CN104511027A - Camptothecin-hydrotalcite-like nanohybrid and preparation method thereof - Google Patents
Camptothecin-hydrotalcite-like nanohybrid and preparation method thereof Download PDFInfo
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- CN104511027A CN104511027A CN201410821526.6A CN201410821526A CN104511027A CN 104511027 A CN104511027 A CN 104511027A CN 201410821526 A CN201410821526 A CN 201410821526A CN 104511027 A CN104511027 A CN 104511027A
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- camptothecine
- hydrotalcite
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- 238000002360 preparation method Methods 0.000 title claims abstract description 30
- 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 claims abstract description 39
- 150000002596 lactones Chemical class 0.000 claims abstract description 13
- 239000006185 dispersion Substances 0.000 claims abstract description 10
- 239000002253 acid Substances 0.000 claims abstract description 8
- 239000004094 surface-active agent Substances 0.000 claims abstract description 8
- 150000007942 carboxylates Chemical class 0.000 claims abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 14
- 230000002687 intercalation Effects 0.000 claims description 14
- 238000009830 intercalation Methods 0.000 claims description 14
- 238000002156 mixing Methods 0.000 claims description 14
- 239000000047 product Substances 0.000 claims description 14
- 239000012266 salt solution Substances 0.000 claims description 14
- 239000000243 solution Substances 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- 239000000725 suspension Substances 0.000 claims description 11
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- 238000001935 peptisation Methods 0.000 claims description 7
- 229910021645 metal ion Inorganic materials 0.000 claims description 6
- 238000013019 agitation Methods 0.000 claims description 5
- 239000002244 precipitate Substances 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 4
- -1 N-dodecyl hydroxyethyl ammonium phosphate ester Chemical class 0.000 claims description 4
- 235000011054 acetic acid Nutrition 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 150000001450 anions Chemical class 0.000 claims description 4
- 239000008367 deionised water Substances 0.000 claims description 4
- 229910021641 deionized water Inorganic materials 0.000 claims description 4
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 4
- 150000002500 ions Chemical class 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 239000011229 interlayer Substances 0.000 claims description 3
- 229920001223 polyethylene glycol Polymers 0.000 claims description 3
- 229940116351 sebacate Drugs 0.000 claims description 3
- CXMXRPHRNRROMY-UHFFFAOYSA-L sebacate(2-) Chemical compound [O-]C(=O)CCCCCCCCC([O-])=O CXMXRPHRNRROMY-UHFFFAOYSA-L 0.000 claims description 3
- 235000010413 sodium alginate Nutrition 0.000 claims description 3
- 239000000661 sodium alginate Substances 0.000 claims description 3
- 229940005550 sodium alginate Drugs 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- 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 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- JWGGSJFIGIGFSQ-UHFFFAOYSA-N N-dodecanoylglycine Chemical compound CCCCCCCCCCCC(=O)NCC(O)=O JWGGSJFIGIGFSQ-UHFFFAOYSA-N 0.000 claims description 2
- APUPDPNHNDZOEU-TYOUJGAFSA-N N[C@@H](C)C(=O)O.C(CCCCCCCCCCC)N[Na] Chemical compound N[C@@H](C)C(=O)O.C(CCCCCCCCCCC)N[Na] APUPDPNHNDZOEU-TYOUJGAFSA-N 0.000 claims description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Natural products OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
- 235000015165 citric acid Nutrition 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 239000000693 micelle Substances 0.000 claims description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- FCBUKWWQSZQDDI-UHFFFAOYSA-N rhamnolipid Chemical compound CCCCCCCC(CC(O)=O)OC(=O)CC(CCCCCCC)OC1OC(C)C(O)C(O)C1OC1C(O)C(O)C(O)C(C)O1 FCBUKWWQSZQDDI-UHFFFAOYSA-N 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 23
- 229940127093 camptothecin Drugs 0.000 abstract description 18
- 229940079593 drug Drugs 0.000 abstract description 16
- 238000011068 loading method Methods 0.000 abstract description 9
- 238000000034 method Methods 0.000 abstract description 4
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 abstract description 3
- 230000004071 biological effect Effects 0.000 abstract description 3
- 238000000975 co-precipitation Methods 0.000 abstract description 3
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 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 abstract 1
- 229960001545 hydrotalcite Drugs 0.000 abstract 1
- 229910001701 hydrotalcite Inorganic materials 0.000 abstract 1
- 230000009466 transformation Effects 0.000 abstract 1
- 230000001131 transforming effect Effects 0.000 abstract 1
- 230000005540 biological transmission Effects 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- 235000011121 sodium hydroxide Nutrition 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 235000011114 ammonium hydroxide Nutrition 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- PAEZRCINULFAGO-OAQYLSRUSA-N (R)-homocamptothecin Chemical compound CC[C@@]1(O)CC(=O)OCC(C2=O)=C1C=C1N2CC2=CC3=CC=CC=C3N=C21 PAEZRCINULFAGO-OAQYLSRUSA-N 0.000 description 1
- FXALIOUHXMVTMJ-UHFFFAOYSA-N CCCCCCCCCCCC([Na])=O Chemical compound CCCCCCCCCCCC([Na])=O FXALIOUHXMVTMJ-UHFFFAOYSA-N 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 235000013905 glycine and its sodium salt Nutrition 0.000 description 1
- 239000004247 glycine and its sodium salt Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 238000007634 remodeling Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 229940029258 sodium glycinate Drugs 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a preparation method of a camptothecin-hydrotalcite-like nanohybrid. The preparation method comprises the following steps: firstly, preparing a camptothecin-intercalated hydrotalcite-like nanohybrid by using a microreactor by a coprecipitation method; secondly, according to reversibility of structural transformation of lactone and carboxylate in a camptothecin molecule, transforming a drug into a lactone structure with high biological activity by using weak acid; finally, processing the lactone structure by using a surfactant. The obtained hybrid is high in drug loading capacity, good in slow-release performance and high in dispersion; the drug exists between hydrotalcite layers in form of the lactone structure with high biological activity; the camptothecin-hydrotalcite-like nanohybrid prepared by the preparation method is beneficial to clinical application.
Description
Technical field
The invention belongs to technical field of nanometer material preparation, be specifically related to a kind of camptothecine-hydrotalcite-like compounds nano hybrid with polymolecularity and preparation method thereof.
Background technology
Camptothecine (Camptothecin, CPT) be the cancer therapy drug of a class clinical practice, lactone structure in its molecule is unstable, but, it is transsexual that lactone type structure and the inactive carboxylic acid type structure of camptothecine tool activity have the corresponding reversible of pH, that is: in acid condition, low bioactive drug molecule can be converted to the drug molecule with high bioactivity.
Because houghite (HTlc) has good biocompatibility, intercalation and controlled release properties, receive much concern in drug conveying and controlled release field, common medicine-HTlc nano hybrid preparation method has coprecipitation, ion exchange, structural remodeling method, altogether construction from part, secondary intercalation method etc.Due to the pH sensitivity of HCPT, camptothecine-HTlc hybrid drug loading prepared by coprecipitation is high, but medicine exists and the bad dispersibility of hybrid with low bioactive carboxylate structure, camptothecine modified by the surfactant (sodium cholate) of the report such as Tyner, intercalation is realized by ion exchange, although medicine exists with lactone structure, but the bad dispersibility of hybrid and low [the Tyner K.M. of drug loading, Schiffman S.R., Giannelis E.P., Nanobiohybrids as delivery vehicles for camptothecin, J.Control.Release, 2004, 95 (3): 501-504.], with regard to present result of study, dispersibility is the major issue that houghite base nano hybrid exists, it restricts greatly the clinical practice of medicine-hybrid.And for hydrophobic drug camptothecine, except the dispersion problem of hybrid will be solved, the biological activity problem of drug loading and medicine also to be solved.
Summary of the invention
An object of the present invention is to provide a kind of camptothecine-hydrotalcite-like compounds nano hybrid and preparation method thereof, and the product grain of current preparation is large, dispersibility and slow-releasing difference and the low problem of drug loading to utilize content of the present invention to solve.
Camptothecine-hydrotalcite-like compounds nano hybrid provided by the invention, its general formula is [M
2+ (1-X)m
3+ x(OH)
2] (Y
n)
a(CPT)
bmH
2o, wherein, M
2+for bivalent metal ion, M
3+for trivalent metal ion, Y
n-for n valency anion, n is anion valence mumber, and CPT is camptothecine, and X is the M in every mole of houghite
3+molal quantity, m is the molal quantity of every mole of houghite interlayer water of crystallization, a=0.1 ~ 0.33, b=0.02 ~ 1.Wherein, M
2+comprise ION Mg
2+, Fe
2+, Zn
2+, and Ca
2+in one or more, M
3+comprise ion A l
3+, Fe
3+in one, Y
ncomprise Cl
-, NO
3 -, HCO
3 -, CO
3 2-, ClO
3 -in one or more.
The preparation method of camptothecine-hydrotalcite-like compounds nano hybrid provided by the invention, comprises the following steps:
By solubility bivalent inorganic salt M
2+y and trivalent inorganic salt M
3+y presses M
2+: M
3+mol ratio is that the ratio of 2:1-4:1 mixes and dissolves and is configured to mixing salt solution in deionized water;
Preparation aqueous slkali, is dissolved in camptothecine in aqueous slkali, is mixed with camptothecine aqueous slkali;
By mixing salt solution and camptothecine aqueous slkali, hybrid reaction in micro passage reaction is precipitated thing;
Be separated through centrifuge by the precipitate obtained and fully wash with deionized water, then at 60 DEG C, peptization forms dispersion liquid in 12 hours, obtains the camptothecine intercalation hydrotalcite-like nanometer hybrid of carboxylate structure, is designated as CPT
c-LDH;
Weak acid solution is dropwise added CPT
cin the dispersion liquid of-LDH, adjust ph is 5-6.5, stirs and forms suspension in 6-24 hour, obtain the nano hybrid of the camptothecine intercalation houghite of lactone structure, be designated as CPT at 30-80 DEG C
l-LDH;
Surfactant is added in above-mentioned suspension, centrifugal and dry after Keep agitation, obtain product.
In preparation method, the metal ion total concentration of described mixing salt solution is 0.01-1mol/L; M
2+comprise ION Mg
2+, Fe
2+, Zn
2+, and Ca
2+in one or both, M
3+comprise ion A l
3+, Fe
3+in one, Y
ncomprise Cl
-, NO
3 -, HCO
3 -in one or both.
In preparation method, described aqueous slkali is one or both in sodium hydroxide, potassium hydroxide and ammonia, and the concentration of sodium hydroxide or potassium hydroxide solution is 0.01-1mol/L; The mass concentration of ammonia is 5-15%.
In preparation method, the concentration of described camptothecine aqueous slkali is 0.005-0.05mol/L.
In preparation method, in described micro passage reaction, the flow velocity of mixing salt solution and camptothecine aqueous slkali is 5-25ml/min, and control as 9-11 from the pH value of the product suspension of micro passage reaction outlet outflow, reaction temperature is 20-80 DEG C; Described micro passage reaction is T-shaped, and the width of microchannel is 0.2-0.9mm, and the degree of depth is 0.2-0.8mm, and length is 5-50mm.
In preparation method, described weak acid solution is one or more in citric acid, tartaric acid, formic acid, acetic acid, propanoic acid, ethanedioic acid, malonic acid, succinic acid, and the volumetric concentration of described weak acid solution is 5-10%.
In preparation method; described surfactant is one or more in rhamnolipid, Polyethylene Glycol sebacate, sodium alginate, dodecylamino Sodium L-alaninate, lauroyl Glycine sodium, N-dodecyl hydroxyethyl ammonium phosphate ester or N, N-dibutyl dodecyl hydroxyethyl ammonium phosphate ester.
In preparation method, the concentration of described surfactant in suspension is 0.1-10 doubly its critical micelle concentration.
Beneficial effect of the present invention is: compared with prior art, and the present invention has prepared the nano hybrid of short grained camptothecine intercalation houghite, and medicine exists with the lactone structure of high bioactivity at houghite interlayer, and drug loading is high, and sustained release performance is good.The preparation condition of this preparation method is gentle, and prepared hybrid good dispersion, is conducive to the clinical practice of camptothecine-hydrotalcite-like compounds nano hybrid.
Accompanying drawing explanation
Fig. 1 is the TEM photo of embodiment 1 products therefrom that the present invention relates to;
Fig. 2 is the TEM photo of embodiment 2 products therefrom that the present invention relates to;
Fig. 3 is the TEM photo of embodiment 3 products therefrom that the present invention relates to.
Detailed description of the invention
Hereafter will describe content of the present invention in conjunction with specific embodiments in detail.It should be noted that the combination of technical characteristic or the technical characteristic described in following embodiment should not be considered to isolated, they can mutually be combined thus be reached better technique effect.
Embodiment 1
Fig. 1 is the TEM photo of embodiment 1 products therefrom that the present invention relates to.
First take the Al (NO of 0.375g
3)
39H
2zn (the NO of O and 0.297g
3)
26H
2o is dissolved in 20ml water, obtain mixing salt solution, 0.0085g camptothecine being dissolved in 20ml concentration is be mixed with camptothecine aqueous slkali in the sodium hydrate aqueous solution of 0.05mol/L, at reaction temperature is 25 DEG C, T-shaped microreactor is utilized to be mixed by two kinds of solution, the flow velocity of mixing salt solution and camptothecine aqueous slkali is 20ml/min, in microreactor, hybrid reaction is precipitated thing, precipitate is fully washed and centrifugal after at 60 DEG C peptization 12 hours, obtain the camptothecine intercalation hydrotalcite-like nanometer hybrid of carboxylate structure, be designated as CPT
c-LDH.By volumetric concentration be 5% dilute acetic acid solution dropwise add CPT
cin the dispersion liquid of-ZnAl-LDH, adjust ph is 5.5, stirs 6 hours, obtain the nano hybrid of the camptothecine intercalation houghite of lactone structure, be designated as CPT at 60 DEG C
l-ZnAl-LDH.In above-mentioned suspension, add the Polyethylene Glycol sebacate that concentration is 0.05g/L, Keep agitation is centrifugal and dry after 24 hours, obtains product.
The drug loading of the hybrid that the present embodiment obtains is 12.2%, the time that medicine discharges completely in the buffer solution of pH7.2 is 25.1 hours, the pattern of JEM-2100 type transmission electron microscope TEM to sample is adopted to characterize, found that, obtain the product of polymolecularity, electromicroscopic photograph as shown in Figure 1.
Embodiment 2
Fig. 2 is the TEM photo of embodiment 2 products therefrom that the present invention relates to.
Take 0.375g Al (NO
3)
39H
2o and 0.297g Zn (NO
3)
26H
2o is dissolved in 20ml water, obtain mixing salt solution, 0.0089g camptothecine being dissolved in 20ml mass concentration is make camptothecine aqueous slkali in the dilute ammonia solution of 7%, at reaction temperature is 25 DEG C, T-shaped microreactor is utilized to be mixed by two kinds of solution, the flow velocity of mixing salt solution and camptothecine aqueous slkali is 20ml/min, in microreactor, hybrid reaction is precipitated thing, precipitate is fully washed and centrifugal after at 60 DEG C peptization 12 hours, obtain the camptothecine intercalation hydrotalcite-like nanometer hybrid of carboxylate structure, be designated as CPT
c-ZnAl-LDH.By volumetric concentration be 5% dilute acetic acid solution dropwise add CPT
cin the dispersion liquid of-ZnAl-LDH, adjust ph is 5.5, stirs 6 hours, obtain the nano hybrid of the camptothecine intercalation houghite of lactone structure, be designated as CPT at 60 DEG C
l-ZnAl-LDH.In above-mentioned suspension, add the sodium alginate soln that concentration is 0.02g/L, Keep agitation is centrifugal and dry after 24 hours, obtains product.
The drug loading of the hybrid that the present embodiment obtains is 15.2%, the time that medicine discharges completely in the buffer solution of pH7.2 is 22.0 hours, adopt the pattern of JEM-2100 type transmission electron microscope TEM to sample to characterize, electromicroscopic photograph result as shown in Figure 2.
Embodiment 3
Fig. 3 is the TEM photo of embodiment 3 products therefrom that the present invention relates to.
Take 0.375g Al (NO
3)
39H
2o and 0.256g Mg (NO
3)
26H
2o is dissolved in 20ml water, obtain mixing salt solution, 0.0089g camptothecine being dissolved in 20ml mass concentration is make camptothecine aqueous slkali in the dilute ammonia solution of 7%, at reaction temperature is 25 DEG C, T-shaped microreactor is utilized to be mixed by two kinds of solution, the flow velocity of mixing salt solution and camptothecine aqueous slkali is 20ml/min, in microreactor, hybrid reaction is precipitated thing, precipitate is fully washed and centrifugal after at 60 DEG C peptization 24 hours, obtain the camptothecine intercalation hydrotalcite-like nanometer hybrid of carboxylate structure, be designated as CPT
c-MgAl-LDH.By mass concentration be 0.5% citric acid solution dropwise add CPT
cin the dispersion liquid of-MgAl-LDH, adjust ph is 6.0, stirs 12 hours, obtain the nano hybrid of the camptothecine intercalation houghite of lactone structure, be designated as CPT at 60 DEG C
l-MgAl-LDH.In above-mentioned suspension, add concentration is 6.46 × 10
-3the lauroyl sodium glycinate solution of mol/L, Keep agitation is centrifugal and dry after 24 hours, obtains product.
The drug loading of the hybrid that the present embodiment obtains is 13.6%, and the time that medicine discharges completely in the buffer solution of pH7.2 is 5.7 hours, and adopt the pattern of JEM-2100 type transmission electron microscope TEM to sample to characterize, photographic result as shown in Figure 3.
Although give some embodiments of the present invention, it will be understood by those of skill in the art that without departing from the spirit of the invention herein, can change embodiment herein.Above-described embodiment is exemplary, should using embodiment herein as the restriction of interest field of the present invention.
Claims (10)
1. camptothecine-hydrotalcite-like compounds nano hybrid, is characterized in that, the general formula of described camptothecine-hydrotalcite-like compounds nano hybrid is [M
2+ (1-X)m
3+ x(OH)
2] (Y
n)
a(CPT)
bmH
2o, wherein, M
2+for bivalent metal ion, M
3+for trivalent metal ion, Y
n-for n valency anion, n is anion valence mumber, and CPT is camptothecine, and X is the M in every mole of houghite
3+molal quantity, m is the molal quantity of every mole of houghite interlayer water of crystallization, a=0.1 ~ 0.33, b=0.02 ~ 1.
2. a kind of camptothecine-hydrotalcite-like compounds nano hybrid as claimed in claim 1, is characterized in that, described M
2+comprise ION Mg
2+, Fe
2+, Zn
2+, and Ca
2+in one or both, described M
3+comprise ion A l
3+, Fe
3+in one, described Y
ncomprise Cl
-, NO
3 -, HCO
3 -, CO
3 2-, ClO
3 -in one or both.
3. a preparation method for camptothecine-hydrotalcite-like compounds nano hybrid, is characterized in that, comprises the following steps:
By solubility bivalent inorganic salt M
2+y and trivalent inorganic salt M
3+y presses M
2+: M
3+mol ratio is that the ratio of 2:1-4:1 mixes and dissolves and is configured to mixing salt solution in deionized water;
Preparation aqueous slkali, is dissolved in camptothecine in described aqueous slkali, is mixed with camptothecine aqueous slkali;
By described mixing salt solution and described camptothecine aqueous slkali, hybrid reaction in micro passage reaction is precipitated thing;
The precipitate obtained be separated through centrifuge and fully wash with deionized water, then carrying out peptization and form dispersion liquid, obtain the camptothecine intercalation hydrotalcite-like nanometer hybrid of carboxylate structure, be designated as CPT
c-LDH;
Weak acid solution is dropwise added CPT
cin the dispersion liquid of-LDH, adjust ph is 5-6.5, stirs and forms suspension in 6-24 hour, obtain the nano hybrid of the camptothecine intercalation houghite of lactone structure, be designated as CPT at 30-80 DEG C
l-LDH;
Surfactant is added in above-mentioned suspension, centrifugal and dry after Keep agitation, obtain camptothecine-hydrotalcite-like compounds nano hybrid.
4. the preparation method of camptothecine-hydrotalcite-like compounds nano hybrid as claimed in claim 3, it is characterized in that, the metal ion total concentration of described mixing salt solution is 0.01-1mol/L; Described M
2+comprise ION Mg
2+, Fe
2+, Zn
2+, and Ca
2+in one or both, described M
3+comprise ion A l
3+, Fe
3+in one, described Y
ncomprise Cl
-, NO
3 -, HCO
3 -in one or both.
5. the preparation method of camptothecine-hydrotalcite-like compounds nano hybrid as claimed in claim 3, it is characterized in that, described aqueous slkali is one or both in sodium hydroxide, potassium hydroxide and ammonia, and the concentration of described sodium hydroxide or potassium hydroxide solution is 0.01-1mol/L; The mass concentration of described ammonia is 5-15%.
6. the preparation method of camptothecine-hydrotalcite-like compounds nano hybrid as claimed in claim 3, it is characterized in that, the concentration of described camptothecine aqueous slkali is 0.005-0.05mol/L, and described peptization is peptization 12 hours at 60 DEG C.
7. the preparation method of camptothecine-hydrotalcite-like compounds nano hybrid as claimed in claim 3, it is characterized in that, in described micro passage reaction, the flow velocity of mixing salt solution and camptothecine aqueous slkali is 5-25ml/min, control as 9-11 from the pH value of the product suspension of described micro passage reaction outlet outflow, reaction temperature is 20-80 DEG C; Described micro passage reaction is T-shaped, and the width of microchannel is 0.2-0.9mm, and the degree of depth is 0.2-0.8mm, and length is 5-50mm.
8. the preparation method of camptothecine-hydrotalcite-like compounds nano hybrid as claimed in claim 3, it is characterized in that, described weak acid solution is one or more in citric acid, tartaric acid, formic acid, acetic acid, propanoic acid, ethanedioic acid, malonic acid, succinic acid, and the volumetric concentration of described weak acid solution is 5-10%.
9. the preparation method of camptothecine-hydrotalcite-like compounds nano hybrid as claimed in claim 3; it is characterized in that; described surfactant is one or more in rhamnolipid, Polyethylene Glycol sebacate, sodium alginate, dodecylamino Sodium L-alaninate, lauroyl Glycine sodium, N-dodecyl hydroxyethyl ammonium phosphate ester or N, N-dibutyl dodecyl hydroxyethyl ammonium phosphate ester.
10. the preparation method of camptothecine-hydrotalcite-like compounds nano hybrid as claimed in claim 3, is characterized in that, the concentration of described surfactant in suspension is 0.1-10 doubly its critical micelle concentration.
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