CN107648606A - Collect chemotherapy and the preparation method of thermotherapy integrated nuclear shell nanometer material and products thereof and application - Google Patents
Collect chemotherapy and the preparation method of thermotherapy integrated nuclear shell nanometer material and products thereof and application Download PDFInfo
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- CN107648606A CN107648606A CN201711098477.8A CN201711098477A CN107648606A CN 107648606 A CN107648606 A CN 107648606A CN 201711098477 A CN201711098477 A CN 201711098477A CN 107648606 A CN107648606 A CN 107648606A
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- preparation
- thermotherapy
- chemotherapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5123—Organic compounds, e.g. fats, sugars
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5138—Organic macromolecular compounds; Dendrimers obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
Abstract
Collect chemotherapy and the preparation method of thermotherapy integrated nuclear shell nanometer material and products thereof and application the present invention relates to a kind of, include the preparation of nanometer gold bar and the preparation of Au@Zif 8/DOX core-shell nano materials, above-mentioned adriamycin is mixed with Au@Zif 8, ratio 1:1~1:10, stir 10 ~ 24 hours, product is filtered, washed three times with absolute ethyl alcohol, deionized water, vacuum is drained, and obtains Au@Zif 8/DOX, that is, obtains the nano material of nanometer gold bar and chemotherapeutic drugs Doxorubicin simultaneously.The nano material has the characteristics that size uniformity, stable performance, good biocompatibility, sustained drug release effect are good.The product of gained can meet the needs of clinical practice.Preparation method technique in the present invention is simple, workable, can meet the market demand for further producing and applying.
Description
Technical field
Collect chemotherapy and the preparation method of thermotherapy integrated nuclear shell nanometer material and products thereof and application the present invention relates to a kind of,
It is Jie more particularly to a kind of metal organic frame (Metal-Organic Frameworks, abbreviation MOFs) with high-ratio surface
Matter, while connect the technology of preparing of chemotherapy-thermotherapy nano material of gold nanorods and chemotherapeutic drugs Doxorubicin.The invention belongs to receive
Rice biological medicine Material Field.
Background technology
Currently, the early detection for cancer and diagnosis have turned into the focus of numerous biomedical research focus of attention.Gold
Nanometer rods have to be changed with draw ratio, from the surface plasma body resonant vibration wavelength of visible near-infrared continuously adjustabe, and from 50%
To the photo-thermal conversion efficiency of 100% continuously adjustabe, near infrared light can be converted into heat, tissue temperature rise is killed so as to reach
The purpose of cancer cell, be advantageous to the treatment of deep tissues lesion.Therefore gold nanorods are expected to turn into effective photo-thermal treatment material.
Nano metal organic frame(MOFs)It is a kind of novel porous materials, because it has high porosity, low-density, big
The advantages that specific surface area, duct rule, aperture can adjust, it is widely applied to gas storage, catalysis, carries the fields such as medicine.Cancer therapy drug
It by MOFs pay(useful) loads, can be for a long time sustained in vivo, extend drug effect.
The content of the invention
For overcome the deficiencies in the prior art, present invention aims at:A kind of collection chemotherapy nucleocapsid integrated with thermotherapy is provided to receive
The preparation method of rice material.
Still a further object of the present invention is:Product prepared by a kind of above method is provided.
Another object of the present invention is:A kind of application of the said goods is provided.
The object of the invention is realized by following proposal:It is a kind of to collect chemotherapy and the preparation side of thermotherapy integrated nuclear shell nanometer material
Method, using Zif-8 metal-organic frameworks as carrier, while nanometer gold bar and chemotherapeutic drugs Doxorubicin are connected, comprised the following steps:
(1)The preparation of nanometer gold bar
In mass fraction is 10 ~ 50 parts of distilled water, perchloric acid gold and surfactant are added, keeps its mol ratio 0.1:1, stir
After mixing uniformly, reducing agent is added, reducing agent is 1 with the golden mol ratio of perchloric acid:1, continue to stir, when solution is by dark brown yellow
After becoming colorless, add 10 μ L gold seedses, after solution-stabilized, add a certain amount of salting liquid, keep reaction temperature 15 ~
30 DEG C, after reacting 8 ~ 24 hours, centrifuge, washing, obtain nanometer gold bar;
(2)The preparation of Au@Zif-8/DOX core-shell nano materials
The organic zinc salt for taking mass fraction to be 1 ~ 3 part, 1 ~ 10 part of polyvinylpyrrolidone, is dissolved in 2 ~ 10 parts of alcoholic solutions, stirs
Solution A is formed to being completely dissolved, takes 1 ~ 3 part of 2-methylimidazole, it is B solution to be dissolved in 2 ~ 10 parts of alcoholic solutions;A, B solution are put into 4
DEG C refrigerator in be incubated 1.5h, A, B solution are mixed at room temperature with above-mentioned nanometer gold bar, place 0.5-30h, centrifugation, washing
Au@Zif-8 are obtained for several times;
Above-mentioned adriamycin is mixed with Au@Zif-8, ratio 1:1~1:10, stir 10 ~ 24 hours, product is filtered, use is anhydrous
Three times, vacuum is drained, and obtains Au@Zif-8/DOX for ethanol, deionized water washing, that is, obtains nanometer gold bar and chemotherapeutics simultaneously
The nano material of adriamycin.
In the inventive solutions, using Zif-8 metal-organic frameworks as carrier, in-situ reactive synthesis core shell structure
Au Zif-8, the nano material of photothermal deformation is obtained, further by loading chemotherapeutic drugs Doxorubicin, synthesis Au Zif-8/
DOX, you can obtain possessing thermotherapy, chemotherapy multifunctional nano material.
On the basis of such scheme, described surfactant is Triton X-100, cetyl trimethyl
One kind in ammonium bromide, polyoxyethylene.
Described salt is one kind in sodium chloride, magnesium chloride, calcium chloride, sodium sulphate, potassium nitrate, sodium nitrate.
Described organic zinc salt is zinc acetate, zinc lactate, one kind of zinc citrate.
Described alcoholic solution is one kind in methanol, ethanol, propyl alcohol, butanol.
Described reducing agent is one kind in sodium borohydride, trisodium citrate, vitamin C, potassium borohydride.
The present invention provides a kind of collection chemotherapy and thermotherapy integrated nuclear shell nanometer material, is prepared according to any of the above-described methods described
Obtain.
The present invention prepares the Au@Zif-8 of core shell structure by controlling reaction condition, while contains a certain amount of chemotherapeutics
Adriamycin, so as to obtain multifunctional nano diagnosis and treatment material.The nano material has size uniformity, stable performance, biocompatibility
Well, the features such as sustained drug release effect is good.The product of gained can meet the needs of clinical practice.
The present invention provides a kind of application for collecting chemotherapy with thermotherapy integrated nuclear shell nanometer material in chemotherapy and thermotherapy medicine.
The advantage of the invention is that:
(1)Zif-8 is coated on gold nano by the present invention using metal organic frame Zif-8 as carrier by the method for fabricated in situ
Rod surface, you can obtain Au@Zif-8 thermotherapy nano materials.Raw materials used biological safety is high, and compatibility is good, further passes through
Load chemotherapeutic drugs Doxorubicin, synthesis Au Zif-8/DOX, you can obtain possessing thermotherapy and be combined multifunctional nano with chemotherapy
Material.
(2)It is excellent that nanometer diagnosis and treatment probe prepared by the present invention has good physical and chemical stability, biological shape dissolubility good etc.
Gesture.
(3)Preparation method technique in the present invention is simple, workable, can meet the market for further producing and applying
Demand.
Brief description of the drawings
Fig. 1 is the transmission electron microscope figure of the Zif-8 prepared by embodiment 1;
Fig. 2 is the transmission electron microscope figure of the Au@Zif-8 prepared by embodiment 1.
Embodiment
Embodiment 1
In the distilled water that mass fraction is 20 parts, perchloric acid gold and Triton X-100 are added, keeps its mol ratio
0.1:1, after stirring, trisodium citrate is added, trisodium citrate is 1 with the golden mol ratio of perchloric acid:1, continue to stir, when
After solution are become colorless by dark brown yellow, 10 μ L gold seedses are added, after solution-stabilized, add a certain amount of sodium chloride solution,
30 DEG C of reaction temperature is kept, after reacting 10 hours, centrifuges, washing, obtains nanometer gold bar;
The zinc acetate for taking mass fraction to be 3 parts, 10 parts of polyvinylpyrrolidone, is dissolved in 10 parts of ethanol solutions, stirs to complete
Dissolving forms solution A.3 parts of 2-methylimidazoles are taken, it is B solution to be dissolved in 8 parts of methanol solutions, and Fig. 1 is Zif-8 manufactured in the present embodiment
Transmission electron microscope figure;A, B solution are put into 4 DEG C of refrigerator and are incubated 1.5h, A, B solution and above-mentioned nanometer gold bar are existed
Mix at room temperature, place 10h, centrifugation, washing obtain Au@Zif-8 for several times.Fig. 2 is the saturating of Au@Zif-8 manufactured in the present embodiment
Penetrate electron microscope picture.
Above-mentioned adriamycin is mixed with Au@Zif-8, ratio 1:2, stir 12 hours, product is filtered, with anhydrous second
Three times, vacuum is drained, and obtains Au@Zif-8/DOX for alcohol, deionized water washing, that is, obtain nanometer gold bar simultaneously and chemotherapeutics Ah
The nano material of mycin.
Embodiment 2
In the distilled water that mass fraction is 10 parts, perchloric acid gold and cetyl trimethylammonium bromide are added, keeps its mole
Than 0.1:1, after stirring, trisodium citrate is added, trisodium citrate is 1 with the golden mol ratio of perchloric acid:1, continue to stir,
After solution is become colorless by dark brown yellow, 10 μ L gold seedses are added, after solution-stabilized, it is molten to add a certain amount of calcium chloride
Liquid, 30 DEG C of reaction temperature is kept, after reacting 20 hours, centrifuge, washing, obtain nanometer gold bar;
The zinc citrate for taking mass fraction to be 3 parts, 10 parts of polyvinylpyrrolidone, is dissolved in 10 parts of methanol solutions, stirs to complete
Fully dissolved forms solution A.3 parts of 2-methylimidazoles are taken, it is B solution to be dissolved in 8 parts of methanol solutions.A, B solution are put into 4 DEG C of refrigerator
Middle insulation 1.5h, A, B solution are mixed at room temperature with above-mentioned nanometer gold bar, place 18h, centrifugation, washing obtain Au@for several times
Zif-8。
Above-mentioned adriamycin is mixed with Au@Zif-8, ratio 1:10, stir 12 hours, product is filtered, with anhydrous second
Three times, vacuum is drained, and obtains Au@Zif-8/DOX for alcohol, deionized water washing, that is, obtain nanometer gold bar simultaneously and chemotherapeutics Ah
The nano material of mycin.
Embodiment 3
In mass fraction is 30 parts of distilled water, perchloric acid gold and polyoxyethylene are added, keeps its mol ratio 0.1:1, stirring is equal
After even, potassium borohydride is added, potassium borohydride is 1 with the golden mol ratio of perchloric acid:1, continue to stir, when solution is become by dark brown yellow
After colourless, 10 μ L gold seedses are added, after solution-stabilized, a certain amount of salting liquid is added, keeps reaction temperature 15 ~ 30
DEG C, after reacting 18 hours, centrifuge, washing, obtain nanometer gold bar;
The organic zinc salt for taking mass fraction to be 2 parts, 2 parts of polyvinylpyrrolidone, is dissolved in 10 parts of methanol solutions, stirs to complete
Fully dissolved forms solution A.1 part of 2-methylimidazole is taken, it is B solution to be dissolved in 10 parts of methanol solutions.A, B solution are put into 4 DEG C of ice
1.5h is incubated in case, A, B solution are mixed at room temperature with above-mentioned nanometer gold bar, places 10h, centrifugation, washing obtain Au@for several times
Zif-8。
Above-mentioned adriamycin is mixed with Au@Zif-8, ratio 1:10, stir 24 hours, product is filtered, with anhydrous second
Three times, vacuum is drained, and obtains Au@Zif-8/DOX for alcohol, deionized water washing, that is, obtain nanometer gold bar simultaneously and chemotherapeutics Ah
The nano material of mycin.
Claims (8)
1. a kind of collect chemotherapy and the preparation method of thermotherapy integrated nuclear shell nanometer material, it is characterised in that with metal organic frame
Structural material is medium, while connects nanometer gold bar and chemotherapeutic drugs Doxorubicin, is comprised the following steps:
(1)The preparation of nanometer gold bar
In mass fraction is 10 ~ 50 parts of distilled water, perchloric acid gold and surfactant are added, keeps its mol ratio 0.1:1, stir
After mixing uniformly, reducing agent is added, reducing agent is 1 with the golden mol ratio of perchloric acid:1, continue to stir, when solution is by dark brown yellow
After becoming colorless, add 10 μ L gold seedses, after solution-stabilized, add a certain amount of salting liquid, keep reaction temperature 15 ~
30 DEG C, after reacting 8 ~ 24 hours, centrifuge, washing, obtain nanometer gold bar;
(2)The preparation of Au@Zif-8/DOX core-shell nano materials
The organic zinc salt for taking mass fraction to be 1 ~ 3 part, 1 ~ 10 part of polyvinylpyrrolidone, is dissolved in 2 ~ 10 parts of alcoholic solutions, stirs
Solution A is formed to being completely dissolved, takes 1 ~ 3 part of 2-methylimidazole, it is B solution to be dissolved in 2 ~ 10 parts of alcoholic solutions;A, B solution are put into 4
DEG C refrigerator in be incubated 1.5h, A, B solution are mixed at room temperature with above-mentioned nanometer gold bar, place 0.5-30h, centrifugation, washing
Au@Zif-8 are obtained for several times;
Above-mentioned adriamycin is mixed with Au@Zif-8, ratio 1:1~1:10, stir 10 ~ 24 hours, product is filtered, use is anhydrous
Three times, vacuum is drained, and obtains Au@Zif-8/DOX for ethanol, deionized water washing, that is, obtains nanometer gold bar and chemotherapeutics simultaneously
The nano material of adriamycin.
2. collect chemotherapy and the preparation method of thermotherapy integrated nuclear shell nanometer material according to claim 1, it is characterised in that institute
The surfactant stated is one kind in Triton X-100, cetyl trimethylammonium bromide, polyoxyethylene.
3. collect chemotherapy and the preparation method of thermotherapy integrated nuclear shell nanometer material according to claim 1, it is characterised in that institute
The salt stated is one kind in sodium chloride, magnesium chloride, calcium chloride, sodium sulphate, potassium nitrate, sodium nitrate.
4. collect chemotherapy and the preparation method of thermotherapy integrated nuclear shell nanometer material according to claim 1, it is characterised in that institute
The organic zinc salt stated is zinc acetate, zinc lactate, one kind of zinc citrate.
5. collect chemotherapy and the preparation method of thermotherapy integrated nuclear shell nanometer material according to claim 1, it is characterised in that institute
The alcoholic solution stated is one kind in methanol, ethanol, propyl alcohol, butanol.
6. collect chemotherapy and the preparation method of thermotherapy integrated nuclear shell nanometer material according to claim 1, it is characterised in that institute
The reducing agent stated is one kind in sodium borohydride, trisodium citrate, vitamin C, potassium borohydride.
7. one kind collection chemotherapy and thermotherapy integrated nuclear shell nanometer material, it is characterised in that according to any sides of claim 1-6
Method is prepared.
8. collect chemotherapy according to claim 7 with thermotherapy integrated nuclear shell nanometer material in chemotherapy and answering in thermotherapy medicine
With.
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Cited By (8)
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---|---|---|---|---|
CN108379601A (en) * | 2018-02-26 | 2018-08-10 | 上海师范大学 | A kind of applications of the Au@ZIF-8 of glutathione triggering on preparing photo-acoustic detection tumor reagent |
CN108524935A (en) * | 2018-05-17 | 2018-09-14 | 山东大学 | A kind of Quercetin drug-loading system based on copper sulfide-metal-organic framework material |
CN109512797A (en) * | 2018-12-21 | 2019-03-26 | 上海纳米技术及应用国家工程研究中心有限公司 | The preparation method of nano-medicament carrier and products thereof based on metal organic frame |
CN110179818A (en) * | 2019-05-27 | 2019-08-30 | 河北大学 | CaO2@DOX@ZIF-67 nano material and the preparation method and application thereof |
CN111012925A (en) * | 2019-12-30 | 2020-04-17 | 上海纳米技术及应用国家工程研究中心有限公司 | Preparation method of metal organic framework-based SERS (surface enhanced Raman Scattering) nanoprobe, product and application thereof |
CN111558051A (en) * | 2020-07-08 | 2020-08-21 | 中国科学院深圳先进技术研究院 | Composite nano-microsphere with rapid mucus penetration effect and preparation method and application thereof |
CN111592661A (en) * | 2020-06-16 | 2020-08-28 | 南京邮电大学 | Preparation method of high-dispersity organic metal framework nano material |
WO2021103232A1 (en) * | 2019-11-25 | 2021-06-03 | 上海纳米技术及应用国家工程研究中心有限公司 | Preparation method for core-shell nanoparticles based on lipid membrane and metal organic framework |
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Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN108379601A (en) * | 2018-02-26 | 2018-08-10 | 上海师范大学 | A kind of applications of the Au@ZIF-8 of glutathione triggering on preparing photo-acoustic detection tumor reagent |
CN108524935A (en) * | 2018-05-17 | 2018-09-14 | 山东大学 | A kind of Quercetin drug-loading system based on copper sulfide-metal-organic framework material |
CN108524935B (en) * | 2018-05-17 | 2020-11-06 | 山东大学 | Quercetin drug delivery system based on copper sulfide-metal organic framework material |
CN109512797A (en) * | 2018-12-21 | 2019-03-26 | 上海纳米技术及应用国家工程研究中心有限公司 | The preparation method of nano-medicament carrier and products thereof based on metal organic frame |
CN110179818A (en) * | 2019-05-27 | 2019-08-30 | 河北大学 | CaO2@DOX@ZIF-67 nano material and the preparation method and application thereof |
CN110179818B (en) * | 2019-05-27 | 2021-10-15 | 河北大学 | CaO2@ DOX @ ZIF-67 nano material and preparation method and application thereof |
WO2021103232A1 (en) * | 2019-11-25 | 2021-06-03 | 上海纳米技术及应用国家工程研究中心有限公司 | Preparation method for core-shell nanoparticles based on lipid membrane and metal organic framework |
CN111012925A (en) * | 2019-12-30 | 2020-04-17 | 上海纳米技术及应用国家工程研究中心有限公司 | Preparation method of metal organic framework-based SERS (surface enhanced Raman Scattering) nanoprobe, product and application thereof |
CN111592661A (en) * | 2020-06-16 | 2020-08-28 | 南京邮电大学 | Preparation method of high-dispersity organic metal framework nano material |
CN111558051A (en) * | 2020-07-08 | 2020-08-21 | 中国科学院深圳先进技术研究院 | Composite nano-microsphere with rapid mucus penetration effect and preparation method and application thereof |
CN111558051B (en) * | 2020-07-08 | 2021-06-25 | 中国科学院深圳先进技术研究院 | Composite nano-microsphere with rapid mucus penetration effect and preparation method and application thereof |
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Application publication date: 20180202 |