breaks, its content cancer therapy drug leaked prematurely before arriving tumor locus, did not reach the effect of slow release, had had a strong impact on their application clinically.
Silica nodule is a kind of lipoid plastid, the novel lipid molecule be made up of a point of sub-connection two hydrophobic carbochains and a hydrophilic organosilane molecules, this molecule forms vesicle by sol-gel and self assembling process in water, vesicle surface is coated with the inorganic silicate shell of nanometer grade thickness, inorganic layer and organic two points of daughters is linked together with stable Si-C key.
Silica nodule, compared with traditional liposome vesicle, is a kind of highly stable imitated vesicle structure, is the hybrid material of organic and inorganic.Compared with traditional conventional liposome, the siloxane network on silica nodule surface significantly increases the stability of liposome, and Surfactant, soda acid have good stability.Silica nodule solves all deficiencies of liposome well as pharmaceutical carrier, but there is a problem simultaneously, be exactly that silica nodule particle size distribution range is wider, cannot make its uniform particle diameter with customary preparation methods, this have impact on the practical application in their futures to a certain extent.If can accurately control its particle size range, will be significant.
Summary of the invention
The object of this invention is to provide a kind of uniform particle diameter, stability strong, can load hydrophilic and hydrophobic anticancer drug in silicon plastid microcapsule and preparation method thereof of one.
To achieve these goals, the present invention adopts following technical scheme:
The present invention is directed to some problems of current liposome and silica nodule existence, utilize template synthesis to obtain a kind of new drug carrier---silicon plastid microcapsule.The size of the hollow microcapsule that template synthesis obtains is more easy to control, also more even.Silica nodule poor stability, particle size distribution heterogeneity, uncontrollable shortcoming will be solved well.The outer surface of silicon plastid microcapsule is the double membrane structure of lipoid plastid, and centre is aqueous phase, so not only can coated water-soluble cancer therapy drug but also can wrap up fat-soluble cancer therapy drug.Specific as follows:
A preparation method for anti-cancer medicament silicon plastid microcapsule, comprises the steps:
(1) organic-inorganic compound lipid and hydrophobic drug are jointly dissolved in organic solvent, rotary evaporation removes organic solvent, forms one deck lipid membrane; Described hydrophobic anticancer drug is paclitaxel, docetaxel, camptothecine, hydroxy camptothecin or vincristine;
(2) by CaCO
3template microsphere solution joins in lipid membrane, hatches;
(3) mixed solution that step (2) obtains is carried out water bath sonicator;
(4) solution chamber obtained after ultrasonic is gentle and quiet puts, and treats that template microsphere surface forms inorganic silicate shell;
(5) by the CaCO of surface coverage organic-inorganic compound lipid
3template microsphere, with the EDTA solution of 0.02M or the ethanedioic acid solution of pH=4 by CaCO
3template microsphere is removed, and namely obtains silicon plastid microcapsule;
(6) silicon plastid microcapsule is being hatched with water soluble drug the microcapsule obtaining wrapping up hydrophilic medicament jointly; Water soluble drug is doxorubicin hydrochloride, daunorubicin, cytosine arabinoside, cisplatin or 5-fluorouracil.
In the preparation method of above-mentioned anti-cancer medicament silicon plastid microcapsule, described organic solvent is any one or multiple mixing in chloroform, dichloromethane, methanol, ethanol.
In the preparation method of above-mentioned anti-cancer medicament silicon plastid microcapsule, the structure of described organic-inorganic compound lipid is as organic-inorganic compound lipid 1 or 2:
Organic-inorganic compound lipid 1:
Organic-inorganic compound lipid 2:
Or
.
In the preparation method of above-mentioned anti-cancer medicament silicon plastid microcapsule, the incubation temperature described in step (2) is 40 DEG C ~ 45 DEG C, and incubation time is 30min.
In the preparation method of above-mentioned anti-cancer medicament silicon plastid microcapsule, the ultrasonic power described in step (3) is 100W, and ultrasonic time is 5 ~ 10min.
Compared with prior art, the present invention has following beneficial effect:
The invention provides a kind of preparation method of anti-cancer medicament silicon plastid microcapsule, silica nodule is a kind of hybrid inorganic-organic materials, it be lipids containing silicon ether group in aqueous, template microsphere surface is coated on by the self assembling process of sol-gel, surface forms the three-dimensional netted silicate sturcture of one deck simultaneously, and inorganic layer and organic two points of daughters link together by stable Si-C key.To be crosslinkedly to complete, adopt the method for physics or chemistry to remove template, can silicon plastid microcapsule be obtained.The silicate sturcture on surface significantly enhances the stability of microcapsule, and can wrap up liposoluble substance between the duplicature of silica nodule.Therefore, the silicon plastid microcapsule in the present invention have good stability, uniform particle diameter controlled, the advantage such as water solublity and fat-soluble cancer therapy drug can be carried.Silicon plastid microcapsule is applied to the parcel of cancer therapy drug and induction system will have broad prospects.
Accompanying drawing explanation
Fig. 1 is the structural representation of silica nodule;
Fig. 2 is CaCO in embodiment 1
3the laser co-focusing photo of microsphere;
Fig. 3 is the laser co-focusing photo of embodiment 1 silicon plastid microcapsule;
Fig. 4 is the laser co-focusing photo in embodiment 1 after silicon plastid microcapsule load doxorubicin hydrochloride;
Fig. 5 is doxorubicin hydrochloride silicon plastid microcapsule drug release patterns in embodiment 2 (release conditions is in the phosphate buffered solution of pH=7.4 and pH=5.0);
Fig. 6 is the laser co-focusing photo in embodiment 3 after silicon plastid microcapsule load doxorubicin hydrochloride;
Fig. 7 is the laser co-focusing photo in embodiment 4 after the fat-soluble Coumarin-6 of silicon plastid microcapsule load;
Fig. 8 is the stereoscan photograph of paclitaxel silicon plastid microcapsule in embodiment 5.
Detailed description of the invention
Embodiment 1:
(1) Na of 0.025M is prepared respectively
2cO
3,ca (NO
3)
2the each 100mL of solution
ca (NO
3)
2add 400mg kayexalate (PSS) in solution, after it dissolves completely, add Na fast
2cO
3solution, 600 rpm stir 15s, and leave standstill 20min, centrifuge washing obtains calcium carbonate microparticle three times, and particle diameter is 5 microns, and Fig. 2 is shown in by laser co-focusing photo.
(2) precision takes 10mg organic-inorganic compound lipid 1 and is dissolved in 2mL chloroform, and rotary evaporation removing chloroform, forms the lipid membrane of layer of transparent at the bottom of eggplant-shape bottle bottle.By 4mg/mL uniform particle diameter and the CaCO of positively charged
3the solution 5mL of microsphere joins in lipid membrane, and water bath sonicator 5min after 30min is hatched in 45 DEG C of water-baths.After room temperature leaves standstill 12h, after adding 0.2M EDTA solution reaction a period of time, centrifugal except supernatant, above process can repeat 3-5 time, in order to thoroughly to remove calcium carbonate, obtains the silica nodule microcapsule of uniform particle diameter after enucleation.Fig. 3 is shown in by laser co-focusing photo.
(3) by the ammonium sulfate incubated at room of silicon plastid microcapsule preparation-obtained in embodiment 1 and 0.03M, after reaction 30min, the silica nodule microcapsule containing ammonium sulfate in capsule is obtained through sephadex column.By product and after doxorubicin hydrochloride incubated at room a period of time.The centrifugal 5min of 5000rpm/min is except supernatant, and obtain the uniform particle diameter silicon plastid microcapsule of load doxorubicin hydrochloride, the envelop rate of doxorubicin hydrochloride is 89.2%, and Fig. 4 is shown in by laser co-focusing photo.
Embodiment 2:
(1) with embodiment 1 step 1;
(2) with embodiment 1 step 2;
(3) with embodiment 1 step 3, the silicon plastid microcapsule of load doxorubicin hydrochloride is discharged medicine in the phosphate buffered solution of pH=7.4 and pH=5.0, detection of drugs rate of release, is shown in Fig. 5.This experimental group can illustrate that doxorubicin hydrochloride is wrapped in silicon plastid microcapsule can play slow releasing function to medicine, under neutrality or acid condition, have good slow release effect.
Embodiment 3:
(1) with embodiment 1 step 1;
(2) with embodiment 1 step 2, difference is that lipid used is organic-inorganic compound lipid 2.
(3) with embodiment 1 step 3, the envelop rate of doxorubicin hydrochloride is 84.4%.Illustrate and adopt organic-inorganic compound lipid 2 to have the ability of wrapping up hydrophilic medicament for silicon plastid microcapsule prepared by raw material, and envelop rate is very high.
Embodiment 4:
(1) with embodiment 1 step 1;
(2) with embodiment 1 step 2, difference is in organic-inorganic compound lipid solution, add a certain amount of fat-soluble Coumarin-6 (with green fluorescence simulation fat-soluble medicine), and Fig. 6 is shown in by laser co-focusing photo.
The microcapsule that this experimental group can obtain can be scattered in water uniformly, and laser confocal microscope photo is sectional view, can illustrate that silicon plastid microcapsule can wrap up hydrophobicity and hydrophilic medicament simultaneously.
Embodiment 5:
(1) with embodiment 1 step 1;
(2) with embodiment 1 step 2, difference is to get 0.1mL fat-soluble medicine paclitaxel alcoholic solution (concentration is 5mg/mL) and organic-inorganic compound lipid 1 is dissolved in 2mL chloroform together.In this embodiment, the envelop rate of paclitaxel reaches 92.8%, illustrate that silicon plastid microcapsule has the ability of load fat-soluble medicine, and envelop rate is very high.Scanning electron microscopic observation paclitaxel silicon plastid microcapsule has spherical structure and uniform particle diameter, good dispersion, sees Fig. 7.
Embodiment 6:
With embodiment 5, difference is that the lipid adopted is organic-inorganic compound lipid 2.In this embodiment, the envelop rate of paclitaxel reaches 90.5%, the ability adopting the silicon plastid microcapsule of organic-inorganic compound lipid 2 to have the fat-soluble medicine of load is described, and envelop rate is very high.
Claims (1)
1. a preparation method for paclitaxel silicon plastid microcapsule, is characterized in that comprising the steps:
(1) Na of 0.025M is prepared respectively
2cO
3, Ca (NO
3)
2the each 100mL Ca of solution (NO
3)
2add 400mg kayexalate in solution, after it dissolves completely, add Na fast
2cO
3solution, 600rpm stirs 15s, and leave standstill 20min, centrifuge washing obtains calcium carbonate microparticle three times, and particle diameter is 5 microns;
(2) precision takes 0.1mL fat-soluble medicine paclitaxel alcoholic solution, and concentration is 5mg/mL, is dissolved in 2mL chloroform together with organic-inorganic compound lipid 2, and rotary evaporation removing chloroform, forms the lipid membrane of layer of transparent at the bottom of eggplant-shape bottle bottle; By 4mg/mL uniform particle diameter and the CaCO of positively charged
3the solution 5mL of microsphere joins in lipid membrane, and water bath sonicator 5min after 30min is hatched in 45 DEG C of water-baths; After room temperature leaves standstill 12h, after adding 0.2M EDTA solution reaction, centrifugal except supernatant, above process repeats 3-5 time, in order to thoroughly to remove calcium carbonate, obtains the silica nodule microcapsule of uniform particle diameter after enucleation;
Organic-inorganic compound lipid 2:
Or
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210407849.1A CN102895216B (en) | 2012-10-24 | 2012-10-24 | Anti-cancer medicament silicon plastid microcapsule and preparation method thereof |
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| CN201210407849.1A Division CN102895216B (en) | 2012-10-24 | 2012-10-24 | Anti-cancer medicament silicon plastid microcapsule and preparation method thereof |
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| Publication Number | Publication Date |
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| CN103585132A CN103585132A (en) | 2014-02-19 |
| CN103585132B true CN103585132B (en) | 2015-07-22 |
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| CN104031080B (en) * | 2014-06-20 | 2016-07-13 | 东北林业大学 | Silica nodule being loaded with 10-hydroxycamptothecine and preparation method thereof |
| CN105708800B (en) * | 2016-02-02 | 2017-09-12 | 湖南师范大学 | A kind of Lovastatin silica nodule for targetting breast carcinoma stem cell |
| CN107158473B (en) * | 2017-05-08 | 2019-12-27 | 上海纳米技术及应用国家工程研究中心有限公司 | Calcium phosphate bone cement embedded with drug-loaded silica plastid and preparation method and application thereof |
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| 基于硅质体的新型纳米药物载体材料的研究;曹众;《哈尔滨工业大学博士学位论文2011》;20110715;第25-30页 * |
| 基于硅质体的紫杉醇抗癌药物释放系统;戴志飞等;《黑龙江大学自然科学学报》;20111030;第28卷(第5期);696-697 * |
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