A method for preparing curcumin-ar-tumerone nanocrystals, a preparation and applications thereof

Abstract

The application discloses a method for preparing curcumin-ar-tumerone nanocrystals, a preparation and application, wherein curcumin powder is added into a 1-2% fenugreek gum solution under stirring, so that the final concentration of the curcumin is 1-2%, then ar-tumerone and an emulsifier are added, so that the final mass concentration of the ar-tumerone is 1-2%, and the final mass concentration of the emulsifier is 0.1-0.5%, and the curcumin-ar-tumerone crystal mixture liquid is obtained after mixing; the curcumin-ar-tumerone crystal mixture liquid is subjected to high-speed shearing and high-pressure homogenization, so that the curcumin-ar-tumerone nanocrystal liquid is prepared, and then drying is carried out, so that the curcumin-ar-tumerone nanocrystal preparation is obtained. The curcumin-ar-tumerone nanocrystal preparation is prepared by using food-grade polysaccharide fenugreek gum as a stabilizer, the dispersibility and bioavailability of curcumin and ar-tumerone are improved under the premise of retaining the bioactivity of the curcumin and ar-tumerone, and the product is food-grade, so that the curcumin-ar-tumerone nanocrystal preparation can be used for preparing a nutrition preparation for supplementing curcumin.

Description

Technical Field

[0001] This invention relates to a method, formulation, and application for preparing curcumin-aromatic curcumin nanocrystals. Background Technology

[0002] Curcumin and aromatic curcuminone are both active ingredients derived from the traditional Chinese medicine turmeric, with molecular formulas C10 and C20, respectively. 21 H 20 O6 and C 15 H 22 Curcumin and aromatic curcumin possess various activities, including anti-inflammatory, anti-tumor, antioxidant, and hepatoprotective effects. However, the solubility of curcumin and aromatic curcumin in water is less than 0.01%, meaning they are almost entirely unabsorbed and unutilized by the human body after oral administration. This is a significant factor hindering their use as nutritional supplements. In recent years, numerous studies have focused on preparing curcumin and aromatic curcumin into amorphous states to increase their solubility and bioavailability. However, the production process requires the use of large amounts of organic reagents to dissolve curcumin and aromatic curcumin, posing a risk of fire and explosion. Furthermore, residual organic solvents may pose hazards to production personnel and consumers.

[0003] Nanocrystals are a novel drug delivery method that has emerged in recent years, significantly increasing the efficiency of human absorption. The principle involves mechanically breaking down water-insoluble drugs into nanoscale crystals, allowing intestinal cells to directly absorb them through endocytosis, thereby improving drug bioavailability. Currently, more than 20 nanocrystal drugs have been approved for marketing. Nanocrystal drugs are prepared mechanically, requiring no organic solvents, making production safe and environmentally friendly. Stabilizers are needed to prevent nanocrystal aggregation in nanocrystal drugs. Stabilizers are generally amphiphilic polymers. Almost all reported stabilizers are synthetic polymers, such as polyvinyl alcohol (PVA), poloxamer P188, and polyethylene glycol (PEG4000). These synthetic polymers are currently not suitable for use in food due to safety concerns. Polysaccharides are natural polymers commonly used as stabilizers and emulsifiers in food, and are expected to replace synthetic polymers as stabilizers in nanocrystal delivery systems. However, polysaccharides currently cannot achieve the same stability performance as synthetic polymers for nanocrystal drugs. Further optimization of formulations is needed to ensure efficient and stable nanocrystal delivery systems.

[0004] Fenugreek gum, derived from fenugreek seeds, is a heteropolysaccharide composed of a β-(1-4)-D-mannan backbone and individual D-galactose branches linked by α-(1-6) bonds. It is a novel functional dietary fiber ingredient, commonly used as a stabilizer and emulsifier in food. The mannan backbone of fenugreek gum is hydrophobic, while the galactose side chains are hydrophilic, making it an amphiphilic polysaccharide. Currently, there are no reports on the use of fenugreek gum in nanocrystalline formulations. Summary of the Invention

[0005] The purpose of this invention is to provide a novel method for preparing curcumin-aromatic curcumin nanocrystals.

[0006] The technical solution adopted in this invention is as follows:

[0007] A method for preparing curcumin-aromatic curcumin nanocrystals, the method comprising the following steps:

[0008] (1) Preparation of curcumin-aromatic curcumin crystal mixture: Add curcumin powder to fenugreek gum solution with a mass fraction of 1-2% under stirring to make the final concentration of curcumin 1-2%, then add aromatic curcumin and emulsifier to make the final mass concentration of aromatic curcumin 1-2% and the final mass concentration of emulsifier 0.1-0.5%, mix well to obtain curcumin-aromatic curcumin crystal mixture;

[0009] (2) Curcumin-aromatic curcumin crystal suspension was obtained by high-speed shearing of the curcumin-aromatic curcumin crystal mixture. The curcumin-aromatic curcumin crystal suspension was homogenized under high pressure to obtain curcumin-aromatic curcumin nanocrystalline liquid.

[0010] In step (1), the fenugreek gum solution is generally prepared by the following method: fenugreek gum is added to water at a mass fraction of 1~2%, and stirred at a constant speed of 450 r / min at 50~60℃ for 1~2h to obtain a fully swollen fenugreek gum solution.

[0011] The preferred mass fraction of fenugreek gum solution is 1.5%.

[0012] The preferred final concentration of curcumin is 1.5%, and the preferred final mass concentration of aromatic curcumin is 1%.

[0013] The emulsifier is Tween or Span, preferably Tween 80.

[0014] The preferred final mass concentration of the emulsifier is 0.1~0.2%.

[0015] In step (2), a high-speed shearing machine is generally used to shear the curcumin-aromatic curcumin crystal suspension at a speed of 8000~10000 rpm for 5~7 min to obtain a uniform curcumin-aromatic curcumin crystal suspension.

[0016] In step (3), a high-pressure homogenizer is generally used to homogenize the curcumin-aromatic curcumin crystal suspension. The homogenization steps are as follows: stabilize at normal pressure for 2 minutes, pressure is 100 bar, homogenize 3 to 4 times to obtain a uniform curcumin-aromatic curcumin nanocrystal liquid.

[0017] In the curcumin-aromatic curcuminone nanocrystalline liquid prepared by this invention, curcumin and aromatic curcuminone exist in nanocrystalline form.

[0018] The method may also include the following steps:

[0019] Curcumin-aromatic curcumin nanocrystals were dried to obtain a curcumin-aromatic curcumin nanocrystal preparation.

[0020] Furthermore, the drying step is preferably:

[0021] Food-grade silica with a final concentration of 0.001~0.005% was added to the curcumin-aromatic curcumin nanocrystal liquid, and then poured into a petri dish for forced air drying to obtain dried curcumin-aromatic curcumin nanocrystals; the dried curcumin-aromatic curcumin nanocrystals were pulverized into powder below 200 mesh to obtain curcumin-aromatic curcumin nanocrystal preparation.

[0022] The final concentration of the food-grade silica is preferably 0.002%.

[0023] The present invention also provides a curcumin-aromatic curcumin nanocrystal preparation obtained by the above method.

[0024] And the application of curcumin-aromatic curcumin nanocrystal preparations in the preparation of curcumin supplements.

[0025] The formulations include, but are not limited to, beverages, capsules, powders, tablets, etc.

[0026] The preparation method used in this invention is a purely mechanical method. The curcumin-aromatic curcumin nanocrystals prepared by this invention inherit the pharmacological activities of curcumin and aromatic curcumin themselves, and their stability is significantly improved.

[0027] This invention utilizes the amphiphilic polysaccharide properties of fenugreek gum, which can adsorb onto the surface of hydrophobic curcumin and aromatic curcuminone nanocrystals in an aqueous phase, acting as a stabilizer. Furthermore, fenugreek gum can be slowly fermented and decomposed by intestinal microorganisms in the intestines, enabling the sustained release of curcumin and aromatic curcuminone.

[0028] The beneficial effects of this invention are as follows:

[0029] 1. Applicable to water- and oil-insoluble compounds, solving the problem of drug delivery that is not necessary for dissolution.

[0030] 2. Using food-grade natural polymer polysaccharides as stabilizers, it complies with the national standard GB2760 for food additives, is safe and healthy, and is edible. It can be used to prepare various nutritional foods.

[0031] 3. Nutrient preparations are made using purely mechanical methods, which are simple in process and eliminate the potential hazards of organic reagents.

[0032] 4. In the prepared formulation, curcumin and aromatic curcumin exist in the form of nanocrystals, which improves the physicochemical stability of curcumin and aromatic curcumin.

[0033] 5. For the first time, aromatic curcumin has been added to curcumin products, which increases the efficacy of curcumin nanocrystals and gives them a rich turmeric flavor.

[0034] 6. Food-grade SiO2 was added as an anti-caking agent to inhibit the aggregation of powder formulations.

[0035] 7. A small amount of food-grade emulsifier was used, and the amount of emulsifier was extremely small. Fenugreek gum was mainly used as the main stabilizer.

[0036] This invention employs a purely mechanical method to prepare a curcumin-aromatic curcumin nanocrystal delivery system using food-grade polysaccharide fenugreek gum as a stabilizer. While retaining the bioactivity of curcumin and aromatic curcumin, it improves the dispersibility and bioavailability of curcumin and aromatic curcumin. Furthermore, since the stabilizer is a food-grade polysaccharide, the product can be used to prepare nutritional food formulations. Attached Figure Description

[0037] Figure 1 X-ray diffraction patterns of curcumin crystals and the curcumin-aromatic curcumin nanocrystal formulation prepared in Example 1.

[0038] Figure 2 TEM images of the curcumin-aromatic curcumin nanocrystal preparation prepared in Example 1; where A image has a scale bar of 1 μm and B image has a scale bar of 100 nm.

[0039] Figure 3 Figure 1 shows the physicochemical and functional properties of the curcumin-aromatic curcumin nanocrystal preparation prepared in Example 1; Figure A is a bar chart of average particle size and thermal stability; Figure B is a bar chart of in vitro antioxidant and anti-cancer cell proliferation activity; Figure C is an in vitro dissolution curve of simulated gastric juice (pH 1.2); Figure D is an in vitro dissolution curve of simulated intestinal juice (pH 7.4). Detailed Implementation

[0040] To make the technical solution of this application clearer, the technical solution of the present invention will be described in detail below with reference to the accompanying drawings and embodiments. These embodiments are within the protection scope of the present invention, but do not limit the protection scope of the present invention.

[0041] Example 1: Curcumin-aromatic curcumin nanocrystal formulation was used to prepare a curcumin-aromatic curcumin supplement beverage. The steps are as follows:

[0042] (1) Accurately weigh 15 g of fenugreek gum powder and place it in 1 L of water. Stir at 450 r / min at 60℃ for 1 h to obtain a fully swollen fenugreek gum solution.

[0043] (2) Accurately weigh 15 g of curcumin powder and add it to the fenugreek gum solution obtained in step 1 with uniform stirring, so that the total mass fraction of solid powder is 3%. Continue to stir at 450 r / min at 60℃ for 1 h, then add 10 g of aromatic curcuminone and 2 g of Tween 80, so that the final mass fractions are 1% and 0.2%, respectively. Mix evenly to obtain a curcumin-aromatic curcuminone crystal mixture.

[0044] (3) The curcumin-aromatic curcumin crystal mixture obtained in step 2 was subjected to high-speed shearing at a speed of 8000 rpm for 5 min to obtain a uniform curcumin-aromatic curcumin crystal suspension.

[0045] (4) The curcumin-aromatic curcumin crystal suspension obtained in step 3 was homogenized using a high-pressure homogenizer. The homogenization steps were: stabilized at atmospheric pressure for 2 min, homogenized 3 times at 100 bar, to obtain a uniform curcumin-aromatic curcumin nanocrystal liquid.

[0046] (5) Weigh 0.002% food-grade SiO2 and add it to the curcumin-aromatic curcumin nanocrystal liquid obtained in step 4. After mixing evenly, pour the mixture into a petri dish and dry it in a 50℃ oven for 24 h. Then, use a small traditional Chinese medicine pulverizer to pulverize the dried curcumin-aromatic curcumin nanocrystal to below 200 mesh to obtain the curcumin-aromatic curcumin nanocrystal preparation. Perform physicochemical properties and in vitro dissolution tests. The results are as follows: Figures 1-3 As shown.

[0047] (6) Accurately weigh 1 g of curcumin-aromatic curcumin nanocrystal preparation and dissolve it in 100 mL of water. Stir well to obtain curcumin-aromatic curcumin supplement beverage.

[0048] X-ray diffraction patterns of curcumin crystals and the curcumin-aromatic curcumin nanocrystal formulation prepared in Example 1 are shown below. Figure 1 As shown. Figure 1 The results showed that curcumin-aromatic curcumin nanocrystals contained curcumin-specific diffraction peaks, indicating that the method did not destroy the crystal structure of curcumin during preparation.

[0049] TEM image of the curcumin-aromatic curcumin nanocrystal preparation prepared in Example 1 is shown below. Figure 2 As shown, Figure A has a scale bar of 1 μm; Figure B has a scale bar of 100 nm. Figure 2 The results showed that the nanocrystals exhibited good dispersibility, with a particle size of approximately 200-500 nm.

[0050] The physicochemical and functional properties of the curcumin-aromatic curcumin nanocrystal preparation prepared in Example 1 are shown in the figure below. Figure 3As shown, Figure A is a bar chart of average particle size and thermal stability; Figure B is a bar chart of in vitro antioxidant and anti-cancer cell proliferation activity; Figure C is an in vitro dissolution curve of simulated gastric juice (pH 1.2); and Figure D is an in vitro dissolution curve of simulated intestinal juice (pH 7.4).

[0051] Figure 3 The results showed that compared with pure curcumin, the curcumin-aromatic curcumin nanocrystal formulation had a nanoscale particle size and significantly improved thermal stability. In vitro antioxidant activity was enhanced, and the activity against protein denaturation was significantly increased, indicating that the curcumin-aromatic curcumin nanocrystal formulation improved the anti-inflammatory effect of curcumin alone and strengthened its protective effect against proteins. Furthermore, the anti-cancer cell proliferation activity of the curcumin-aromatic curcumin nanocrystal formulation increased to 90%, demonstrating a significant improvement in efficacy.

[0052] Based on the in vitro dissolution curves, the in vitro dissolution rate of curcumin-aromatic curcumin nanocrystal formulation in simulated gastric fluid is more than 10 times that of curcumin, and the in vitro dissolution rate in simulated intestinal fluid can reach 70%, significantly improving bioavailability.

[0053] Example 2: Curcumin-aromatic curcumin nanocrystal formulation was used to prepare curcumin-aromatic curcumin supplement capsules. The steps are as follows:

[0054] (1) Accurately weigh 10g of fenugreek gum powder and place it in 1L of water. Stir at 450 r / min at 60℃ for 1 h to obtain a fully swollen fenugreek gum solution.

[0055] (2) Accurately weigh 20 g of curcumin powder and add it to the fenugreek gum solution obtained in step 1 with uniform stirring, so that the total mass fraction of solid powder is 3%. Continue to stir at 450 r / min at 60℃ for 1 h, then add aromatic curcumin and Tween 80 with a mass fraction of 1% and 0.15% respectively, mix evenly, and obtain curcumin-aromatic curcumin crystal mixture.

[0056] (3) The curcumin-aromatic curcumin crystal mixture obtained in step 2 was subjected to high-speed shearing at a speed of 8000 rpm for 5 min to obtain a uniform curcumin-aromatic curcumin crystal suspension.

[0057] (4) The curcumin-aromatic curcumin crystal suspension obtained in step 3 was homogenized using a high-pressure homogenizer. The homogenization steps were: stabilized at atmospheric pressure for 2 min, and circulated 3 times at 100 bar to obtain a uniform curcumin-aromatic curcumin nanocrystal liquid.

[0058] (5) Weigh 0.002% of food-grade SiO2 and add it to the curcumin-aromatic curcumin nanocrystal liquid obtained in step 4. After mixing evenly, pour it into a petri dish and dry it in a 50°C oven for 24 hours. Then, use a small Chinese medicine pulverizer to pulverize the dried curcumin-aromatic curcumin nanocrystal to below 200 mesh to obtain the curcumin-aromatic curcumin nanocrystal preparation.

[0059] (6) 0.25 g of curcumin-aromatic curcumin nanocrystals were placed in a purchased enteric-coated capsule to obtain curcumin-aromatic curcumin supplement capsules.

Claims

1. A method of preparing curcumin- ar-turmerone nanocrystals, characterized by, The method comprises the following steps: (1) preparing a curcumin-ar-tumerone crystal mixture: curcumin powder is added into a 1-2% mass fraction of fenugreek gum solution under stirring, so that the final concentration of curcumin is 1-2%, ar-tumerone and an emulsifier are then added, so that the final mass concentration of ar-tumerone is 1-2% and the final mass concentration of the emulsifier is 0.1-0.2%, and the mixture is uniformly mixed to obtain a curcumin-ar-tumerone crystal mixture; (2) high-speed shearing of the curcumin-ar-tumerone crystal mixture to obtain a curcumin-ar-tumerone crystal suspension, and high-pressure homogenization of the curcumin-ar-tumerone crystal suspension to obtain a curcumin-ar-tumerone nanocrystal liquid; (3) adding 0.001-0.005% of food-grade silicon dioxide into the curcumin-ar-tumerone nanocrystal liquid, and then pouring the mixture into a flat dish for air blowing drying to obtain a curcumin-ar-tumerone nanocrystal dry product; the curcumin-ar-tumerone nanocrystal dry product is crushed into a powder with a particle size of 200 mesh or less to obtain a curcumin-ar-tumerone nanocrystal preparation.

2. The method of claim 1, wherein, In the step (1), the fenugreek gum solution is prepared as follows: fenugreek gum is added into water at a mass fraction of 1-2%, and stirred at a speed of 450 r / min at 50-60°C for 1-2h to obtain a fully swollen fenugreek gum solution.

3. The method of claim 1, wherein, In the step (1), the mass fraction of the fenugreek gum solution is 1.5%.

4. The method of claim 1, wherein, In the step (1), the final concentration of curcumin is 1.5% and the final mass concentration of ar-tumerone is 1%.

5. The method of claim 1, wherein, In the step (1), the emulsifier is Tween or Span.

6. The curcumin-ar-tumerone nanocrystal preparation prepared by the method of claim 1.

7. Use of the curcumin-ar-tumerone nanocrystal preparation of claim 6 in the preparation of a curcumin nutritional supplement.

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