Alginic acid salt / nano lanthanum hydroxide composite microspheres, and preparation method and application thereof

Abstract

The present application relates to the technical field of medicine and chemical industry, in particular to a kind of alginate / nano lanthanum hydroxide composite microspheres and its preparation method and application.The composite microspheres use sodium alginate as organic matrix material, and nano lanthanum hydroxide as inorganic filling phase, which are prepared by electrospray technology, and can realize the uniform dispersion and wrapping of nano lanthanum hydroxide in alginate microspheres.The size of the composite microspheres can be adjusted as needed between 235.5 μm and 748.4 μm, and the mass ratio of alginate to nano lanthanum hydroxide can be adjusted as needed within 1: (0.5-1.5).The composite microspheres of the present application have a phosphorus binding capacity of 41.0 mg / g-90.0 mg / g in a gastric acid environment with pH=2, and excellent phosphorus binding ability, which can be used as an oral phosphorus binding agent for the treatment of hyperphosphatemia, providing a new technical solution for clinical intervention of hyperphosphatemia.

Description

An alginate / nano-lanthanum hydroxide composite microsphere, its preparation method and application Technical Field

[0001] This invention relates to the technical field of pharmaceutical and chemical engineering, specifically to an alginate / nano-lanthanum hydroxide composite microsphere, its preparation method, and its application. Background Technology

[0002] According to the World Health Organization, kidney disease has risen to become one of the top ten causes of death worldwide. Hyperphosphatemia is a common complication in patients with end-stage renal disease and a risk factor for death. Oral phosphate binders are an important clinical treatment for hyperphosphatemia. The development of oral phosphate binders can be traced back to the 1940s, gradually evolving from traditional aluminum-based and calcium-based phosphate binders to novel non-aluminum and non-calcium phosphate binders.

[0003] While traditional oral phosphate binders offer good therapeutic effects, they also present several challenges. For instance, aluminum-based phosphate binders can accumulate in the body and lead to low-turnover bone diseases (osteomalformation or dynamic bone), encephalopathy, or microcytic anemia. Calcium-based phosphate binders, due to their calcium absorption, can easily cause hypercalcemia, leading to excessive suppression of parathyroid hormone (PTH) and the development of dynamic bone diseases. Newer oral phosphate binders, free of aluminum and calcium, do not cause hypercalcemia and can reduce cardiovascular risks. Currently, newer oral phosphate binders can be classified into three categories: lanthanum-based phosphate binders, iron-based phosphate binders, and polymer-based phosphate binders. Lanthanum-based phosphate binders have the strongest phosphorus-binding capacity and mainly include lanthanum carbonate, lanthanum polystyrene sulfonate, lanthanum oxycarbonate, and lanthanum hydroxide. Among these, lanthanum hydroxide tablets have the lowest phosphorus burden, achieving good phosphorus control at relatively low doses.

[0004] Studies have shown that nano-lanthanum hydroxide possesses a larger specific surface area and stronger solubility, and this nanostructure further enhances its phosphorus removal effect. However, nano-sized lanthanum hydroxide is more prone to absorbing moisture and reacting with carbon dioxide when exposed to air, and its tendency to agglomerate can affect its application effectiveness. Compared to tablet (chewable tablet) dosage forms, microencapsulation technology is more helpful in improving the stability of nano-lanthanum hydroxide, reducing nanoparticle agglomeration, improving phosphorus removal efficiency, and reducing the safety hazards caused by human absorption.

[0005] Therefore, there is an urgent need to develop a microencapsulation preparation method that can improve the stability of nano-lanthanum hydroxide, inhibit its aggregation, and at the same time retain or even enhance its phosphorus binding capacity, so as to promote the research and development of efficient and safe new oral phosphorus binders and meet the clinical treatment needs of hyperphosphatemia. Summary of the Invention

[0006] In view of this, this invention proposes an alginate / nano-lanthanum hydroxide composite microsphere, its preparation method, and its application. By employing an alginate-nano-lanthanum hydroxide composite method combined with electrospray splatter technology to construct nanocomposite microspheres, the microencapsulation of nano-lanthanum hydroxide is achieved, which is an effective way to solve the aforementioned problems. The technical solution of this invention is implemented as follows:

[0007] In a first aspect, the present invention provides a method for preparing alginate / nano-lanthanum hydroxide composite microspheres, comprising the following steps:

[0008] S1. Prepare an alginate solution, add nano-lanthanum hydroxide to obtain a suspension, which is used as the electrospray solution;

[0009] S2. Prepare an aqueous solution containing lanthanum salt as the receiving liquid;

[0010] S3. The electrospray liquid is dropped into the receiving liquid, cross-linked and cured to form microspheres, and washed to obtain the alginate / nano lanthanum hydroxide composite microspheres.

[0011] Preferably, in step S1, the concentration of alginate in the electrospray fluid is 1% to 3%.

[0012] Specifically, when the concentration of alginate is too low, the composite microspheres ejected by electro-spraying are not strong enough, are easily broken, and are difficult to maintain their spherical shape; when the concentration of alginate is too high, the viscosity of the electro-spraying liquid is too high, making it difficult to spray out and affecting the formation of microspheres.

[0013] Preferably, in step S1, the mass ratio of alginate to nano-lanthanum hydroxide in the electrospray liquid is 1:(0.5-1.5).

[0014] Specifically, if the content of nano-lanthanum hydroxide is too high, it will affect the stability of the electro-spraying liquid. The nano-lanthanum hydroxide is prone to precipitation and cannot be completely encapsulated in the microspheres, resulting in a lower actual content of nano-lanthanum hydroxide in the composite microspheres. It is also prone to clogging the needle and affecting the electro-spraying process. If the content of nano-lanthanum hydroxide is too low, although the composite microspheres can be formed smoothly, the phosphorus binding capacity is much weaker due to the low content, and the phosphorus removal effect cannot be achieved, affecting the expected application.

[0015] Preferably, in step S2, the concentration of lanthanum salt in the receiving liquid is 1% to 3%.

[0016] Specifically, the receiving liquid at this concentration can ensure that the microspheres are fully cross-linked and cured. If the concentration is too low, the cross-linking will be insufficient and the microspheres will be easily broken. If the concentration is too high, it will cause waste of raw materials.

[0017] Preferably, in step S3, the electro-injection process parameters include: receiving distance of 5cm~30cm, needle size of 21G~30G, voltage of 8KV~16KV, flow rate of 1mL / h~5mL / h; and the crosslinking time of 30min~3h.

[0018] Specifically, if the receiving distance is too short and too close to the liquid surface, it will affect the electro-spraying effect; the needle specification is used to control the size of the microspheres, and if it is too small, it will affect the spraying and be prone to clogging; if the voltage is too low, it will affect the spraying, and if the voltage is too high, it will lead to voltage instability and easy breakdown; the flow rate mainly affects the yield, and in actual production applications, low voltage and high flow rate are preferred; the crosslinking time is preferably shorter to increase efficiency.

[0019] Preferably, in step S1, the nano-lanthanum hydroxide includes nanorod-shaped lanthanum hydroxide, the length of which is 29.6±10.8 nm and the width is 6.4±2.0 nm.

[0020] Preferably, in step S3, the size of the alginate / nano lanthanum hydroxide composite microspheres is 235.5 μm to 748.4 μm.

[0021] Specifically, if the size of the alginate / nano lanthanum hydroxide composite microspheres is too large, the cross-linking and curing will be slow and they will easily collapse; if the size is too small, it will be difficult to encapsulate nano lanthanum hydroxide.

[0022] In a second aspect, the present invention provides alginate / nano-lanthanum hydroxide composite microspheres obtained by the preparation method described in the first aspect.

[0023] Thirdly, the present invention provides the application of alginate / nano-lanthanum hydroxide composite microspheres as described in the second aspect in the preparation of oral phosphate binders for the treatment of hyperphosphatemia.

[0024] Compared with the prior art, the advantages of the present invention are as follows:

[0025] (1) The present invention uses an electrospray physical method to prepare alginate / nano lanthanum hydroxide composite microspheres. Compared with the chemical method, no organic solvent is required. The microspheres prepared have uniform particle size and controllable size. The preparation process is simple, easy to control, low in cost, and easy to scale up.

[0026] (2) By optimizing the composition and ratio of the electrospray liquid, the present invention effectively improves the stable dispersion of nano lanthanum hydroxide in the electrospray liquid, ensuring that there is no phase separation during the electrospraying process. The alginate component of the composite microsphere organic matrix is ​​used as a stabilizer for nano lanthanum hydroxide, reducing the agglomeration and precipitation of nano lanthanum hydroxide. No additional stabilizer is required, and the mass ratio of nano lanthanum hydroxide to alginate can reach up to 1.5:1, while still maintaining good stability.

[0027] (3) This invention utilizes alginate polymer microspheres to achieve uniform dispersion and encapsulation of nano-lanthanum hydroxide; the electrostatic interaction between the anionic groups rich in sodium alginate and the lanthanum ions on the surface of nano-lanthanum hydroxide helps to uniformly disperse nano-lanthanum hydroxide in the alginate matrix and reduces the problem of nano-lanthanum hydroxide agglomeration; the composite microspheres can not only improve the stability of nano-lanthanum hydroxide, but also effectively fix it, and as an oral phosphate binder, it can reduce the risk of absorption by the human body while playing a phosphorus removal role. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0029] Figure 1 shows the morphology of the nano-lanthanum hydroxide prepared in Example 1;

[0030] Figure 2 shows the morphology of the composite microspheres prepared in Example 2;

[0031] Figure 3 shows the morphology of the composite microspheres prepared in Example 3;

[0032] Figure 4 shows the morphology of the composite microspheres prepared in Example 4;

[0033] Figure 5 shows the morphology of the composite microspheres prepared in Example 5;

[0034] Figure 6 shows the morphology of the composite microspheres prepared in Example 6;

[0035] Figure 7 shows the morphology of the composite microspheres prepared in Example 7;

[0036] Figure 8 shows the morphology of the composite microspheres prepared in Example 8;

[0037] Figure 9 shows the morphology of the composite microspheres prepared in Example 9;

[0038] Figure 10 shows the morphology of the composite microspheres prepared in Example 10;

[0039] Figure 11 shows the morphology of the composite microspheres prepared in Example 11;

[0040] Figure 12 shows the morphology of the composite microspheres prepared in Example 12;

[0041] Figure 13 shows the morphology of the composite microspheres prepared in Example 13. Detailed Implementation

[0042] Embodiments of the present invention are described in detail below, examples of which are illustrated in the accompanying drawings. The embodiments described below with reference to the accompanying drawings are exemplary and intended to explain the present invention, and should not be construed as limiting the present invention.

[0043] It should be noted that the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include one or more of that feature. Furthermore, in the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0044] In this document, the terms “containing,” “comprising,” or “including” are open-ended expressions, meaning they include the contents specified in this invention but do not exclude other aspects.

[0045] In this document, the terms “optional,” “optionally,” or “optional” generally refer to an event or condition that may, but may not, occur, and the description includes both cases in which the event or condition occurs and cases in which the event or condition does not occur.

[0046] All materials used in this invention were purchased from the market. Sodium hydroxide and sodium alginate were purchased from Sinopharm Chemical Reagent Co., Ltd., and LaCl3·7H2O was purchased from Shanghai Maclean Biochemical Technology Co., Ltd.

[0047] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the protection scope of the present invention.

[0048] Preferably, the present invention provides a method for preparing alginate / nano-lanthanum hydroxide composite microspheres, comprising the following steps:

[0049] S1. Prepare sodium alginate solution, dissolve it completely, add nano lanthanum hydroxide, sonicate for 2 hours, and stir for more than 12 hours to obtain a homogeneous mixture, which is used as the electrospray fluid.

[0050] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare an aqueous solution of lanthanum chloride, which is used as the receiving solution;

[0051] S3. Place the electrospray liquid into a 10 mL syringe, connect the tubing with a Luer connector, and then connect the stainless steel flat-tipped needle to the nozzle holder. Set the electrospray process parameters. Under the action of the syringe's pushing force and the high-voltage electrostatic field, the electrospray liquid drips through the stainless steel nozzle into the stirring receiving liquid. After cross-linking for a period of time and solidification, microspheres are formed. Wash the microspheres repeatedly with ultrapure water three times to obtain the alginate / nano lanthanum hydroxide composite microspheres.

[0052] Preferably, in step S1, the concentration of sodium alginate in the electrospray fluid is 1% to 3%.

[0053] Preferably, in step S1, the mass ratio of sodium alginate to nano-lanthanum hydroxide in the electrospray fluid is 1:(0.5-1.5).

[0054] Preferably, in step S2, the concentration of lanthanum chloride in the receiving liquid is 1% to 3%.

[0055] Preferably, in step S3, the parameters of the electro-injection process include: receiving distance of 5cm to 30cm, needle size of 21G to 30G, voltage of 8KV to 16KV, flow rate of 1mL / h to 5mL / h; and crosslinking time of 30min to 3h.

[0056] Preferably, in step S1, the nano-lanthanum hydroxide includes nanorod-shaped lanthanum hydroxide with a length of 29.6±10.8 nm and a width of 6.4±2.0 nm.

[0057] Preferably, in step S3, the size of the alginate / nano-lanthanum hydroxide composite microspheres is 235.5 μm to 748.4 μm.

[0058] Example 1

[0059] This embodiment provides a method for preparing nano-lanthanum hydroxide by precipitation, including the following steps:

[0060] S1. Dissolve 0.738g of sodium hydroxide in 150mL of ultrapure water to prepare a 0.123M NaOH solution, and dissolve 2.2283g of LaCl3·7H2O in 50mL of ultrapure water to prepare a 0.12M LaCl3 solution.

[0061] S2. According to the volume ratio of NaOH solution to LaCl3 solution of 1.025:1, the LaCl3 solution was added dropwise to the NaOH solution kept at 80℃ using a peristaltic pump. After the addition of the solution was completed, the reaction was timed for 2 hours. After the reaction was completed, the solution was allowed to stand, and after centrifugation, a white precipitate was obtained. The precipitate was washed 4 times by centrifugation with NaOH solution at pH 11.4, and after freeze-drying, nano-lanthanum hydroxide was obtained. The morphology was short rod-shaped. As shown in Figure 1, the length was 29.6±10.8 nm and the width was 6.4±2.0 nm.

[0062] Example 2

[0063] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0064] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.5.

[0065] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0066] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 27G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 1mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 5cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0067] As shown in Figure 2, the average size of the composite microspheres prepared in Example 2 is 426.5 μm. The composite microspheres were placed in a phosphate solution at pH 7 (simulating the intestinal environment), and after 24 hours, a phosphorus binding capacity test was performed. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 2 was 9.0 mg / g.

[0068] Specifically, the method for testing phosphorus binding capacity is as follows: First, prepare phosphate solutions with low concentration gradients (0, 0.5, 1.0, 1.5, 2.0 mg / L) and medium-high concentration gradients (2.0, 5.0, 8.0, 11.0, 14.0, 17.0, 20.0 mg / L) using potassium dihydrogen phosphate. The concentration gradient for curve 01 (range 0-2) is set to 0.5 mg / L, and the concentration gradient for curve 02 (range 2-20) is set to 3 mg / L. After the phosphate solution is prepared and developed with phosphate reagent, the readings are taken in a phosphate detector, and a phosphate concentration-transmittance curve is plotted. Fitting the curve yields the standard curve for the phosphate detector. Then, 0.02 g of microspheres are added to 40 mL of... In a 50 mg / L phosphate solution, the pH value of the solution was adjusted as needed between 2 and 8, referring to the gastric and intestinal environment. The reaction was carried out in a constant temperature shaking incubator at 37℃ for 24 h, and the shaking speed was set to 150 r / min. After the reaction was completed, a certain amount of solution was taken, filtered through a 0.45 μm water filter, and then a sample was prepared for testing.

[0069] Phosphate binding capacity It can be calculated using the following formula:

[0070]

[0071] In the formula: C0 is the initial concentration of the phosphate solution, in mg / L; C t t represents the concentration of the phosphate solution at time t, in mg / L; V represents the volume of the phosphate solution, in mL; and m represents the mass of n-LH (nano lanthanum hydroxide), in g.

[0072] Example 3

[0073] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0074] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.5.

[0075] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0076] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 27G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 1mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 30cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0077] As shown in Figure 3, the average size of the composite microspheres prepared in Example 3 is 412.8 μm. The composite microspheres were placed in a phosphate solution with a pH of 3 (simulating the gastric environment), and after 24 hours, a phosphorus binding capacity test was performed. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 3 was 24.0 mg / g.

[0078] Example 4

[0079] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0080] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.5.

[0081] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0082] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 21G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 1mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0083] As shown in Figure 4, the average size of the composite microspheres prepared in Example 4 was 748.4 μm. The composite microspheres were placed in a phosphate solution with a pH of 3 (simulating the gastric environment), and after 24 hours, a phosphorus binding capacity test was performed. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 4 was 21.1 mg / g.

[0084] Example 5

[0085] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0086] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.5.

[0087] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0088] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 30G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 1mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0089] As shown in Figure 5, the average size of the composite microspheres prepared in Example 5 was 291.9 μm. The composite microspheres were placed in a phosphate solution at pH 7 (simulating the intestinal environment), and after 24 hours, a phosphorus binding capacity test was performed. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 5 was 21.1 mg / g.

[0090] Example 6

[0091] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0092] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:1.

[0093] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0094] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 30G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 1mL / h) and the high-voltage electrostatic field (voltage 8KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0095] As shown in Figure 6, the average size of the composite microspheres prepared in Example 6 is 298.9 μm. The composite microspheres were placed in a phosphate solution with a pH of 2 (simulating the gastric environment), and after 24 hours, a phosphorus binding capacity test was performed. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 6 was 62.0 mg / g.

[0096] Example 7

[0097] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0098] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.5.

[0099] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0100] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 30G stainless steel flat-tipped needle to the nozzle holder. Under the driving force of the syringe (flow rate 1mL / h) and the high-voltage electrostatic field (voltage 16KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0101] As shown in Figure 7, the average size of the composite microspheres prepared in Example 7 is 247.9 μm. The composite microspheres were placed in a phosphate solution with a pH of 2 (simulating the gastric environment), and after 24 hours, a phosphorus binding capacity test was performed. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 7 was 45.0 mg / g.

[0102] Example 8

[0103] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0104] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.5.

[0105] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0106] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 30G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 1mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0107] As shown in Figure 8, the average size of the composite microspheres prepared in Example 8 was 284.3 μm. The composite microspheres were placed in a phosphate solution at pH 6 (simulating the intestinal environment), and after 24 hours, their phosphorus binding capacity was tested. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 8 was 15.3 mg / g.

[0108] Example 9

[0109] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0110] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.5.

[0111] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0112] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 30G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 5mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0113] As shown in Figure 9, the average size of the composite microspheres prepared in Example 9 is 370.0 μm. The composite microspheres were placed in a phosphate solution at pH 7 (simulating the intestinal environment), and after 24 hours, a phosphorus binding capacity test was performed. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 9 was 9.8 mg / g.

[0114] Example 10

[0115] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0116] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 1% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:1.

[0117] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0118] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 30G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 4mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0119] As shown in Figure 10, the average size of the composite microspheres prepared in Example 10 is 235.5 μm. The composite microspheres were placed in a phosphate solution with a pH of 2 (simulating the gastric environment), and after 24 hours, a phosphorus binding capacity test was performed. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 10 was 64.0 mg / g.

[0120] Example 11

[0121] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0122] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 3% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:1.

[0123] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0124] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 30G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 4mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0125] As shown in Figure 11, the average size of the composite microspheres prepared in Example 11 is 571.7 μm. The composite microspheres were placed in a phosphate solution with a pH of 2 (simulating the gastric environment), and after 24 hours, a phosphorus binding capacity test was performed. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 11 was 60 mg / g.

[0126] Example 12

[0127] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0128] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, wherein the concentration of sodium alginate is 1.5% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.5.

[0129] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0130] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 27G stainless steel flat-tipped needle to the nozzle holder. Under the influence of the syringe's propulsion (flow rate 4mL / h) and a high-voltage electrostatic field (voltage 15KV), the electrospray liquid drips through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0131] As shown in Figure 12, the average size of the composite microspheres prepared in Example 12 is 409.9 μm. The composite microspheres were placed in a phosphate solution with a pH of 2 (simulating the gastric environment), and after 24 hours, a phosphorus binding capacity test was performed. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 12 was 41.0 mg / g.

[0132] Example 13

[0133] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0134] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, wherein the concentration of sodium alginate is 1.5% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:1.5.

[0135] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0136] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 27G stainless steel flat-tipped needle to the nozzle holder. Under the influence of the syringe's propulsion (flow rate 4mL / h) and a high-voltage electrostatic field (voltage 15KV), the electrospray liquid drips through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0137] As shown in Figure 13, the average size of the composite microspheres prepared in Example 13 was 446.7 μm. The composite microspheres were placed in a phosphate solution at pH 7 (simulating the intestinal environment), and after 24 hours, a phosphorus binding capacity test was performed. The results showed that the phosphorus binding capacity of the composite microspheres prepared in Example 13 was 26.4 mg / g.

[0138] Example 14

[0139] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0140] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.5.

[0141] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0142] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 30G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 4mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0143] The composite microspheres were placed in a phosphate solution with a pH of 2 (simulating the stomach environment), and the phosphorus binding capacity was tested after 24 hours. It was found that the phosphorus binding capacity of the composite microspheres prepared in Example 14 was 42.5 mg / g.

[0144] Example 15

[0145] This embodiment provides an electrospray preparation method for alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0146] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:1.5.

[0147] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 1% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0148] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 30G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 4mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 30min, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0149] Because the proportion of sodium alginate was reduced in Example 15, curing could be completed with a low concentration of crosslinking agent and a short crosslinking time. The composite microspheres were placed in a phosphate solution with a pH of 2 (simulating the stomach environment), and the phosphorus binding capacity was tested after 24 hours. It was found that the phosphorus binding capacity of the composite microspheres prepared in Example 15 was 90.0 mg / g.

[0150] Comparative Example 1

[0151] This comparative example provides a method for preparing comparative alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0152] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, wherein the concentration of sodium alginate is 0.5% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.5.

[0153] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0154] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 27G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 1mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 30cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0155] The composite microspheres were placed in a phosphate solution with a pH of 3 (simulating the stomach environment), and the phosphorus binding capacity was tested after 24 hours. It was found that the phosphorus binding capacity of the composite microspheres prepared in Comparative Example 1 was 16.6 mg / g. The performance was lower than that of Example 3. This is because the microspheres ruptured, resulting in a decrease in the content of nano-lanthanum hydroxide.

[0156] Comparative Example 2

[0157] This comparative example provides a method for preparing comparative alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0158] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 3.5% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.5.

[0159] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0160] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 21G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 1mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0161] The composite microspheres were placed in a phosphate solution with a pH of 3 (simulating the stomach environment). After 24 hours, the phosphorus binding capacity was tested. It was found that the phosphorus binding capacity of the composite microspheres prepared in Comparative Example 2 was 19.7 mg / g. The performance was not much different from that in Example 4. However, due to the high concentration, the viscosity of the electrospray liquid was too high, making it difficult to spray out, which affected the formation and yield of microspheres. The composite microspheres were irregular in shape and were elliptical.

[0162] Comparative Example 3

[0163] This comparative example provides a method for preparing comparative alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0164] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:0.2.

[0165] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 3% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0166] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 30G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 4mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 3 hours, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0167] The composite microspheres were placed in a phosphate solution with a pH of 2 (simulating the gastric environment), and the phosphorus binding capacity was tested after 24 hours. It was found that the phosphorus binding capacity of the composite microspheres prepared in Comparative Example 3 was 20.5 mg / g. At this ratio, the content of nano lanthanum hydroxide was too low. Although the composite microspheres could be formed smoothly, the phosphorus binding capacity was insufficient due to the low content of nano lanthanum hydroxide, which required an increased dosage and affected the expected application.

[0168] Comparative Example 4

[0169] This comparative example provides a method for preparing comparative alginate / nano-lanthanum hydroxide composite microspheres, including the following steps:

[0170] S1. Dissolve sodium alginate in ultrapure water to prepare a sodium alginate solution. After it is fully dissolved, add nano lanthanum hydroxide in a certain proportion and sonicate for 2 hours to disperse it evenly to obtain a suspension. Continue stirring for 12 hours to obtain an electrospray liquid, in which the concentration of sodium alginate is 2% and the mass ratio of sodium alginate to nano lanthanum hydroxide is 1:2.0.

[0171] S2. Dissolve LaCl3·7H2O in ultrapure water to prepare a 1% lanthanum chloride aqueous solution. This solution will be used as the receiving liquid.

[0172] S3. Place the electrospray liquid into a 10mL syringe, connect the tubing with a Luer connector, and then attach a 30G stainless steel flat-tipped needle to the nozzle holder. Under the force of the syringe (flow rate 4mL / h) and the high-voltage electrostatic field (voltage 12KV), the electrospray liquid is dripped through the stainless steel nozzle into the stirring receiving liquid at a receiving distance of 20cm. After cross-linking for 30min, it solidifies to form microspheres. Wash three times with ultrapure water to obtain alginate / nano-lanthanum hydroxide composite microspheres.

[0173] The composite microspheres were placed in a phosphate solution with a pH of 2 (simulating the stomach environment), and the phosphorus binding capacity was tested after 24 hours. It was found that the phosphorus binding capacity of the composite microspheres prepared in Comparative Example 4 was 101.5 mg / g. According to Examples 14-15, the phosphorus binding capacity should increase by 25 mg / g for every 0.5% increase in the proportion of lanthanum hydroxide. Therefore, at this ratio, the actual effect was lower than the expected phosphorus removal capacity of 115.0 mg / g. The actual content of nano-lanthanum hydroxide in the composite microspheres was lower than expected due to the precipitation of nano-lanthanum hydroxide. This ratio would result in a waste of nano-lanthanum hydroxide raw materials.

[0174] Table 1. Preparation parameters and performance results of composite microspheres in the examples and comparative examples.

[0175]

[0176] As shown in Table 1, the concentration of sodium alginate and the mass ratio of sodium alginate to nano-lanthanum hydroxide are the core factors controlling the quality of composite microspheres. When the concentration of sodium alginate is controlled at 1%~3%, composite microspheres with regular morphology and no breakage can be prepared, and the electro-spraying process can be ensured smoothly. If the concentration is below 1%, the microspheres will break due to insufficient matrix support, and the phosphorus binding capacity will drop to 16.6 mg / g. If the concentration is above 3%, the viscosity of the electro-spraying liquid will increase sharply, which will not only make it difficult to spray and affect the yield, but also cause the microspheres to have irregular shapes such as elliptical shapes.

[0177] Regarding the mass ratio of sodium alginate to nano-lanthanum hydroxide, 1:0.5 to 1:1.5 is the optimal range for balancing phosphorus binding capacity and raw material utilization. When the ratio is increased to 1:1.5, the phosphorus binding capacity of the composite microspheres at pH=2 (simulating the gastric environment) reaches 90.0 mg / g, which is the highest among all examples. If the ratio is lower than 1:0.5, the insufficient lanthanum hydroxide content will result in a phosphorus binding capacity of only 20.5 mg / g, requiring an increased dosage to meet the phosphorus control requirements, thus affecting clinical application. If the ratio is higher than 1:1.5, lanthanum hydroxide will precipitate out due to exceeding the dispersion carrying capacity of alginate. Although the measured phosphorus binding capacity is 101.5 mg / g, it is lower than the expected value of 112.0 mg / g, resulting in raw material waste and lacking practical application value.

[0178] The alginate / nano-lanthanum hydroxide composite microspheres of this invention exhibit significant adaptability in application at different pH values: At pH=2 (simulating an empty stomach), the phosphorus binding capacity is strongest, ranging from 41.0 mg / g to 90.0 mg / g, effectively blocking phosphorus absorption in the stomach during meals, meeting the core therapeutic needs of oral phosphate binders; at pH=3 (simulating a postprandial stomach), the capacity is stable (16.6 mg / g to 24.0 mg / g), continuously exerting a postprandial phosphorus removal effect; at pH=6 (simulating the upper small intestine), the capacity is moderate (15.3 mg / g), assisting in capturing residual phosphorus; at pH=7 (simulating the middle and lower small intestine), the capacity is low (9.0 mg / g to 26.4 mg / g); throughout the gastrointestinal tract, the immobilization effect of the alginate microspheres helps reduce the risk of lanthanum ion absorption by the human body.

[0179] The embodiments described above are some, but not all, of the embodiments of the present invention. The detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely to illustrate selected embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

Claims

1. A method for preparing alginate / lanthanum hydroxide nanocomposite microspheres, characterized in that, The process includes the following steps: S1, preparing an alginate solution, adding nano-lanthanum hydroxide to obtain a suspension, which is used as the electrospray solution; S2, preparing an aqueous solution containing lanthanum salt, which is used as the receiving solution; S3, dropping the electrospray solution into the receiving solution, cross-linking and solidifying to form microspheres, and washing to obtain the alginate / nano-lanthanum hydroxide composite microspheres; in step S1, the concentration of alginate in the electrospray solution is 1%~3%; the mass ratio of alginate to nano-lanthanum hydroxide in the electrospray solution is 1:(0.5-1.5).

2. The preparation method of alginate / nano-lanthanum hydroxide composite microspheres as described in claim 1, characterized in that, In step S2, the concentration of lanthanum salt in the receiving liquid is 1% to 3%.

3. The method for preparing alginate / nano-lanthanum hydroxide composite microspheres as described in claim 1, characterized in that, In step S3, the parameters of the electro-injection process include: receiving distance of 5cm to 30cm, needle size of 21G to 30G, voltage of 8KV to 16KV, and flow rate of 1mL / h to 5mL / h.

4. The method for preparing alginate / nano-lanthanum hydroxide composite microspheres as described in claim 1, characterized in that, In step S3, the crosslinking time is 30 min to 3 h.

5. The method for preparing alginate / nano-lanthanum hydroxide composite microspheres as described in claim 1, characterized in that, In step S1, the nano-lanthanum hydroxide includes nanorod-shaped lanthanum hydroxide with a length of 29.6±10.8 nm and a width of 6.4±2.0 nm.

6. The method for preparing alginate / nano-lanthanum hydroxide composite microspheres as described in claim 1, characterized in that, In step S3, the size of the alginate / nano-lanthanum hydroxide composite microspheres is 235.5 μm to 748.4 μm.

7. An alginate / nano-lanthanum hydroxide composite microsphere obtained by the preparation method according to any one of claims 1 to 6.

8. The application of the alginate / nano-lanthanum hydroxide composite microspheres as described in claim 7 in the preparation of oral phosphate binders, characterized in that, The oral phosphate binder is used for the treatment of hyperphosphatemia.

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