A polycyclodextrin / dimethoxyglycine composite nanoparticle, its preparation method and application

Abstract

This invention belongs to the field of pharmaceutical technology, specifically relating to a polycyclodextrin / dimethoxyglycine composite nanoparticle, its preparation method, and its application. The composite nanoparticle consists of a polycyclodextrin carrier and a dimethoxyglycine inhibitor. The polycyclodextrin is a poly(isobutylene-maleic anhydride) modified β-cyclodextrin with substituents; the substituents are amino-containing and hydroxyl-containing groups. This composite nanoparticle can effectively improve the stability of DMOGs and achieve polyamine-responsive drug release and polyamine molecule capture. It can achieve dual synergistic effects within the same drug carrier, improving drug bioavailability, reducing toxic side effects, regulating the physicochemical properties of drug molecules, improving the inflammatory microenvironment, and effectively alleviating inflammation by clearing excess polyamines. Simultaneously, the size matching between the cyclodextrin cavity and the polyamine and drug molecules provides favorable conditions for drug delivery and polyamine capture.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, specifically relating to a polycyclodextrin / dimethoxyglycine composite nanoparticle, its preparation method, and its application. Background Technology

[0002] Chronic inflammation is closely related to the occurrence and development of various diseases, and is accompanied by changes in the microenvironment, such as alterations in reactive oxygen species (ROS), pH, enzymes, and polyamine levels. Natural polyamines are a class of low-molecular-weight aliphatic amines that participate in cell growth and differentiation, serving as biomarkers for various diseases and are closely related to their development. Furthermore, polyamine metabolism plays a crucial role in guiding the fate selection of mouse CD4+ T cells, making the study of polyamine metabolism in inflammatory diseases significant. Studies have shown that polyamine levels are significantly increased in the tissues and gingival crevicular fluid of patients with periodontal inflammation, which can exacerbate periodontal inflammation and promote bacterial proliferation; the concentration is closely related to the severity of periodontitis. Imbalances in polyamine metabolism at the site of inflammation can lead to cell dysfunction or apoptosis; clearing excess polyamines can effectively alleviate inflammation.

[0003] Cyclodextrin molecules possess a slightly conical, hollow cylindrical three-dimensional ring structure. Within this hollow structure, the upper outer end (larger opening) is composed of C2 and C3 secondary hydroxyl groups, while the lower end (smaller opening) is composed of C6 primary hydroxyl groups, exhibiting hydrophilicity. The cavity, shielded by CH bonds, forms a hydrophobic region. Among numerous macrocyclic molecules, cyclodextrin can act as a host to encapsulate various suitable guests, such as organic molecules, inorganic ions, and gas molecules. Through host-guest interactions, cyclodextrin molecules form inclusion complexes with various drug molecules, improving drug solubility, increasing drug stability, enhancing bioavailability, and reducing toxicity, thus achieving the regulation of drug physicochemical properties. It has been applied as an additive in pharmaceutical formulations. The size matching between the cyclodextrin cavity and polyamine and drug molecules provides favorable conditions for drug delivery and polyamine capture. Its hydrophobic interior and hydrophilic exterior properties allow it to form inclusion complexes and molecular assembly systems with many organic and inorganic molecules based on van der Waals forces, hydrophobic interactions, and the matching effects between host and guest molecules. Therefore, it has become a research object of interest to chemical and chemical engineering researchers.

[0004] Dimethyloxalylycine (DMOG), as a small molecule inhibitor, can promote angiogenesis and bone tissue repair by inhibiting the activity of proline hydroxylase and stabilizing the expression of hypoxia-inducible factor HIF-1α. Although DMOG has been shown to have various biological effects, its poor stability, short half-life, and ease of clearance are significant drawbacks limiting its clinical development. Due to the asymmetric structure of DMOG, it readily hydrolyzes to form MOG in culture media or aqueous solutions. MOG requires monocarboxylic acid transporter 2 (MCT2) for transport into cells. While MOG can also be transported into cells via MCT1 or MCT4, their transport efficiency is lower than that of MCT2. MCT2 is only elevated in human tumor tissues; therefore, finding suitable carriers to transport DMOG and improve its stability is crucial. Current techniques utilize cyclodextrin molecules as carriers to form inclusion complexes with DMOG, but these methods suffer from low drug encapsulation efficiency and lack in-depth research into the impact of inclusion complex formation on DMOG stability. Summary of the Invention

[0005] The purpose of this invention is to provide a polycyclodextrin / dimethoxyglycine composite nanoparticle, its preparation method, and its application, thereby overcoming the shortcomings of the prior art. The synthesized polycyclodextrin / dimethoxyglycine composite nanoparticle can effectively improve the stability of dimethoxyglycine molecules and achieve polyamine-responsive drug release and polyamine molecule capture. It can achieve dual synergistic effects in the same drug carrier and improve the inflammatory microenvironment.

[0006] To achieve the above objectives, the technical solution of the present invention is as follows:

[0007] In a first aspect, the present invention provides a polycyclodextrin / dimethoxyglycine composite nanoparticle, wherein the composite nanoparticle is composed of a polycyclodextrin carrier and a dimethoxyglycine inhibitor, wherein the polycyclodextrin is polymerized from poly(isobutylene-maleic anhydride) and β-cyclodextrin containing substituents.

[0008] In some other embodiments, the β-cyclodextrin containing the substituent has the structural formula shown in Formula I: R1 is selected from -CH2OH, -CH2NH2, -CH2NH(CH2)3NH2, -CH2NH(CH2CH2NH)2CH2CH2NH2 and -CH2NH(CH2CH2NH)3CH2CH2NH2; R2 is selected from -NH2 and -OH; wherein R1 and R2 are not simultaneously substituents containing amino and hydroxyl groups;

[0009]

[0010] In some other embodiments, the molar ratio of the polycyclodextrin to dimethoxyglycine is 1:(1-5).

[0011] In some other embodiments, the molecular weight of the poly(isobutylene-maleic anhydride) is 3-10 kDa; the molar ratio of the poly(isobutylene-maleic anhydride) to the substituted β-cyclodextrin is 1:(6-10).

[0012] In a second aspect, the present invention provides a method for preparing the polycyclodextrin / dimethoxyglycine composite nanoparticles described in the first aspect, comprising the following steps:

[0013] (1) Poly(isobutylene-maleic anhydride), β-cyclodextrin containing substituents and catalyst were added to a solvent and heated to react. Polycyclodextrin was obtained by dialysis and freeze drying.

[0014] (2) Polycyclodextrin and dimethoxyglycine were mixed in an inorganic solvent and dried to obtain polycyclodextrin / dimethoxyglycine composite nanoparticles.

[0015] In some other embodiments, in step (1), the catalyst is selected from N,N-diisopropylethylamine, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide;

[0016] The molar ratio of the catalyst to the substituted β-cyclodextrin is 1:(10-30).

[0017] In some other embodiments, in step (1), the solvent is selected from N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile and deionized water; the amount of solvent added is 5-20 mL.

[0018] In some other embodiments, in step (1), the conditions for the heating reaction are: the heating temperature is 30-70°C and the heating time is 6-20h;

[0019] Alternatively, the dialysis may be performed using a dialysis bag for 2-3 days.

[0020] In some other embodiments, in step (2), the inorganic solvent is a water and phosphate buffer solution; the mixing is performed by stirring or sonication for 12-24 hours.

[0021] Alternatively, the drying process may be freeze-drying.

[0022] Thirdly, the present invention provides the application of the polycyclodextrin / dimethoxyglycine composite nanoparticles described in the first aspect in the preparation of anti-inflammatory drugs.

[0023] The beneficial effects of this invention are:

[0024] 1. The polycyclodextrin / dimethoxyglycine composite nanoparticles prepared by this invention improve the stability of dimethoxyglycine molecules and realize the release of polyamine-responsive drugs and the capture of polyamine molecules. They can achieve dual synergistic effects in the same drug carrier, improve the bioavailability of drugs, reduce toxic side effects, and achieve the regulation of the physicochemical properties of drug molecules.

[0025] 2. The polycyclodextrin / dimethoxyglycine composite nanoparticles prepared in this invention can significantly improve the inflammatory microenvironment by scavenging excess polyamines and reducing cellular oxidative stress levels, effectively alleviating inflammation. Simultaneously, the size matching between the cyclodextrin cavity and the polyamine and drug molecules provides favorable conditions for drug delivery and validation of the improved microenvironment. Attached Figure Description

[0026] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0027] Figure 1 The reaction route for preparing polycyclodextrin in Example 1 of this invention;

[0028] Figure 2 This is a particle size distribution diagram of polycyclodextrin and polycyclodextrin / dimethoxyglycine composite nanoparticles in Example 1 of the present invention.

[0029] Figure 3 The polycyclodextrin / dimethoxyglycine composite nanoparticles of Example 1 of this invention 1 H- 1 H

[0030] NOESY spectrum;

[0031] Figure 4 The diagram shows the effect of polycyclodextrin / dimethoxyglycine composite nanoparticles on improving the stability of dimethoxyglycine and delaying hydrolysis in Examples 1 and 3 of this invention.

[0032] Figure 5 This is a diagram illustrating the effect of polycyclodextrin / dimethoxyglycine composite nanoparticles on scavenging intracellular ROS in Example 1 of the present invention.

[0033] Figure 6 This is a diagram illustrating the effect of polycyclodextrin / dimethoxyglycine composite nanoparticles on clearing intracellular polyamines under LPS-induced inflammatory conditions, as shown in Example 1 of this invention.

[0034] Figure 7This is a diagram illustrating the effect of polycyclodextrin / dimethoxyglycine composite nanoparticles on regulating the expression level of inflammatory factors in Example 1 of the present invention under a high concentration of SP environment. Detailed Implementation

[0035] Unless otherwise specified, the experimental methods described in the following examples are conventional methods; unless otherwise specified, the reagents and materials are commercially available.

[0036] Example 1

[0037] A method for preparing polycyclodextrin / dimethoxyglycine composite nanoparticles, such as Figure 1 As shown, the steps are as follows:

[0038] Weigh 0.2 g of poly(isobutylene-maleic anhydride) with a molecular weight of 6 kDa, 0.22 g of R1-R2 substituted β-cyclodextrin (R1 is -CH2NH2, R2 is -OH), and 1 mL of N,N-diisopropylethylamine (DIPEA) into a 25 mL round-bottom flask. Add 15 mL of N,N-dimethylformamide, heat at 50 °C for 16 h, remove the solvent by rotary evaporation, dissolve the remaining solid in deionized water, dialyze in a MWCO3500 dialysis bag for 2-3 days, and freeze-dry to obtain a white product (labeled as PCD).

[0039] Based on the grafting ratio of CD in the NMR results, the molecular weight of the polymer grafted with monocyclodextrin (CD) was calculated. A deionized aqueous solution of polycyclodextrin and DMOG at a molar ratio of 1:5 was prepared and stirred for 12 hours to obtain a D / PCD solution.

[0040] Example 2

[0041] Weigh 0.2 g of poly(isobutylene-maleic anhydride) with a molecular weight of 6 kDa, 0.22 g of R1-R2 substituted β-cyclodextrin (R1 is -CH2NHCH2CH2CH2NH2, R2 is -OH), and 1 mL of N,N-diisopropylethylamine (DIPEA) into a 25 mL round-bottom flask. Add 15 mL of dimethyl sulfoxide and heat at 50 °C for 16 h. Remove the solvent by rotary evaporation. Dissolve the remaining solid in deionized water and dialyze it in a MWCO3500 dialysis bag for 2-3 days. Freeze-dry to obtain the white product PCD1.

[0042] Based on the grafting ratio of CDs in the NMR results, the molecular weight of the polymer grafted with a single CD was calculated. A deionized aqueous solution containing monopolycyclodextrin and DMOG at a molar ratio of 1:1 was prepared and stirred for 12 hours to achieve homogeneity, yielding a D / PCD1 solution.

[0043] Example 3

[0044] Weigh 0.2 g of poly(isobutylene-maleic anhydride) with a molecular weight of 6 kDa, 0.22 g of R1-R2 substituted β-cyclodextrin (R1 is -CH2OH, R2 is -NH2), add 0.57 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 0.34 g of N-hydroxythiosuccinimide (NHS), place in a 25 mL round-bottom flask, add 15 mL of acetonitrile, heat at 50 °C for 16 h, remove the solvent acetonitrile by rotary evaporation, dissolve the remaining solid in deionized water, dialyze in a MWCO3500 dialysis bag for 2-3 days, and freeze-dry to obtain the white product PCD2.

[0045] Based on the grafting ratio of CDs in the NMR results, the molecular weight of the polymer grafted with a single CD was calculated. A deionized aqueous solution containing monopolycyclodextrin and DMOG at a molar ratio of 1:1 was prepared and stirred for 12 hours to achieve homogeneity, yielding a D / PCD2 solution.

[0046] Performance testing

[0047] (1) Particle size distribution of polycyclodextrin and polycyclodextrin / dimethoxyglycine composite nanoparticles

[0048] Figure 2 This is a particle size distribution diagram of the polycyclodextrin and polycyclodextrin / dimethoxyglycine composite nanoparticles in Example 1 of the present invention; wherein PCD represents polycyclodextrin, and D / PCD represents polycyclodextrin / dimethoxyglycine composite nanoparticles. Figure 2 It can be seen that after forming composite nanoparticles with dimethoxyglycine, the D / PCD particle size increases significantly, proving that polycyclodextrin and dimethoxyglycine form a host-guest inclusion complex.

[0049] (2) Polycyclodextrin / dimethoxyglycine composite nanoparticles 1 H- 1 H NOESY spectrum

[0050] 600 μL of 2 mM D / PCD (molar ratio of D to PCD 1:1) was prepared using deuterated water, and the concentration was obtained using two-dimensional NMR spectroscopy. 1 H- 1 H NOESY spectrum.

[0051] Figure 3 This is the 1H-1HNOESY spectrum of the polycyclodextrin / dimethoxyglycine composite nanoparticles of Example 1 of the present invention; wherein, the positions of peaks a, b, and c are the corresponding proton peaks at positions a, b, and c in the DMOG compound. Figure 3As can be seen, the a, b, and c proton peaks in PCD and DMOG have cross-peaks above and below the diagonal of the spectrum, confirming the host-guest interaction between PCD and DMOG. Furthermore, some other markings in the figure are data inherent to the NMR data; their lack of clarity does not affect the overall picture.

[0052] (3) The role of dimethoxyglycine in stabilizing and delaying hydrolysis

[0053] 3 mL of 0.1 mM D solution, 3 mL of 0.1 mM D / PCD2 solution (D to PCD2 molar ratio of 1:1), and 3 mL of 0.1 mM D / PCD solution (D to PCD molar ratio of 1:1) were prepared using PBS. The hydrolysis efficiency of D, D / PCD2, and D / PCD at different time points was monitored using a UV-Vis spectrophotometer. The UV-Vis absorption spectra of D + 0.5 mM NaOH, D / PCD2 + 0.5 mM NaOH, and D / PCD + 0.5 mM NaOH solutions were used as standards for complete hydrolysis. The hydrolysis ratio was determined based on the absorbance at 224 nm for each group.

[0054] Figure 4 This diagram illustrates the effect of the D / PCD composite nanoparticles from Examples 1 and 3 of the present invention on improving the stability and delaying hydrolysis of dimethoxyglycine; where D represents dimethoxyglycine, and D / PCD represents polycyclodextrin / dimethoxyglycine composite nanoparticles. Figure 4 It can be seen that within 30 minutes, the hydrolysis rates of drug molecules in group D, group D / PCD2, and group D / PCD were 39.9%, 52.6%, and 57.6%, respectively. This indicates that the D / PCD composite nanoparticles significantly enhanced the stability of the drug and delayed the hydrolysis process, showing better performance than the D / PCD2 composite nanoparticles. This is because the cyclodextrin has greater steric hindrance during the preparation of PCD2, resulting in a lower cyclodextrin grafting rate and thus a slightly poorer encapsulation effect on DMOG.

[0055] (4) The role of LPS in clearing intracellular ROS under inflammatory conditions

[0056] The intracellular ROS level in NIH3T3 cells stimulated with high concentrations of polyamines was detected using a ROS detection kit. NIH3T3 cells were cultured at 2.5 × 10⁻⁶ cells / cells. 4 Cells were seeded at a density of 1 cell / well in 48-well plates and co-cultured with the probe. After incubation with 5 μg / mL LPS for 24 h, the cells were treated with D, PCD, and D / PCD for 24 h to remove excess nanomaterials. The cells were washed with PBS and co-cultured with the DCFH-DA probe for 30 min. The intracellular ROS content of each group was observed using a fluorescence microscope (Leica, Wetzlar, Germany).

[0057] Figure 5 This image shows the effect of the D / PCD composite nanoparticles on scavenging intracellular ROS in Example 1 of the present invention. In the image, Con represents the blank control group, LPS represents the lipopolysaccharide-stimulated inflammation-simulated group, D represents the LPS-stimulated cell group followed by the addition of dimethoxyglycine, PCD represents the LPS-stimulated cell group followed by the addition of polycyclodextrin, and D / PCD represents the LPS-stimulated cell group followed by the addition of polycyclodextrin / dimethoxyglycine composite nanoparticles. Merged represents the fusion state, DCFH Channel represents the DCFH fluorescent probe signal channel, and Bright Field represents the bright field image. Figure 5 As can be seen, the fluorescence intensity of both groups D and PCD was slightly lower than that of the LPS group, but the difference between the two groups was not statistically significant. The addition of D / PCD composite nanoparticles led to a significant decrease in fluorescence intensity, indicating that the D / PCD composite nanoparticles enhanced ROS scavenging ability through the synergistic effect of anti-inflammatory drug release and polyamine binding.

[0058] (5) The role of LPS in clearing intracellular polyamines under inflammatory conditions

[0059] Intracellular polyamine concentrations were determined using a total polyamine assay kit (Abcam, ab239728). NIH3T3 cells were cultured at 2 × 10⁻⁶ cells per cell line. 5 Cells were seeded at a density of cells / well in 6-well plates, then incubated with 5 μg / mL LPS for 24 h, followed by further treatment with D, PCD, and D / PCD for 24 h. Finally, intracellular polyamine concentrations for different groups were obtained according to the manufacturer's instructions, including sample and reaction mixture preparation, sample and reaction mixture incubation, and fluorescence measurement.

[0060] Figure 6 This is a graph illustrating the effect of polycyclodextrin / dimethoxyglycine composite nanoparticles on scavenging intracellular polyamines under LPS-induced inflammatory conditions, as shown in Example 1 of this invention. In the graph, Con represents the blank control group, LPS represents the lipopolysaccharide-stimulated simulated inflammation group, D represents the LPS-stimulated cell group followed by the addition of dimethoxyglycine, PCD represents the LPS-stimulated cell group followed by the addition of polycyclodextrin, and D / PCD represents the LPS-stimulated cell group followed by the addition of polycyclodextrin / dimethoxyglycine composite nanoparticles. Figure 6 It can be seen that, Figure 5The results described in the D / PCD group indicated that LPS stimulation led to a significant increase in intracellular polyamine content (2-fold increase compared to the control group). Both the D and PCD groups showed a slight decrease in intracellular polyamine content, which was attributed to the anti-inflammatory properties of D and the polyamine-binding properties of PCD. The polyamine levels of the D / PCD composite nanoparticles decreased significantly after 24 hours of co-culture, which is a result of the synergistic effect of anti-inflammatory drug release and PCD binding to polyamines.

[0061] (6) Effect of SP on regulating the expression level of inflammatory factors in a high concentration environment.

[0062] NIH3T3 cells were used at a rate of 2 × 10 5 Cells were seeded at a density of cells / well in 6-well plates, then 10 μM spermine (SP) was added, and the cells were incubated for 24 h. Cells were further treated with D, PCD, and D / PCD for 24 h. Total RNA from NIH3T3 cells was collected using Trizol reagent. The RNA extraction process generally includes phase separation, RNA separation, and washing. RNA concentration was determined using a NanoDrop OneC ultraviolet spectrophotometer (Thermo Fisher, USA). qRT-PCR analysis was performed using 2×SYBR Green qPCR Mix (SparkJade, Shandong, China) and the Sparkscript 1st Strand cDNA Synthesis Kit (SparkJade, Shandong, China). The reaction was then measured using a Roche LightCycler 480II PCR instrument (Basel, Switzerland). -ΔΔCT The method normalized the mRNA expression of the detected gene in each experimental group to the mRNA expression of GAPDH. Each experiment was repeated at least 3 times.

[0063] Figure 7 This is a graph illustrating the effect of polycyclodextrin / dimethoxyglycine composite nanoparticles on regulating the expression level of inflammatory factors in Example 1 of the present invention under a 10 μM SP environment; where Con is the blank control group, LPS is the lipopolysaccharide-stimulated simulated inflammation group, D is the LPS-stimulated cell group followed by the addition of dimethoxyglycine, PCD is the LPS-stimulated cell group followed by the addition of polycyclodextrin, and D / PCD is the LPS-stimulated cell group followed by the addition of polycyclodextrin / dimethoxyglycine composite nanoparticles. Figure 7It can be seen that in the inflammatory microenvironment, excessive SP accumulation induces oxidative stress, leading to the overexpression of inflammatory factors. The anti-inflammatory effect of D / PCD composite nanoparticles was evaluated by detecting the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) using qRT-PCR. Compared with the control group, SP stimulation significantly increased the relative mRNA expression levels of TNF-α and IL-1β. Compared with the SP group, the expression of these genes was significantly reduced in the D / PCD group, while the reduction was less pronounced in the D and PCD groups. These results indicate that the addition of D / PCD composite nanoparticles can effectively attenuate the SP-induced inflammatory response by modulating the inflammatory microenvironment through downregulation of pro-inflammatory gene expression.

[0064] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. The application of a polycyclodextrin / dimethoxyglycine composite nanoparticle in the preparation of anti-inflammatory drugs, characterized in that, The composite nanoparticles consist of a polycyclodextrin carrier and a dimethoxyglycine inhibitor, wherein the polycyclodextrin is polymerized from poly(isobutylene-maleic anhydride) and β-cyclodextrin containing substituents; The structural formula of the substituted β-cyclodextrin is shown in Formula I: R1 is selected from -CH2OH, -CH2NH2, -CH2NH(CH2)3NH2, -CH2NH(CH2CH2NH)2CH2CH2NH2 and -CH2NH(CH2CH2NH)3CH2CH2NH2; R2 is selected from -NH2 and -OH; wherein R1 and R2 are not simultaneously substituents containing amino and hydroxyl groups; Formula I; The molar ratio of the polycyclodextrin to dimethoxyglycine is 1:5-25.

2. The application according to claim 1, characterized in that, The molecular weight of the poly(isobutylene-maleic anhydride) is 3-10 kDa; the molar ratio of the poly(isobutylene-maleic anhydride) to the substituted β-cyclodextrin is 1:6-10.

3. A method for preparing polycyclodextrin / dimethoxyglycine composite nanoparticles, characterized in that, The preparation of polycyclodextrin / dimethoxyglycine composite nanoparticles for the application described in claim 1 comprises the following steps: (1) Poly(isobutylene-maleic anhydride), β-cyclodextrin with substituents and catalyst were added to a solvent and heated to react. Polycyclodextrin was obtained by dialysis and freeze drying. (2) Polycyclodextrin and dimethoxyglycine were mixed in an inorganic solvent and dried to obtain polycyclodextrin / dimethoxyglycine composite nanoparticles.

4. The method for preparing polycyclodextrin / dimethoxyglycine composite nanoparticles according to claim 3, characterized in that, In step (1), the catalyst is selected from N,N-diisopropylethylamine, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide and N-hydroxysuccinimide; The molar ratio of the catalyst to the substituted β-cyclodextrin is 1:10-30.

5. The method for preparing polycyclodextrin / dimethoxyglycine composite nanoparticles according to claim 3, characterized in that, In step (1), the solvent is selected from N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile and deionized water; the amount of solvent added is 5-20 mL.

6. The method for preparing polycyclodextrin / dimethoxyglycine composite nanoparticles according to claim 3, characterized in that, In step (1), the conditions for the heating reaction are: the heating temperature is 30-70℃ and the heating time is 6-20 h; Alternatively, the dialysis may be performed using a dialysis bag for 2-3 days.

7. The method for preparing polycyclodextrin / dimethoxyglycine composite nanoparticles according to claim 3, characterized in that, In step (2), the inorganic solvent is a water and phosphate buffer solution; the mixing is carried out by stirring or sonication for 12 h-24 h. Alternatively, the drying process may be freeze-drying.

Images