CN107739506B - Light-operated nitric oxide releasing composite film material and preparation method and application thereof - Google Patents
Light-operated nitric oxide releasing composite film material and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a composite membrane material for releasing nitric oxide by light control, and a preparation method and application thereof. The preparation method of the material comprises the following steps: firstly, spherical dendritic polyamide-amine (N-N-PAMAM-D) is synthesized3) Then modifying the surface of the gold nano-particles with uniform particle size with N-N-PAMAM-D3Preparing N-N-PAMAM modified nano-gold, and loading nitric oxide to obtain the light-operated nitric oxide release composite membrane material. The composite film material for optically controlling and releasing nitric oxide and Polycaprolactone (PCL) are blended, freeze-dried and pressed into a film, and the near infrared ray-controlled release film can be obtainedA composite membrane material for controlling the released nitric oxide under laser irradiation. The material has the advantages of uniform particle size, sensitive response, large NO loading and storage capacity, long release time and good biocompatibility, can be applied to the field of biomedical engineering materials, can effectively inhibit the growth and reproduction of bacteria and fungi, and can be used for preparing antibacterial drugs.
Description
Technical Field
The invention belongs to the field of biomedical engineering materials, and particularly relates to a composite membrane material for optically controlling release of nitric oxide, and a preparation method and application thereof.
Background
Since Furchgott et al discovered in 1980 that vascular endothelial cells can synthesize and secrete vascular Endothelial Derived Relaxant (EDRF), two independent subjects, Furchgott and Ignarro, demonstrated that EDRF was NO in 1986, basic and clinical studies on NO, which became one of the most attractive biomolecules in recent years, have been vigorously developed. A large number of researches show that NO is an important biological messenger molecule, participates in processes such as vascular regulation, neurotransmission, inflammation and immune response, is widely distributed and extends to various organs such as brain, blood vessels, immunity, lung, reproduction and the like.
In recent years, NO is found to destroy cell membranes and gene information of bacteria and prevent the bacteria from obtaining energy, has the characteristics of high-efficiency bacteriostasis, difficult generation of drug resistance and the like, so that the application of the NO in the antibacterial field is more and more concerned, and more novel antibacterial materials capable of releasing NO appear in the visual field of people.
Such as: smith et al first proposed in 1996 that the nucleophilic NO donor N-diazeniumdiolate could be used to prepare NO-releasable polymeric materials (Chemistry 1996,39: 1148-; the journal Oh Kima et al (International journal of Biological Macromolecules 2015,79:217-225) prepared a chitosan film capable of releasing NO, and the chitosan film is used for the research on the aspects of antibiosis and wound healing, and the research shows that NO can effectively inhibit the growth and propagation of bacteria and has obvious effect on wound healing. Dongsik Park et al (Advanced healthcare materials 2016,5: 2019-. Although NO exhibits excellent antibacterial effects and is not easily resistant to drug, NO is greatly hindered from clinical use due to problems such as short gas properties and half-life, too low content of NO supported by the material, and difficulty in long-term storage. Therefore, the site-directed local controlled release of NO is an essential feature in NO delivery systems, and is an important issue to be solved in the biomedical engineering field. Hitherto, a gold composite membrane material covered on the surface is finally prepared by modifying the surface of a gold composite membrane material (Au) with spherical dendritic polyamide-amine (N-N-PAMAM) as an NO donor, then coating with Polycaprolactone (PCL), freeze-drying and pressing to form a membrane, wherein the spherical dendritic polyamide-amine is used as a matrix, the outermost layer is a thin film material of the polycaprolactone, and the thin film composite material capable of controlling to release nitric oxide under the irradiation of near-infrared laser and the application thereof are not reported.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provides a preparation method of a composite membrane material for releasing nitric oxide under light control.
The invention also aims to provide the composite membrane material for optically controlling and releasing nitric oxide, which is prepared by the method.
Still another object of the present invention is to provide an application of the light-controlled nitric oxide releasing composite film material.
The purpose of the invention is realized by the following technical scheme: a preparation method of a composite film material for releasing nitric oxide under light control comprises the following steps:
(1) N-N-PAMAM motif (N-N-PAMAM-D) with 3-generation ethylenediamine as core3) Synthesis of (2)
a. Dripping the methanol solution of ethylenediamine into the methanol solution of methyl acrylate under the condition of ice-water bath, uniformly stirring, heating to room temperature, and stirring for reaction to obtain N-N-PAMAM-D0.5(0.5 generation ethylenediamine is nuclear PAMAM motif); dissolving in methanol under ice water bath condition, dripping into methanol solution of ethylenediamine, stirring, heating to room temperature, and stirring for reaction to obtain N-N-PAMAM-D1(N-N-PAMAM motif with 1 generation ethylenediamine as nucleus);
b. b, mixing the N-N-PAMAM-D obtained in the step a1Replacing ethylenediamine, and repeating the operation of the step a to obtain N-N-PAMAM-D2(PAMAM motifs with ethylenediamine 2 as the nucleus); then N-N-PAMAM-D2(PAMAM element with 2 generation ethylenediamine as core) instead of ethylenediamine, and repeating the step a to obtain N-N-PAMAM-D3(3-generation ethylenediamine cored dendritic polyamidoamine);
(2) preparation of N-N-PAMAM modified nanogold material (Au @ N-N-PAMAM)
The N-N-PAMAM-D obtained in the step (1) b3(3 generation ethylenediamine as core dendritic polyamide-amine) dissolved in water, and chloroauric acid (HAuCl) added dropwise4) Stirring at room temperature, adding NaBH4Continuously stirring, dialyzing and drying the solution to obtain Au @ N-N-PAMAM (N-N-PAMAM modified nano-gold material);
(3) synthesis of composite membrane material (Au @ N-N-PAMAM/NONONAte) capable of releasing nitric oxide under light control
And (3) dissolving the Au @ N-N-PAMAM obtained in the step (2) in absolute methanol, adding sodium methoxide, performing ultrasonic stabilization for 10-30 min, introducing NO gas, reacting at room temperature, washing after the reaction is finished, and drying to obtain the light-operated nitric oxide releasing composite membrane material (Au @ N-N-PAMAM/NONONAte).
The room temperature in the steps (1) a, (2) and (3) is 5-35 ℃.
The temperature of the ice-water bath in step (1) a was 0 ℃.
The stirring reaction time in the step (1) a is 12-48 h.
The ethylenediamine in the step (1) a is dried ethylenediamine (anhydrous ethylenediamine).
The anhydrous ethylenediamine is preferably prepared by the following steps: adding anhydrous potassium hydroxide into ethylenediamine, stirring for 6-24 hours, and then distilling under reduced pressure to obtain anhydrous ethylenediamine; the addition amount of the anhydrous potassium hydroxide is calculated according to the proportion of 2-4 g of anhydrous potassium hydroxide in each liter of ethylenediamine.
The methyl acrylate in the step (1) a is dried methyl acrylate (anhydrous methyl acrylate).
The anhydrous methyl acrylate is preferably prepared by the following steps: adding anhydrous sodium sulfate into methyl acrylate, stirring for 6-24 hours, and then distilling at normal pressure to obtain anhydrous methyl acrylate; the addition amount of the anhydrous sodium sulfate is calculated according to 2-4 g of anhydrous sodium sulfate in the proportion of methyl acrylate per liter.
The methanol solution of the ethylenediamine in the step (1) a is prepared by mixing methanol and ethylenediamine according to a volume ratio of 10: 1-5.
The methyl acrylate methanol solution in the step (1) a is prepared by mixing methanol and methyl acrylate according to the volume ratio of 10: 1-5.
The molar ratio of the ethylenediamine to the methyl acrylate in the step (1) a is 1: 4-8 (molar ratio of ethylenediamine to methyl acrylate in the reaction).
The N-N-PAMAM-D in the step (1) a0.5The molar ratio of the ethylene diamine to the ethylene diamine is 1: 4-24; preferably 1: 4-12 (N-N-PAMAM-D)0.5The molar ratio of the two when reacted with ethylenediamine).
The N-N-PAMAM-D in the step (1) a0.5The dosage of the compound is 0.5-5 g N-N-PAMAM-D per milliliter of methanol0.5And (4) calculating.
The N-N-PAMAM-D in the step (1) b1The molar ratio of the acrylic acid to the methyl acrylate is preferably 1:8 to 16.
The N-N-PAMAM-D in the step (1) b1Replacing ethylenediamine, and repeating the operation of the step a to obtain the intermediate product N-N-PAMAM-D1.5The molar ratio of the ethylene diamine to the ethylene diamine is preferably 1:8 to 24.
N-N as described in step (1) b-PAMAM-D2The molar ratio of the acrylic acid to the methyl acrylate is preferably 1:16 to 32.
The N-N-PAMAM-D in the step (1) b2Replacing ethylenediamine, and repeating the operation of the step a to obtain the intermediate product N-N-PAMAM-D2.5The molar ratio of the ethylene diamine to the ethylene diamine is preferably 1:16 to 48.
The dissolution in step (2) is preferably ultrasonic dissolution.
The stirring time in the step (2) is preferably 0.5-24 h.
The time for continuing stirring in the step (2) is preferably 2-4 h.
The dialysis in the step (2) is dialysis in a dialysis bag; preferably dialyzing in a dialysis bag with the molecular weight cutoff of 3000-5000; more preferably dialyzed in a dialysis bag with molecular weight cutoff of 3000-5000 for 1-3 days.
The drying conditions in the step (2) are as follows: drying for 12-48 hours at 50-80 ℃; preferably: freeze-drying, and then drying in a vacuum drying oven at 50-80 ℃ for 12-48 hours.
The N-N-PAMAM-D in the step (2)3The molar ratio of the chloroauric acid to the sodium borohydride is 1: 20-50: 100 to 250.
The N-N-PAMAM-D in the step (2)3The dosage of the N-N-PAMAM-D is 0.2 to 1mg per milliliter of water3And (4) calculating.
The water in the step (2) is preferably ultrapure water.
The anhydrous methanol described in the step (3) is preferably prepared by the following steps: adding calcium hydride into methanol, stirring for 6-24 hours, and then distilling at normal pressure to obtain anhydrous methanol; the dosage of the calcium hydride is calculated according to 2-4 g of calcium hydride in a proportion of methanol per liter.
The molar ratio of Au @ N-N-PAMAM to sodium methoxide in the step (3) is 1: 400-450.
In the step (3), the addition amount of the sodium methoxide is calculated according to the final concentration of the sodium methoxide in the reaction system being 5-20% (w/w).
The dosage of the Au @ N-N-PAMAM in the step (3) is calculated according to the proportion of 0.05-0.2 g of Au @ N-N-PAMAM per milliliter of anhydrous methanol.
The reaction in the step (3) is carried out in a high-pressure reaction kettle; preferably by the following steps: introducing high-purity nitrogen to maintain the reaction kettle (10-20 psi) for 5-15 min, removing air in the reaction kettle, then reacting, and after the reaction is finished, introducing the high-purity nitrogen with 10-20 psi to maintain for 10-20 min, and discharging NO.
The reaction time in the step (3) is preferably 3 to 7 days.
The washing in the step (3) is carried out by using anhydrous methanol and ice anhydrous ether; preferably, the washing is carried out for 1-3 times by using anhydrous methanol and then for 1-2 times by using ice anhydrous ether.
A composite membrane material for optically controlling release of nitric oxide is prepared by any one of the methods.
A polycaprolactone-coated composite membrane material for light-operated release of nitric oxide is obtained by coating the PCL (polycaprolactone) on the composite membrane material for light-operated release of nitric oxide.
The preparation method of the polycaprolactone-coated light-operated nitric oxide release composite film material comprises the following steps:
(I) adding PCL (polycaprolactone) into a mixed solution of N, N-Dimethylformamide (DMF) and trichloromethane, and uniformly stirring to obtain a PCL solution;
and (II) dispersing the Au @ N-N-PAMAM/NONONAte (the light-operated nitric oxide releasing composite film material) into the PCL solution obtained in the step (I), and then stirring the solution to volatilize the solvent to obtain the polycaprolactone-coated light-operated nitric oxide releasing composite film material (Au @ N-N-PAMAM/NONONONAte @ PCL).
The molecular weight of the PCL (polycaprolactone) in the step (I) is preferably 5000-50000.
The volume ratio of the N, N-Dimethylformamide (DMF) to the trichloromethane in the step (I) is 1: 1-4.
The stirring time in the step (I) is 1-2 h.
The concentration of the PCL solution in the step (I) is 5-30% by mass.
The mass ratio of the PCL to the Au @ N-N-PAMAM/NONOnoate (light-operated nitric oxide releasing composite film material) in the step (I) is 1: 0.05-5.
The dispersion described in step (II) is preferably achieved by: after 100-300W ultrasonic oscillation is carried out for 30-60 min, the cell is placed in an ice bath and is subjected to ultrasonic treatment by a 1-3 KW ultrasonic cell crusher for 5-30 min.
The stirring time in the step (II) is preferably 5-24 h.
The light-operated nitric oxide releasing composite film material or the polycaprolactone-coated light-operated nitric oxide releasing composite film material is applied to biomedical engineering materials.
The application of the light-operated nitric oxide releasing composite film material or the polycaprolactone-coated light-operated nitric oxide releasing composite film material in the preparation of antibacterial drugs.
The antibacterial drugs include drugs for inhibiting the growth and reproduction of bacteria and fungi.
The bacterium is preferably staphylococcus aureus.
The composite membrane material for optically controlling and releasing nitric oxide or the composite membrane material for optically controlling and releasing nitric oxide coated by polycaprolactone can also be used for preparing medicaments for promoting wound healing and diminishing inflammation.
Compared with the prior art, the invention has the following advantages and effects:
(1) the invention discloses a preparation method of a composite membrane material for controlling the release of nitric oxide under the irradiation of near-infrared laser; the method prepares and synthesizes spherical dendritic polyamide-amine (N-N-PAMAM); then preparing gold nanoparticles with uniform particle size, modifying N-N-PAMAM on the surface of the gold nanoparticles by a certain chemical method to prepare N-N-PAMAM modified nanogold, loading nitric oxide in a high-pressure reaction kettle to obtain a spherical dendritic polyamide-amine modified Au composite membrane material serving as a nitric oxide donor
(Au @ N-N-PAMAM/NOnoate); and then dispersing Au @ N-N-PAMAM/NONOATE in an organic solvent, blending with Polycaprolactone (PCL), and performing freeze drying and pressing to form a film, thereby finally obtaining the film composite antibacterial material capable of controlling to release nitric oxide under the irradiation of near-infrared laser.
(2) The invention adopts high-algebraic spherical polyamide-amine as NO donor, greatly improves NO loading capacity, has obvious inhibiting effect on the influence of bacterial biofilm, and can well adsorb negatively charged bacteria and kill the negatively charged bacteria to a certain extent.
(3) The invention adopts one-pot method to mix the dendritic polyamide-amine with the nano-gold, has high reaction efficiency, easy and accurate structure control and single molecular weight distribution.
(4) The invention takes Au as a core, can quickly raise the temperature under the irradiation of near-infrared laser, has a certain killing effect on bacteria, and quickly dissolves the PCL coating on the surface, so that the NO-loaded cationic polymer is exposed outside, thereby playing the role of controlling and releasing NO.
(5) The invention takes Au as a core, and the cationic polymer polyamide-amine as an outer layer can effectively adsorb a large amount of bacteria, thereby greatly improving the sterilization effect.
(6) According to the invention, PCL is used as a hydrophobic material of the surface coating, so that an NO donor can be well wrapped inside, and a large amount of NO can be protected and stored; the melting point is low, and the material can quickly respond under near-infrared irradiation, so that the intelligent response effect of the material is realized; the PCL is soft and can be made into various shapes, such as thin film, round sphere, cube, etc.
(7) The material of the invention is beneficial to reducing the cytotoxicity of the product, and has potential application value in the field of antibacterial drug co-delivery as an antibacterial drug controlled release carrier.
(8) The NO donor product obtained in the invention has the advantages of effectively inhibiting the growth and reproduction of bacteria and fungi, having obvious inhibiting effect on common pathogenic bacteria, dermatophytes, wound infectious bacteria and the like, having the functions of promoting wound healing, diminishing inflammation and the like, and providing support for the application of the NO donor product in the preparation of biomedical engineering materials.
(9) The invention provides a novel antibacterial material which can store a large amount of NO and can be released in a controlled manner according to requirements; the nano material has the advantages of uniform particle size, sensitive response, large NO loading and storage capacity, long release time, good biocompatibility and obvious antibacterial effect, and shows an important application prospect in the antibacterial aspect.
Drawings
FIG. 1 is a schematic view of the structure of the composite membrane material of the present invention.
FIG. 2 is a potential diagram of Au @ N-N-PAMAM, Au and N-N-PAMAM.
FIG. 3 is a graph showing the temperature rise of Au @ N-N-PAMAM, Au and N-N-PAMAM under near infrared irradiation.
FIG. 4 is a graph of the NO release of Au @ N-N-PAMAM/NONOnoate @ PCL under various conditions.
FIG. 5 is a graph comparing the bacteriostatic effect of Au @ N-N-PAMAM @ PCL and Au @ N-N-PAMAM on Escherichia coli under laser irradiation by turbidity; wherein 1 represents Au @ N-N-PAMAM/NONONAte +808nm, 2 represents Au @ N-PAMAM/NONONONAte @ PCL +808nm, and 3 represents blank control.
Detailed Description
The present invention will be described in further detail with reference to examples, but the embodiments of the present invention are not limited thereto.
1. The following examples use the following procedure for the preparation of anhydrous methanol: adding calcium hydride into methanol, stirring for 6-24 hours, and then distilling at normal pressure to obtain anhydrous methanol, wherein the addition amount of the calcium hydride is 1-2 g per 500mL of methanol.
2. The methyl acrylate used in the following examples was anhydrous methyl acrylate prepared according to the following procedure: adding anhydrous sodium sulfate into methyl acrylate, stirring for 6-24 hours, and then distilling at normal pressure to obtain anhydrous methyl acrylate, wherein the addition amount of the anhydrous sodium sulfate is 1-2 g per 500mL of methyl acrylate.
3. The ethylenediamine used in the following examples was anhydrous ethylenediamine, which was prepared according to the following procedure: adding anhydrous potassium hydroxide into ethylenediamine, stirring for 6-24 hours, and then distilling under reduced pressure to obtain anhydrous ethylenediamine, wherein the addition amount of the anhydrous potassium hydroxide is 1-2 g per 500mL of ethylenediamine.
4. The procedure used in the following examples to prepare the dried Au @ N-N-PAMAM was as follows: and (3) placing the Au @ N-N-PAMAM into a vacuum drying oven, and drying for 12-48 hours at the temperature of 40-80 ℃.
Example 1
(1) Synthesis of 3-generation spherical dendritic polyamidoamine:
dissolving ethylenediamine in methanol in ice water bath at 0 deg.C, dripping into methanol solution of methyl acrylate, stirring, heating to 25 deg.C, stirring, and reacting for 12 hr to obtain PAMAM (N-N-P AMAM-D) with ethylenediamine as core of 0.5 generation0.5) (ii) a Adding N-N-PAMAM-D in ice-water bath0.5Dissolving in methanol, dripping into methanol solution of ethylenediamine, stirring, heating to 25 deg.C, stirring, and reacting for 12 hr to obtain N-N-PAM AM (N-N-PAMAM-D) element with 1 generation ethylenediamine as core1) (ii) a Wherein the molar ratio of the ethylenediamine to the methyl acrylate is 1: 4; the N-N-PAMAM-D0.5The molar ratio of the ethylene diamine to the ethylene diamine is 1: 4; the amount of methanol is calculated by dissolving 1ml of methyl acrylate in every 10ml of methanol; the amount of the methanol is calculated by dissolving 1ml of ethylenediamine in every 10ml of methanol; the N-N-PAMAM-D0.5The dosage of the methanol is 0.5g N-N-PAM AM-D per milliliter0.5And (6) counting.
(2) Synthesis of dendritic polyamide N-N-PAMAM with 3-generation ethylenediamine as core
Adding N-N-PAMAM-D in ice water bath at 0 deg.C1Dissolving in methanol, dripping into methyl acrylate methanol solution, stirring, heating to 25 deg.C, stirring, and reacting for 12 hr to obtain 1.5-substituted ethylenediamine (PAMAM) as core PAMAM element (N-N-PAMAM-D)1.5) (ii) a Adding N-N-PAMAM-D in ice-water bath1.5Dissolving in methanol, dripping into methanol solution of ethylenediamine, stirring, heating to 25 deg.C, stirring, and reacting for 12 hr to obtain N-N-PAMAM (N-N-PAMAM-D) with 2 generation ethylenediamine as core2) (ii) a Adding N-N-PAMAM-D in ice water bath at 0 deg.C2Dissolving in methanol, dripping into methyl acrylate methanol solution, stirring, heating to 25 deg.C, stirring, and reacting for 12 hr to obtain 2.5-generation ethylenediamine (N-N-PAMAM-D) PAMAM element2.5) (ii) a Adding N-N-PAMAM-D in ice water bath at 0 deg.C2.5Dissolving in methanol, dripping into methanol solution of ethylenediamine, stirring, heating to 25 deg.C, stirring, and reacting for 12 hr to obtain N-N-PAMAM (N-N-PAM AM-D) with 3 generation ethylenediamine as core3) (ii) a Wherein, the N-N-PAMAM-D1With acrylic acidMolar ratio of methyl ester 1: 8; the N-N-PAMAM-D2The molar ratio to methyl acrylate was 1: 16; the N-N-PAMAM-D1.5The molar ratio of the ethylene diamine to the ethylene diamine is 1: 8; the N-N-PAMAM-D2.5The molar ratio of ethylene diamine to ethylene diamine is 1: 16; the amount of methanol is calculated by dissolving 1ml of methyl acrylate in every 10ml of methanol; the amount of the methanol is calculated by dissolving 1ml of ethylenediamine in every 10ml of methanol; the N-N-PAMAM-D1(N-N-PAMAM-D1.5，N-N-PA MAM-D2，N-N-PAMAM-D2.5) The dosage of the methanol is 0.5g N-N-PAMAM-D per milliliter1(N-N-PAMAM-D1.5，N-N-PAMAM-D2，N-N-PAMAM-D2.5) And (6) counting.
Example 2
(1) Synthesis of 3-generation spherical dendritic polyamidoamine:
dissolving ethylenediamine in methanol at 0 deg.C in ice water bath, adding dropwise into methyl acrylate methanol solution, stirring, heating to 35 deg.C, stirring, and reacting for 48 hr to obtain PAMAM (N-N-PAMAM-D) with ethylenediamine as core of 0.5 generation0.5) (ii) a Adding N-N-PAMAM-D in ice-water bath0.5Dissolving in methanol, dripping into methanol solution of ethylenediamine, stirring, heating to 35 deg.C, stirring, and reacting for 48 hr to obtain N-N-PAMAM (N-N-PAMAM-D) with 1 generation ethylenediamine as core1) (ii) a Wherein the molar ratio of the ethylenediamine to the methyl acrylate is 1: 8; the N-N-PAMAM-D0.5The molar ratio of the ethylene diamine to the ethylene diamine is 1: 12; the amount of methanol is calculated by dissolving 5ml of methyl acrylate in every 10ml of methanol; the amount of the methanol is that 5ml of ethylenediamine is dissolved in every 10ml of methanol; the N-N-PAMAM-D0.5The dosage of the methanol is 5g N-N-PAMAM-D0.5And (6) counting.
(2) Synthesis of dendritic polyamide N-N-PAMAM with 3-generation ethylenediamine as core
Adding N-N-PAMAM-D in ice water bath at 0 deg.C1Dissolving in methanol, adding methyl acrylate solution, stirring, heating to 35 deg.C, stirring, and reacting for 48 hr to obtain 1.5-generation ethylenediamine (PAMAM) as core PAMAM (N-N-PAMAM-D)1.5) (ii) a Adding N-N-PAMAM-D in ice-water bath1.5Dissolving in methanol, dripping into methanol solution of ethylenediamine, stirring, heating to 35 deg.C, and stirringReacting for 48h to obtain N-N-PAMAM motif (N-N-PAMAM-D) taking 2-generation ethylenediamine as core2) (ii) a Adding N-N-PAMAM-D in ice water bath at 0 deg.C2Dissolving in methanol, adding methyl acrylate solution, stirring, heating to 35 deg.C, stirring, and reacting for 48 hr to obtain 2.5-generation ethylenediamine (PAMAM) as core PAMAM (N-N-PAMAM-D)2.5) (ii) a Adding N-N-PAMAM-D in ice water bath at 0 deg.C2.5Dissolving in methanol, dripping into methanol solution of ethylenediamine, stirring, heating to 35 deg.C, stirring, and reacting for 48 hr to obtain N-N-PAMAM (N-N-PAMAM-D) with 3 generation ethylenediamine as core3) (ii) a Wherein the N-N-PAMAM (D)1) Molar ratio to methyl acrylate 1: 16; the N-N-PAM AM-D2The molar ratio of the N-N-PAMAM-D to the methyl acrylate is 1:321.5The molar ratio of ethylene diamine to ethylene diamine is 1: 24; the N-N-PAMAM-D2.5The molar ratio of the ethylene diamine to the ethylene diamine is 1: 48; the amount of methanol is calculated by dissolving 5ml of methyl acrylate in every 10ml of methanol; the amount of methanol is calculated by dissolving 5ml of ethylenediamine in every 10ml of methanol; the N-N-PAMAM-D1(N-N-PAMAM-D1.5，N-N-PAMAM-D2，N-N-PAMAM-D2.5) The dosage of the methanol is 5g N-N-PAMAM-D1(N-N-PA MAM-D1.5，N-N-PAMAM-D2，N-N-PAMAM-D2.5) And (6) counting.
Example 3
(1) Synthesis of 3-generation spherical dendritic polyamidoamine:
dissolving ethylenediamine in methanol at 0 deg.C in ice water bath, adding dropwise into methyl acrylate methanol solution, stirring, heating to 30 deg.C, stirring, and reacting for 24 hr to obtain PAMAM (N-N-PA MAM-D) with ethylenediamine as core of 0.5 generation0.5) (ii) a Adding N-N-PAMAM-D in ice-water bath0.5Dissolving in methanol, dripping into methanol solution of ethylenediamine, stirring, heating to 35 deg.C, stirring, and reacting for 24 hr to obtain N-N-PAMA M-D with 1 generation ethylenediamine as core1) (ii) a Wherein the molar ratio of the ethylenediamine to the methyl acrylate is 1: 6; the N-N-PAMAM-D0.5The molar ratio of the ethylene diamine to the ethylene diamine is 1: 8; the amount of methanol is calculated by dissolving 3ml of methyl acrylate in every 10ml of methanol; the amount of methanol is calculated by dissolving 3ml of ethylenediamine in every 10ml of methanol; the N-N-PAMAM-D0.5The dosage of the methanol is 2.5g N-N-PAMAM-D per milliliter0.5And (6) counting.
(2) Synthesis of dendritic polyamide N-N-PAMAM with 3-generation ethylenediamine as core
Adding N-N-PAMAM-D in ice water bath at 0 deg.C1Dissolving in methanol, adding methyl acrylate solution, stirring, heating to 30 deg.C, stirring, and reacting for 24 hr to obtain 1.5-substituted ethylenediamine (PAMAM) as core PAMAM (N-N-PAMAM-D)1.5) (ii) a Adding N-N-PAMAM-D in ice-water bath1.5Dissolving in methanol, dripping into methanol solution of ethylenediamine, stirring, heating to 30 deg.C, stirring, and reacting for 24 hr to obtain N-N-PAMAM (N-N-PAMAM-D) with 2 generation ethylenediamine as core2) (ii) a Adding N-N-PAMAM-D in ice water bath at 0 deg.C2Dissolving in methanol, adding methyl acrylate solution, stirring, heating to 30 deg.C, stirring, and reacting for 24 hr to obtain 2.5-generation ethylenediamine (PAMAM) as core PAMAM (N-N-PAMAM-D)2.5) (ii) a Adding N-N-PAMAM-D in ice water bath at 0 deg.C2.5Dissolving in methanol, dripping into methanol solution of ethylenediamine, stirring, heating to 35 deg.C, stirring, and reacting for 24 hr to obtain N-N-PAMAM (N-N-PAMAM-D) with 3 generation ethylenediamine as core3) (ii) a Wherein the N-N-PAMAM (D)1) Molar ratio to methyl acrylate 1: 12; the N-N-PAM AM-D2The molar ratio to methyl acrylate was 1: 25; the N-N-PAMAM-D1.5The molar ratio of ethylene diamine to ethylene diamine is 1: 16; the N-N-PAMAM-D2.5The molar ratio of ethylene diamine to ethylene diamine is 1: 32; the amount of methanol is calculated by dissolving 3ml of methyl acrylate in every 10ml of methanol; the amount of methanol is calculated by dissolving 3ml of ethylenediamine in every 10ml of methanol; the N-N-PAMAM-D1(N-N-PAMAM-D1.5，N-N-PAMAM-D2，N-N-PAMAM-D2.5) The dosage of the methanol is 2.5g of N-N-PAMAM-D per ml1(N-N-PAM AM-D1.5，N-N-PAMAM-D2，N-N-PAMAM-D2.5) And (6) counting.
Example 4N-N-PAMAM modified Nanogold Material preparation
A certain mass of the 3 rd generation ethylenediamine cored dendritic polyamidoamine (N-N-PAMAM-D) obtained in example 1 was weighed3) Dissolving in ultrapure water, and ultrasonic dissolving. Chloroauric acid and dendrimersMacromolecule is added dropwise with chloroauric acid (HAuCl) according to a certain molar ratio4) Stirring at room temperature for 30min, and rapidly adding NaBH4Continuously stirring for 2h, transferring the reaction solution into a dialysis bag with the molecular weight cutoff of 3000 after the reaction is finished, dialyzing for 1 day, removing part of precipitate (the part of precipitate is an Au composite membrane material and is reserved for standby), and freeze-drying to obtain a final product Au @ N-N-PAMAM; wherein, the N-N-PAMAM-D3Chloroauric acid and sodium borohydride (NaBH)4) In a molar ratio of 1:20: 100; the amount of the ultrapure water added is such that 1mg of N-N-PAMAM-D is dissolved in 5ml of the ultrapure water3And (6) counting.
Example 5N-N-PAMAM modified Nanogold Material preparation
A certain mass of the 3 rd generation ethylenediamine cored dendritic polyamidoamine (N-N-PAMAM-D) obtained in example 2 was weighed3) Dissolving in ultrapure water, and ultrasonic dissolving. Chloroauric acid and dendrimer are added dropwise into the chloroauric acid (HAuCl) according to a certain molar ratio4) Stirring at room temperature for 24h, and rapidly adding NaBH4Continuously stirring for 4h, transferring the reaction solution into a dialysis bag with the molecular weight cutoff of 5000 after the reaction is finished, dialyzing for 3 days, removing part of precipitate (the part of precipitate is an Au composite membrane material and is reserved for standby application), and freeze-drying to obtain a final product Au @ N-N-PAMAM; wherein, the N-N-PAMAM-D3The molar ratio of chloroauric acid to sodium borohydride is 1: 50: 250 of (a); the amount of the ultrapure water added is 5mg of N-N-PAMAM-D dissolved in 5ml of the ultrapure water3And (6) counting.
Example 6N-N-PAMAM modified Nanogold Material preparation
A certain mass of the dendrimer polyamidoamine (N-N-PAMAM-D) having 3 rd generation ethylenediamine as core obtained in example 3 was weighed3) Dissolving in ultrapure water, and ultrasonic dissolving. Chloroauric acid and dendrimer are added dropwise into the chloroauric acid (HAuCl) according to a certain molar ratio4) Stirring at room temperature for 12h, and rapidly adding NaBH4Continuously stirring for 3h, transferring the reaction solution into a dialysis bag with the molecular weight cutoff of 4000 after the reaction is finished, dialyzing for 2 days, removing part of precipitate (the part of precipitate is an Au composite membrane material and is reserved for standby application), and freeze-drying to obtain a final product Au @ N-N-PAMAM; wherein, the N-N-PAMAM-D3Molar ratio of chloroauric acid to sodium borohydrideIs 1: 30: 150; the amount of the ultrapure water added is such that 3mg of N-N-PAMAM-D is dissolved in 5ml of the ultrapure water3And (6) counting.
EXAMPLE 7 Synthesis of nanoparticles of releasable nitric oxide (Au @ N-N-PAMAM/NONOnoate)
And (3) drying the Au @ N-N-PAMAM obtained in the step 4, dissolving the dried Au @ N-N-PAMAM in absolute methanol, adding sodium methoxide, performing ultrasonic stabilization for 10min, placing the mixture in a high-pressure reaction kettle, sealing and detecting the air tightness. The reaction kettle (10psi) is maintained by high-purity nitrogen for 5min to remove air in the reaction kettle, and then NO gas (40psi) is introduced to react for 3 days at room temperature. After the reaction is finished, discharging NO by high-purity nitrogen with 10psi, continuously maintaining for 10-20 min, opening the reaction kettle, and taking out the reaction product. Washed 2 times with anhydrous methanol and 1 time with ice anhydrous ether, and dried under vacuum to obtain the final product (Au @ N-N-PAMAM/NONONOATE). Wherein the molar ratio of Au @ N-N-PAMAM to sodium methoxide is 1: 400; the concentration of the sodium methoxide is 5 percent by mass; the absolute methanol is calculated by dissolving 0.5g of Au @ N-N-PAMAM in each 10 ml; the preparation method of the dried Au @ N-N-PAMAM comprises the following operation steps: placing Au @ N-N-PAMAM in a vacuum drying oven, and drying for 12 hours at the temperature of 50 ℃.
EXAMPLE 8 Synthesis of nanoparticles of releasable nitric oxide (Au @ N-N-PAMAM/NOnoate)
And (3) drying the Au @ N-N-PAMAM obtained in the step 5, dissolving the dried Au @ N-N-PAMAM in absolute methanol, adding sodium methoxide, performing ultrasonic stabilization for 30min, placing the mixture in a high-pressure reaction kettle, sealing and detecting the air tightness. The reaction kettle (20psi) is maintained by high-purity nitrogen for 15min to remove air in the reaction kettle, and then NO gas (80psi) is introduced to react for 7 days at room temperature. After the reaction is finished, discharging NO by high-purity nitrogen of 10 psi-20 psi, continuously maintaining for 20min, opening the reaction kettle, and taking out a reaction product. Washed 3 times with anhydrous methanol and 2 times with ice anhydrous ether, and dried under vacuum to give the final product (Au @ N-N-PAMAM/NONONOATE). Wherein the molar ratio of Au @ N-N-PAMAM to sodium methoxide is 1: 450; the concentration of the sodium methoxide is 20 percent by mass; the absolute methanol is calculated by dissolving 2g of Au @ N-N-PAMAM in each 10 ml; the preparation method of the dried Au @ N-N-PAMAM comprises the following operation steps: placing Au @ N-N-PAMAM in a vacuum drying oven, and drying at 80 ℃ for 48 hours.
Example 9 Synthesis of nanoparticles of releasable nitric oxide (Au @ N-N-PAMAM/NOnoate)
And drying the Au @ N-N-PAMAM obtained in the step 6, dissolving the dried Au @ N-N-PAMAM in absolute methanol, adding sodium methoxide, performing ultrasonic stabilization for 20min, placing the mixture in a high-pressure reaction kettle, sealing and detecting the air tightness. The reaction kettle (20psi) is maintained by high-purity nitrogen for 10min to remove air in the reaction kettle, and then NO gas (60psi) is introduced to react for 5 days at room temperature. After the reaction is finished, discharging NO by high-purity nitrogen with the pressure of 20psi, continuously maintaining for 20min, opening the reaction kettle, and taking out a reaction product. Washed 2 times with anhydrous methanol and 2 times with ice anhydrous ether, and dried under vacuum to give the final product (Au @ N-N-PAMAM/NONONOATE). Wherein the molar ratio of Au @ N-N-PAMAM to sodium methoxide is 1: 420; the concentration of the sodium methoxide is 15% by mass; the absolute methanol is calculated by dissolving 1g of Au @ N-N-PAMAM in each 10 ml; the preparation method of the dried Au @ N-N-PAMAM comprises the following operation steps: and (3) drying the Au @ N-N-PAMAM for 36 hours in a vacuum drying oven at the temperature of 60-80 ℃.
EXAMPLE 10 Synthesis of polycaprolactone-coated nitric oxide controllably-releasing composite film Material
Weighing a certain amount of PCL (polycaprolactone molecular weight is 5000) particles, dissolving the PCL particles in a mixed solution of N, N-Dimethylformamide (DMF) and trichloromethane with a volume ratio of 1:1 to prepare a PCL solution with the concentration of 5% by mass, fully stirring the solution at room temperature for 1h until the solution is uniform and stable, and weighing the Au @ N-N-PAMAM/NONONONAte magnetic composite film material obtained in the embodiment 7 and adding the Au @ N-N-PAMAM/NONONONONAte magnetic composite film material into the prepared PCL solution. And (2) after ultrasonic 150W ultrasonic oscillation for 30min, putting the solution in an ice bath, and performing ultrasonic treatment by using an ultrasonic cell crusher (ultrasonic treatment is performed for 1KW/5min, so that the magnetic nanoparticles are uniformly dispersed in the PCL solution, and then mechanically and rapidly stirring for 5h to volatilize the solvent, thereby obtaining a final product polycaprolactone-coated composite film material (Au @ N-N-PAMAM/NONONONONOATE @ PCL) capable of controlling release of nitric oxide, wherein the mass ratio of the PCL to the Au @ N-N-PAMAM/NONAte is 1: 5.
EXAMPLE 11 Synthesis of polycaprolactone-coated nitric oxide controllably-releasing composite film Material
Weighing a certain amount of PCL (polycaprolactone molecular weight of 50000) particles, and dissolving in a solvent with a volume ratio of 1:4, preparing a PCL solution with the concentration of 30% by mass in a mixed solution of N, N-Dimethylformamide (DMF) and trichloromethane, fully stirring for 2 hours at room temperature until the solution is uniform and stable, and then weighing the Au @ N-N-PAMAM/NONONONAte magnetic composite membrane material obtained in the example 8 and adding the Au @ N-PAMAM/NONONAte magnetic composite membrane material into the prepared PCL solution. After 300W ultrasonic oscillation for 60min, putting the solution in an ice bath, and ultrasonically treating the solution for 3KW/5min by using an ultrasonic cell crusher to uniformly disperse the magnetic nanoparticles in the PCL solution, and then mechanically and rapidly stirring the solution for 24h to volatilize the solvent to obtain a final product, namely a polycaprolactone-coated composite film material (Au @ N-N-PAMAM/NONONAte @ PCL) capable of controllably releasing nitric oxide; wherein the mass ratio of the PCL to the Au @ N-N-PAMAM/NONONAte is 1: 0.05.
EXAMPLE 12 Synthesis of polycaprolactone-coated nitric oxide controllably-releasing composite film Material
Weighing a certain amount of PCL (polycaprolactone molecular weight 30000) particles, dissolving the PCL particles in a mixed solution of N, N-Dimethylformamide (DMF) and trichloromethane with a volume ratio of 1:2 to prepare a PCL solution with a concentration of 20% by mass, fully stirring the PCL solution at room temperature for 1.5 hours until the solution is uniform and stable, and weighing the Au @ N-N-PAMAM/NONONONAte magnetic composite membrane material obtained in the example 9 and adding the Au @ N-N-PAMAM/NONONONAte magnetic composite membrane material into the prepared PCL solution. After ultrasonic oscillation at 200W for 40min, putting the solution in an ice bath, and ultrasonically treating the solution for 2KW/5min by using an ultrasonic cell crusher to uniformly disperse magnetic nanoparticles in a PCL solution, and then mechanically and rapidly stirring the solution for 12h to volatilize the solvent to obtain a final product, namely a polycaprolactone-coated composite film material (Au @ N-N-PAMAM/NONONAte @ PCL) capable of controllably releasing nitric oxide; wherein the mass ratio of the PCL to the Au @ N-N-PAMAM/NONONAte is 1: 2.
Example 13
The Au @ N-N-PAMAM obtained in example 4, the Au precipitate obtained in example 4 and the N-N-PAMAM obtained in example 1 are respectively weighed to prepare 0.1mg/ml solution, the solution is uniformly dissolved by ultrasonic, the measured potential is shown in figure 2, the Au surface is negatively charged, the N-N-PAMAM is positively charged, and the Au @ N-N-PAMAM is positively charged, which indicates that the N-N-PAMAM has successfully attached with the nanogold.
Example 14
The Au @ N-N-PAMAM obtained in the example 4, the Au precipitate obtained in the example 4 and the N-N-PAMAM obtained in the example 1 are respectively weighed to be prepared into a concentration of 1mg/ml, and the mixture is irradiated for a certain time under near infrared of 808nm, and the experimental result is shown in figure 3, so that the Au @ N-N-PAMAM and Au have obvious photothermal effect, and the successful combination of Au and N-N-PAMAM can be further illustrated.
Example 15
The Au @ N-N-PAMAM/NONONOATE @ PCL obtained in example 12 is weighed to prepare 1mg/ml concentration, one group is irradiated by near infrared (the wavelength is 808nm), the other group is blank control, the experimental result is shown in figure 4, the Au @ N-N-PAMAM/NONONOATE @ PCL which is not irradiated by the near infrared is found to have long-time drug release effect, the NO of the experimental group irradiated by the infrared has obvious burst release phenomenon, and finally, the fact that the PCL successfully coats an NO donor is determined, and the controlled release effect of the material is obvious.
Example 16
0.25mg each of Au @ N-N-PAMAM/NONONOATE @ PCL obtained in example 12 and Au @ N-N-PAMAM/NONONAte obtained in example 9 was weighed out and dissolved in 5ml of physiological saline, and 50. mu.l (absorbance OD) was added thereto5901) staphylococcus aureus (ATCC29213), wherein the test tube 1 is Au @ N-N-PAMAM/NONONONOATE @ PCL, the culture is continued for 12h after 5min of near infrared irradiation, the test tube 2 is Au @ N-N-PAMAM/NONONOATE, the culture is continued for 12h after 5min of near infrared irradiation, the test tube 3 is a blank control and the culture is continued for 12h after 5min of near infrared irradiation, and the experimental result is shown in figure 5 through comparison of the Bridgman turbidity method.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (8)
1. A polycaprolactone-coated light-operated nitric oxide release composite membrane material is characterized in that the preparation method comprises the following steps:
(I) adding polycaprolactone into the mixed solution of N, N-dimethylformamide and trichloromethane, and uniformly stirring to obtain a polycaprolactone solution;
(II) dispersing the light-operated nitric oxide releasing composite film material into the polycaprolactone solution obtained in the step (I), and then stirring and volatilizing the solvent to obtain a polycaprolactone-coated light-operated nitric oxide releasing composite film material;
the composite membrane material for optically controlling and releasing nitric oxide is prepared by the following method:
(1) synthesis of N-N-PAMAM element with 3 generation ethylenediamine as core
a. Dripping the methanol solution of ethylenediamine into the methanol solution of methyl acrylate under the condition of ice-water bath, uniformly stirring, heating to room temperature, and stirring for reaction to obtain N-N-PAMAM-D0.5(ii) a Dissolving in methanol under ice water bath condition, dripping into methanol solution of ethylenediamine, stirring, heating to room temperature, and stirring for reaction to obtain N-N-PAMAM-D1；
b. B, mixing the N-N-PAMAM-D obtained in the step a1Replacing ethylenediamine, and repeating the operation of the step a to obtain N-N-PAMAM-D2(ii) a Then N-N-PAMAM-D2Replacing ethylenediamine, and repeating the operation of the step a to obtain N-N-PAMAM-D3；
(2) Preparation of N-N-PAMAM modified nano-gold material
The N-N-PAMAM-D obtained in the step (1) b3Dissolving in water, dropwise adding chloroauric acid, stirring at room temperature, and adding NaBH4Continuously stirring, dialyzing and drying to obtain Au @ N-N-PA MAM;
(3) synthesis of composite membrane material for light-operated release of nitric oxide
And (3) dissolving the Au @ N-N-PAMAM obtained in the step (2) in absolute methanol, adding sodium methoxide, performing ultrasonic stabilization for 10-30 min, introducing NO gas, reacting at room temperature, washing after the reaction is finished, and drying to obtain the light-operated nitric oxide release composite membrane material.
2. The polycaprolactone-coated light-operated nitric oxide releasing composite film material of claim 1, wherein:
the molar ratio of the ethylenediamine to the methyl acrylate in the step (1) a is 1: 4-8;
the N-N-PAMAM-D in the step (1) a0.5The molar ratio of the ethylene diamine to the ethylene diamine is 1: 4-24;
the N-N-PAMAM-D in the step (2)3Chloroauric acid and NaBH4The molar ratio of (A) to (B) is 1: 20-50: 100-250;
the molar ratio of Au @ N-N-PAMAM to sodium methoxide in the step (3) is 1: 400-450.
3. The polycaprolactone-coated light-operated nitric oxide releasing composite film material of claim 1, wherein:
the methanol solution of the ethylenediamine in the step (1) a is a solution prepared by mixing methanol and ethylenediamine according to a volume ratio of 10: 1-5;
the methyl acrylate methanol solution in the step (1) a is prepared by mixing methanol and methyl acrylate according to the volume ratio of 10: 1-5.
4. The polycaprolactone-coated light-operated nitric oxide releasing composite film material of claim 1, wherein:
the N-N-PAMAM-D in the step (1) a0.5The dosage of the compound is 0.5-5 g N-N-PAMAM-D per milliliter of methanol0.5Calculating;
the N-N-PAMAM-D in the step (2)3The dosage of the N-N-PAMAM-D is 0.2 to 1mg per milliliter of water3Calculating;
the dosage of the Au @ N-N-PAMAM in the step (3) is calculated according to the proportion of 0.05-0.2 g of Au @ N-N-PAMAM per milliliter of anhydrous methanol.
5. The polycaprolactone-coated light-operated nitric oxide releasing composite film material of claim 1, wherein:
the stirring reaction time in the step (1) a is 12-48 h;
the stirring time in the step (2) is 0.5-24 h;
the continuous stirring time in the step (2) is 2-4 h;
the dialysis in the step (2) is carried out in a dialysis bag with the molecular weight cutoff of 3000-5000;
the drying conditions in the step (2) are as follows: drying for 12-48 hours at 50-80 ℃;
the reaction time in the step (3) is 3-7 days;
the washing in the step (3) is carried out by using anhydrous methanol and ice anhydrous ether.
6. The polycaprolactone-coated light-operated nitric oxide releasing composite film material of claim 1, wherein:
the molecular weight of the polycaprolactone in the step (I) is 5000-50000;
the volume ratio of the N, N-dimethylformamide to the trichloromethane in the step (I) is 1: 1-4;
the concentration of the polycaprolactone solution in the step (I) is 5-30% by mass;
the mass ratio of the polycaprolactone to the light-operated nitric oxide releasing composite film material in the step (I) is 1: 0.05-5.
7. The application of the polycaprolactone-coated light-operated nitric oxide release composite film material of any one of claims 1 to 6 in preparation of biomedical engineering materials.
8. The application of the polycaprolactone-coated light-operated nitric oxide release composite membrane material of any one of claims 1 to 6 in preparation of antibacterial drugs.
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Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101220154A (en) * | 2008-01-31 | 2008-07-16 | 上海交通大学 | Crosslinked polyalcohol membrana body material, method for producing the same and process of using |
| CN101225227A (en) * | 2008-01-31 | 2008-07-23 | 上海交通大学 | Over-branched polyamidoamine and metal nano compound as well as preparation method and uses thereof |
| CN101367802A (en) * | 2008-09-27 | 2009-02-18 | 暨南大学 | Beta-kabarin alkaloids in quassia wood, preparation method and application thereof |
| CN101712798A (en) * | 2009-11-12 | 2010-05-26 | 浙江大学 | Compound consisting of metal nano-particles and cell membrane biomimetic-modification arborized polyamide-amine and preparation method |
| CN103304523A (en) * | 2012-11-30 | 2013-09-18 | 暨南大学 | Andrographolide derivative nitric oxide donor compound as well as preparation method and application thereof |
| CN104209539A (en) * | 2014-09-28 | 2014-12-17 | 中南大学 | Method for preparing gold nanoparticles based on polyamidoamine amine supermolecular hyperbranched polymer |
| CN106046382A (en) * | 2016-05-25 | 2016-10-26 | 暨南大学 | Nitric oxide loaded cationic polymer, preparation method therefor and application of nitric oxide loaded cationic polymer |
-
2017
- 2017-10-25 CN CN201711011405.5A patent/CN107739506B/en active Active
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101220154A (en) * | 2008-01-31 | 2008-07-16 | 上海交通大学 | Crosslinked polyalcohol membrana body material, method for producing the same and process of using |
| CN101225227A (en) * | 2008-01-31 | 2008-07-23 | 上海交通大学 | Over-branched polyamidoamine and metal nano compound as well as preparation method and uses thereof |
| CN101367802A (en) * | 2008-09-27 | 2009-02-18 | 暨南大学 | Beta-kabarin alkaloids in quassia wood, preparation method and application thereof |
| CN101712798A (en) * | 2009-11-12 | 2010-05-26 | 浙江大学 | Compound consisting of metal nano-particles and cell membrane biomimetic-modification arborized polyamide-amine and preparation method |
| CN103304523A (en) * | 2012-11-30 | 2013-09-18 | 暨南大学 | Andrographolide derivative nitric oxide donor compound as well as preparation method and application thereof |
| CN104209539A (en) * | 2014-09-28 | 2014-12-17 | 中南大学 | Method for preparing gold nanoparticles based on polyamidoamine amine supermolecular hyperbranched polymer |
| CN106046382A (en) * | 2016-05-25 | 2016-10-26 | 暨南大学 | Nitric oxide loaded cationic polymer, preparation method therefor and application of nitric oxide loaded cationic polymer |
Non-Patent Citations (2)
| Title |
|---|
| 《Nitric Oxide Releasing Nanomaterials for Cancer Treatment: Current Status and Perspectives》;medea B. Seabra等;《Current Topics in Medicinal Chemistry》;20151231;第15卷(第4期);第298-308页 * |
| 《树状大分子包裹金纳米颗粒的制备、尺寸控制和稳定性研究》;郭睿等;《高分子通报》;20100831(第8期);第78-84页 * |
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