CN105497911B - The preparation method of daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system is carried altogether - Google Patents
The preparation method of daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system is carried altogether Download PDFInfo
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- CN105497911B CN105497911B CN201610010573.1A CN201610010573A CN105497911B CN 105497911 B CN105497911 B CN 105497911B CN 201610010573 A CN201610010573 A CN 201610010573A CN 105497911 B CN105497911 B CN 105497911B
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- GEZHEQNLKAOMCA-RRZNCOCZSA-N (-)-gambogic acid Chemical compound C([C@@H]1[C@]2([C@@](C3=O)(C\C=C(\C)C(O)=O)OC1(C)C)O1)[C@H]3C=C2C(=O)C2=C1C(CC=C(C)C)=C1O[C@@](CCC=C(C)C)(C)C=CC1=C2O GEZHEQNLKAOMCA-RRZNCOCZSA-N 0.000 title claims abstract description 77
- GEZHEQNLKAOMCA-UHFFFAOYSA-N epiisogambogic acid Natural products O1C2(C(C3=O)(CC=C(C)C(O)=O)OC4(C)C)C4CC3C=C2C(=O)C2=C1C(CC=C(C)C)=C1OC(CCC=C(C)C)(C)C=CC1=C2O GEZHEQNLKAOMCA-UHFFFAOYSA-N 0.000 title claims abstract description 77
- GEZHEQNLKAOMCA-GXSDCXQCSA-N gambogic acid Natural products C([C@@H]1[C@]2([C@@](C3=O)(C\C=C(/C)C(O)=O)OC1(C)C)O1)[C@H]3C=C2C(=O)C2=C1C(CC=C(C)C)=C1O[C@@](CCC=C(C)C)(C)C=CC1=C2O GEZHEQNLKAOMCA-GXSDCXQCSA-N 0.000 title claims abstract description 77
- QALPNMQDVCOSMJ-UHFFFAOYSA-N isogambogic acid Natural products CC(=CCc1c2OC(C)(CC=C(C)C)C=Cc2c(O)c3C(=O)C4=CC5CC6C(C)(C)OC(CC=C(C)/C(=O)O)(C5=O)C46Oc13)C QALPNMQDVCOSMJ-UHFFFAOYSA-N 0.000 title claims abstract description 77
- 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 title claims abstract description 72
- 229960000975 daunorubicin Drugs 0.000 title claims abstract description 72
- 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 title claims abstract description 69
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 229910004613 CdTe Inorganic materials 0.000 title abstract 5
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 30
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- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 8
- VTLHPSMQDDEFRU-UHFFFAOYSA-N tellane Chemical compound [TeH2] VTLHPSMQDDEFRU-UHFFFAOYSA-N 0.000 claims description 7
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- PSIBWKDABMPMJN-UHFFFAOYSA-L cadmium(2+);diperchlorate Chemical compound [Cd+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O PSIBWKDABMPMJN-UHFFFAOYSA-L 0.000 claims 1
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims 1
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- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
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- 238000004847 absorption spectroscopy Methods 0.000 description 1
- 239000003817 anthracycline antibiotic agent Substances 0.000 description 1
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- 239000008280 blood Substances 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
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- 230000004663 cell proliferation Effects 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 229940044683 chemotherapy drug Drugs 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 229940117709 gamboge Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
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- 230000002209 hydrophobic effect Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses the preparation methods of total load daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system to be related to a kind of preparation process of nanometer medicine-carried system of carrying anti-tumor drug and reverse multiple drug resistance of tumor drug altogether.High molecular polymer polyethylene glycol functional modification CdTe is used first, then BMPH is added dropwise in the DMF solution of dissolution daunorubicin, reaction is stirred at room temperature and obtains DNR-- carbamyl maleimide, the CdTe solution collective oscillation through modified is added to be incubated for, filtering, the novel medicine-carried system CdTe-DNR for obtaining PH sensitivity after purification, CdTe-DNR solution and gambogicacid (GA) solution are mixed in a certain ratio again, it is centrifuged water washing and precipitating after being protected from light, obtains total load daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system.
Description
Technical field
The invention belongs to pharmaceutical fields, more particularly to a kind of load daunorubicin and gambogicacid CdTe quantum nano drug-carrying altogether
The preparation method of system.
Background technique
Tumour is to seriously threaten a big disease of human health, current treatment method mainly include operative treatment, chemotherapy,
Radiotherapy and targeted therapy.Malignant tumor patient perioperatively more is aided with chemotherapy, and the infeasible operative treatment of part patients with terminal, because
This, chemotherapy still has considerable status in oncotherapy at present.But it is shown according to American Cancer Society's statistics, 90%
The cause of the death of above cancer patient is related with tumor multi-medicine drug-resistant, and multidrug resistance is to lead to the major reason of chemotherapy failure, therefore
Prevention and reversing clinical tumor multi-medicine drug-resistant, to improving, chemotherapeutic efficacy is particularly significant.
Daunorubicin has preferable antitumor action as a kind of anthracycline antibiotic, but some researches show that energy
Tumour cell is induced to over-express mdr-1 mRNA, enhancing tumour cell acts on the outlet of drug, so as to cause tumour cell
Drug resistance.Studies have found that and our previous work also have verified that the main active gambogicacid of Chinese medicine gamboge can cooperate with
Daunorubicin inhibits drug-resistant cell strain K562/A02 cell Proliferation, promotes Apoptosis, and can lower persister mdr-1 mRNA
Expression, thus the multidrug resistance of reverse both strain.Therefore, collaboration can effectively improve chemotherapy using daunorubicin and gambogicacid and treat
Effect.
However in chemotherapy process, while chemotherapeutics killing tumor cell, often also normal tissue and organ are made
At irreversible damage, chemotherapy is made to fall flat.As daunorubicin can produce apparent poison pair while antitumor
Effect, including bone marrow suppression, cardiac toxic, digestive tract reaction, hypoimmunity etc., seriously affect its application clinically.
Therefore, anti-tumor drug can be carried to inside tumor cells or surrounding and had with the pharmaceutical carrier for reducing drug side-effect by exploitation
Highly important meaning.
Current pharmaceutical carrier mainly includes nano-carrier, liposome vectors, particulate carrier, bio-carrier etc., but will be soft
The drug that erythromycin, gambogicacid and pharmaceutical carrier combine is not reported but.
Summary of the invention
For overcome the deficiencies in the prior art, the purpose of the present invention is to provide a kind of realizations to collect reverse multiple drug resistance of tumor
A variety of advantages such as drug and chemotherapeutics synergistic effect, nano drug-carrying controllable sustained-release, PH sensitivity target tumor are in one, to subtract
Few chemotherapeutics usage amount, reduces chemical therapy toxic side effect, enhances chemotherapeutic efficacy, and the one kind for playing better antitumor action carries altogether
The preparation method of daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system.
In order to achieve the above objectives, the present invention is achieved by the following technical solutions.
The preparation method of daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system is carried altogether, which is characterized in that including
Following steps:
(1) high molecular polymer polyethylene glycol (PEG) functional modification cadmium telluride (CdTe) is used: by Cd (ClO4)2•H2O is molten
Solution in water, is added with stirring cysteamine hydrochloride (Cys), tune pH value to 5.9, then is passed through Ar gas, is added with stirring H2Te, mixing
10 min of object back flow reaction to 9 h is eventually adding high molecular polymer polyethylene glycol (PEG) reaction for 24 hours；
(2) 1H- pyrroles -1- third is added dropwise after dissolving daunorubicin (DNR) with dimethylformamide (DMF) solution
Acid, 2,5- dihydro -2,5- dioxies-hydrazides (BMPH) are stirred to react at 10 ~ 30 DEG C of temperature and obtain DNR- carbamyl maleimide
Amine, cadmium telluride (CdTe) the solution collective oscillation for adding step (1) modified are incubated for 180-300min, filter, purify later,
Obtain nanometer medicine-carried system CdTe-DNR；
(3) CdTe-DNR prepared by step (2) is dissolved with water, at 10-30 DEG C by CdTe-DNR solution and gambogicacid
(GA) solution mixes, and is stirred to react, and is centrifuged, precipitating is washed with water, and load daunorubicin and gambogicacid CdTe quantum altogether is made and receives
Rice medicine-carried system (CdTe-DNR/GA).
Further Cd (ClO in the step (1)4)2•H2O, cysteamine hydrochloride (Cys), H2Te, high molecular polymer are poly-
The molar ratio of ethylene glycol (PEG) is 1:2.4:0.2:1.6.
Further H in the step (1)2Te is Al2Te3The H of sum2SO4Reaction generates.
The reaction time that DNR- carbamyl maleimide is further prepared in the step (2) is 1 ~ 3 hour.
The membrane filtration using 0.2 μm is further filtered in the step (2).
Further purifying is purified using sephadex chromatography analytical column (PDG-25) in the step (2).
Further the step (2), DNR concentration is 10-50mg/mL, CdTe-DNR solution concentration 10- in step (3)
15nmol/L, gambogicacid (GA) solution concentration are 5-10mg/mL.
Further CdTe-DNR solution and gambogicacid (GA) solution are 1 ~ 2:2 ~ 3 by volume in the step (3)
Ratio mixing.
The rate further stirred in the step (3) is 100 ~ 150rpm, the reaction time 4 ~ 8 hours；Centrifugation with
10000 ~ 15000rpm rate is centrifuged 10 ~ 30 minutes.
Further the operation in the step (2) and step (3) should carry out under the conditions of being protected from light.
Nano-carrier mainly has the advantage that (1) drug encapsulation ability with higher, the drug range that can be contained
It is relatively wide, it can be hydrophobic drug and be also possible to hydrophilic medicament, and no matter folk prescription medicine or compound medicine can contain；(2)
Water-wet side can be formed by modification, to prevent the absorption of protein, hides the capture of reticuloendothelial system；(3) partial size it is small and
Narrowly distributing has unique distribution characteristics easily by physiologic barrier in vivo.The distribution of nanoparticle in vivo depends primarily on grain
The pharmaceutical properties relationship wrapped up in the size and configuration of surface, with core of diameter is little；(4) there is slow releasing function, be able to extend drug
Action time；(5) by connection target body, targeting moiety, such as tumor tissues can actively be reached；It (6) can be before guaranteeing drug effect
It puts, dosage is reduced, so that toxic side effect be alleviated or avoided.The CdTe Nanoparticle Size of functional modification is about 3nm
Left and right, as a kind of nano-carrier drug controlled release and disease in terms of have good application value.Poly- second
Glycol because have amphipathic, good biocompatibility, safe and nontoxic, low immunogenicity, can avoid to the greatest extent albumen and
A variety of advantages such as cell non-specific adsorption, range of molecular weight distributions are wide, choice is big become modification carrier at present, keep away it
Exempt from one of the most frequently used high molecular polymer swallowed by endothelium network.Experiment shows that polyethyleneglycol modified CdTe has
Good dispersibility and preferable crystal structure.Daunorubicin and modified CdTe quantum can pass through hydrazone bond (C=N-N)
Connection, hydrazone bond is a kind of chemical bond of pH sensitive, is introduced into medicine-carried system, can use the characteristic of its acid labile, i.e.,
Acidic environment, in lymphoma cell, pH=6.0, drug release rate is accelerated；Neutral environment, such as normal tissue, blood, pH=
7.4, slow down or shield non-specific drug release, to assign the controllability of pharmaceutical carrier drug release, this is for reducing drug loss
General toxicity is particularly significant with reducing.It is novel that experiment shows that the CdTe nanoparticle of functional modification and gambogicacid are capable of forming
Nano medication compound, the Nano medication compound carrying drug ratio with higher and entrapment efficiency of the type, can significantly increase
Strong concentration of the drug in tumour cell, the especially intracellular concentration of persister, for improve drug drug effect and utilization rate,
The targeting for improving drug plays an important role.
The utility model has the advantages that compared with the prior art, the advantages of the present invention are as follows:
1) present invention can prevent the absorption of protein, hide using the CdTe quantum of functional modification as medicine particle is carried
The phagocytosis of endothelium network is kept away, and there is good dispersibility, higher encapsulation rate and contain rate.
2) nanometer medicine-carried system partial size prepared by the present invention is smaller, easily by various physiologic barriers, can be formed in vivo solely
Special distribution characteristics.
3) nanometer medicine-carried system carries chemotherapeutics and reverse multiple drug resistance of tumor drug altogether, and two kinds of drugs is made to play collaboration
Effect, it is more preferable than single load chemotherapy medicine antitumor effect.
4) nanometer medicine-carried system have sustained releasing character, can in a long time stable maintenance chemotherapy drug in lesions position
Concentration, extend chemotherapeutics action time in the cell, enhance antitumor action.
5) nanometer medicine-carried system of the invention has pH sensitivity characteristic, has certain targeting to the acidic environment of tumour,
Dosage can be reduced, the damage of normal tissue, cell can be reduced, to mitigate toxic side effect, improves chemotherapy effect.If connection
Tumour-specific target body is connect, it can be achieved that more accurately targeted therapy, therefore is had broad application prospects.
Detailed description of the invention
Fig. 1 is that scanning electron microscope is intuitively characterized to through polyethyleneglycol modified CdTe quantum.It is average
Partial size is 10nm or so, and spacing of lattice is about 0.23nm, shows that the quantum dot has good dispersibility and preferable crystal knot
Structure.
Fig. 2 is ultraviolet absorption spectroscopy, and QD represents the CdTe quantum modified through PEG in figure, and DNR represents soft red mould
Element, GA represent gambogicacid, and QD-DNR-GA is represented and carried daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system altogether, in figure
It can be seen that respective characteristic peak.
Fig. 3 is infrared absorption spectrum analysis, and QD represents the CdTe quantum modified through PEG in figure, and DNR represents soft red mould
Element, GA represent gambogicacid, and QD+DNR represents single CdTe quantum for carrying daunorubicin, and QD+DNR+GA representative carries daunorubicin altogether
With gambogicacid CdTe quantum nanometer medicine-carried system, visible respective characteristic peak in figure.
Fig. 4 is release profiles of the CdTe quantum to GA at different pH, illustrates that CdTe contains GA nanometer medicine-carried system
Drug release has good sustained releasing character, and pH sensibility, the life of (pH 6.0) than human normal under acidic environment is presented
The rate of release of reason environment (pH 7.4) is fast and preparation is more.
Fig. 5 is with nano particle size and the single hydration kinetics radius for carrying DNR CdTe quantum of electrokinetic potential analyzer measurement.
It is 94 nm, polydispersity coefficient 0.132 that it, which is averagely hydrated radius,.
Fig. 6 is the hydration kinetics half for carrying DNR and GA CdTe quantum altogether with nano particle size and the measurement of electrokinetic potential analyzer
Diameter.It is 135 nm, polydispersity coefficient 0.185 that it, which is averagely hydrated radius,.
Fig. 7 is the total In-vitro release curves for carrying DNR and GA CdTe quantum, illustrates that the nanometer medicine-carried system has drug
Slow-release function.
Specific embodiment
Below with reference to example, the present invention is described in further detail.
Embodiment 1
A kind of preparation method carrying daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system altogether, it is characterised in that should
Method the following steps are included:
(1) high molecular polymer polyethylene glycol (PEG) functional modification cadmium telluride (CdTe) is used: with 0.23 mmol's
Al2Te3With the H of 15 mL, 0.5 M2SO4Reaction generates H2Te is spare；By the Cd (ClO of 2.3mmol4)2•H2O is dissolved in 125 mL
In ultrapure water, under stirring conditions, the cysteamine hydrochloride (Cys) of 5.5 mmol is added dropwise, pH value is then adjusted to 5.9, then lead to
Enter 30 min of Ar gas, H obtained is then added dropwise2Te, 10 min of mixture back flow reaction to 9 h, to control CdTe quantum dot
Growth, is eventually adding the high molecular polymer polyethylene glycol (PEG) of rear 1.84mmol, and reaction obtains the cadmium telluride of modified for 24 hours
(CdTe) solution；
It (2) is to be added dropwise after 10mg/mL daunorubicin (DNR) is dissolved with dimethylformamide (DMF) solution by concentration
1H- pyrroles's -1- propionic acid, 2,5- dihydro -2,5- dioxies-hydrazides (BMPH), in 20 DEG C, be protected from light and be stirred to react 1 hour, obtain DNR-
Carbamyl maleimide, cadmium telluride (CdTe) the solution collective oscillation for adding step (1) modified are incubated for 240min, it
It is purified afterwards with 0.2 μm of membrane filtration, with sephadex chromatography analytical column (PDG-25), obtains nanometer medicine-carried system CdTe-
DNR；
(3) CdTe-DNR prepared by step (2) is dissolved with ultrapure water, ultrasonic disperse is uniform, and it is containing CdTe- that concentration, which is made,
The solution of DNR 12.5nmol/L, it is at 20 DEG C that the CdTe-DNR solution and concentration is molten for the gambogicacid (GA) of the 5mg/mL containing GA
Liquid is the ratio mixing of 1:2 by volume, is protected from light, is at the uniform velocity stirred to react 6 hours, stirring rate 100rpm, with 10000rpm
Rate is centrifuged 20 minutes, and precipitating is washed with deionized, and is made and is carried daunorubicin and gambogicacid CdTe quantum nano drug-carrying altogether
System (CdTe-DNR/GA).
Embodiment 2
A kind of preparation method carrying daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system altogether, it is characterised in that should
Method the following steps are included:
(1) high molecular polymer polyethylene glycol (PEG) functional modification cadmium telluride (CdTe) is used: with 0.23 mmol's
Al2Te3With the H of 15 mL, 0.5 M2SO4Reaction generates H2Te is spare；By the Cd (ClO of 2.3mmol4)2•H2O is dissolved in 125 mL
In ultrapure water, under stirring conditions, the cysteamine hydrochloride (Cys) of 5.5 mmol is added dropwise, pH value is then adjusted to 5.9, then lead to
Enter 30 min of Ar gas, H obtained is then added dropwise2Te, 10 min of mixture back flow reaction to 9 h, to control CdTe quantum dot
Growth, is eventually adding the high molecular polymer polyethylene glycol (PEG) of rear 1.84mmol, and reaction obtains the cadmium telluride of modified for 24 hours
(CdTe) solution；
It (2) is to be added dropwise after 50mg/mL daunorubicin (DNR) is dissolved with dimethylformamide (DMF) solution by concentration
1H- pyrroles's -1- propionic acid, 2,5- dihydro -2,5- dioxies-hydrazides (BMPH), in 10 DEG C, be protected from light and be stirred to react 3 hours, obtain DNR-
Carbamyl maleimide, cadmium telluride (CdTe) the solution collective oscillation for adding step (1) modified are incubated for 300min, it
It is purified afterwards with 0.2 μm of membrane filtration, with sephadex chromatography analytical column (PDG-25), obtains nanometer medicine-carried system CdTe-
DNR；
(3) CdTe-DNR prepared by step (2) is dissolved with ultrapure water, ultrasonic disperse is uniform, and it is containing CdTe- that concentration, which is made,
The solution of DNR 15nmol/L, gambogicacid (GA) solution for being the 5mg/mL containing GA by the CdTe-DNR solution and concentration at 10 DEG C
It is mixed by volume for the ratio of 1:3, is protected from light, is at the uniform velocity stirred to react 4 hours, stirring rate 150rpm, with 15000rpm speed
Rate is centrifuged 10 minutes, and precipitating is washed with deionized, and is made and is carried daunorubicin and gambogicacid CdTe quantum nano drug-carrying body altogether
It is (CdTe-DNR/GA).
Embodiment 3
A kind of preparation method carrying daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system altogether, it is characterised in that should
Method the following steps are included:
(1) high molecular polymer polyethylene glycol (PEG) functional modification cadmium telluride (CdTe) is used: with 0.23 mmol's
Al2Te3With the H of 15 mL, 0.5 M2SO4Reaction generates H2Te is spare；By the Cd (ClO of 2.3mmol4)2•H2O is dissolved in 125 mL
In ultrapure water, under stirring conditions, the cysteamine hydrochloride (Cys) of 5.5 mmol is added dropwise, pH value is then adjusted to 5.9, then lead to
Enter 30 min of Ar gas, H obtained is then added dropwise2Te, 10 min of mixture back flow reaction to 9 h, to control CdTe quantum dot
Growth, is eventually adding the high molecular polymer polyethylene glycol (PEG) of rear 1.84mmol, and reaction obtains the cadmium telluride of modified for 24 hours
(CdTe) solution；
It (2) is to be added dropwise after 30mg/mL daunorubicin (DNR) is dissolved with dimethylformamide (DMF) solution by concentration
1H- pyrroles's -1- propionic acid, 2,5- dihydro -2,5- dioxies-hydrazides (BMPH), in 30 DEG C, be protected from light and be stirred to react 2 hours, obtain DNR-
Carbamyl maleimide, cadmium telluride (CdTe) the solution collective oscillation for adding step (1) modified are incubated for 180min, it
It is purified afterwards with 0.2 μm of membrane filtration, with sephadex chromatography analytical column (PDG-25), obtains nanometer medicine-carried system CdTe-
DNR；
(3) CdTe-DNR prepared by step (2) is dissolved with ultrapure water, ultrasonic disperse is uniform, and it is containing CdTe- that concentration, which is made,
The solution of DNR 10nmol/L, gambogicacid (GA) solution for being the 5mg/mL containing GA by the CdTe-DNR solution and concentration at 30 DEG C
It is mixed by volume for the ratio of 2:3, is protected from light, is at the uniform velocity stirred to react 8 hours, stirring rate 120rpm, with 12000rpm speed
Rate is centrifuged 30 minutes, and precipitating is washed with deionized, and is made and is carried daunorubicin and gambogicacid CdTe quantum nano drug-carrying body altogether
It is (CdTe-DNR/GA).
It is intuitively characterized using scanning electron microscope to through polyethyleneglycol modified CdTe quantum, it is flat to measure it
Equal partial size is 10nm or so, and spacing of lattice is about 0.23nm, shows that the quantum dot has good dispersibility and preferable crystal
Structure is shown in Fig. 1.
Using ultra-violet absorption spectrum to CdTe quantum, DNR, GA and the feature suction of the CdTe quantum of load DNR and GA altogether
It receives peak and carries out analysis comparison, CdTe quantum has apparent absorption peak at 525nm, and DNR has apparent absorption at 484nm
Peak, and the CdTe quantum of the DOX and GA visible apparent absorption peak at 484nm and 525nm is carried altogether, show CdTe quantum
It puts and has successfully contained DNR, see Fig. 2.
Using infrared absorption spectrum to CdTe quantum, DNR, GA, the CdTe quantum for containing DNR and altogether carry DNR and GA
The absorption peak of CdTe quantum carry out analysis comparison, CdTe quantum has characteristic absorption peak at 1577cm-1,1404cm-1,
DNR has characteristic absorption peak at 1284cm-1,1207cm-1, and GA has feature suction at 1670cm-1,1256cm-1,804cm-1
Peak is received, and contains the visible CdTe quantum of CdTe quantum infrared absorption spectrum of DNR and the characteristic absorption peak of DNR, carries DNR altogether
In the infrared absorption spectrum of the CdTe quantum of GA, CdTe quantum, the characteristic absorption peak of DNR, GA are equal as it can be seen that showing
CdTe quantum can successfully contain DNR and GA, see Fig. 3.
By the release profiles at different pH, the drug release for illustrating that CdTe contains GA nanometer medicine-carried system has well
Sustained releasing character, and pH sensibility is presented, the physiological environment (pH 7.4) of (pH 6.0) than human normal under acidic environment
Rate of release is fast and preparation is more, sees Fig. 4.
It measures the CdTe quantum for containing DNR respectively using nano particle size and electrokinetic potential analyzer and carries DNR's and GA altogether
The hydration radius and polydispersity coefficient of CdTe quantum, the visible hydration radius distribution narrower width of two kinds of nano particles, show
Two kinds of nano particle sizes are uniform.See Fig. 5, Fig. 6.
The In-vitro release curves for carrying the CdTe quantum of DNR and GA altogether by measuring, illustrate that the nanometer medicine-carried system has
Drug slow release function is shown in Fig. 7.
The present invention is illustrated according to above-described embodiment, it should be understood that above-described embodiment does not limit this in any form
Invention, it is all to use equivalent substitution or equivalent transformation mode technical solution obtained, it is within the scope of the present invention.
Claims (7)
1. altogether carry daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system preparation method, which is characterized in that including with
Lower step:
(1) high molecular polymer polyethylene glycol (PEG) functional modification cadmium telluride (CdTe) is used: by Cd (ClO4)2•H2O is dissolved in
It in water, is added with stirring cysteamine hydrochloride (Cys), tune pH value to 5.9, then is passed through Ar gas, be added with stirring H2Te, mixture return
Stream reaction 10 min to 9 h, are eventually adding high molecular polymer polyethylene glycol (PEG) reaction for 24 hours；Cd(ClO4)2•H2O, hydrochloric acid
Cysteamine (Cys), H2Te, high molecular polymer polyethylene glycol (PEG) molar ratio be 1:2.4:0.2:1.6；
(2) it is added dropwise 1H- pyrroles's -1- propionic acid after dissolving daunorubicin (DNR) with dimethylformamide (DMF) solution, 2,
5- dihydro -2,5- dioxy-hydrazides (BMPH) is stirred to react at 10 ~ 30 DEG C of temperature and obtains DNR- carbamyl maleimide, then
Cadmium telluride (CdTe) the solution collective oscillation that step (1) modified is added is incubated for 180-300min, filters, purifies later, must receive
Rice medicine-carried system CdTe-DNR；
(3) CdTe-DNR prepared by step (2) is dissolved with water, it is at 10-30 DEG C that CdTe-DNR solution and gambogicacid (GA) is molten
Liquid mixing, is stirred to react, and is centrifuged, precipitating is washed with water, and is made and carries daunorubicin and gambogicacid CdTe quantum nano drug-carrying altogether
System (CdTe-DNR/GA)；CdTe-DNR solution and gambogicacid (GA) solution are the ratio mixing of 1 ~ 2:2 ~ 3 by volume；
DNR concentration is 10-50 mg/mL in the step (2), step (3), and CdTe-DNR solution concentration is 10-15nmol/L,
Gambogicacid (GA) solution concentration is 5-10mg/mL.
2. the preparation side according to claim 1 for carrying daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system altogether
Method, which is characterized in that H in the step (1)2Te is Al2Te3The H of sum2SO4Reaction generates.
3. the preparation side according to claim 1 for carrying daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system altogether
Method, which is characterized in that the reaction time that DNR- carbamyl maleimide is prepared in the step (2) is 1 ~ 3 hour.
4. the preparation side according to claim 1 for carrying daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system altogether
Method, which is characterized in that filtering uses 0.2 μm of membrane filtration in the step (2).
5. the preparation side according to claim 1 for carrying daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system altogether
Method, which is characterized in that purifying is purified using sephadex chromatography analytical column PDG-25 in the step (2).
6. the preparation side according to claim 1 for carrying daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system altogether
Method, which is characterized in that the rate stirred in the step (3) is 100 ~ 150rpm, the reaction time 4 ~ 8 hours；Centrifugation is with 10000
~ 15000rpm rate is centrifuged 10 ~ 30 minutes.
7. the preparation side according to claim 1 for carrying daunorubicin and gambogicacid CdTe quantum nanometer medicine-carried system altogether
Method, which is characterized in that the operation in the step (2) and step (3) should carry out under the conditions of being protected from light.
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