阅读说明：本技术 一种硼酸催化羧基化β-环糊精接枝四氧化三铁及其制备方法 (Boric acid-catalyzed carboxylated beta-cyclodextrin grafted ferroferric oxide and preparation method thereof ) 是由 王景昌 赵宇 赵启成 詹世平 于 2021-01-21 设计创作，主要内容包括：一种硼酸催化羧基化β-环糊精接枝四氧化三铁及其制备方法,属于载体材料领域。本发明采用3-氨丙基三乙氧基硅烷改性四氧化三铁得到具有氨基结构的Fe-3O-4；再用羧基化β-环糊精和氨基化四氧化三铁为原料,硼酸为催化剂,通过酰胺化反应制备得到β-环糊精接枝氨基化四氧化三铁的产物β-CD-Fe-3O-4。本发明方法制备的产物的综合性能得到进一步的改善,具有良好生物相容性和磁性能,该制备方法具有原料和催化剂绿色、反应条件温和,反应时间短,且接枝率高的特点。(Boric acid-catalyzed carboxylation beta-cyclodextrin grafted ferroferric oxide and a preparation method thereof, belonging to the field of carrier materials. The invention adopts 3-aminopropyltriethoxysilane to modify ferroferric oxide to obtain Fe with amino structure 3 O 4 (ii) a Then carboxylated beta-cyclodextrin and aminated ferroferric oxide are used as raw materials, boric acid is used as a catalyst, and the beta-cyclodextrin grafted aminated ferroferric oxide product beta-CD-Fe is prepared through amidation reaction 3 O 4 . The product prepared by the method has the characteristics of further improved comprehensive performance, good biocompatibility and magnetic property, green raw materials and catalyst, mild reaction condition, short reaction time and high grafting rate.)

1. A preparation method of boric acid-catalyzed carboxylated beta-cyclodextrin grafted ferroferric oxide is characterized by comprising the following steps:

s1. preparation of aminated ferroferric oxidePreparing: weighing Fe₃O₄Dissolving the particles in a three-neck flask containing absolute ethyl alcohol and deionized water, uniformly dispersing in ultrasound, heating to 80 ℃, adding 3-aminopropyltriethoxysilane under the protection of nitrogen, reacting at the speed of 180r/min for 6 hours under mechanical stirring, standing, cooling, performing suction filtration, and drying to obtain aminated ferroferric oxide;

s2, preparation of a beta-cyclodextrin magnetic product: weighing carboxylated beta-cyclodextrin and aminated ferroferric oxide, adding the weighed carboxylated beta-cyclodextrin and aminated ferroferric oxide into a three-neck flask containing dimethyl sulfoxide, carrying out ultrasonic treatment on the mixture for 10min, weighing boric acid, heating to react under the protection of nitrogen, cooling to room temperature after the reaction is finished, diluting and dissolving the mixture with absolute ethyl alcohol, repeating magnetic decantation for 2-3 times to obtain a product, and storing the dried product.

2. The method for preparing ferroferric oxide grafted by beta-cyclodextrin under catalysis of boric acid according to claim 1, wherein Fe in step S1₃O₄The amount of the particles was 3g, the amount of absolute ethanol was 150ml, and the amount of deionized water was 2 ml.

3. The method for preparing ferroferric oxide grafted by beta-cyclodextrin under the catalysis of boric acid according to claim 1, wherein 3ml of 3-aminopropyltriethoxysilane is used in step S1.

4. The preparation method of boric acid-catalyzed carboxylated beta-cyclodextrin-grafted ferroferric oxide according to claim 1, wherein the reaction temperature in the step S2 is 60-80 ℃, and the reaction time is 4-8 hours.

5. The method for preparing ferroferric oxide grafted by beta-cyclodextrin under catalysis of boric acid according to claim 1, wherein beta-CD-COOH and Fe in step S2₃O₄-NH₂The mass ratio of beta-CD-COOH to the catalyst is 10: 2-6, and the mass ratio of beta-CD-COOH to the catalyst is 10: 2-4.

6. The method for preparing ferroferric oxide grafted by boric acid-catalyzed carboxylation beta-cyclodextrin according to claim 1, wherein the amount of dimethyl sulfoxide in the three-neck flask in the step S2 is 15 ml.

7. A boric acid catalyzed carboxylated beta-cyclodextrin grafted ferroferric oxide prepared using the method of claim 1.

Technical Field

The invention belongs to the field of carrier materials, and particularly relates to boric acid-catalyzed carboxylation beta-cyclodextrin grafted ferroferric oxide and a preparation method thereof.

Background

With the development of medical science and technology, ferroferric oxide (Fe)₃O₄) The potential medical applications of magnetic nanoparticles in tumor diagnosis and targeted therapy have attracted a great deal of attention, for example, as a key cause for magnetic resonance imagingA contrast agent component as a medium for magnetocaloric hyperthermia or as a targeting medium for drug delivery. Beta-cyclodextrin is cyclic oligosaccharide with 7D-glucopyranoside units linked by 1, 4-glycosidic bonds, has the advantages of amphipathy, good biocompatibility, low immunogenicity, wide sources and low price, can improve the solubility and stability of drugs, strengthen the drug absorption, cover unnecessary odor and taste, control the drug release, improve the permeability of drugs through biological barriers (carriers), and is widely applied to the fields of pharmaceutical preparations, foods, spices, cosmetics, packaging, textiles and the like. The beta-cyclodextrin with good biocompatibility is used for coating the magnetic substance, so that the biocompatibility of the magnetic nanoparticles can be improved, and the application range of the magnetic nanoparticles in the biomedical field can be expanded. The existing magnetic substance has low grafting rate and long reaction time, and is not beneficial to industrial utilization.

Disclosure of Invention

Aiming at the defects, the invention provides boric acid-catalyzed carboxylated beta-cyclodextrin grafted ferroferric oxide and a preparation method thereof.

The preparation method for solving the technical problem comprises the following steps:

(1) preparation of aminated ferroferric oxide: 3g of Fe are weighed₃O₄Dissolving the particles in a three-neck flask containing 150mL of anhydrous ethanol and 2mL of deionized water, uniformly dispersing in ultrasound, heating to 80 ℃, adding 3mL of 3-Aminopropyltriethoxysilane (ATPES) under the protection of nitrogen, reacting for 6h at the speed of 180r/min under mechanical stirring, standing, cooling, performing suction filtration, and drying to obtain the amino ferroferric oxide (Fe)₃O₄-NH₂)；

(2) Preparation of a beta-cyclodextrin magnetic product: weighing a certain amount of beta-CD-COOH and Fe₃O₄-NH₂Adding into a three-neck flask containing 15mL of dimethyl sulfoxide, carrying out ultrasonic treatment on the mixture for 10min, weighing a certain amount of boric acid, heating to a certain temperature under the protection of nitrogen, reacting for a certain time, cooling to room temperature, diluting with 80mL of absolute ethyl alcohol for desolvation,repeating magnetic decantation for 2-3 times to obtain a product, and storing the dried product;

in step (2), the operating parameter ranges are: the reaction temperature is 60-80 ℃, the reaction time is 4-8 h, and beta-CD-COOH and Fe₃O₄-NH₂The mass ratio of beta-CD-COOH to the catalyst is 10: 2-6, and the mass ratio of beta-CD-COOH to the catalyst is 10: 2-4.

The principle is as follows: the invention adopts 3-aminopropyl triethoxysilane (APTES) to modify ferroferric oxide (Fe)₃O₄) To obtain Fe having an amino structure₃O₄(ii) a Then carboxylated beta-cyclodextrin (beta-CD-COOH) and aminated ferroferric oxide (Fe)₃O₄-NH₂) Taking boric acid as a catalyst as a raw material, and preparing a product beta-CD-Fe of beta-cyclodextrin grafted aminated ferroferric oxide by amidation reaction₃O₄. Product beta-CD-Fe₃O₄Has good hydrophilic and magnetic properties, and can be used as a targeting carrier of a drug delivery system. Carboxylated beta-cyclodextrin and aminated Fe₃O₄The method for measuring the grafting ratio comprises the following steps: according to the Beer-Lambert law, the relative grafting rate of the product is determined by adopting a quantitative analysis method of infrared spectrum. By corresponding carboxylated beta-cyclodextrin and aminated Fe in the infrared spectrogram of the product₃O₄The relative content of the two is determined, and the relative content is used for comparing the grafting rate to determine the optimal operation condition.

Has the advantages that: the product prepared by the method has the characteristics of further improved comprehensive performance, good biocompatibility and magnetic property, green raw materials and catalyst, mild reaction condition, short reaction time and high grafting rate.

Drawings

FIG. 1 is a synthetic route diagram of beta-cyclodextrin grafted aminated ferroferric oxide.

FIG. 2 graft product beta-CD-Fe₃O₄FT-IR spectrum of (1): (a) fe₃O₄；(b)Fe₃O₄-NH₂；(c)β-CD-Fe₃O₄。

FIG. 3 graft product beta-CD-Fe₃O₄XRD spectrum of (1): (a) fe₃O₄；(b)Fe₃O₄-NH₂；(c)β-CD-Fe₃O₄。

FIG. 4 graft product beta-CD-Fe₃O₄Magnetic property spectrum of: (a) fe₃O₄-NH₂；(b)β-CD-Fe₃O₄。

Detailed Description

The present invention will be further described with reference to the following examples.

Example 1

0.5g of beta-CD-COOH and 0.25g of Fe were weighed out accurately₃O₄-NH₂Adding the mixture into a three-neck flask containing 15mL of dimethyl sulfoxide, carrying out ultrasonic treatment on the mixture for 10min, weighing 0.15g of boric acid, heating to 70 ℃ under the protection of nitrogen, reacting for 5h, cooling to room temperature, diluting with 80mL of absolute ethyl alcohol for desolvation, repeating magnetic decantation for 2-3 times to obtain a product with the grafting rate of 75.5%;

example 2

0.5g of beta-CD-COOH and 0.25g of Fe were weighed out accurately₃O₄-NH₂Adding the mixture into a three-neck flask containing 15mL of dimethyl sulfoxide, carrying out ultrasonic treatment on the mixture for 10min, weighing 0.15g of boric acid, heating to 80 ℃ under the protection of nitrogen, reacting for 5h, cooling to room temperature, diluting with 80mL of absolute ethyl alcohol for desolvation, repeating magnetic decantation for 2-3 times to obtain a product with the grafting rate of 50.8%;

example 3

0.5g of beta-CD-COOH and 0.125g of Fe were weighed out accurately₃O₄-NH₂Adding the mixture into a three-neck flask containing 15mL of dimethyl sulfoxide, carrying out ultrasonic treatment on the mixture for 10min, weighing 0.15g of boric acid, heating to 70 ℃ under the protection of nitrogen, reacting for 5h, cooling to room temperature, diluting the obtained product with 80mL of anhydrous ethanol for desolvation, and repeating magnetic decantation for 2-3 times to obtain a product with the grafting rate of 65.1%;

example 4

0.5g of beta-CD-COOH and 0.25g of Fe were weighed out accurately₃O₄-NH₂Into a three-necked flask containing 15mL of dimethyl sulfoxide, and mixing the mixturePerforming ultrasonic treatment for 10min, weighing 0.13g of boric acid, heating to 70 ℃ under the protection of nitrogen, reacting for 5h, cooling to room temperature, diluting with 80mL of absolute ethanol for desolvation, and repeating magnetic decantation for 2-3 times to obtain a product with the grafting rate of 73.4%;

FIG. 2 shows the graft product beta-CD-Fe₃O₄FT-IR spectrum of (1), corresponding to Fe₃O₄With strong absorption bands at 638 and 561cm^-1Left and right, since it is at 570cm^-1The resulting split corresponds to Fe₃O₄Movement of Fe-O bond of (2), 445cm^-1Also due to Fe-O bonds at 375cm^-1The movement of (a); after APTES modification, the three characteristic bands can be observed, and Fe₃O₄In contrast, APTES-Fe₃O₄The appearance was at 2926 and 2857cm^-1Has a telescopic vibration absorption band of C-H bond of propylamine group, silica is connected to the surface of the particle through Fe-O-Si bond, and the corresponding absorption band appears at 587cm^-1Left and right and overlapped with the vibration of the Fe-O bond. However, APTES-Fe₃O₄The silane polymer of (A) can be bonded on the surface with SiO-H and Si-O-Si at 1030 and 1111cm^-1The nearby absorption band confirms. At 1643 and 3419cm^-1Two peaks due to-NH₂Bending vibration and N-H stretching vibration. For beta-CD-COOH-Fe₃O₄Sample at 3316cm^-1And 3134cm^-1Stretching vibration at-OH and N-H at 1190-910cm^-1The broadband in the range is beta-CD and the characteristic absorption peak of ether bond in ferroferric oxide, and CH is also observed in a spectrogram₂The vibration of the method O-H in C-H and-OH is 1465cm^-1And 1310cm^-1In the meantime.

FIG. 3 shows the graft product of beta-CD-Fe₃O₄XRD spectrum of (1), wherein standard Fe₃O₄Having a cubic spinel structure in Fe₃O₄The curves (220), (311), (400), (422), (511) and (440) have distinct diffraction peaks, and there are no characteristic diffraction peaks for goethite and hematite at (110) and (104), i.e., 2 θ 21.228 ° and 2 θ 33.158 °, indicating that at Fe, Fe is present₃O₄No FeOOH and Fe₂O₃Is present. It is clear that the following description of the preferred embodiments,experimental Fe₃O₄XRD of magnetic nanoparticles vs. standard Fe₃O₄The XRD patterns of the spinel structure are very consistent. In Fe₃O₄-NH₂And beta-CD-Fe₃O₄In the XRD curve of (A), APTES and beta-CD-COOH grafting and Fe are shown₃O₄The reaction does not lead to Fe₃O₄Phase transition of (2). And in Fe₃O₄-NH₂And beta-CD-Fe₃O₄A weak broad band, i.e. 2 θ 18-25 °, appears in the curve, which can be attributed to Fe₃O₄APTES with aminosilane surrounding and the effect of β -CD macromolecules.

FIG. 4 shows the graft product of beta-CD-Fe₃O₄Magnetic property spectrum of beta-CD-Fe₃O₄And Fe₃O₄-NH₂The values of magnetization of the magnetic particles are 57.99 and 62.05emu/g respectively, no hysteresis phenomenon exists, and the remanence and the coercive force are zero, which indicates that the magnetic particles have superparamagnetism. Superparamagnetic means that when the magnetic carrier particles are dispersed in a solution, no serious aggregation of the ferromagnetic nanoparticles occurs. Due to beta-CD-Fe₃O₄Curve ratio of (1) Fe₃O₄-NH₂The curve of (a) is enriched with macromolecules of beta-CD-COOH, so that the value of the magnetic carrier particles is slightly lower than that of Fe₃O₄-NH₂. When applied in the fields of medicine and the like, this feature indicates that the magnetic particles can be used for high-efficiency magnetic operation or applied in the field of relatively low external magnetic fields.

The foregoing examples are provided for illustration and description of the invention only and are not intended to limit the invention to the scope of the described examples. Furthermore, it will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, and that many variations and modifications may be made in accordance with the teachings of the present invention, which variations and modifications are within the scope of the present invention as claimed.