Curcumin preparation and preparation method thereof

Abstract

The invention provides a curcumin preparation and a preparation method thereof. The preparation method comprises the following steps: stirring and mixing whey protein and water; adding a NaOH solution into the system, and stirring and mixing; adding zein into the system, and continuously stirring; adding curcumin, propylene sulfide and soya bean lecithin into the system, stirring and mixing, and adjusting the pH value to 6.5; adding mannitol into the system, stirring until the mannitol is dissolved, and then performing vacuum freeze drying to obtain a dry sample; and mixing with auxiliary materials to obtain the curcumin preparation. The powdery curcumin preparation is prepared through a protein encapsulation method, soybean lecithin is added in the protein encapsulation process, the encapsulation efficiency can reach 92.35%, the particle size of effective components is smaller than 100 nm, particle size distribution is concentrated, the water solubility of curcumin is improved, and the bioavailability of curcumin is improved; a small amount of propylene sulfide is added in the curcumin encapsulation process, and it is found that due to addition of propylene sulfide, curcumin and propylene sulfide generate a synergistic effect, and the anti-inflammatory effect of the preparation is promoted.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical technologies, and more particularly, relates to a curcumin preparation and a method for preparing the same. Background Art

[0002] Curcumin, also known as turmeric yellow and acid yellow, is a natural phenolic antioxidant extracted from the rhizomes of Zingiberaceae plants such as turmeric, zedoary, mustard, curry, and turmeric. Its main chain consists of unsaturated aliphatic and aromatic groups. It is a pigment with diketone that is rare in the plant kingdom and belongs to diketone compounds. It is a commonly used condiment and food coloring, non-toxic, and has various pharmacological effects such as cholagogic, anti-infective, causing uterine paroxysmal contractions, reducing blood cholesterol, antiviral, antibacterial, antioxidant (with stronger antioxidant effect than α-tocopherol), anticoagulant, lipid-lowering, and anti-atherosclerotic effects, and is widely used in industries such as medicine, textile dyeing, and feed.

[0003] Drug solubility is one of the important factors affecting drug bioavailability. Poorly soluble drugs have low solubility or even insoluble in water, resulting in low bioavailability and poor drug efficacy. Curcumin belongs to poorly soluble plant compounds, which are insoluble in water and ether and soluble in ethanol and glacial acetic acid. Due to problems such as poor water solubility of curcumin, large particle size, easy oxidation in vitro, easy degradation under light, rapid metabolism in the body by the intestine and liver, and low oral bioavailability, its clinical application has been greatly limited. Therefore, it is necessary to further study how to improve the solubility and bioavailability of curcumin.

[0004] It should be noted that the information disclosed in the above background art section is only used to enhance the understanding of the background of the present disclosure. Summary of the Invention

[0005] In order to overcome the disadvantages and deficiencies of the prior art, the purpose of the present invention is to provide a curcumin preparation and a method for preparing the same.

[0006] The purpose of the present invention is achieved by the following technical solutions:

[0007] A method for preparing a curcumin preparation, the method comprising the following steps:

[0008] (1) Adding whey protein to water and stirring to mix;

[0009] (2) Adding an NaOH solution to the system after step (1) and stirring to mix;

[0010] (3) Adding zein to the system after step (2) and continuing to stir;

[0011] (4) Adding curcumin, allyl sulfide, and soy lecithin to the system after step (3) and stirring to mix, and then adjusting the pH of the system to 6.5;

[0012] (5) Add mannitol to the system after step (4) and stir until dissolved, then perform vacuum freeze-drying to obtain a dried sample;

[0013] (6) Mix the dried sample obtained in step (5) with pharmaceutically acceptable excipients to obtain a curcumin preparation.

[0014] Preferably, in step (1), the mass ratio of whey protein to water is 1:(20 - 30), and the stirring and mixing time is 20 - 40 min.

[0015] Preferably, in step (2), the concentration of the NaOH solution is 1 M, the addition amount is 5 - 10% of the volume of water used in step (1), and the stirring and mixing time is 5 - 10 min.

[0016] Preferably, in step (3), the addition amount of zein is 10 - 15 wt% of the amount of whey protein used in step (1), and the stirring time is 10 - 20 min.

[0017] Preferably, in step (4), the total addition amount of curcumin, allyl sulfide, and soy lecithin is 10 - 15 wt% of the amount of whey protein used in step (1), the stirring time is 20 - 40 min, and the mass ratio of curcumin, allyl sulfide, and soy lecithin is 20:(0.1 - 0.5):(1 - 2).

[0018] Preferably, in step (4), the concentration of citric acid is 0.5 M.

[0019] Preferably, in step (5), the addition amount of mannitol is 2 - 3 times the amount of whey protein used in step (1).

[0020] Preferably, in step (6), the pharmaceutically acceptable excipients are composed of mannitol, sodium alginate, and glycyrrhizic acid in a mass ratio of 30:(5 - 6):(1 - 2).

[0021] Preferably, in step (6), the amount of the excipients used is 3 times the amount of mannitol used in step (5), and the mixing is carried out at 10 - 15 rpm for 20 - 30 min. After mixing, the curcumin preparation is stored in the dark.

[0022] The curcumin preparation prepared by the above method for preparing a curcumin preparation.

[0023] The present invention has the following advantages and effects compared with the prior art:

[0024] (1) The present invention prepares a powdered curcumin preparation by the protein encapsulation method. During the protein encapsulation process, soy lecithin is added, and the encapsulation rate can be as high as 92.35%. The particle size of the active ingredient is less than 100 nm and the particle size distribution is concentrated, which is beneficial to improving the water solubility of curcumin and thus enhancing its bioavailability.

[0025] (2) During the process of encapsulating curcumin, a small amount of allyl sulfide is added in the present invention. It is found that the addition of allyl sulfide enables curcumin to have a synergistic effect with it, promoting the anti-inflammatory effect of the preparation.

[0026] (3) In the curcumin preparation prepared in the present invention, excipients sodium alginate and glycyrrhizic acid are added. The addition of sodium alginate and glycyrrhizic acid can in-situ form a gel network structure, forming a protective barrier in the gastric juice environment to extend the release time of the active ingredient, protecting curcumin and delivering it to the intestinal juice environment, and rapidly releasing it in the intestinal juice environment, thereby enhancing the bioavailability of curcumin.

[0027] It should be understood that the above general description and the following detailed description are only exemplary and explanatory, and cannot limit the present disclosure. Description of the Drawings

[0028] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0029] Figure 1 It is a photo of the curcumin preparation sample prepared in Example 1 of the present invention.

[0030] Figure 2 It is the water solubility test result of the curcumin preparation prepared in Example 1 of the present invention.

[0031] Figure 3 It is the water solubility test result of the curcumin preparation prepared in Example 1 of the present invention.

[0032] Figure 4 It is the test result of the curcumin release rate of the curcumin preparations prepared in Example 1 and Comparative Examples 1 and 4 of the present invention in a simulated gastrointestinal digestion environment. Detailed Embodiments

[0033] The embodiments of the present invention will be clearly and completely described below in conjunction with the examples. The described examples are only a part of the embodiments of the present invention, rather than all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and in no way limits the present invention and its application or use. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts belong to the scope of protection of the present invention.

[0034] For the reagents or instruments used in the present invention, if the manufacturer is not specified, they are all conventional products that can be obtained through commercial purchase. For the process parameters not specifically mentioned, conventional techniques can be referred to.

[0035] The whey protein used in the specific implementation was purchased from Panier (Shaanxi) Industrial Co., Ltd., the zein was purchased from Sigma-Aldrich (Shanghai) Trading Co., Ltd., the curcumin was purchased from Sigma-Aldrich (Shanghai) Trading Co., Ltd., the allyl sulfide was purchased from Shanghai Macklin Biochemical Co., Ltd., and the soy lecithin was purchased from Shanghai Aladdin Biochemical Technology Co., Ltd.

[0036] The method for testing the encapsulation rate of curcumin in the present invention is as follows: The dried sample obtained by vacuum freeze-drying is ultrasonically assisted to dissolve in 100 mL of 70% ethanol aqueous solution, and the supernatant is collected after centrifugation at 4000 rpm for 10 min; the precipitate is washed 3 times with 70% ethanol aqueous solution, and the supernatant is collected after centrifugation; the encapsulation rate is determined by the ratio of the curcumin content in the supernatant to the total curcumin amount. The content of curcumin in the supernatant is measured at 426 nm using a UV-2600 spectrophotometer.

[0037] Example 1

[0038] This example provides a preparation method of a curcumin preparation, and the method includes the following steps:

[0039] (1) Add 32.4 g of whey protein to 861.6 mL of deionized water and stir and mix for 30 min;

[0040] (2) Add 60 mL of 1 M NaOH aqueous solution to the system after step (1) and stir and mix for 5 min;

[0041] (3) Add 3.6 g of zein to the system after step (2) and continue to stir for 10 min;

[0042] (4) Add 3.6 g of curcumin, 0.036 g of allyl sulfide and 0.2 g of soy lecithin to the system after step (3) and stir and mix for 30 min. Cover and avoid light with aluminum foil during the stirring process, and then adjust the pH of the system to 6.5 with 0.5 M citric acid aqueous solution;

[0043] (5) Add 80 g of mannitol to the system after step (4) and stir until dissolved. Then pour the liquid into the sample tray of the freeze dryer and perform vacuum freeze drying under light protection with aluminum foil to obtain a dried sample;

[0044] (6) Transfer the dried sample obtained in step (5) to a V-type mixer, add 240 g of mannitol, sodium alginate, and glycyrrhizic acid that have passed through a 100-mesh sieve, and mix at a rotation speed of 15 rpm for 20 min. The mass ratio of mannitol, sodium alginate, and glycyrrhizic acid is 30:5:1.5. Then collect the sample powder to obtain the curcumin preparation and store it in the dark.

[0045] After testing, the curcumin encapsulation rate of the dried sample in this example is 92.35%, the average particle size is 84.63 nm, and PDI = 0.317.

[0046] Figure 1 This is a photo of the curcumin preparation sample prepared in this example. As can be seen from the figure, the preparation is a delicate dark yellow powder.

[0047] Example 2

[0048] This example provides a preparation method of a curcumin preparation, and the method includes the following steps:

[0049] (1) Add 32.4 g of whey protein to 900 mL of deionized water and stir and mix for 30 min;

[0050] (2) Add 60 mL of 1 M NaOH aqueous solution to the system after step (1) and stir and mix for 5 min;

[0051] (3) Add 3.6 g of zein to the system after step (2) and continue to stir for 10 min;

[0052] (4) Add 3.6 g of curcumin, 0.09 g of allyl sulfide, and 0.3 g of soy lecithin to the system after step (3) and stir and mix for 30 min. During the stirring process, cover it with aluminum foil to protect from light, and then adjust the pH of the system to 6.5 with 0.5 M citric acid aqueous solution;

[0053] (5) Add 80 g of mannitol to the system after step (4) and stir until dissolved. Then pour the liquid into the sample tray of the freeze dryer and perform vacuum freeze drying under light protection with aluminum foil to obtain a dried sample;

[0054] (6) Transfer the dried sample obtained in step (5) to a V-type mixer, add 240 g of mannitol, sodium alginate, and glycyrrhizic acid that have passed through a 100-mesh sieve, and mix at a rotation speed of 15 rpm for 20 min. The mass ratio of mannitol, sodium alginate, and glycyrrhizic acid is 30:6:1. Then collect the sample powder to obtain the curcumin preparation and store it in the dark.

[0055] After testing, the curcumin encapsulation efficiency of the dried sample in this example is 91.41%, the average particle size is 85.57 nm, and PDI = 0.344.

[0056] Example 3

[0057] This example provides a preparation method of a curcumin preparation, and the method includes the following steps:

[0058] (1) Add 32.4 g of whey protein to 810 mL of deionized water and stir and mix for 25 min;

[0059] (2) Add 60 mL of 1 M NaOH aqueous solution to the system after step (1) and stir and mix for 8 min;

[0060] (3) Add 4 g of zein to the system after step (2) and continue to stir for 15 min;

[0061] (4) Add 3.8 g of curcumin, 0.057 g of allyl sulfide, and 0.3 g of soybean lecithin to the system after step (3) and stir and mix for 40 min. During the stirring process, cover it with aluminum foil to avoid light, and then adjust the pH of the system to 6.5 with 0.5 M citric acid aqueous solution;

[0062] (5) Add 85 g of mannitol to the system after step (4) and stir until dissolved, then pour the liquid into the sample tray of the freeze dryer and perform vacuum freeze drying with aluminum foil to avoid light to obtain a dried sample;

[0063] (6) Transfer the dried sample obtained in step (5) to a V-type mixer, add 255 g of mannitol, sodium alginate, and glycyrrhizic acid that have passed through a 100-mesh sieve, and mix at a rotation speed of 10 rpm for 30 min. The mass ratio of mannitol, sodium alginate, and glycyrrhizic acid is 30:5:2, and then collect the sample powder to obtain a curcumin preparation and store it in the dark.

[0064] After testing, the curcumin encapsulation efficiency of the dried sample in this example is 91.03%, the average particle size is 85.65 nm, and PDI = 0.323.

[0065] Example 4

[0066] This example provides a preparation method of a curcumin preparation, and the method includes the following steps:

[0067] (1) Add 32.4 g of whey protein to 800 mL of deionized water and stir and mix for 25 min;

[0068] (2) Add 60 mL of 1 M NaOH aqueous solution to the system after step (1) and stir and mix for 8 min;

[0069] (3) Add 4 g of zein to the system after step (2) and continue stirring for 15 min;

[0070] (4) Add 3.8 g of curcumin, 0.04 g of allyl sulfide, and 0.35 g of soy lecithin to the system after step (3), stir and mix for 40 min. Cover the system with aluminum foil to avoid light during the stirring process, and then adjust the pH of the system to 6.5 with 0.5 M citric acid aqueous solution;

[0071] (5) Add 85 g of mannitol to the system after step (4) and stir until dissolved. Then pour the liquid into the sample tray of the freeze dryer and perform vacuum freeze drying under aluminum foil light shielding to obtain a dry sample;

[0072] (6) Transfer the dry sample obtained in step (5) to a V-type mixer, add 255 g of mannitol, sodium alginate, and glycyrrhizic acid that have passed through a 100-mesh sieve, and mix at a rotation speed of 10 rpm for 30 min. The mass ratio of mannitol, sodium alginate, and glycyrrhizic acid is 30:6:2. Then collect the sample powder to obtain a curcumin preparation and store it in the dark.

[0073] After testing, the curcumin encapsulation rate of the dry sample in this example is 90.78%, the average particle size is 85.87 nm, and PDI = 0.331.

[0074] Example 5

[0075] This example provides a method for preparing a curcumin preparation, and the method includes the following steps:

[0076] (1) Add 36 g of whey protein to 860 mL of deionized water and stir and mix for 30 min;

[0077] (2) Add 60 mL of 1 M NaOH aqueous solution to the system after step (1) and stir and mix for 5 min;

[0078] (3) Add 3.6 g of zein to the system after step (2) and continue stirring for 10 min;

[0079] (4) Add 3.6 g of curcumin, 0.07 g of allyl sulfide, and 0.3 g of soy lecithin to the system after step (3), stir and mix for 30 min. Cover the system with aluminum foil to avoid light during the stirring process, and then adjust the pH of the system to 6.5 with 0.5 M citric acid aqueous solution;

[0080] (5) Add 80 g of mannitol to the system after step (4) and stir until dissolved. Then pour the liquid into the sample tray of the freeze dryer and perform vacuum freeze drying under aluminum foil light shielding to obtain a dry sample;

[0081] (6) Transfer the dried sample obtained in step (5) to a V-type mixer, add 240 g of mannitol, sodium alginate, and glycyrrhizic acid that have passed through a 100-mesh sieve, and mix at a rotation speed of 15 rpm for 20 min. The mass ratio of mannitol, sodium alginate, and glycyrrhizic acid is 30:6:1.5. Then collect the sample powder to obtain the curcumin preparation and store it in the dark.

[0082] After testing, the curcumin encapsulation rate of the dried sample in this example is 91.72%, the average particle size is 88.49 nm, and PDI = 0.355.

[0083] Comparative Example 1

[0084] This comparative example provides a method for preparing a curcumin preparation, and the method includes the following steps:

[0085] (1) After mixing 861.6 mL of deionized water and 60 mL of 1M NaOH aqueous solution, add 3.6 g of curcumin, 0.036 g of allyl isothiocyanate, and 0.2 g of soy lecithin, and stir and mix for 30 min. During the stirring process, cover it with aluminum foil to avoid light, and then adjust the pH of the system to 6.5 with 0.5M citric acid aqueous solution;

[0086] (2) Add 80 g of mannitol to the system after step (1) and stir until dissolved. Then pour the liquid into the sample tray of the freeze dryer and perform vacuum freeze drying in the dark with aluminum foil to obtain a dried sample;

[0087] (3) Transfer the dried sample obtained in step (2) to a V-type mixer, add 240 g of mannitol, sodium alginate, and glycyrrhizic acid that have passed through a 100-mesh sieve, and mix at a rotation speed of 15 rpm for 20 min. The mass ratio of mannitol, sodium alginate, and glycyrrhizic acid is 30:5:1.5. Then collect the sample powder to obtain the curcumin preparation and store it in the dark.

[0088] That is, compared with Example 1, this comparative example is different in that curcumin is not encapsulated with protein.

[0089] After testing, the average particle size of the dried sample in this comparative example is 202.06 nm, and PDI = 0.683.

[0090] Comparative Example 2

[0091] This comparative example provides a method for preparing a curcumin preparation, and the method includes the following steps:

[0092] (1) Add 32.4 g of whey protein to 861.6 mL of deionized water and stir and mix for 30 min;

[0093] (2) Add 60 mL of 1M NaOH aqueous solution to the system after step (1) and stir and mix for 5 min;

[0094] (3) Add 3.6 g of zein to the system after step (2) and continue stirring for 10 min;

[0095] (4) Add 3.6 g of curcumin and 0.036 g of allyl sulfide to the system after step (3), stir and mix for 30 min. Cover the system with aluminum foil to avoid light during stirring, and then adjust the pH of the system to 6.5 with 0.5 M aqueous citric acid solution;

[0096] (5) Add 80 g of mannitol to the system after step (4) and stir until dissolved. Then pour the liquid into the sample tray of the freeze dryer, and perform vacuum freeze drying under aluminum foil light shielding to obtain a dried sample;

[0097] (6) Transfer the dried sample obtained in step (5) to a V-type mixer, add 240 g of mannitol, sodium alginate and glycyrrhizic acid that have passed through a 100-mesh sieve, and mix at a rotation speed of 15 rpm for 20 min. The mass ratio of mannitol, sodium alginate and glycyrrhizic acid is 30:5:1.5. Then collect the sample powder to obtain a curcumin preparation and store it in the dark.

[0098] After testing, the curcumin encapsulation rate of the dried sample in this comparative example is 91.1%, the average particle size is 89.56 nm, and PDI = 0.362.

[0099] That is, compared with Example 1, this comparative example is different in that soy lecithin is not added during the preparation process.

[0100] Comparative Example 3

[0101] This comparative example provides a method for preparing a curcumin preparation, and the method includes the following steps:

[0102] (1) Add 32.4 g of whey protein to 861.6 mL of deionized water and stir and mix for 30 min;

[0103] (2) Add 60 mL of 1 M aqueous NaOH solution to the system after step (1) and stir and mix for 5 min;

[0104] (3) Add 3.6 g of zein to the system after step (2) and continue stirring for 10 min;

[0105] (4) Add 3.6 g of curcumin and 0.2 g of soy lecithin to the system after step (3), stir and mix for 30 min. Cover the system with aluminum foil to avoid light during stirring, and then adjust the pH of the system to 6.5 with 0.5 M aqueous citric acid solution;

[0106] (5) Add 80 g of mannitol to the system after step (4) and stir until dissolved. Then pour the liquid into the sample tray of the freeze dryer, and perform vacuum freeze drying under aluminum foil light shielding to obtain a dried sample;

[0107] (6) Transfer the dried sample obtained in step (5) to a V-type mixer, add 240 g of mannitol, sodium alginate, and glycyrrhizic acid that have passed through a 100-mesh sieve, and mix at a rotation speed of 15 rpm for 20 min. The mass ratio of mannitol, sodium alginate, and glycyrrhizic acid is 30:5:1.5. Then collect the sample powder to obtain the curcumin preparation and store it in the dark.

[0108] After testing, the curcumin encapsulation rate of the dried sample in this comparative example is 92.32%, the average particle size is 84.70 nm, and PDI = 0.320.

[0109] That is, compared with Example 1, the difference in this comparative example is that allyl sulfide is not added during the preparation process.

[0110] Comparative Example 4

[0111] This comparative example provides a method for preparing a curcumin preparation, and the method includes the following steps:

[0112] (1) Add 32.4 g of whey protein to 861.6 mL of deionized water and stir and mix for 30 min;

[0113] (2) Add 60 mL of 1 M NaOH aqueous solution to the system after step (1) and stir and mix for 5 min;

[0114] (3) Add 3.6 g of zein to the system after step (2) and continue to stir for 10 min;

[0115] (4) Add 3.6 g of curcumin, 0.036 g of allyl sulfide, and 0.2 g of soy lecithin to the system after step (3) and stir and mix for 30 min. During the stirring process, cover it with aluminum foil to avoid light, and then adjust the pH of the system to 6.5 with 0.5 M citric acid aqueous solution;

[0116] (5) Add 80 g of mannitol to the system after step (4) and stir until dissolved. Then pour the liquid into the sample tray of the freeze dryer and perform vacuum freeze drying with aluminum foil to avoid light to obtain a dried sample;

[0117] (6) Transfer the dried sample obtained in step (5) to a V-type mixer, add 240 g of mannitol that has passed through a 100-mesh sieve, and mix at a rotation speed of 15 rpm for 20 min. Then collect the sample powder to obtain the curcumin preparation and store it in the dark.

[0118] After testing, the curcumin encapsulation rate of the dried sample in this comparative example is 92.35%, the average particle size is 84.63 nm, and PDI = 0.317.

[0119] That is, compared with Example 1, the difference in this comparative example is that the excipients do not contain sodium alginate and glycyrrhizic acid.

[0120] Comparative Example 5

[0121] This comparative example provides a method for preparing a propylene sulfide preparation, and the method comprises the following steps:

[0122] (1) Add 32.4 g of whey protein to 861.6 mL of deionized water and stir and mix for 30 min;

[0123] (2) Add 60 mL of 1 M NaOH aqueous solution to the system after step (1) and stir and mix for 5 min;

[0124] (3) Add 3.6 g of zein to the system after step (2) and continue to stir for 10 min;

[0125] (4) Add 3.636 g of propylene sulfide and 0.2 g of soybean lecithin to the system after step (3) and stir and mix for 30 min. Cover and avoid light with aluminum foil during the stirring process, and then adjust the pH of the system to 6.5 with 0.5 M citric acid aqueous solution;

[0126] (5) Add 80 g of mannitol to the system after step (4) and stir until dissolved, then pour the liquid into the sample tray of a freeze dryer, and perform vacuum freeze drying with aluminum foil to avoid light to obtain a dried sample;

[0127] (6) Transfer the dried sample obtained in step (5) to a V-type mixer, add 240 g of mannitol, sodium alginate and glycyrrhizic acid that have passed through a 100-mesh sieve, and mix at a rotation speed of 15 rpm for 20 min. The mass ratio of mannitol, sodium alginate and glycyrrhizic acid is 30:5:1.5, and then collect the sample powder to obtain a propylene sulfide preparation and store it in the dark.

[0128] That is, compared with Example 1, this comparative example is different in that curcumin is replaced with an equal amount of propylene sulfide during the preparation process.

[0129] Product testing

[0130] In order to further prove the beneficial effects of the present invention, the preparations prepared in the above examples and comparative examples were tested as follows:

[0131] 1. Solubility test

[0132] According to the solubility test method of the Chinese Pharmacopoeia, 0.1 g of the curcumin preparations prepared in Examples 1-5 and Comparative Examples 1-4 were weighed separately and added to 3 mL of distilled water at 25 ± 2 °C. The mixture was shaken for 30 seconds every 5 minutes, and the dissolution was observed within 0.5 hours. If there were no visually visible particles, it was considered completely dissolved. The results showed that except for the solution corresponding to the curcumin preparation prepared in Comparative Example 1 having visually visible particles, the solutions corresponding to the curcumin preparations prepared in Examples 1-5 and Comparative Examples 2-4 had no visually visible particles and were considered completely dissolved. Figure 2 and Figure 3 Figure Figure 2 shows the dissolution of the curcumin preparation prepared in Example 1 in water. It can be seen from the figure that the solution is clear and transparent without visually visible particles.

[0133] The results indicated that the solubility of the curcumin preparations prepared in Examples 1-5 and Comparative Examples 2-4 in water was not less than 33 mg / mL. However, in Comparative Example 1, since curcumin was not encapsulated with protein, the water solubility of curcumin could not be effectively improved.

[0134] The solubility of the curcumin preparations prepared in Examples 1-5 and Comparative Examples 2-4 in water was tested with reference to the determination method of "Test for Water Solubility of Chemicals (GB / T 21845-2008)", and converted into the solubility of curcumin. The test results were: 355.89 μg / mL (Example 1), 339.41 μg / mL (Example 2), 331.78 μg / mL (Example 3), 323.62 μg / mL (Example 4), 346.57 μg / mL (Example 5), 307.23 μg / mL (Comparative Example 2), 352.23 μg / mL (Comparative Example 3), 350.50 μg / mL (Comparative Example 4).

[0135] The results showed that: the curcumin preparations prepared in the examples significantly improved the water solubility of curcumin. In Comparative Example 2, soy lecithin was not added during the protein encapsulation process, and the water solubility of curcumin in the obtained preparation was significantly lower than that in Example 1. The possible reason is that after soy lecithin forms a complex with protein, it can increase the exposure of protein hydrophobic sites, making the particle size smaller and the distribution more uniform, thus helping to improve the solubility of curcumin.

[0136] 2. Anti-inflammatory effect in vitro

[0137] The RAW264.7 cell model was used to test the anti-inflammatory effect in vitro of the curcumin preparation and the allyl sulfide preparation: RAW264.7 cells were seeded in a 12-well plate (1×10 6(Cells / well), incubated at 37 °C in a CO₂ incubator for 12 h to adhere. Lipopolysaccharide LPS (5 μg / mL) was added to stimulate the inflammatory response of RAW264.7 cells. After 6 h, 50 μL of blank MRS medium and an aqueous solution of curcumin preparation (0.5 mg / mL) were added respectively, and incubated at 37 °C in a CO₂ incubator for 24 h. The level of inflammatory factor IL-6 in the cell supernatant was detected using a mouse IL-6 (Beyotime, PI326) ELISA kit. The ELISA analysis results were as follows: the IL-6 level in the blank MRS medium control group was 46.8 ng / mL, in Example 1 it was 4.9 ng / mL, in Example 2 it was 5.3 ng / mL, in Example 3 it was 5.1 ng / mL, in Example 4 it was 5.7 ng / mL, in Example 5 it was 5.5 ng / mL, in Comparative Example 2 it was 5.4 ng / mL, in Comparative Example 3 it was 8.0 ng / mL, in Comparative Example 4 it was 6.3 ng / mL, and in Comparative Example 5 it was 16.2 ng / mL.

[0138] It can be seen from the in vitro anti-inflammatory effect test results that the curcumin preparation of the present invention can significantly inhibit the secretion of pro-inflammatory cytokine IL-6. The anti-inflammatory effect of Comparative Example 2 decreased compared with that of Example 1. The reason is that the solubility of curcumin in the preparation of the curcumin preparation in Comparative Example 2 decreased significantly due to the absence of soy lecithin added during the preparation process, resulting in a decrease in the anti-inflammatory effect. The anti-inflammatory effect of Comparative Example 3 decreased significantly compared with that of Example 1. The possible reason is that the addition of allyl sulfide makes curcumin produce a synergistic effect with it, promoting the anti-inflammatory effect of the preparation. The anti-inflammatory effect of Comparative Example 4 also decreased compared with that of Example 1. The reason is that the addition of sodium alginate and glycyrrhizic acid can in-situ form a gel network structure, prolonging the release time of the active ingredient, thus promoting the anti-inflammatory effect of the preparation. The anti-inflammatory effect of Comparative Example 5 decreased significantly compared with that of Example 1, indicating that although allyl sulfide alone also has anti-inflammatory effects, when allyl sulfide is used in combination with curcumin, the anti-inflammatory effect is significantly improved. The possible reason is that the combination of allyl sulfide and curcumin can produce a synergistic effect.

[0139] 3. Simulate gastrointestinal digestion

[0140] In a conical flask with a cork, 0.1 g of curcumin preparation was mixed with 100 mL of simulated gastric fluid (SGF: NaCl 2.0 mg / mL, pepsin 3.2 mg / mL, pH = 1.2), and then the mixture was placed in a temperature-controlled shaking water bath (37.0 °C, 100 rpm, 120 min). The release rate of curcumin was measured every 30 min, and the test results are as Figure 4 shown.

[0141] In a conical flask with a cork, 0.1 g of the curcumin preparation was mixed with 100 mL of simulated intestinal fluid (SIF: bile salts 12.0 mg / mL, pancreatin 2.0 mg / mL, NaCl 8.8 mg / mL, KH2PO4 6.8 mg / mL, pH = 7.6). Then the mixture was placed in a temperature-controlled shaking water bath (37.0 °C, 100 rpm, 120 min), and the release rate of curcumin was measured every 30 min. The test results are as Figure 4 shown.

[0142] From the test results, it can be seen that compared with Example 1, the curcumin preparation of Comparative Example 1 was rapidly released in the gastric juice environment because it was not protein-encapsulated, which would make it difficult to deliver curcumin to the next-stage intestinal fluid environment, thus unable to effectively improve the bioavailability of curcumin. Compared with Example 1, the curcumin preparation of Comparative Example 4 did not contain sodium alginate and glycyrrhizic acid in the excipients, so it could not form a gelation network structure in situ by sodium alginate and glycyrrhizic acid, and could not form a protective barrier in the gastric juice environment to extend the release time of the active ingredient. The curcumin preparation prepared by the present invention can effectively inhibit the release of curcumin in the gastric environment, protect curcumin and deliver it to the next stage; in the intestinal fluid stage, curcumin can be rapidly released to play a role, improving the bioavailability of curcumin.

[0143] Based on the above test results, it can be seen that the present invention prepares a powdery curcumin preparation by the protein encapsulation method. During the protein encapsulation process, soybean lecithin is added, and the encapsulation rate can be as high as 92.35%. The particle size of the active ingredient is less than 100 nm and the particle size distribution is concentrated, which is beneficial to improving the water solubility of curcumin and thus its bioavailability. A small amount of allyl sulfide was added during the encapsulation of curcumin in the present invention, and it was found that the addition of allyl sulfide made curcumin produce a synergistic effect with it to promote the anti-inflammatory effect of the preparation. Sodium alginate and glycyrrhizic acid were added to the prepared curcumin preparation of the present invention. The addition of sodium alginate and glycyrrhizic acid can form a gelation network structure in situ, form a protective barrier in the gastric juice environment to extend the release time of the active ingredient, protect curcumin and deliver it to the intestinal fluid environment, and be rapidly released in the intestinal fluid environment, thereby improving the bioavailability of curcumin.

[0144] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited by the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. A method for preparing a curcumin preparation, characterized in that, The method comprises the following steps: (1) adding whey protein into water and stirring to mix; (2) adding NaOH solution to the system after step (1) and stirring to mix; (3) adding zein to the system after step (2) and continuing to stir; (4) adding curcumin, propylene sulfide and soybean lecithin to the system after step (3), stirring and mixing, and then adjusting the pH of the system to 6.5; (5) adding mannitol to the system after step (4), stirring until dissolved, and then performing vacuum freeze drying to obtain a dry sample; (6) mixing the dried sample obtained in step (5) with a pharmaceutically acceptable excipient to obtain a curcumin preparation.

2. The method for preparing the curcumin preparation according to claim 1, wherein In step (1), the mass ratio of whey protein to water is 1:(20-30), and the stirring and mixing time is 20-40 minutes.

3. The method for preparing the curcumin preparation according to claim 1, characterized in that: The concentration of the NaOH solution in step (2) is 1 M, the amount added is 5-10% of the volume of water used in step (1), and the stirring and mixing time is 5-10 minutes.

4. The method for preparing the curcumin preparation according to claim 1, wherein The amount of zein added in step (3) is 10-15wt% of the amount of whey protein used in step (1), and the stirring time is 10-20min.

5. The method for preparing the curcumin preparation according to claim 1, characterized in that: The total amount of curcumin, propylene sulfide and soy lecithin added in step (4) is 10-15wt% of the amount of whey protein used in step (1), and the stirring time is 20-40min, wherein the mass ratio of curcumin, propylene sulfide and soy lecithin is 20:(0.1-0.5):(1-2).

6. The method for preparing the curcumin preparation according to claim 1, characterized in that: The concentration of citric acid in step (4) is 0.5 M.

7. The method for preparing the curcumin preparation according to claim 1, characterized in that: The amount of mannitol added in step (5) is 2-3 times the amount of whey protein in step (1).

8. The method for preparing the curcumin preparation according to claim 1, characterized in that: The pharmaceutically acceptable excipients in step (6) are mannitol, sodium alginate and glycyrrhizic acid in a mass ratio of 30:(5-6):(1-2).

9. The method for preparing the curcumin preparation according to claim 1, characterized in that: The amount of the auxiliary material in step (6) is 3 times the amount of mannitol in step (5), and the mixing is performed at 10-15 rpm for 20-30 min. After the mixing is completed, the curcumin preparation is stored in the dark.

10. The curcumin preparation prepared by the method for preparing the curcumin preparation according to any one of claims 1 to 9.

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