Preparation method and application of curcumin nano preparation

Abstract

The invention discloses a preparation method and application of a curcumin nano preparation. Belongs to the technical field of nano preparations. The preparation method comprises the following steps: compounding curcumin and phenolic acid, preparing a curcumin-phenolic acid compound, mixing the curcumin-phenolic acid compound with n-butyl cyanoacrylate and ethanol, preparing an oil-phase medium, mixing the oil-phase medium with a water-phase system composed of polyvinylpyrrolidone, and carrying out high-speed shearing and high-pressure homogenization to successfully prepare the nano curcumin preparation. The bioavailability of the curcumin is greatly improved, and the curcumin entrapment efficiency and the treatment effect are higher.

Description

Technical Field

[0001] The present invention relates to the technical field of nano preparations, and more particularly to a preparation method and application of a curcumin nano preparation. Background Art

[0002] Curcumin is a natural active ingredient extracted from the rhizomes of Curcuma longa (Zingiber officinale), Curcuma zedoaria (Zhizhu), and Curcuma aromatica (Turmeric). Pharmacological studies have shown that curcumin exhibits multiple pharmacological effects, including anti-inflammatory, anti-cancer, and antioxidant properties, including kidney protection, inhibition of pulmonary and liver fibrosis, muscle repair, cataract treatment, and anti-parasitic effects. Curcumin also exhibits minimal toxicity and side effects, is safe to use, and has promising clinical application prospects. However, curcumin is virtually insoluble in water and has poor solubility in various oils, resulting in poor gastrointestinal absorption and low oral bioavailability. Furthermore, injection is inconvenient, preventing patients from taking the drug on their own, and results in poor compliance, severely impacting its clinical use.

[0003] Currently, the poor solubility of curcumin is a technical bottleneck in its drug development. The main approach to improving the solubility and bioavailability of curcumin is through the preparation of new pharmaceutical dosage forms, such as microemulsions, microspheres, solid dispersions, liposomes, phospholipid complexes, and nanoformulations. Nanoformulations are an advanced drug delivery system that encapsulates drug particles or encapsulates the drug in a specific carrier to produce nanoparticles. Nanoformulations have a small drug particle size, which effectively increases the surface area of ​​the drug and improves its bioavailability. Furthermore, due to the addition of special carriers, they can increase the targeting and stability of the drug, improving its efficacy. Nanoformulations are a commonly used pharmaceutical dosage form in medicine.

[0004] At present, there are also some nano dosage forms of curcumin, such as the patent application number 201911054453.1, entitled "A method for preparing a nano-curcumin composite preparation using an ultra-concentrated emulsion". This patent provides a nano-curcumin composite preparation, but the preparation only improves the drug agglomeration and sustained-release properties of the composite preparation, and does not improve the bioavailability of curcumin after it acts on the human body, nor does it mention any improvement in therapeutic efficacy.

[0005] Therefore, it is a technical problem that those skilled in the art need to solve urgently to provide a curcumin nanoformulation that effectively improves the bioavailability of curcumin and enhances its therapeutic effect. Summary of the Invention

[0006] In view of this, the present invention provides a preparation method and application of a curcumin nanoformulation, which not only improves the bioavailability of curcumin, but also provides a higher encapsulation rate and higher therapeutic effect.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] A method for preparing a curcumin nanoformulation comprises the following steps:

[0009] (1) mixing curcumin and phenolic acid powders, grinding and refining to prepare a curcumin-phenolic acid mixture, and setting aside;

[0010] (2) taking a curcumin-phenolic acid mixture, placing it in an oil phase medium consisting of n-butyl cyanoacrylate and ethanol, and homogenizing at high speed to prepare an oil phase system;

[0011] (3) dissolving polyvinyl pyrrolidone in deionized water and performing magnetic stirring to uniformly disperse the components to prepare an aqueous phase system;

[0012] (4) slowly adding the obtained oil phase system to the water phase system while stirring to prepare a mixed system;

[0013] (5) subjecting the mixed system obtained in step (4) to high-speed shearing, standing for stabilization, and then high-pressure emulsification to obtain a curcumin nanoparticle preparation.

[0014] Preferably, in step (1), the weight ratio of curcumin to phenolic acid is 20-50:1-2; and the curcumin is ground into 2-10 μm.

[0015] Preferably, the weight ratio of n-butyl cyanoacrylate to ethanol in step (2) is 2-3:12-16; and the curcumin-phenolic acid mixture accounts for 12-18% of the total weight of the oil phase system.

[0016] Preferably, the rotation speed of the high-speed homogenizer in step (2) is 5000-15000 r / min; and the homogenization time is 4-6 min.

[0017] Preferably, in step (3), the weight-to-volume ratio of the polyvinyl pyrrolidone to deionized water is 3-4:200-400; the rotation speed of the magnetic stirring is 600-1000 rpm, and the stirring time is 3-5 min.

[0018] Preferably, the weight ratio of the oil phase system to the water phase system in step (4) is 2-3:2-4.

[0019] Preferably, the high-speed shearing time in step (5) is 4-10 min, the rotation speed is 500-1500 rpm, and the temperature during shearing is 20-30° C.; the pressure of the high-pressure emulsification is 1000-1500 bar, and the number of cycles is 2-10 times.

[0020] Another object of the present invention is to provide: a nano-curcumin preparation prepared by the above method.

[0021] Another object of the present invention is to provide: use of the above-mentioned nano-curcumin preparation in the preparation of a drug for protecting the central nervous system.

[0022] Another object of the present invention is to provide: application of the above method in preparing nano-curcumin preparations.

[0023] It can be seen from the above technical solutions that compared with the prior art, the present invention has the following beneficial effects:

[0024] The method of the present invention comprises compounding curcumin and phenolic acid to prepare a curcumin-phenolic acid complex, mixing the complex with n-butyl cyanoacrylate and ethanol to prepare an oil phase medium, and then mixing the complex with an aqueous phase system consisting of polyvinyl pyrrolidone. The mixture is subjected to high-speed shearing and high-pressure homogenization to successfully prepare a nano-curcumin preparation. By optimizing the preparation method and parameters, the bioavailability of curcumin is greatly improved, and the compound has a higher encapsulation rate and better therapeutic effect. DETAILED DESCRIPTION

[0025] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0026] Example 1

[0027] A method for preparing a curcumin nanoformulation comprises the following steps:

[0028] (1) Mix 20 g of curcumin and 1 g of phenolic acid powder, grind to 2 μm, and prepare a curcumin-phenolic acid mixture for later use;

[0029] (2) The curcumin-phenolic acid mixture was placed in an oil phase medium consisting of 22 g of n-butyl cyanoacrylate and 132 g of ethanol, and homogenized at a high speed of 5000 rpm for 6 min to prepare an oil phase system;

[0030] (3) 5.17 g of polyvinyl pyrrolidone was dissolved in 344.83 g of deionized water and stirred magnetically at 600 rpm for 5 min to uniformly disperse the components to prepare an aqueous phase system;

[0031] (4) slowly adding the obtained oil phase system to the water phase system while stirring to prepare a mixed system;

[0032] (5) The mixed system obtained in step (4) was placed under high-speed shearing at 500 rpm and 20-30° C. for 10 min. After being allowed to stand for stabilization, the mixed system was placed under high-pressure emulsification at 1000 bar. The number of cycles was 10 to obtain a curcumin nanoformulation.

[0033] Example 2

[0034] A method for preparing a curcumin nanoformulation comprises the following steps:

[0035] (1) 50 g of curcumin and 2 g of phenolic acid powder were mixed and ground into 10 μm to prepare a curcumin-phenolic acid mixture, which was set aside;

[0036] (2) The curcumin-phenolic acid mixture was placed in an oil phase medium consisting of 37.41 g of n-butyl cyanoacrylate and 199.57 g of ethanol, and homogenized at a high speed of 15,000 rpm for 4 min to prepare an oil phase system;

[0037] (3) 1.90 g of polyvinyl pyrrolidone was dissolved in 190.70 g of deionized water and stirred magnetically for 3 min at a speed of 1000 rpm to uniformly disperse the components to prepare an aqueous phase system;

[0038] (4) slowly adding the obtained oil phase system to the water phase system while stirring to prepare a mixed system;

[0039] (5) The mixed system obtained in step (4) was placed under high-speed shearing at 1500 rpm and 20-30° C. for 4 min. After being allowed to stand for stabilization, it was placed under high-pressure emulsification at 1500 bar. The number of cycles was 2 to obtain a curcumin nanoformulation.

[0040] Example 3

[0041] A method for preparing a curcumin nanoformulation comprises the following steps:

[0042] (1) 35 g of curcumin and 2 g of phenolic acid powder were mixed and ground into 6 μm to prepare a curcumin-phenolic acid mixture, which was set aside;

[0043] (2) The curcumin-phenolic acid mixture was placed in an oil phase medium consisting of 37.05 g of n-butyl cyanoacrylate and 172.90 g of ethanol, and homogenized at a high speed of 10,000 rpm for 5 min to prepare an oil phase system;

[0044] (3) 3.25 g of polyvinyl pyrrolidone was dissolved in 243.75 g of deionized water and stirred magnetically at 800 rpm for 4 min to uniformly disperse the components to prepare an aqueous phase system;

[0045] (4) slowly adding the obtained oil phase system to the water phase system while stirring to prepare a mixed system;

[0046] (5) The mixed system obtained in step (4) was placed under high-speed shearing at 1000 rpm and 20-30° C. for 6 min. After being allowed to stand for stabilization, it was placed under high-pressure emulsification at 1250 bar. The number of cycles was 7 to obtain a curcumin nanoformulation.

[0047] Comparative Example 1

[0048] A method for preparing a curcumin nanoformulation comprises the following steps:

[0049] (1) Grind 35 g of curcumin to 6 μm to obtain curcumin powder, which is then set aside.

[0050] (2) Curcumin powder was placed in an oil phase medium consisting of 37.05 g of n-butyl cyanoacrylate and 172.90 g of ethanol, and homogenized at a high speed of 10,000 rpm for 5 min to prepare an oil phase system;

[0051] (3) 3.25 g of polyvinyl pyrrolidone was dissolved in 243.75 g of deionized water and stirred magnetically at 800 rpm for 4 min to uniformly disperse the components to prepare an aqueous phase system;

[0052] (4) slowly adding the obtained oil phase system to the water phase system while stirring to prepare a mixed system;

[0053] (5) The mixed system obtained in step (4) was placed under high-speed shearing at 1000 rpm and 20-30° C. for 6 min. After being allowed to stand for stabilization, it was placed under high-pressure emulsification at 1250 bar. The number of cycles was 7 to obtain a curcumin nanoformulation.

[0054] Bioavailability experiments

[0055] In order to compare the oral bioavailability of the curcumin nanoformulations prepared in Examples 1-3 and Comparative Example 1, an oral administration experiment was conducted on mice, which were divided into five groups: a nanocurcumin preparation group prepared in Examples 1-3; a nanocurcumin preparation group prepared in Comparative Example 1; and a curcumin suspension group. The specific experimental process is as follows:

[0056] Fifty healthy rats were fasted for 24 hours and randomly divided into five groups. The five groups of drugs were administered orally at a dose of 200 mg / kg. Approximately 0.3 mL of blood was collected from the orbits at 5, 10, 30, 60, 120, 240, 300, 360, 480, 600, and 720 minutes after administration. The blood was placed in a heparin-coated centrifuge tube for processing, and the blood concentration (Cmax) and the area under the concentration-time curve (AUC(0-∞)) of the drug were calculated. The experimental results are shown in Table 1:

[0057] Table 1 Blood drug concentration and area under the concentration-time curve in different groups

[0058]

[0059]

[0060] Result analysis: By comparison, it can be seen that compared with the curcumin mixed group and the comparative example 1 group, the compounding of curcumin and phenolic acid in the present invention can significantly increase the maximum blood drug concentration in rats, and also increase the area under the drug-time curve, thereby effectively improving the oral bioavailability of curcumin.

[0061] Encapsulation efficiency experiment

[0062] The encapsulation efficiency of Examples 1-3 and Comparative Example 1 was statistically analyzed, and the experimental data are shown in Table 2. The encapsulation efficiency is calculated as follows:

[0063]

[0064] C f : is the amount of free drug;

[0065] C t : is the total amount of drug in the nanoparticle or liposome suspension

[0066] Table 2 Encapsulation efficiency of curcumin in different groups

[0067] Group Example 1 group Example 2 group Example 3 group Comparative Example 1 Encapsulation efficiency 96.4％ 96.7％ 97.5％ 52.8％

[0068] Analysis of the results: As can be seen from Table 2, the encapsulation efficiency of Examples 1-3 is at a relatively high level, significantly higher than that of Comparative Example 1, indicating that the present invention adopts a compound of curcumin and phenolic acid, and due to the interaction between curcumin and phenolic acid, the free amount of curcumin is reduced, thereby significantly improving the encapsulation efficiency.

[0069] Neuroprotective effect test

[0070] In order to explore the neuroprotective effect of the curcumin nanoformulations prepared in Examples 1-3 and Comparative Example 1, rats were used as experimental animals to construct a rat model of cerebral ischemia-reperfusion. The rats were divided into the following groups: a sham operation group, a group orally administered with the nanocurcumin preparations of Examples 1, 2, 3 or Comparative Example 1, and a group orally administered with a curcumin suspension. The dosage was 100 mg / kg in terms of curcumin. The ischemia-reperfusion model was established 0.5 hours after administration. The rats were killed 48 hours later, and brain sections were prepared and stained for observation. The specific results are shown in Table 3:

[0071] Table 3 Neuroprotective effects of different groups on rats

[0072]

[0073] Results analysis: As shown in Table 3, no white ischemic area appeared in the sham-operated group, while large white ischemic areas appeared in the oral curcumin suspension group. The white ischemic area in the comparative example 1 group was reduced to a certain extent compared with the curcumin suspension group, and the white ischemic area in the examples 1-3 groups was further reduced compared with the comparative example 1 group. At the same time, by comparing the infarct area, it can be seen that the examples 1-3 groups were able to significantly reduce the volume of tissue damaged by cerebral ischemia, effectively protecting the central nervous system.

[0074] The various embodiments in this specification are described in a progressive manner, and each embodiment focuses on the differences from other embodiments. The same or similar parts between the various embodiments can be referenced to each other.

[0075] The above description of the disclosed embodiments is intended to enable one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be readily apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention is not limited to the embodiments shown herein but is intended to conform to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A method for preparing a curcumin nanoformulation, characterized in that: The steps include: (1) mixing curcumin and phenolic acid powders, grinding and refining to prepare a curcumin-phenolic acid mixture, and setting aside; (2) taking a curcumin-phenolic acid mixture, placing it in an oil phase medium consisting of n-butyl cyanoacrylate and ethanol, and homogenizing at high speed to prepare an oil phase system; (3) dissolving polyvinyl pyrrolidone in deionized water and performing magnetic stirring to uniformly disperse the components to prepare an aqueous phase system; (4) slowly adding the obtained oil phase system to the water phase system while stirring to prepare a mixed system; (5) subjecting the mixed system obtained in step (4) to high-speed shearing, standing for stabilization, and then high-pressure emulsification to obtain a curcumin nanoparticle preparation.

2. The method for preparing a curcumin nanoparticle preparation according to claim 1, wherein In step (1), the weight ratio of curcumin to phenolic acid is 20-50:1-2; and the curcumin is ground into 2-10 μm.

3. The method for preparing a curcumin nanoparticle preparation according to claim 1, wherein In step (2), the weight ratio of n-butyl cyanoacrylate to ethanol is 2-3:12-16; and the curcumin-phenolic acid mixture accounts for 12-18% of the total weight of the oil phase system.

4. The method for preparing the curcumin nanoformulation according to claim 1, wherein The rotation speed of the high-speed homogenizer in step (2) is 5000-15000 r / min; the homogenization time is 4-6 min.

5. The method for preparing the curcumin nanoformulation according to claim 1, wherein In step (3), the weight ratio of polyvinyl pyrrolidone to deionized water is 3-4:200-400; the rotation speed of the magnetic stirring is 600-1000 rpm, and the stirring time is 3-5 min.

6. The method for preparing the curcumin nanoformulation according to claim 1, wherein The weight ratio of the oil phase system to the water phase system in step (4) is 2-3:2-4.

7. The method for preparing the curcumin nanoformulation according to claim 1, wherein The high-speed shearing time in step (5) is 4-10 min, the rotation speed is 500-1500 rpm, and the temperature during shearing is 20-30° C.; the pressure of the high-pressure emulsification is 1000-1500 bar, and the number of cycles is 2-10 times.

8. The nano-curcumin preparation prepared by the method according to any one of claims 1 to 7.

9. Use of the nano-curcumin preparation according to claim 8 in preparing a drug for protecting the central nervous system.

10. Use of any one of the methods of claims 1-7 in preparing a nano-curcumin preparation.

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