Calcium phosphate organic-inorganic hybrid nanomaterial, and preparation method and application thereof

Abstract

The application discloses a calcium phosphate organic-inorganic hybrid nanomaterial and a preparation method and application thereof. N-stearoyl-L-hydroxyproline chelated calcium is used as a calcium source and a structure directing agent for crystal growth, tetra-n-butylammonium phosphate is used as a phosphorus source and an intercalating agent for a two-dimensional structure crystal, and oleic acid is used as a solvent. The calcium phosphate organic-inorganic hybrid nanomaterial is prepared through a solvothermal reaction. The calcium phosphate organic-inorganic hybrid nanomaterial has a regular rhombic morphology and a two-dimensional multi-layer structure, has excellent biocompatibility and biodegradability, can realize efficient loading of drugs, and has the advantages of simple preparation method, low cost and convenience for practical promotion. The calcium phosphate organic-inorganic hybrid nanomaterial is related to the field of biological materials and has application potential in aspects of drug delivery carriers, gene delivery carriers, protein delivery carriers, hard tissue defect repair materials and biological imaging.

Description

Technical Field

[0001] This invention relates to the field of biomaterials technology, specifically to a calcium phosphate organic-inorganic hybrid nanomaterial, its preparation method, and its application. Background Technology

[0002] Two-dimensional materials, represented by graphene, MXenes, hexagonal boron nitride, and black phosphorus, are a class of emerging nanomaterials with sheet-like morphologies. Their lateral dimensions range from hundreds of nanometers to tens of micrometers, but their thickness is only one or a few atomic layers. These emerging nanomaterials possess high bioactivity and material properties, showing broad application prospects in electronics / optoelectronics, catalysis, energy storage, and biomedicine. Currently, the types of two-dimensional materials and their preparation methods are still very limited. Therefore, developing a simple method for preparing calcium phosphate-based hybrid nanosheet materials and expanding their applications is of great significance.

[0003] Calcium phosphate-based nanomaterials are widely found in nature and in biological hard tissues such as bones and teeth. Their degradation products, such as calcium ions and phosphate ions, are also safe components commonly found in blood and can participate in normal physiological metabolism. Therefore, calcium phosphate-based nanomaterials can serve as excellent biomedical materials that combine biocompatibility and functionality. Furthermore, compared to many other common biocompatible nanomaterials such as Au / Ag clusters, magnetite, silica, or certain micelles and polymers, calcium-based nanomaterials can decompose naturally in acidic environments, exhibiting excellent biodegradability and sensitivity to the tumor microenvironment. They are also easy to prepare and have low toxicity, making them suitable for preparing materials with bone regeneration properties and nanodelivery systems to enhance targeted therapy efficacy. Tian et al. proposed a method for preparing nanoflower-structured calcium phosphate and its application in bone regeneration (see: Tian T.R.ACS Appl. Mater. Interfaces. 2017, 9(36):30437-30447); Liu Hailong et al. invented a method for preparing nano-calcium phosphate for enrichment of polyphosphatidylcholine and identification of phosphorylation sites and its application (see: authorized Chinese invention patent CN112499607B); He et al. simulated the biosilicification process of diatoms and synthesized a series of biodegradable polyethyleneimine / calcium phosphate composite materials, which were applied to transient ultrasound and photoluminescence imaging (see: He T.Y. Chem. Mater. 2022, 34(16), 7220-7231). However, the crystallization process of calcium phosphate is very rapid and the synthesis is complex. How to mass-produce multifunctional calcium phosphate-based nanomaterials with controllable size and uniform shape, especially those with two-dimensional sheet-like morphology, remains a challenge. To address the aforementioned problems, it is essential to research and design a novel calcium phosphate organic-inorganic hybrid nanomaterial, its preparation method, and its applications, thereby overcoming the existing issues in the production of calcium phosphate-based nanomaterials. Summary of the Invention

[0004] To address the shortcomings of existing technologies, the present invention aims to provide a method for preparing and applying calcium phosphate organic-inorganic hybrid nanomaterials that are made from inexpensive and readily available raw materials, have a simple preparation method, good biocompatibility, are biodegradable, have low toxicity, and possess a two-dimensional multilayer structure.

[0005] The technical solution adopted by the present invention to achieve the above-mentioned objective is: a calcium phosphate organic-inorganic hybrid nanomaterial, comprising N-stearoyl-L-hydroxyproline chelated calcium and tetra-n-butylammonium phosphate; the calcium ions provided by the N-stearoyl-L-hydroxyproline chelated calcium and the phosphate ions provided by the tetra-n-butylammonium phosphate rapidly combine through ionic interactions, and under solvothermal reaction conditions, they co-crystallize with organic molecules to form a calcium phosphate organic-inorganic hybrid nanomaterial.

[0006] According to some embodiments of the calcium phosphate organic-inorganic hybrid nanomaterials of this application, the chemical structural formula of N-stearoyl-L-hydroxyproline chelated calcium in step S1 is as follows:

[0007]

[0008] N-Stearyl-L-hydroxyproline chelate calcium is prepared by a one-step complexation reaction between amphiphilic N-stearoyl-L-hydroxyproline and calcium chloride under strongly alkaline conditions of tetramethylammonium hydroxide solution.

[0009] According to some embodiments of this application, the calcium phosphate organic-inorganic hybrid nanomaterial is a two-dimensional multi-layer structure with a regular rhombic morphology, a lateral dimension of 0.9-1.1 μm, and a layer thickness of 0.004-0.006 μm.

[0010] According to some embodiments of this application, the calcium phosphate organic-inorganic hybrid nanomaterial is a two-dimensional multi-layer structure with a regular rhombic morphology, a lateral dimension of 1 μm, and a layer thickness of 0.005 μm.

[0011] This invention also provides a method for preparing any of the above-mentioned calcium phosphate organic-inorganic hybrid nanomaterials, comprising the following steps:

[0012] S1. Prepare a 4.5%-5% N-stearoyl-L-hydroxyproline methanol solution and a 20%-30% tetramethylammonium hydroxide methanol solution. Add the tetramethylammonium hydroxide methanol solution to the N-stearoyl-L-hydroxyproline methanol solution and heat to 45℃-65℃ to obtain mixed solution A. Slowly add calcium chloride methanol solution to the mixed solution A while maintaining a constant temperature and stirring. After the reaction stops, cool the reaction solution to room temperature, centrifuge and filter to obtain the filter residue. Wash the filter residue repeatedly with acetone and then vacuum dry to obtain N-stearoyl-L-hydroxyproline chelated calcium.

[0013] S2. Under nitrogen protection at 75℃~85℃, with oleic acid as the reaction environment, N-stearoyl-L-hydroxyproline chelate calcium was added to oleic acid. After uniform stirring, the temperature was raised to 100℃~200℃. Then, tetra-n-butyl phosphate ammonium was dissolved in oleic acid and quickly added to the oleic acid solution of N-stearoyl-L-hydroxyproline chelate calcium. The molar ratio of N-stearoyl-L-hydroxyproline chelate calcium to tetra-n-butyl phosphate ammonium was 1:1.8~2.5. The temperature was kept constant and the mixture was stirred. The reaction was carried out in a solvothermal manner. After the reaction was stopped, the reaction solution was cooled to room temperature. The residue was obtained by centrifugation and filtration. The residue was repeatedly washed with acetone and chloroform and then vacuum dried to obtain calcium phosphate organic-inorganic hybrid nanomaterials.

[0014] According to the preparation method of calcium phosphate organic-inorganic hybrid nanomaterials according to some embodiments of this application, in step S1, the mass fraction of tetramethylammonium hydroxide methanol solution is 25%. The addition of tetramethylammonium hydroxide solution provides strong alkaline conditions to convert the carboxyl group in N-stearoyl-L-hydroxyproline into a carboxylate ion, and to make it easy to chelate with calcium ions. N-stearoyl-L-hydroxyproline is a chelating molecule for calcium ions and a structure guiding agent for the growth of two-dimensional calcium phosphate crystals. Tetra-n-butylammonium phosphate is a source of phosphate and an intercalating agent for regulating the growth of two-dimensional calcium phosphate crystals. After adding the tetramethylammonium hydroxide methanol solution to the N-stearoyl-L-hydroxyproline solution, the temperature is raised to 50-60°C.

[0015] According to the method for preparing calcium phosphate organic-inorganic hybrid nanomaterials according to some embodiments of this application, in step S1, the calcium chloride methanol solution is added at a rate of 2 to 3 drops per second, and the constant temperature stirring time is 2 hours.

[0016] According to the method for preparing calcium phosphate organic-inorganic hybrid nanomaterials according to some embodiments of this application, in step S1, the molar ratio of N-stearoyl-L-hydroxyproline to calcium chloride is 1:2 to 2.5, so that calcium ions coordinate with the two carboxyl groups.

[0017] According to the preparation method of calcium phosphate organic-inorganic hybrid nanomaterials according to some embodiments of this application, in step S2, the temperature when adding N-stearoyl-L-hydroxyproline chelated calcium to oleic acid is 80°C. After adding N-stearoyl-L-hydroxyproline chelated calcium and oleic acid, the mixture is stirred evenly for 20 minutes. After stirring is completed, the temperature is raised to 120-180°C.

[0018] According to the method for preparing calcium phosphate organic-inorganic hybrid nanomaterials according to some embodiments of this application, in step S2, the temperature of the solvothermal reaction is 120-180°C and the reaction time is 4-6 hours.

[0019] This invention also provides an application of calcium phosphate organic-inorganic hybrid nanomaterials, which can be practically applied in biomedical fields such as drug / gene / protein delivery carriers, hard tissue defect repair materials, bioimaging, and cancer treatment.

[0020] This invention discloses a calcium phosphate organic-inorganic hybrid nanomaterial, its preparation method, and its application. The prepared N-stearoyl-L-hydroxyproline chelated calcium utilizes N-stearoyl-L-hydroxyproline, an alkylated modified amino acid that is widely available, inexpensive, and has low toxicity, as the chelating molecule for calcium ions. The preparation process is simple, rapid, and allows for mass production. The prepared N-stearoyl-L-hydroxyproline chelated calcium contains amphiphilic organic molecules with long alkyl chains, which can function as structure-directing agents during the growth of calcium phosphate crystals, regulating the subsequent growth process of two-dimensional crystals. The calcium phosphate organic-inorganic hybrid nanomaterial prepared by this invention possesses a regular rhombic morphology and a two-dimensional multilayered structure, effectively expanding the types and applications of two-dimensional materials. Its two-dimensional multilayered structure can provide a stable loading space for affinity substances such as drugs, genes, and proteins. The calcium phosphate organic-inorganic hybrid nanomaterials prepared in this invention are mainly based on calcium phosphate materials, exhibiting good biocompatibility and biodegradability. In slightly acidic environments such as tumor microenvironments, they can naturally decompose into calcium ions and phosphate ions, participating in the normal metabolism of living organisms. They can be used to prepare targeted cancer treatment systems. The calcium phosphate organic-inorganic hybrid nanomaterials prepared in this invention can serve as ideal sustained-release carriers for anticancer drugs such as doxorubicin and as bone repair materials. Furthermore, these nanomaterials have enormous application potential in bioimaging and biomedical materials. Attached Figure Description

[0021] Figure 1 This is a scanning electron microscope image of the calcium phosphate organic-inorganic hybrid nanomaterial prepared in Example 2 of the present invention;

[0022] Figure 2 This is an atomic force microscope image of the calcium phosphate organic-inorganic hybrid nanomaterial prepared in Example 2 of the present invention;

[0023] Figure 3 The Fourier transform infrared spectra of the raw material N-stearoyl-L-hydroxyproline, the prepared N-stearoyl-L-hydroxyproline chelated calcium and calcium phosphate organic-inorganic hybrid nanomaterials in Example 2 of this invention;

[0024] Figure 4 The X-ray diffraction patterns of the raw material N-stearoyl-L-hydroxyproline, the prepared N-stearoyl-L-hydroxyproline chelated calcium and calcium phosphate organic-inorganic hybrid nanomaterials in Example 2 of this invention;

[0025] Figure 5 The nitrogen adsorption / desorption isotherm and pore size distribution diagram of the calcium phosphate organic-inorganic hybrid nanomaterial prepared in Example 2 of this invention are shown.

[0026] Figure 6 This is a Zeta potential diagram of the raw material N-stearoyl-L-hydroxyproline, the prepared N-stearoyl-L-hydroxyproline chelated calcium and calcium phosphate organic-inorganic hybrid nanomaterials in Example 2 of the present invention;

[0027] Figure 7 The graph shows the loading capacity and encapsulation efficiency of the calcium phosphate organic-inorganic hybrid nanomaterial prepared in Example 2 of this invention as a carrier for the anticancer drug doxorubicin.

[0028] Figure 8 Transmission electron microscopy (TEM) images of the calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2 of this invention after incubation in a phosphate buffer solution at pH 5.0 for 30 minutes, 4 hours, 36 hours, and 72 hours, respectively. Detailed Implementation

[0029] The embodiments of the present invention will be described in further detail below with reference to the accompanying drawings and examples. The following examples are for illustrative purposes only and should not be construed as limiting the scope of the invention.

[0030] Example 1

[0031] This embodiment describes a method for preparing calcium phosphate organic-inorganic hybrid nanomaterials, comprising the following steps:

[0032] Preparation of S1.N-stearoyl-L-hydroxyproline chelated calcium

[0033] 7.95 g of N-stearoyl-L-hydroxyproline was dissolved in 200 mL of methanol, and 8.4 mL of a methanol solution of tetramethylammonium hydroxide (25% by mass) was added. The mixture was then heated to 50 °C, and 1.11 g of calcium chloride was placed in 15 mL of the methanol solution. The methanol solution of calcium chloride was then slowly added dropwise to the mixture at a rate of 2–3 drops per second, and the mixture was stirred at a constant temperature for 2 hours. After the reaction stopped, the reaction solution was cooled to room temperature, centrifuged, and filtered to obtain the residue. The residue was repeatedly washed with acetone and then vacuum dried to obtain a white solid, which was N-stearoyl-L-hydroxyproline chelated calcium.

[0034] S2. Preparation of calcium phosphate organic-inorganic hybrid nanomaterials

[0035] Under nitrogen protection at 80°C, 71.8 mg of N-stearoyl-L-hydroxyproline chelated calcium and 30 mL of oleic acid were added to a three-necked flask. After stirring evenly for 20 minutes, the temperature was raised to 120°C. Subsequently, 58.5 mg of tetra-n-butylammonium phosphate was dissolved in 10 mL of oleic acid and quickly added to the three-necked flask. The mixture was stirred at a constant temperature for 5 hours. After the reaction stopped, the reaction solution was cooled to room temperature, centrifuged, and filtered to obtain the residue. The residue was repeatedly washed with acetone and chloroform, and then vacuum dried to obtain a light yellow solid, which is the calcium phosphate organic-inorganic hybrid nanomaterial.

[0036] Example 2

[0037] This embodiment describes a method for preparing calcium phosphate organic-inorganic hybrid nanomaterials, comprising the following steps:

[0038] The preparation of S1.N-stearoyl-L-hydroxyproline chelated calcium is the same as step S1 in Example 1.

[0039] S2. Preparation of calcium phosphate organic-inorganic hybrid nanomaterials

[0040] Under nitrogen protection at 80°C, 71.8 mg of N-stearoyl-L-hydroxyproline chelated calcium and 30 mL of oleic acid were added to a three-necked flask. After stirring evenly for 20 minutes, the temperature was raised to 150°C. Subsequently, 58.5 mg of tetra-n-butylammonium phosphate was dissolved in 10 mL of oleic acid and quickly added to the three-necked flask. The mixture was stirred at a constant temperature for 4 hours. After the reaction stopped, the reaction solution was cooled to room temperature, centrifuged, and filtered to obtain the residue. The residue was repeatedly washed with acetone and chloroform, and then vacuum dried to obtain a light yellow solid, which is the calcium phosphate organic-inorganic hybrid nanomaterial.

[0041] Example 3

[0042] The calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2 were applied to drug carriers.

[0043] Using the tumor chemotherapy agent doxorubicin as a drug model, the calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2 were used as a carrier. First, the prepared calcium phosphate nanomaterials were prepared into a uniformly suspended aqueous solution with a concentration of 0.15 mg / mL, and mixed with aqueous solutions of doxorubicin hydrochloride at concentrations ranging from 0.05 to 1.5 mg / mL. Both solutions were incubated together at room temperature for 24 hours. Then, the dispersion was dialyzed in ultrapure water for 24 hours to remove free doxorubicin molecules. After dialyzing, the supernatant was collected by centrifugation, and the doxorubicin content in the supernatant was analyzed using UV-Vis spectrophotometry at a wavelength of λ = 480 nm. The loading capacity and encapsulation efficiency of the calcium phosphate nanomaterials for doxorubicin were evaluated using the formulas: loading capacity = (mass of loaded drug / total mass of the drug carrier) × 100%; encapsulation efficiency = (mass of loaded drug / total mass of drug) × 100%.

[0044] Example 4

[0045] The following performance tests were performed on the calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2:

[0046] (1) The microstructure of the calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2 was characterized by scanning electron microscopy, such as... Figure 1 As shown, the calcium phosphate organic-inorganic hybrid nanomaterial has a regular rhombic morphology and a two-dimensional multilayer structure, with a lateral dimension of about 1 μm.

[0047] (2) The microstructure of the calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2 was characterized by atomic force microscopy, such as... Figure 2 As shown, the thickness of a single layer of calcium phosphate organic-inorganic hybrid nanomaterial is approximately 0.005 μm.

[0048] (3) The main functional groups in the calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2 were characterized and analyzed, such as... Figure 3 As shown. The hydroxyl group in the raw material N-stearoyl-L-hydroxyproline reacts with the hydroxide ion (OH) of the carboxyl group. - The characteristic absorption peak is at 3445 cm⁻¹ -1 The stretching vibration peak of the carboxyl group OC=O is at 1741 cm⁻¹. -1 The stretching vibration peak of the amide bond NC=O is at 1617 cm⁻¹. -1 The characteristic absorption peaks of -CH3 and -CH2 in the alkyl chain are at 2933 cm⁻¹. -1 and 2851cm -1 Nearby. After the formation of N-stearoyl-L-hydroxyproline chelated calcium, at 3340 cm⁻¹ -1 Quaternary ammonium salt N appeared + The characteristic absorption peaks of hydroxyl radicals (OH) and hydroxyl radicals (OH)- The intensity of the characteristic absorption peak is significantly reduced, and the elution position of the corresponding carboxyl group OC=O shows a significant blue shift, with the absorption peak at 1587 cm⁻¹. -1 This indicates that the carboxyl group in N-stearoyl-L-hydroxyproline chelates with calcium ions. For calcium phosphate organic-inorganic hybrid nanomaterials, in addition to the aforementioned functional groups, there are also [missing information - likely related to a specific structure or feature] at 1131 cm⁻¹. -1 1062cm -1 1003cm -1 and 580cm -1 527cm -1 Phosphoric acid and PO4 were present at the location. 3- The stretching vibration of PO indicates the successful preparation of calcium phosphate organic-inorganic hybrid nanomaterials.

[0049] (4) The phase and crystal structure of the calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2 were characterized and analyzed, such as... Figure 4 As shown, the diffraction peaks of the calcium phosphate organic-inorganic hybrid nanomaterials and the standard card (JCPSD#09-0080) of hydroxyapatite are highly consistent, indicating that the calcium phosphate organic-inorganic hybrid nanomaterials have a crystal structure similar to hydroxyapatite. Furthermore, the diffraction peak near 2θ = 20.84° is consistent with the characteristic peak of N-stearoyl-L-hydroxyproline, indicating that both N-stearoyl-L-hydroxyproline chelated calcium and calcium phosphate organic-inorganic hybrid nanomaterials contain organic components.

[0050] (5) Nitrogen adsorption / desorption experiments were conducted on the calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2, and the results are as follows: Figure 5 As shown, the nitrogen adsorption / desorption isotherm exhibits an H3-type hysteresis loop, indicating that the calcium phosphate organic-inorganic hybrid nanomaterial possesses slit-mesopores generated by its layered structure. Its specific surface area is 47.48 m². 2 / g, pore volume approximately 0.24cm³ 3 / g, and exhibits a multi-pore size distribution, with pore sizes of 20.03nm, 45.02nm and 84.22nm, etc.

[0051] (6) The surface potential of the calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2 was measured and analyzed. For example... Figure 6 As shown, the Zeta potentials of the surfaces of N-stearoyl-L-hydroxyproline, N-stearoyl-L-hydroxyproline chelated calcium, and calcium phosphate organic-inorganic hybrid nanomaterials are -21.23 mV, -19.07 mV, and -13.60 mV, respectively, indicating that the prepared materials have a negative charge on their surfaces and can therefore effectively adsorb positively charged protein or drug molecules, such as doxorubicin.

[0052] (7) The drug loading capacity of the calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2 was evaluated. The specific experimental methods were as described in Example 3. The results are as follows: Figure 7 As shown, when the mass ratio of doxorubicin to calcium phosphate organic-inorganic hybrid nanomaterials is 0.75:1, the maximum loading capacity of 48% and the encapsulation efficiency of 92% can be obtained after co-incubation.

[0053] (8) The degradability of the calcium phosphate organic-inorganic hybrid nanomaterials prepared in Example 2 was evaluated. For example... Figure 8 As shown, the morphological changes of calcium phosphate organic-inorganic hybrid nanomaterials during degradation were monitored using transmission electron microscopy (TEM). The results showed that as the incubation time of the calcium phosphate organic-inorganic hybrid nanomaterials in a simulated slightly acidic environment (phosphate buffer solution, pH 5.0) increased, the nanosheets gradually degraded and broke down from their rhomboid morphology after 30 minutes of incubation, eventually becoming fine fragments after 72 hours. After 4 hours of incubation, TEM images showed that the nanosheets became significantly lighter and less uniform in color, indicating that the outer nanosheets had degraded and peeled off, resulting in a reduced sheet thickness. After 36 hours of incubation, obvious corrosion marks appeared on the outer edges of the material, indicating that the material began to degrade rapidly. Ultimately, the calcium phosphate organic-inorganic hybrid nanomaterials could be almost completely degraded in the acidic phosphate buffer solution, demonstrating its great application potential in the preparation of pH-sensitive biomaterials.

[0054] The embodiments of the present invention are given for illustrative and descriptive purposes only, and are not intended to be exhaustive or to limit the invention to the forms disclosed. Many modifications and variations will be apparent to those skilled in the art. The embodiments were chosen and described in order to better illustrate the principles and practical application of the invention, and to enable those skilled in the art to understand the invention and to design various embodiments with various modifications suitable for a particular purpose.

Claims

1. A calcium phosphate organic-inorganic hybrid nanomaterial, characterized in that, It includes N-stearoyl-L-hydroxyproline chelated calcium and tetra-n-butylammonium phosphate; the calcium ions provided by the N-stearoyl-L-hydroxyproline chelated calcium and the phosphate ions provided by the tetra-n-butylammonium phosphate rapidly combine through ionic interactions, and under solvothermal reaction conditions, they co-crystallize with organic molecules to form calcium phosphate organic-inorganic hybrid nanomaterials.

2. The calcium phosphate organic-inorganic hybrid nanomaterial according to claim 1, characterized in that, In step S1, the chemical structural formula of N-stearoyl-L-hydroxyproline chelated calcium is shown below: 。 3. The calcium phosphate organic-inorganic hybrid nanomaterial according to claim 1, characterized in that, The calcium phosphate organic-inorganic hybrid nanomaterial is a two-dimensional multi-layered structure with a regular rhombic morphology, a lateral dimension of 0.9-1.1 μm, and a layer thickness of 0.004-0.006 μm.

4. A method for preparing the calcium phosphate organic-inorganic hybrid nanomaterial according to any one of claims 1-3, characterized in that, Includes the following steps: S1. Prepare a 4.5%-5% N-stearoyl-L-hydroxyproline methanol solution and a 20%-30% tetramethylammonium hydroxide methanol solution. Add the tetramethylammonium hydroxide methanol solution to the N-stearoyl-L-hydroxyproline methanol solution and heat to 45℃-65℃ to obtain mixed solution A. Slowly add calcium chloride methanol solution to the mixed solution A while maintaining a constant temperature and stirring. After the reaction stops, cool the reaction solution to room temperature, centrifuge and filter to obtain the filter residue. Wash the filter residue repeatedly with acetone and then vacuum dry to obtain N-stearoyl-L-hydroxyproline chelated calcium. S2. Under nitrogen protection at 75℃~85℃, with oleic acid as the reaction environment, N-stearoyl-L-hydroxyproline chelate calcium was added to oleic acid. After uniform stirring, the temperature was raised to 100℃~200℃. Then, tetra-n-butyl phosphate ammonium was dissolved in oleic acid and quickly added to the oleic acid solution of N-stearoyl-L-hydroxyproline chelate calcium. The molar ratio of N-stearoyl-L-hydroxyproline chelate calcium to tetra-n-butyl phosphate ammonium was 1:1.8~2.

5. The temperature was kept constant and the mixture was stirred. The reaction was carried out in a solvothermal manner. After the reaction stopped, the reaction solution was cooled to room temperature. The residue was obtained by centrifugation and filtration. The residue was repeatedly washed with acetone and chloroform and then vacuum dried to obtain calcium phosphate organic-inorganic hybrid nanomaterials.

5. The method for preparing a calcium phosphate organic-inorganic hybrid nanomaterial according to claim 4, characterized in that, In step S1, the mass fraction of the tetramethylammonium hydroxide methanol solution is 25%. After adding the tetramethylammonium hydroxide methanol solution to the N-stearoyl-L-hydroxyproline solution, the temperature is raised to 50°C~60°C.

6. The method for preparing a calcium phosphate organic-inorganic hybrid nanomaterial according to claim 4, characterized in that, In step S1, the calcium chloride methanol solution is added at a rate of 2-3 drops per second, and the stirring time is 2 hours.

7. The method for preparing a calcium phosphate organic-inorganic hybrid nanomaterial according to claim 4, characterized in that, In step S1, the molar ratio of N-stearoyl-L-hydroxyproline to calcium chloride is 1:2~2.

5.

8. The method for preparing a calcium phosphate organic-inorganic hybrid nanomaterial according to claim 4, characterized in that, In step S2, the temperature when adding N-stearoyl-L-hydroxyproline chelated calcium to oleic acid is 80°C. After adding N-stearoyl-L-hydroxyproline chelated calcium and oleic acid, stir evenly for 20 minutes. After stirring, raise the temperature to 120~180°C.

9. The method for preparing a calcium phosphate organic-inorganic hybrid nanomaterial according to claim 4, characterized in that, In step S2, the temperature of the solvothermal reaction is 120~180℃, and the reaction time is 4~6 hours.

10. An application of the calcium phosphate organic-inorganic hybrid nanomaterial according to any one of claims 1-3, characterized in that, Applications in the preparation of drug delivery carriers.

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