CN103191049A - Tegafur/layered double hydroxide (TF/LDHs) nanohybrid-magnetic matrix compound and preparation method thereof - Google Patents
Tegafur/layered double hydroxide (TF/LDHs) nanohybrid-magnetic matrix compound and preparation method thereof Download PDFInfo
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- CN103191049A CN103191049A CN2012104947410A CN201210494741A CN103191049A CN 103191049 A CN103191049 A CN 103191049A CN 2012104947410 A CN2012104947410 A CN 2012104947410A CN 201210494741 A CN201210494741 A CN 201210494741A CN 103191049 A CN103191049 A CN 103191049A
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- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 title claims abstract description 60
- 229960001674 tegafur Drugs 0.000 title claims abstract description 45
- 238000002360 preparation method Methods 0.000 title claims abstract description 37
- 150000001875 compounds Chemical class 0.000 title claims abstract description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 title abstract description 5
- 239000011159 matrix material Substances 0.000 title abstract 10
- 238000006243 chemical reaction Methods 0.000 claims abstract description 15
- 239000000203 mixture Substances 0.000 claims abstract description 7
- SZVJSHCCFOBDDC-UHFFFAOYSA-N ferrosoferric oxide Chemical compound O=[Fe]O[Fe]O[Fe]=O SZVJSHCCFOBDDC-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000000758 substrate Substances 0.000 claims description 50
- 239000000243 solution Substances 0.000 claims description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 18
- 238000003756 stirring Methods 0.000 claims description 13
- 206010013786 Dry skin Diseases 0.000 claims description 10
- 239000003513 alkali Substances 0.000 claims description 10
- 239000007864 aqueous solution Substances 0.000 claims description 10
- 238000001035 drying Methods 0.000 claims description 10
- 229910052751 metal Inorganic materials 0.000 claims description 10
- 239000002184 metal Substances 0.000 claims description 10
- 229910021645 metal ion Inorganic materials 0.000 claims description 10
- 230000007935 neutral effect Effects 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 238000005406 washing Methods 0.000 claims description 10
- 150000001450 anions Chemical class 0.000 claims description 9
- 239000011229 interlayer Substances 0.000 claims description 6
- 230000032683 aging Effects 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 239000012266 salt solution Substances 0.000 claims description 4
- 239000013078 crystal Substances 0.000 claims description 3
- 229910052599 brucite Inorganic materials 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 36
- 229940079593 drug Drugs 0.000 abstract description 19
- 230000000694 effects Effects 0.000 abstract description 13
- 238000013270 controlled release Methods 0.000 abstract description 7
- 230000015572 biosynthetic process Effects 0.000 abstract description 5
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 231100000331 toxic Toxicity 0.000 abstract description 4
- 230000002588 toxic effect Effects 0.000 abstract description 4
- 238000000975 co-precipitation Methods 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 230000000857 drug effect Effects 0.000 abstract description 2
- 239000000969 carrier Substances 0.000 abstract 1
- 230000005389 magnetism Effects 0.000 abstract 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 9
- 229960004630 chlorambucil Drugs 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- 239000008367 deionised water Substances 0.000 description 8
- 229910021641 deionized water Inorganic materials 0.000 description 8
- 238000002798 spectrophotometry method Methods 0.000 description 8
- 230000005415 magnetization Effects 0.000 description 6
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 238000013211 curve analysis Methods 0.000 description 3
- 230000005408 paramagnetism Effects 0.000 description 3
- 239000006069 physical mixture Substances 0.000 description 3
- 230000008685 targeting Effects 0.000 description 3
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229960002949 fluorouracil Drugs 0.000 description 2
- 239000002114 nanocomposite Substances 0.000 description 2
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000003005 anticarcinogenic agent Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 description 1
- CBMPTFJVXNIWHP-UHFFFAOYSA-L disodium;hydrogen phosphate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].OP([O-])([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O CBMPTFJVXNIWHP-UHFFFAOYSA-L 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229960001545 hydrotalcite Drugs 0.000 description 1
- 229910001701 hydrotalcite Inorganic materials 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
- 230000002687 intercalation Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 229910001172 neodymium magnet Inorganic materials 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 230000003335 steric effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Abstract
The invention discloses a tegafur/layered double hydroxide (TF/LDHs) nanohybrid-magnetic matrix compound and a preparation method thereof. The preparation method utilizes LDHs as carriers to prepare the TF/LDHs nanohybrid-magnetic matrix compound. The TF/LDHs nanohybrid-magnetic matrix compound is used for targeted delivery and controlled release of tegafur, improves drug effects and reduces drug toxic and side effects. By a coprecipitation method, Fe3O4 or MgFe2O4 as a magnetic matrix is synthesized into the TF/LDHs nanohybrid-magnetic matrix compound which is a nano-complex composed of the magnetic matrix and TF intercalated LDHs coated on the magnetic matrix and is recorded as magnetic matrix @ (TF/LDHs). The TF/LDHs nanohybrid-magnetic matrix compound has strong magnetism and has good TF slow release effects. The preparation method has simple processes and allows mild reaction conditions. Through adjustment of magnetic matrix @ (TF/LDHs) nano-compound synthesis conditions and change of a drug concentration, a synthesis temperature, magnetic matrix content and applied magnetic field intensity, the structure, the composition and a release rate of the magnetic matrix @ (TF/LDHs) can be controlled.
Description
Technical field
The invention belongs to material and pharmaceutical preparations technology field, relate to complex of a kind of ftorafur/hydrotalcite-like compounds nano hybrid (TF/LDHs) and magnetic substrate and preparation method thereof.
Background technology
As everyone knows, the medicine particularly serious toxic and side effects of cancer therapy drug is a difficult problem of puzzlement medical profession, and therefore researching and developing new and effective drug targeting-control delivery is one of important topic of medicament educational circles.The magnetic target medicine transmission system is made up of magnetic substrate, carrier material, medicine and other adjuvants usually.By externally-applied magnetic field, the medicine-carried system with magnetic response can be accumulated in target site and discharge medicine, thereby improve the drug level of target site, reduce medicine to the toxic and side effects of normal structure etc.
Houghite claims layered double hydroxide (Layered double hydroxide, LDHs) hydroxide of being made up of bivalent metal ion and trivalent metal ion with hydrotalcite layered structure again.LDHs has the particular structure characteristics: one has layered crystal structure, synusia band structure positive charge; It two is that interlayer exists tradable anion.Special structure is given its special performances, studies have shown that the interlayer of LDHs can be used as miniature reservoir, drug molecule is inserted form medicine-LDH nano hybrid therebetween, because of the interaction between drug molecule and laminate and space steric effect, can realize effective controlled release of medicine.But medicine-LDH nano hybrid lacks the specific selectivity to diseased region, needs to solve its targeting problem.The magnetic substrate particle is wrapped in medicine-LDHs nano hybrid, form medicine-LDHs nano hybrid coated magnetic base complex, being abbreviated as " magnetic substrate @ (TF/LDHs) nano-complex ", constructing the magnetic target medicine transmission system, is one of effective way that solves its targeting.
(Tegafur is the fluorouracil derivant TF) to ftorafur, is used for the treatment of multiple cancers such as stomach, intestinal, liver, improves than the fluorouracil in treatment index, and toxicity reduces, but still has side effect such as bone marrow depression, gastrointestinal reaction, leukocyte and thrombocytopenia.Ftorafur is the time dependent behavior anticarcinogen, and it is relevant with exposing cell time length that namely medicine is killed the usefulness of cancerous cell, and therefore, it is favourable prolonging ftorafur holdup time in blood, tissue.The researcher all wishes by the galenic pharmacy means both at home and abroad at present, increases medicament slow release-controlled-release effect, strengthens drug targeting, reduces drug toxicity.
Summary of the invention
The present invention is directed to the deficiencies in the prior art, is carrier with LDHs, prepares the complex of ftorafur/hydrotalcite-like compounds nano hybrid and magnetic substrate, can be used for targeted and the controlled release of ftorafur, to improve drug effect, reduces poisonous side effect of medicine etc.
Content of the present invention is: with magnetite (Fe
3O
4) or magnoferrite (MgFe
2O
4) be magnetic substrate, adopt the magnetic Nano complex of the tool nucleocapsid structure of synthetic ftorafur (TF) intercalation houghite (LDHs) the coated magnetic substrate of coprecipitation, brief note is magnetic substrate @ (TF/LDHs) nano-complex, can be used for targeted and the slow release of ftorafur, effectively reduce its toxic and side effects.The present invention can realize the control to magnetic substrate @ (TF/LDHs) nanocomposite structures, composition and rate of release by adjusting the synthesis condition of magnetic substrate @ (TF/LDHs) nano-complex.
Concrete technical scheme of the present invention is: the complex of a kind of ftorafur/hydrotalcite-like compounds nano hybrid (TF/LDHs) and magnetic substrate, have the brucite layered crystal structure, and synusia contains bivalent metal ion (M
II) and trivalent metal ion (M
III), interlayer contains anion and ftorafur molecule, wherein: M
IIBe Mg
2+, Mn
2+, Fe
2+, Co
2+, Ni
2+, Cu
2+, Zn
2+In a kind of, M
IIIBe Al
3+, Cr
3+, Mn
3+, Fe
3+, Co
3+, Ni
3+In a kind of, interlayer anion is OH
-, CO
3 2-, SO
4 2-, CI
-, NO
3 -inOne or both; Described magnetic substrate is MgFe
2O
4(magnoferrite) or Fe
3O
4The magnetic retention granule.
Ftorafur quality percentage composition is 10%～35% in the described complex; The quality percentage composition of magnetic substrate is 1%～5%.
Coprecipitation is adopted in the preparation of the complex of described ftorafur/hydrotalcite-like compounds nano hybrid (TF/LDHs) and magnetic substrate, comprises the following steps:
A. compound concentration is 0.2～1.0mol/L solubility bivalent metal ion (M
II) and trivalent metal ion (M
III) mixing salt solution, both mol ratio M
II/ M
III=1～3: 1;
M wherein
IIBe Mg
2+, Mn
2+, Fe
2+, Co
2+, Ni
2+, Cu
2+, Zn
2+In one or both; M
IIIBe Al
3+, Cr
3+, Fe
3+In one or both; The anion of soluble-salt is SO
4 2-, CI
-, NO
3 -In one or both;
B. magnetic substrate is dissolved in the mixed-salt aqueous solution of step a preparation, the mass ratio of magnetic substrate and trivalent metal salt is 1: 100～1: 10;
C. compound concentration is the aqueous slkali of 0.3～3mol/L; Described aqueous slkali is NH
4OH, NaOH and Na
2CO
3In one or both;
D. ftorafur is dissolved in the aqueous alkali of step c preparation, being mixed with concentration is the ftorafur solution of 0.02～0.09mol/L.
E. steps d solution is joined in the step b solution, stirring and controlling pH is 10～12, and reaction temperature is 20～80 ℃; Response time is 1～3 hour, then the gained serosity is worn out 10～36 hours at 20～80 ℃, filters, and water washing is to neutral, and 60 ℃ of dryings obtain magnetic substrate @ (TF/LDHs) nano-complex.
The described mixing salt solution concentration of above-mentioned steps a is preferably 0.5mol/L; The anion of soluble-salt is preferably C
I-and NO
3 -
The preferred NaOH solution of the described aqueous slkali of above-mentioned steps c, concentration is 0.5mol/L.
The described ftorafur solution concentration of above-mentioned steps d is preferably 0.08mol/L.
The described pH value of above-mentioned steps e is preferably 11; Reaction temperature and aging temperature are 65 ℃; The stirring reaction time is 1 hour, and ageing time is 24 hours.
Ftorafur/hydrotalcite-like compounds nano hybrid (TF/LDHs) that preparation method of the present invention is obtained carries out XRD, TEM, FTIR and VSM with the complex (magnetic substrate @ (TF/LDHs)) of magnetic substrate and characterizes, result's demonstration has formed magnetic substrate @ (TF/LDHs) nano-complex, has stronger magnetic and good slow release effect.
Magnetic substrate @ (TF/LDHs) release experiment: magnetic substrate @ (TF/LDHs) the complex sample that takes by weighing 0.0050g, place 500ml sodium hydrogen phosphate-citric acid solution (pH=7.2 or 4.8), constant temperature is 37 ± 0.5 ℃ under stirring, take out the 4ml suspension at regular intervals, use 0.45 μ m membrane filtration immediately, adopt ultraviolet spectrophotometer to measure solution absorbency in wavelength 271nm place, draw the content of TF in the solution according to standard curve, and then calculate the release rate (X of TF
t).The release in vitro of complex sample under externally-applied magnetic field is the same, unique different be to be sidelong the Nd-Fe-B permanent magnet of putting a 1500G at one of beaker, its position keeps constant with respect to beaker.
The invention has the beneficial effects as follows:
1, prepared magnetic substrate @ (TF/LDHs) complex has stronger magnetic, and ftorafur is had the good slow release effect;
2, the preparation method technology that adopts is simple, reaction temperature and;
3, by adjusting the synthesis condition of magnetic substrate @ (TF/LDHs) nano-complex, as change factors such as drug concentrations, synthesis temperature, magnetic substrate content and externally-applied magnetic field intensity, can realize the control to magnetic substrate @ (TF/LDHs) nanocomposite structures, composition and rate of release.
Description of drawings
Fig. 1 is the MgFe of embodiment 1, embodiment 2 and embodiment 3 preparations
2O
4X-ray powder diffraction (XRD) figure of @ (TF/LDHs) nano-complex, other has MgFe
2O
4, TF, LDHs, TF-LDHs and MgFe
2O
4The XRD spectra of @LDHs as a comparison, wherein: a is MgFe
2O
4, b is TF, and c is LDHs, and d is MgFe
2O
4@LDHs, e are TF-LDHs, and f is embodiment 1; G is embodiment 2, and h is embodiment 3;
Fig. 2 is the MgFe of embodiment 1, embodiment 2 and embodiment 3 preparations
2O
4The hysteresis curve of @ (TF/LDHs) nano-complex, wherein: a is embodiment 1, and b is embodiment 2, and c is embodiment 3;
The MgFe of Fig. 3 embodiment 1, embodiment 2 and embodiment 3 preparations
2O
4The drug release kinetics curve of @ (TF/LDHs) nano-complex, A figure is under the no magnetic field condition, and B figure is under the 1500G externally-applied magnetic field condition, wherein: a is embodiment 1, and b is embodiment 2, and c is embodiment 3.
The specific embodiment
Embodiment described herein is some preferred implementation methods, is used for further describing and illustrating the present invention, is not intended to limit the invention to following definite details.
Embodiment 1:
A. with 5.95g (0.02mol) Zn (NO
3)
26H
2O and 3.75g (0.01mol) Al (NO
3)
39H
2O is dissolved in the 150mL deionized water.
B. with magnetic substrate MgFe
2O
4Be dissolved in the mixed-salt aqueous solution of step a preparation, the mass ratio of magnetic substrate and trivalent metal salt is 1: 50;
C. compound concentration is the NaOH solution of 0.3mol/L;
D. the 1.23g ftorafur is dissolved in the aqueous alkali of step c preparation, being mixed with concentration is the ftorafur solution of 0.08mol/L.
E. steps d solution is joined in the step b solution, stirring and controlling pH is 10, and reaction temperature is 20 ℃; Response time is 3 hours, then the gained serosity is worn out 36 hours at 20 ℃, filters, and water washing is to neutral, and 60 ℃ of dryings obtain MgFe
2O
4@ (TF/LDHs) nano-complex.
By XRD spectra (Fig. 1 f) as can be known, this MgFe
2O
4@ (TF/LDHs) nano-complex has the stratiform crystalline structure, and skin is the TF-LDHs nano hybrid, and kernel is MgFe
2O
4Adopt ultraviolet spectrophotometry that sample is analyzed, the content of determining ftorafur is 21.75%; Know that by elementary analysis magnetic substrate content is 2.52%; The hysteresis curve analysis result is seen Fig. 2 a, and visible sample has paramagnetism, and specific saturation magnetization is 0.26emu/g, and coercivity is 0Oe; The drug release experimental result is seen Fig. 3 a, and visible magnetic nuclear content is more big or specific saturation magnetization is more high, and drug release rate is more low, and externally-applied magnetic field can obviously slow down the release of medicine.As seen the rate of release of chlorambucil/LDHs nano hybrid is starkly lower than the physical mixture of the former medicine of chlorambucil and LDHs, shows that chlorambucil/LDHs nano hybrid has the excellent drug controlled-release effect.
Embodiment 2:
A. with 5.95g (0.02mol) Zn (NO
3)
26H
2O and 3.75g (0.01mol) Al (NO
3)
39H
2O is dissolved in the 150mL deionized water.
B. with magnetic substrate MgFe
2O
4Be dissolved in the mixed-salt aqueous solution of step a preparation, the mass ratio of magnetic substrate and trivalent metal salt is 1: 20;
C. compound concentration is the NaCO of 3mol/L
3Solution;
D. the 0.50g ftorafur is dissolved in the aqueous alkali of step c preparation, being mixed with concentration is the ftorafur solution of 0.02mol/L.
E. steps d solution is joined in the step b solution, stirring and controlling pH is 12, and reaction temperature is 80 ℃; Response time is 1 hour, then the gained serosity is worn out 10 hours at 80 ℃, filters, and water washing is to neutral, and 60 ℃ of dryings obtain MgFe
2O
4@ (TF/LDHs) nano-complex.
By XRD spectra (Fig. 1 g) as can be known, this MgFe
2O
4@ (TF/LDHs) nano-complex has the stratiform crystalline structure, and skin is the TF-LDHs nano hybrid, and kernel is MgFe
2O
4Adopt ultraviolet spectrophotometry
Sample is analyzed, and the content of determining ftorafur is 10.11%; Know that by elementary analysis magnetic substrate content is 3.31%; The hysteresis curve analysis result is seen Fig. 2 b, and visible sample has paramagnetism, and specific saturation magnetization is 0.46emu/g, and coercivity is 0Oe; The drug release experimental result is seen Fig. 3 b, and visible magnetic nuclear content is more big or specific saturation magnetization is more high, and drug release rate is more low, and externally-applied magnetic field can obviously slow down the release of medicine.As seen the rate of release of chlorambucil/LDHs nano hybrid is starkly lower than the physical mixture of the former medicine of chlorambucil and LDHs, shows that chlorambucil/LDHs nano hybrid has the excellent drug controlled-release effect.
Embodiment 3:
A. with 5.95g (0.02mol) Zn (NO
3)
26H
2O and 3.75g (0.01mol) Al (NO
3)
39H
2O is dissolved in the 150mL deionized water.
B. with magnetic substrate MgFe
2O
4Be dissolved in the mixed-salt aqueous solution of step a preparation, the mass ratio of magnetic substrate and trivalent metal salt is 1: 10;
C. compound concentration is the NaOH solution of 0.5mol/L;
D. the 1.40g ftorafur is dissolved in the aqueous alkali of step c preparation, being mixed with concentration is the ftorafur solution of 0.09mol/L.
E. steps d solution is joined in the step b solution, stirring and controlling pH is 11, and reaction temperature is 65 ℃; Response time is 2 hours, then the gained serosity is worn out 24 hours at 65 ℃, filters, and water washing is to neutral, and 60 ℃ of dryings obtain MgFe
2O
4@ (TF/LDHs) nano-complex.
By XRD spectra (Fig. 1 h) as can be known, this MgFe
2O
4@ (TF/LDHs) nano-complex has the stratiform crystalline structure, and skin is the TF-LDHs nano hybrid, and kernel is MgFe
2O
4Adopt ultraviolet spectrophotometry that sample is analyzed, the content of determining ftorafur is 35.24%; Know that by elementary analysis magnetic substrate content is 5.05%; The hysteresis curve analysis result is seen Fig. 2 c, and visible sample has paramagnetism, and specific saturation magnetization is 1.38emu/g, and coercivity is 0Oe; The drug release experimental result is seen Fig. 3 c, and visible magnetic nuclear content is more big or specific saturation magnetization is more high, and drug release rate is more low, and externally-applied magnetic field can obviously slow down the release of medicine.As seen the rate of release of chlorambucil/LDHs nano hybrid is starkly lower than the physical mixture of the former medicine of chlorambucil and LDHs, shows that chlorambucil/LDHs nano hybrid has the excellent drug controlled-release effect.
Embodiment 4:
A. with 4.06g (0.02mol) MgCI
26H
2O and 0.01mol Al
2(SO4)
318H
2O is dissolved in the 30mL deionized water.
B. with magnetic substrate MgFe
2O
4Be dissolved in the mixed-salt aqueous solution of step a preparation, the mass ratio of magnetic substrate and trivalent metal salt is 1: 60;
C. compound concentration is the NH of 1.5mol/L
4OH solution;
D. the 0.47g ftorafur is dissolved in the aqueous alkali of step c preparation, being mixed with concentration is the ftorafur solution of 0.03mol/L.
E. steps d solution is joined in the step b solution, stirring and controlling pH is 10.5, and reaction temperature is 50 ℃; Response time is 1.5 hours, then the gained serosity is worn out 18 hours at 50 ℃, filters, and water washing is to neutral, and 60 ℃ of dryings obtain MgFe
2O
4@ (TF/LDHs) nano-complex.
Adopt ultraviolet spectrophotometry that sample is analyzed, the content of determining ftorafur is 15.83%; Know that by elementary analysis magnetic substrate content is 2.15%.
Embodiment 5:
A. with the ZnCI of 0.010mol
26H
2O and 0.010mol AlCI
36H
2O is dissolved in the 35mL deionized water.
B. with magnetic substrate Fe
3O
4Be dissolved in the mixed-salt aqueous solution of step a preparation, the mass ratio of magnetic substrate and trivalent metal salt is 1: 100;
C. compound concentration is the NaOH solution of 1.5mol/L;
D. the 1.23g ftorafur is dissolved in the aqueous alkali of step c preparation, being mixed with concentration is the ftorafur solution of 0.08mol/L.
E. steps d solution is joined in the step b solution, stirring and controlling pH is 10.5, and reaction temperature is 35 ℃; Response time is 2.5 hours, then the gained serosity is worn out 12 hours at 35 ℃, filters, and water washing is to neutral, and 60 ℃ of dryings obtain Fe
3O
4@ (TF/LDHs) nano-complex.
Adopt ultraviolet spectrophotometry that sample is analyzed, the content of determining ftorafur is 31.06%; Know that by elementary analysis magnetic substrate content is 1.09%.
Embodiment 6:
A. with the ZnCI of 0.020mol
2With 0.010mol CrCI
36H
2O is dissolved in the 35ml deionized water.
B. with magnetic substrate Fe
3O
4Be dissolved in the mixed-salt aqueous solution of step a preparation, the mass ratio of magnetic substrate and trivalent metal salt is 1: 90;
C. compound concentration is the NaOH solution of 0.5mol/L;
D. the 1.64g ftorafur is dissolved in the aqueous alkali of step c preparation, being mixed with concentration is the ftorafur solution of 0.06mol/L.
E. steps d solution is joined in the step b solution, stirring and controlling pH is 12, and reaction temperature is 45 ℃; Response time is 3 hours, then the gained serosity is worn out 30 hours at 45 ℃, filters, and water washing is to neutral, and 60 ℃ of dryings obtain Fe
3O
4@ (TF/LDHs) nano-complex.
Adopt ultraviolet spectrophotometry that sample is analyzed, the content of determining ftorafur is 23.92%; Know that by elementary analysis magnetic substrate content is 1.32%.
Embodiment 7:
A. with the FeCI of 0.01mol
24H
2O and 0.01mol AlCI
36H
2O is dissolved in the 35ml deionized water.
B. with magnetic substrate Fe
3O
4Be dissolved in the mixed-salt aqueous solution of step a preparation, the mass ratio of magnetic substrate and trivalent metal salt is 1: 70;
C. compound concentration is the NaOH solution of 1.0mol/L;
D. the 1.23g ftorafur is dissolved in the aqueous alkali of step c preparation, being mixed with concentration is the ftorafur solution of 0.08mol/L.
E. steps d solution is joined in the step b solution, stirring and controlling pH is 12, and reaction temperature is 75 ℃; Response time is 1 hour, then the gained serosity is worn out 10 hours at 75 ℃, filters, and water washing is to neutral, and 60 ℃ of dryings obtain Fe
3O
4@ (TF/LDHs) nano-complex.
Adopt ultraviolet spectrophotometry that sample is analyzed, the content of determining ftorafur is 27.40%; Know that by elementary analysis magnetic substrate content is 1.97%.
Embodiment 8:
A. with the Zn (NO of 0.01mol
3)
26H
2O and 0.01mol Al (NO
3)
39H
2O is dissolved in the 40ml deionized water.
B. with magnetic substrate Fe
3O
4Be dissolved in the mixed-salt aqueous solution of step a preparation, the mass ratio of magnetic substrate and trivalent metal salt is 1: 30;
C. compound concentration is the NaCO of 1.0mol/L
3Solution;
D. the 1.23g ftorafur is dissolved in the aqueous alkali of step c preparation, being mixed with concentration is the ftorafur solution of 0.08mol/L.
E. steps d solution is joined in the step b solution, stirring and controlling pH is 11, and reaction temperature is 55 ℃; Response time is 2 hours, then the gained serosity is worn out 16 hours at 55 ℃, filters, and water washing is to neutral, and 60 ℃ of dryings obtain Fe
3O
4@ (TF/LDHs) nano-complex.
Adopt ultraviolet spectrophotometry that sample is analyzed, the content of determining ftorafur is 25.73%; Know that by elementary analysis magnetic substrate content is 2.98%.
Claims (7)
1. the complex of a ftorafur/hydrotalcite-like compounds nano hybrid (TF/LDHs) and magnetic substrate, it is characterized in that: described ftorafur/hydrotalcite-like compounds nano hybrid has the brucite layered crystal structure, and synusia contains bivalent metal ion (M
II) and trivalent metal ion (M
III), interlayer contains anion and ftorafur molecule, wherein: M
IIBe Mg
2+, Mn
2+, Fe
2+, Co
2+, Ni
2+, Cu
2+, Zn
2+In a kind of, M
IIIBe Al
3+, Cr
3+, Mn
3+, Fe
3+, Co
3+, Ni
3+In a kind of, interlayer anion is OH
-, CO
3 2-, SO
4 2-, CI
-, NO
3 -In one or both; Described magnetic substrate is magnetite (Fe
3O
4) or magnoferrite (MgFe
2O
4).
2. the complex of ftorafur/hydrotalcite-like compounds nano hybrid according to claim 1 (TF/LDHs) and magnetic substrate, it is characterized in that: ftorafur quality percentage composition is 10%～35% in the described complex; The quality percentage composition of magnetic substrate is 1%～5%.
3. the preparation method of the complex of a ftorafur/hydrotalcite-like compounds nano hybrid as claimed in claim 1 (TF/LDHs) and magnetic substrate is characterized in that, comprises the following steps:
A. compound concentration is 0.2～1.0mol/L solubility bivalent metal ion (M
II) and trivalent metal ion (M
III) mixing salt solution, both mol ratio M
II/ M
III=1～3: 1;
M wherein
IIBe Mg
2+, Mn
2+, Fe
2+, Co
2+, Ni
2+, Cu
2+, Zn
2+In one or both; M
IIIBe Al
3+, Cr
3+, Fe
3+In one or both; The anion of soluble-salt is SO
4 2-, CI
-, NO
3 -In one or both;
B. magnetic substrate is dissolved in the mixed-salt aqueous solution of step a preparation, the mass ratio of magnetic substrate and trivalent metal salt is 1: 100～1: 10;
C. compound concentration is the aqueous slkali of 0.3～3mol/L; Described aqueous slkali is NH
4OH, NaOH and Na
2CO
3In one or both;
D. ftorafur is dissolved in the aqueous alkali of step c preparation, being mixed with concentration is the ftorafur solution of 0.02～0.09mol/L.
E. steps d solution is joined in the step b solution, stirring and controlling pH is 10～12, and reaction temperature is 20～80 ℃; Response time is 1～3 hour, then the gained serosity is worn out 10～36 hours at 20～80 ℃, filters, and water washing is to neutral, and 60 ℃ of dryings obtain magnetic substrate @ (TF/LDHs) nano-complex.
4. the preparation method of the complex of ftorafur/hydrotalcite-like compounds nano hybrid according to claim 3 (TF/LDHs) and magnetic substrate, it is characterized in that: the described mixing salt solution concentration of step a is preferably 0.5mol/L; The anion of soluble-salt is preferably CI
-And NO
3 -
5. the preparation method of the complex of ftorafur/hydrotalcite-like compounds nano hybrid according to claim 3 (TF/LDHs) and magnetic substrate, it is characterized in that: the preferred NaOH solution of the described aqueous slkali of step c, concentration is 0.5mol/L.
6. the preparation method of the complex of ftorafur/hydrotalcite-like compounds nano hybrid according to claim 3 (TF/LDHs) and magnetic substrate, it is characterized in that: the described ftorafur solution concentration of steps d is preferably 0.08mol/L.
7. the preparation method of the complex of ftorafur/hydrotalcite-like compounds nano hybrid according to claim 3 (TF/LDHs) and magnetic substrate, it is characterized in that: the described pH value of step e is preferably 11; Reaction temperature and aging temperature are 65 ℃; The stirring reaction time is 1 hour, and ageing time is 24 hours.
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| CN106552269A (en) * | 2015-09-23 | 2017-04-05 | 南京理工大学 | A kind of pH responsive types Fe3O4The Nano medication particle of@LDH load methotrexate (MTX)s, preparation method and applications |
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Cited By (6)
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| CN103505741A (en) * | 2013-09-18 | 2014-01-15 | 青岛科技大学 | Tegafur-layered double-metal hydroxide nanometer hybrid modified with polyethylene glycol derivative on surface and preparation of nanometer hybrid |
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| CN106552269A (en) * | 2015-09-23 | 2017-04-05 | 南京理工大学 | A kind of pH responsive types Fe3O4The Nano medication particle of@LDH load methotrexate (MTX)s, preparation method and applications |
| CN106552269B (en) * | 2015-09-23 | 2019-04-16 | 南京理工大学 | A kind of pH responsive type Fe3O4@LDH loads the Nano medication particle of methotrexate (MTX), preparation method and applications |
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