Metformin hydrochloride-loaded PLGA (poly (lactic-co-glycolic acid)) nanoparticle material as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of medicines, and relates to a metformin hydrochloride-loaded PLGA (poly (lactic-co-glycolic acid)) nanoparticle material as well as a preparation method and application thereof. The preparation method comprises the following steps: carrying out first shear emulsification on a metformin hydrochloride aqueous solution and an organic solution containing a first emulsifier and PLGA (poly (lactic-co-glycolic acid)) to obtain a water-in-oil primary emulsion; carrying out second shear emulsification on the primary emulsion and an aqueous solution containing a second emulsifier to obtain a water-in-oil-in-water type crude emulsion; homogenizing and emulsifying the crude emulsion to obtain a W1 / O / W2 nano-emulsion; and removing the organic solvent from the nano-emulsion, centrifuging and drying to obtain the nano-emulsion. The preparation method disclosed by the invention not only has relatively high reproducibility for preparing the nano-particles, but also obviously reduces the average size of the obtained nano-particles, improves the bioavailability of the medicine, and simultaneously keeps the uniform dispersity and high biocompatibility of the nano-particles.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical technology and relates to a PLGA nanoparticle material loaded with metformin hydrochloride, a preparation method thereof and an application thereof. Background Art

[0002] Disclosing the information of this background art section is only intended to enhance the overall understanding of the present invention, and is not necessarily to be regarded as an admission or an implication in any form that this information constitutes the prior art already known to those of ordinary skill in the art.

[0003] Metformin hydrochloride is a biguanide derivative widely used in the treatment of type 2 diabetes. After oral administration, it is mainly absorbed from the upper part of the small intestine. Its bioavailability is low, its biological half-life is short and variable, and multiple large doses of administration are required to maintain an effective blood drug concentration, resulting in reduced compliance of patients and an increased incidence of side effects. Through encapsulation, drug sustained release can be achieved, thereby reducing the number of drug administrations, reducing the fluctuation of blood drug concentration, and effectively alleviating the irritation of the drug to the gastrointestinal tract.

[0004] Many polymers are used to prepare microsphere drug preparations. By changing the polymer ratio and manufacturing conditions to change the physical and chemical properties such as microsphere particle size and porosity, different drug release curves can be achieved. However, such microspheres generally have a large size, may have an initial burst release, and have a small surface area to volume ratio, which limits their ability to interact with the surrounding environment; while nanoparticles can more easily penetrate cell membranes and biological barriers and have higher biological activity. Therefore, researchers focus on developing nanoparticle-based drug delivery systems with functional surface groups to improve the bioavailability of drugs and reduce the toxic and side effects of drugs. However, these strategies often face the challenge of simultaneously achieving high drug loading and sustained drug release, which makes the delivery process more complex. For the delivery of anti-diabetic drugs such as metformin hydrochloride, a new delivery system with more stable, effective and sustained drug release needs to be developed to achieve effective sustained release and hypoglycemic effects in vivo and in vitro.

[0005] The emulsion evaporation method is a technique for preparing particles by mixing an aqueous phase and an organic phase to form an emulsion, and then evaporating the organic phase. This method usually combines high-speed shearing or high-pressure homogenization techniques to achieve the refinement and homogenization of the emulsion. The high-speed shearing method is a technique for dispersing a liquid or suspension into fine particles by the shearing force generated by mechanical stirring. The core lies in using a high-speed rotating stirrer or shearing device to disperse the raw materials into a uniform emulsion. This method is efficient and simple; however, the inventors have found that the emulsion droplets obtained only by high-speed shearing are difficult to reach the nanoscale, and there are certain limitations in the particle size distribution uniformity and rheological properties. The high-pressure homogenization method accelerates a liquid or suspension through a narrow homogenization valve by a high-pressure pump, and uses the shearing force, impact force, and cavitation effect to break the particles into smaller sizes. The inventors have found that this method can effectively prepare nanoparticles with a uniform particle size distribution, which is suitable for the preparation of high-precision microspheres; while the emulsion droplets obtained only by high-pressure homogenization are generally on the nanoscale, but lack reproducibility between batches. Summary of the Invention

[0006] To solve the deficiencies of the prior art, the object of the present invention is to provide a PLGA nanoparticle material loaded with metformin hydrochloride, its preparation method and application. The preparation method of the present invention not only has high reproducibility in preparing nanoparticles, but also the obtained nanoparticles significantly reduce the average size of the nanoparticles, improve the bioavailability of the drug, and at the same time maintain the uniform dispersion and high biocompatibility of the nanoparticles.

[0007] To achieve the above object, the technical solution of the present invention is as follows:

[0008] In the first aspect, a preparation method of a PLGA nanoparticle material loaded with metformin hydrochloride includes the following steps:

[0009] Perform first shear emulsification on an aqueous solution of metformin hydrochloride and an organic solution containing a first emulsifier and PLGA to obtain a water-in-oil (W1 / O) primary emulsion;

[0010] Perform second shear emulsification on the primary emulsion and an aqueous solution containing a second emulsifier to obtain a water-in-oil-in-water (W1 / O / W2) coarse emulsion;

[0011] Perform homogenization emulsification on the coarse emulsion to obtain a W1 / O / W2 nanoemulsion;

[0012] Remove the organic solvent from the nanoemulsion, centrifuge and dry to obtain the product.

[0013] For water-soluble drugs, the encapsulation efficiency is low with the high-pressure homogenization method, leakage is likely to occur, and the efficiency is low. The coarse emulsion enters the pressurization chamber through the feed inlet for pressurization, forms a high-speed fluid through the micropores of the nozzle and is sprayed into the reaction chamber. The greater the pressure, the greater the flow velocity of the fluid at the slit. Turbulence is formed by convective shearing in the reaction chamber. Although the particle size is effectively reduced, water-soluble drugs are more likely to leak into the external phase during the process of rapid pressure increase in a short time.

[0014] Based on the above process flow, it can be further expanded into the multi-stage shearing and high-pressure homogenization process described below, in order to obtain a smaller particle size, improve efficiency, and reduce drug leakage. For multi-stage high-speed shearing, drug and carrier are initially mixed rapidly for drug loading. The primary emulsion is injected into the secondary high-speed shearing machine through a medical one-way constant-pressure infusion tube for shearing. After obtaining the coarse emulsion of quasi-micron-sized drug-loaded microspheres, the coarse emulsion is injected into a high-pressure homogenizer through a pressurized injection device for homogenization treatment. Replacing the original "pouring" operation with this pressurized injection device realizes automation and multi-stage pressurization, which can not only reduce the particle size but also reduce drug leakage.

[0015] The shear emulsification described in the present invention is carried out by high-speed shearing. Through shear emulsification, a micron-sized W1 / O / W2 emulsion can be obtained. Then, through homogenization emulsification (homogenization by a high-pressure homogenizer, which can also be called high-pressure homogenization), under the action of the shearing force, impact force, and cavitation effect of the homogenization emulsification in the high-pressure homogenizer, the particle size of the micron-sized W1 / O / W2 emulsion is reduced from the micron level to the nano level, thus forming a nanoemulsion. At the same time, during the process of high-pressure homogenization, through the combined action of the first emulsifier and the second emulsifier, it is ensured that the double emulsion containing metformin hydrochloride in the inner aqueous phase maintains the double emulsion structure, so as to ensure the formation of a nanoemulsion by high-pressure homogenization.

[0016] In addition, during high-pressure homogenization, when the micron-sized W1 / O / W2 emulsion forms a nano-sized W1 / O / W2 emulsion, part of the micron-sized W1 / O / W2 emulsion is broken, causing a small part of the metformin hydrochloride originally in the inner aqueous phase to disperse into the outer aqueous phase. During the subsequent process of removing organic solvents and drying, the metformin hydrochloride in the outer aqueous phase can form hydrogen bonds with PLGA, so that the metformin hydrochloride in the outer aqueous phase is loaded onto the surface of the nanoparticles, thereby realizing the sustained release of metformin hydrochloride through the structure.

[0017] In the second aspect, a PLGA nanoparticle material loaded with metformin hydrochloride is obtained by the above preparation method.

[0018] In the third aspect, an application of the above PLGA nanoparticle material loaded with metformin hydrochloride in the preparation of drugs.

[0019] The beneficial effects of the present invention are as follows:

[0020] (1) The preparation method provided by the present invention can significantly refine the particle size of nanoparticles and make their distribution more uniform through the combination of high-speed shearing first and high-pressure homogenization later. High-sphericity particles with a uniform size distribution around 100 nm are obtained, and it has high batch repeatability, which can ensure the quality consistency of products in different batches, providing a reliable technical guarantee for large-scale production.

[0021] (2) The preparation method provided by the present invention can further improve the drug-loading performance of nanoparticles through the combination of high-speed shearing first and high-pressure homogenization later. In addition, the shearing, impact and cavitation effects during the high-pressure homogenization process can effectively disperse metformin hydrochloride and make it evenly distributed in the carrier.

[0022] (3) In the in vitro release test, the PLGA nanoparticles loaded with MH can achieve sustained drug release for 36 hours. The release mechanism is that the drug is first rapidly released from the surface of the nanoparticles, and then the drug is gradually released through the degradation of the carrier material. By continuously releasing the drug, the PLGA nanoparticles can effectively prolong the action time of the drug in vivo.

[0023] (4) The PLGA nanoparticles loaded with MH of the present invention have excellent biocompatibility. Their cytotoxicity and hemolysis rate are much lower than the clinical standards, and they can be efficiently endocytosed by cells and release drugs inside the cells. The small size and surface modification of the nanoparticles enable them to smoothly penetrate the cell membrane and play a role inside the cells. This characteristic significantly improves the targeting of the drug, reduces the loss of the drug outside the cells, and enhances the therapeutic effect of the drug.

[0024] (5) The PLGA nanoparticles loaded with MH of the present invention can be administered through two routes: oral and injection, and achieve hypoglycemic effects in vivo. The slow-release characteristics of the nanoparticles enable their effective action time in vivo to be as long as 8 - 10 hours, significantly prolonging the action time of the drug, reducing the dosing frequency, and improving the compliance of patients. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The specification drawings forming a part of the present invention are used to provide a further understanding of the present invention. The schematic embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute an improper limitation of the present invention.

[0026] Figure 1 It is a schematic diagram of the main operation process of the present invention;

[0027] Figure 2 It is the average particle size distribution and PDI dispersion coefficient of Examples 1 - 3 provided by the present invention;

[0028] Figure 3The surface morphologies of Examples 1 to 3 provided by the present invention, with the upper row being low-magnification pictures and the scale being 10 μm, and the lower row being high-magnification pictures and the scale being 1 μm;

[0029] Figure 4 The encapsulation efficiency of Examples 1 to 3 provided by the present invention;

[0030] Figure 5 The cumulative release rate of in vitro tests of Examples 1 and 3 provided by the present invention;

[0031] Figure 6 The cytotoxicity of Examples 1 and 3 provided by the present invention;

[0032] Figure 7 The blood compatibility of Examples 1 and 3 provided by the present invention;

[0033] Figure 8 The imaging distribution of Example 4 provided by the present invention in hepatocytes;

[0034] Figure 9 The hypoglycemic effect of Example 3 provided by the present invention in mice. Detailed implementation manners

[0035] It should be noted that the following detailed description is exemplary and is intended to provide further illustration of the present invention. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by those of ordinary skill in the technical field to which the present invention belongs.

[0036] It should be noted that the terms used herein are only for describing specific implementation manners and are not intended to limit the exemplary embodiments according to the present invention. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0037] As introduced in the background art, it is difficult to prepare metformin hydrochloride into a nanoparticle-based drug delivery system in the existing emulsification methods. To solve the above technical problems, the present invention proposes a PLGA nanoparticle material loaded with metformin hydrochloride, its preparation method and application.

[0038] A typical implementation manner of the present invention provides a preparation method of a PLGA nanoparticle material loaded with metformin hydrochloride, comprising the following steps:

[0039] The aqueous solution of metformin hydrochloride is subjected to first shear emulsification with an organic solution containing a first emulsifier and PLGA to obtain a water-in-oil (W1 / O) primary emulsion;

[0040] The primary emulsion is subjected to second shear emulsification with an aqueous solution containing a second emulsifier to obtain a water-in-oil-in-water (W1 / O / W2) coarse emulsion;

[0041] The coarse emulsion is subjected to homogenization emulsification to obtain a W1 / O / W2 nanoemulsion;

[0042] The organic solvent is removed from the nanoemulsion, followed by centrifugation and drying to obtain the product.

[0043] The present invention prepares nanoparticle materials with uniform size, high monodispersity, and high bioavailability through the above preparation method.

[0044] In some embodiments, the volume ratio of the aqueous solution of metformin hydrochloride to the organic solution is 1:5 to 50, preferably 1:5 to 15.

[0045] In some embodiments, the solvent of the organic solution is dichloromethane. Using dichloromethane is more convenient in the subsequent step of removing the organic solvent, and only stirring and volatilization are required.

[0046] In some embodiments, the mass ratio of metformin hydrochloride to PLGA is 2:5 to 250, preferably 2:5 to 100, further preferably 2:5 to 50, and even more preferably 2:5 to 25. Specifically, the concentration of PLGA in the organic solution is 1 to 5%.

[0047] In some embodiments, the mass ratio of PLGA to the first emulsifier is 1:0.8 to 1.2.

[0048] In some embodiments, the rotation speed of the first shear emulsification is 6K to 12K RPM.

[0049] In some embodiments, the first emulsifier is sorbitan oleate or polysorbate.

[0050] In some embodiments, the volume ratio of the primary emulsion to the aqueous solution containing the second emulsifier is 1:5 to 50, preferably 1:5 to 15.

[0051] In some embodiments, the concentration of the second emulsifier in the aqueous solution containing the second emulsifier is 0.1 to 10%, preferably 0.2 to 5%, and preferably 0.5 to 2%.

[0052] In some embodiments, the rotation speed of the second shear emulsification is 6K to 12K RPM.

[0053] In some embodiments, the second emulsifier is sorbitan oleate or polysorbate.

[0054] In some embodiments, the pressure of homogeneous emulsification is 3000 - 10000 psi.

[0055] In some embodiments, the number of cycles of homogeneous emulsification is 1 - 3 times.

[0056] Specifically, the steps are as follows:

[0057] Metformin hydrochloride is added to deionized water to make the concentration of metformin hydrochloride in the aqueous solution 0.02 - 0.10 g / mL; PLGA and Span 80 are added to dichloromethane to make the concentrations of PLGA and Span 80 in the organic solution 0.01 - 0.05 g / mL and 0.2% - 3% respectively; the two solutions are mixed at a volume ratio of 1:5 - 1:100 and sheared at a rotation speed of 3K - 12K RPM for 2 - 5 minutes to form a W1 / O primary emulsion with the drug encapsulated in the organic phase.

[0058] Tween 20 is added to deionized water to make the concentration of Tween 20 in the aqueous solution 0.2% - 5%; the W1 / O primary emulsion and the aqueous Tween 20 solution are mixed at a volume ratio of 1:5 - 1:100 and sheared at a rotation speed of 6K - 12K RPM for 2 - 5 minutes to obtain a micron-scale W1 / O / W2 coarse emulsion.

[0059] The coarse emulsion is poured into a high-pressure homogenizer and passed through the inside of the homogenizer under a pressure of 3000 - 10000 psi for 1 - 3 cycles to obtain a W1 / O / W2 nanoemulsion.

[0060] The obtained nanoemulsion is stirred for 4 - 6 hours to remove the organic solvent, centrifuged at a rotation speed of 6000 - 8000 RPM for 10 - 20 minutes, washed with deionized water, and finally the lower layer precipitate is freeze-dried for 6 - 8 hours to obtain nanoparticles.

[0061] Another embodiment of the present invention provides a PLGA nanoparticle material loaded with metformin hydrochloride, which is obtained by the above preparation method.

[0062] The third embodiment of the present invention provides an application of the above PLGA nanoparticle material loaded with metformin hydrochloride in the preparation of drugs.

[0063] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with specific embodiments.

[0064] The reagents and abbreviations used in the embodiments of the present invention are as follows: poly(lactic-co-glycolic acid) (PLGA), metformin hydrochloride (MH), dichloromethane (DCM), sorbitan oleate (Span 80), polysorbate (Tween 20). In the present invention, "%" represents mass / volume percentage (1% represents 0.01 g / mL) unless otherwise specified.

[0065] Example 1

[0066] (1) Prepare a 2% aqueous solution of metformin hydrochloride drug and a dichloromethane solution of 1% polymer PLGA and 3% Span 80, and perform primary shear emulsification at a rotation speed of 6K RPM for 3 minutes according to a volume ratio of 1:10.

[0067] (2) Mix the primary emulsion and deionized water according to a volume ratio of 1:5 and perform secondary shear emulsification at a rotation speed of 12K RPM for 2 minutes. Directly stir and volatilize the obtained emulsion, and centrifugally dry it to obtain micron particles.

[0068] Example 2

[0069] (1) Prepare a 2% aqueous solution of metformin hydrochloride drug and a 5% dichloromethane solution of polymer PLGA, and mix them according to a volume ratio of 1:5 and perform primary shear emulsification at a rotation speed of 3K RPM for 5 minutes.

[0070] (2) Mix the primary emulsion and deionized water added with 2% Tween20 according to a volume ratio of 1:10 and perform secondary shear emulsification at a rotation speed of 12K RPM for 2 minutes. Then add it to a high-pressure homogenizer and homogenize and emulsify it once at a pressure of 6000 psi to obtain a nanoemulsion. Further stir and volatilize, and centrifugally dry it to obtain nanoparticles.

[0071] The preparation process is as Figure 1 shown.

[0072] Example 3

[0073] (1) Prepare a 2% aqueous solution of metformin hydrochloride drug and a dichloromethane solution of 1% polymer PLGA and 1% Span 80, and mix them according to a volume ratio of 1:10 and perform primary shear emulsification at a rotation speed of 9K RPM for 2 minutes.

[0074] (2) Mix the primary emulsion and deionized water added with 0.5% Tween20 according to a volume ratio of 1:10 and perform secondary shear emulsification at a rotation speed of 12K RPM for 2 minutes. Then add it to a high-pressure homogenizer and homogenize and emulsify it once at a pressure of 6000 psi to obtain a nanoemulsion. Further stir and volatilize, and centrifugally dry it to obtain nanoparticles.

[0075] Example 4

[0076] (1) Prepare an aqueous solution of 2% metformin hydrochloride drug, a dichloromethane solution of 1% polymer PLGA and 1% Span 80, and add 3 mg of Nile red fluorescent dye to the dichloromethane solution. Mix them at a volume ratio of 1:10 and perform primary shear emulsification at a speed of 9K RPM for 2 minutes.

[0077] (2) Mix the primary emulsion and deionized water containing 0.5% Tween20 at a volume ratio of 1:10 and perform secondary shear emulsification at a speed of 12K RPM for 2 minutes. Then add it to a high-pressure homogenizer and homogenize and emulsify it once at a pressure of 6000 psi to obtain a nanoemulsion. Further stir to volatilize and centrifuge to dry to obtain fluorescently stained nanoparticles.

[0078] Example 5

[0079] (1) Prepare an aqueous solution of 2% metformin hydrochloride drug and a dichloromethane solution of 5% polymer PLGA, mix them at a volume ratio of 1:10 and perform primary shear emulsification at a speed of 3K RPM.

[0080] (2) Mix the primary emulsion and deionized water containing 2% Tween20 at a volume ratio of 1:10. Then add it to a high-pressure homogenizer and homogenize and emulsify it once at a pressure of 6000 psi to obtain a nanoemulsion. Further stir to volatilize and centrifuge to dry to obtain micron-sized particles.

[0081] Repeat the steps of this example 5 times. The particle sizes of the obtained particles vary greatly. Among them, 2 times are micron-sized particles and 3 times are nano-sized particles. This proves that the reproducibility of directly subjecting the primary emulsion to high-pressure homogenization with an external aqueous phase containing an emulsifier is poor. Repeat the steps of Example 2 5 times, and nano-sized particles can be obtained each time, proving that the reproducibility of obtaining nano-sized particles by using the preparation method of the present invention is good.

[0082] Characterization method:

[0083] Determination of particle size distribution and polydispersity index (PDI): The average particle size and particle size distribution of the prepared PLGA nanoparticles were measured by a nano particle size analyzer using dynamic light scattering technology. As shown in the figure, the particle size distributions of Examples 2-3 treated by pre-shearing and high-pressure homogenization combined show a single-peak normal distribution pattern. The average particle size is much smaller than that of the particles without high-pressure homogenization treatment (Example 1), and the particle size distribution range of the particles without high-pressure homogenization treatment is wide and there are multiple peaks. PDI is a dimensionless number reflecting the uniformity of particle size distribution. The smaller the value of PDI, the more uniform and concentrated the particle size distribution. As Figure 2 shown, the polydispersity coefficients of the particles in Examples 2-3 treated by pre-shearing and high-pressure homogenization combined are all lower than those of the particles without high-pressure homogenization treatment (Example 1), and the polydispersity coefficient of the particles in Example 3 is the smallest and the size is the most uniform.

[0084] Surface morphology: The surface morphology of each example was observed using a scanning electron microscope. As Figure 3 shown, the particle sizes of Examples 2-3 treated by combined pre-shearing and high-pressure homogenization were uniform. Among them, the particles of Example 2 had low monodispersity and the greatest degree of adhesion between particles; the particles of Example 1 without high-pressure homogenization treatment had uneven particle sizes and adhesion on the surface; the particles of Example 3 had the best monodispersity.

[0085] Drug encapsulation efficiency: The encapsulation efficiency is defined as the ratio of the amount of encapsulated drug to the amount of drug used to prepare the nanoparticles. The drug encapsulation efficiency of the particles was determined by ultraviolet spectrophotometry. As Figure 4 shown, the encapsulation efficiencies of Examples 2-3 treated by combined pre-shearing and high-pressure homogenization were lower than those of the particles of Example 1 without high-pressure homogenization treatment. Among them, the particles of Example 2 had the lowest encapsulation efficiency.

[0086] In vitro drug release: The in vitro drug release rate of the particles was determined by the dialysis method. Samples were taken at different time points to measure the absorbance of the dialysis solution and calculate the drug release amount. As Figure 5 shown, Example 1 without high-pressure homogenization treatment and Example 3 treated by combined pre-shearing and high-pressure homogenization could continuously release drugs for 36 h, and the cumulative release reached 88.27%. The cumulative release of the particles of Example 1 without high-pressure homogenization treatment reached 75.33%.

[0087] Cytotoxicity: The cytotoxicity of each example was detected using the CCK8 method. Hepatocytes were co-cultured with the samples of Example 1 and Example 3 for 24 h and 48 h respectively, and the relative viability was calculated. It was found that both Example 3 treated by combined pre-shearing and high-pressure homogenization and Example 1 without high-pressure homogenization treatment had good cytocompatibility effects, and the cell survival rate was close to that of the blank control group, as Figure 6 shown.

[0088] Hemolysis rate determination: Rabbit red blood cells were co-incubated with the samples of Example 1 and Example 3 for 1 hour, and the hemolysis rate was measured to evaluate the blood compatibility of the examples. It was found that both Example 3 treated by combined pre-shearing and high-pressure homogenization and Example 1 without high-pressure homogenization treatment had good blood compatibility effects, and the hemolysis rate was far lower than the clinical standard requirement of 5%, as Figure 7 shown.

[0089] Cell uptake: Hepatocytes were co-cultured with the nanoparticles of Example 4, and the cell uptake was observed using a confocal laser scanning microscope for imaging. It was found that free NR could not enter the cells, and the nanoparticles loaded with Nile red could effectively enter hepatocytes through endocytosis and were well distributed in the cytoplasm, as Figure 8 shown.

[0090] In vivo evaluation: The nanoparticles of Example 3 were studied for in vivo evaluation using DB mice by two routes: oral administration and injection. It was found that both routes could achieve the effect of reducing blood glucose, and the duration of the effective action was 8-10 hours, as Figure 9 shown.

[0091] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and changes. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A preparation method of a PLGA nanoparticle material loaded with metformin hydrochloride, characterized in that, It includes the following steps: Perform first shear emulsification on an aqueous metformin hydrochloride solution and an organic solution containing a first emulsifier and PLGA to obtain a water-in-oil primary emulsion; Perform second shear emulsification on the primary emulsion and an aqueous solution containing a second emulsifier to obtain a water-in-oil-in-water coarse emulsion; Perform homogenization emulsification on the coarse emulsion to obtain a W1 / O / W2 nanoemulsion; Remove the organic solvent from the nanoemulsion, centrifuge and dry it to obtain the product.

2. The preparation method according to claim 1, characterized in that, The volume ratio of the aqueous metformin hydrochloride solution to the organic solution is 1:5 to 50, preferably 1:5 to 15; Alternatively, the solvent of the organic solution is dichloromethane.

3. The preparation method according to claim 1, characterized in that, The mass ratio of metformin hydrochloride to PLGA is 2:5 to 250, preferably 2:5 to 100, more preferably 2:5 to 50, and even more preferably 2:5 to 25; preferably, the concentration of PLGA in the organic solution is 1 to 5%.

4. The preparation method according to claim 1, characterized in that, The mass ratio of PLGA to the first emulsifier is 1:0.8 to 1.2; Alternatively, the rotation speed of the first shear emulsification is 6K to 12K RPM; Alternatively, the first emulsifier is sorbitan oleate or polysorbate.

5. The preparation method according to claim 1, characterized in that, The volume ratio of the primary emulsion to the aqueous solution containing the second emulsifier is 1:5 to 50, preferably 1:5 to 15.

6. The preparation method according to claim 1, characterized in that, The concentration of the second emulsifier in the aqueous solution containing the second emulsifier is 0.1 to 10%, preferably 0.2 to 5%, and preferably 0.5 to 2%.

7. The preparation method according to claim 1, characterized in that, The rotation speed of the second shear emulsification is 6K to 12K RPM; Alternatively, the second emulsifier is sorbitan oleate or polysorbate.

8. The preparation method according to claim 1, characterized in that, The pressure of the homogenization emulsification is 3000 to 10000 psi; Alternatively, the number of cycles of the homogenization emulsification is 1 to 3 times.

9. A PLGA nanoparticle material loaded with metformin hydrochloride, characterized in that, Obtained by the preparation method according to any one of claims 1 to 8.

10. Use of the PLGA nanoparticle material loaded with metformin hydrochloride according to claim 9 in the preparation of a drug.

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