Targeted slow-release curcumin compound with auxiliary liver protection function and preparation method of targeted slow-release curcumin compound

Abstract

The invention discloses a targeted slow-release curcumin compound with an auxiliary liver protection function and a preparation method thereof.The preparation method comprises the steps that whey protein isolate is heated under the acidic condition to prepare whey protein isolate fibers, and then the whey protein isolate fibers are compounded with kappa-carrageenan; adjusting the mixed system to be alkaline by adopting a pH migration method, adding a curcumin alkaline solution, fully dissolving the curcumin alkaline solution, and combining the curcumin alkaline solution with the whey protein isolate fiber-kappa-carrageenan composite system; and adjusting the pH value of the system back to be neutral to obtain the high-load amorphous curcumin solution and the solid preparation. The whey fiber and the kappa-carrageenan are self-assembled in the pH circulation process to form a composite carrier, curcumin is converted into an amorphous state from a crystalline state, the solubility of curcumin is remarkably improved, the loading capacity is greatly improved to 70% at most, the heat stability, oxidation resistance and biological accessibility of curcumin are improved, targeted slow release of curcumin can be achieved, and the curcumin-targeted slow release preparation has a good application prospect. The positioning release performance of the curcumin in the intestinal tract part is improved, and the application form of the curcumin in liver protection function products is expanded.

Description

TECHNICAL FIELD

[0001] The present application relates to a targeted sustained-release curcumin compound with auxiliary liver protection function and a preparation method thereof. BACKGROUND

[0002] As the core metabolic and detoxification organ of the human body, the liver bears the heavy responsibility of processing ingested substances (food, drugs, alcohol and various toxins), and its importance is self-evident. The liver plays a key role in breaking down nutrients (dietary fats, proteins, etc.) and potential toxins through the production of various enzymes, and in the process of energy generation and the construction of hundreds of compounds required for life, such as proteins, carbohydrates and fats. It is also responsible for storing sugar and vitamins and releasing them in time for the body to use. Therefore, it is crucial to maintain liver function through reasonable nutrient intake.

[0003] Curcumin is a recognized ingredient with liver protection function, with anti-inflammatory and anti-fibrosis effects. On the one hand, liver diseases are often accompanied by inflammatory reactions, and curcumin can intervene and inhibit the key inflammatory signaling pathways in this process, thereby reducing the inflammatory state of the liver. On the other hand, liver fibrosis is a response of the liver to chronic injury, and its long-term existence can gradually lead to loss of liver function, while curcumin can block this process through various mechanisms, including inhibition of the activation and proliferation of hepatic stellate cells, promotion of their apoptosis, reduction of oxidative stress levels in liver tissue, reduction of collagen synthesis and extracellular matrix deposition, etc. In addition, studies have shown that curcumin, as a potent natural antioxidant, can enhance the liver's ability to resist oxidative stress by increasing the activity and content of antioxidant enzymes (such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR)) in the liver, thereby protecting the liver from damage caused by free radicals.

[0004] However, the practical application of curcumin faces two major challenges: first, curcumin has very low water solubility and is almost insoluble in water under neutral and acidic conditions, resulting in poor oral bioavailability; second, its molecular structure contains a β-diketone unit and a phenolic hydroxyl group, which are extremely unstable under light, heat and alkaline conditions and are prone to degradation and failure. These inherent defects seriously limit the direct application of curcumin in water-based foods, beverages and oral drug formulations, and constitute a core barrier for its transition from laboratory research to practical application and mass consumer market.

[0005] To improve the solubility and stability of curcumin, various solutions have been proposed in existing technologies. Common strategies include using organic solvents (such as ethanol and acetone) for solubilization, or combining them with synthetic carriers such as synthetic surfactants, cyclodextrin inclusion complexes, liposomes, and nanoemulsions. Although these methods improve apparent solubility to some extent, there is still a risk of organic solvent residue, and the processes are usually complex and costly, making it difficult to meet the stringent safety and large-scale production requirements of the food and pharmaceutical industries. More advanced nanoencapsulation technologies (such as those based on synthetic polymers like PLGA) can achieve effective encapsulation and sustained-release effects, but due to high raw material costs, complex synthesis processes, and strict regulatory approvals, they are currently mainly limited to the pharmaceutical field and difficult to promote for use in functional foods. In addition, some studies have attempted to use proteins or polysaccharides as natural carriers, but these generally suffer from low loading efficiency and poor stability, making it difficult to achieve high-concentration loading and long-term protection of curcumin, and lacking the ability to target release in the gastrointestinal environment.

[0006] Currently, pH-driven self-assembly processes have attracted widespread attention due to their lack of organic solvents and relatively simple operation. However, existing methods still generally suffer from low loading capacity, with loading rates typically around 10-20%, resulting in low drug loading.

[0007] It is necessary to use food-grade raw materials from natural sources to develop new amorphous curcumin preparations and improve the loading capacity, water solubility, and thermal stability of curcumin. Summary of the Invention

[0008] The purpose of this invention is to provide a targeted sustained-release curcumin complex with auxiliary liver protection function and its preparation method. This invention utilizes a whey protein isolate / κ-carrageenan complex, which can achieve a loading of up to 70% of amorphous curcumin without the need for organic solvents.

[0009] The technical solution adopted in this invention is: A method for preparing a targeted sustained-release curcumin complex with auxiliary liver-protective function, the method comprising the following steps: (1) The whey protein isolate solution was allowed to stand and hydrate at 0~4℃, the pH was adjusted to acidic, the reaction was heated and stirred, and then cooled to obtain the whey protein isolate fiber solution; (2) Adjust the pH of the κ-carrageenan aqueous solution to neutral, mix it with the diluted whey protein cellulose isolate solution, and then adjust the pH to alkaline to obtain a mixed solution; (3) Add curcumin alkaline aqueous solution to the mixed solution in step (2) under stirring. After stirring thoroughly, adjust the pH value to neutral to obtain a high-load amorphous curcumin solution. After freeze drying, a high-load amorphous curcumin solid preparation is obtained, which is the targeted sustained-release curcumin complex.

[0010] In the targeted sustained-release curcumin complex prepared by this invention, the loading of amorphous curcumin is 60-70 wt%.

[0011] In step (1), the mass fraction of the whey protein isolate solution is preferably 1.5-3%, more preferably 2%.

[0012] The hydration time is 20 to 30 hours.

[0013] In step (1), after hydration, acid is added to adjust the pH value to 1.5~2, preferably 1.98~2.02.

[0014] Furthermore, in step (1), when adjusting the pH value by adding acid, 3-6M hydrochloric acid is generally added.

[0015] In step (1), the reaction is generally carried out at a temperature of 85~90℃. The preferred reaction time is 5~8 hours.

[0016] In step (1), the stirring speed is generally 300~600 r / min.

[0017] In step (2), κ-carrageenan includes K-type carrageenan from seaweed, agar, and staghorn seaweed.

[0018] The mass concentration of κ-carrageenan aqueous solution is generally 0.05~0.2%, preferably 0.1%.

[0019] The pH value of κ-carrageenan aqueous solution is generally 6.5~7.5, preferably 6.98~7.02.

[0020] In the mixed solution of step (2), the whey protein isolate mass fraction is preferably 0.05-0.25%, more preferably 0.15%, and the mass ratio of whey protein isolate to κ-carrageenan is 1-5:1, preferably 3:1.

[0021] In step (2), the pH of the κ-carrageenan aqueous solution is adjusted to neutral and mixed with the diluted whey protein cellulose isolate solution. The mixture is generally stirred at a constant speed of 300-600 r / min for 1-2 h at room temperature to obtain a mixed solution.

[0022] The mass fraction of the diluted whey protein isolate solution is preferably 0.1-0.5%, more preferably 0.3%.

[0023] The pH of the mixed solution is 11.5–12.5, preferably 11.98–12.02. It is preferable to use 0.5–2 M sodium hydroxide to adjust the pH to alkaline.

[0024] In step (3), the mass fraction of the curcumin alkaline aqueous solution is 0.05-0.2%, preferably 0.1%.

[0025] The pH value of the alkaline aqueous solution of curcumin is 11.5~12.5, preferably 11.98~12.02.

[0026] In step (3), curcumin is generally added to an alkaline aqueous solution and stirred at a constant speed of 500-700 r / min for 0.3-0.5 h at room temperature to obtain a completely dissolved alkaline aqueous solution of curcumin.

[0027] Sodium hydroxide is preferred for preparing alkaline aqueous solutions.

[0028] The mass ratio of curcumin in the alkaline aqueous solution to whey protein isolate in the mixed solution is generally 6:0.5~5, preferably 6:1~3.

[0029] The volume ratio of curcumin alkaline aqueous solution and mixed solution is 1.5~4.5:1, preferably 3:1.

[0030] In step (3), the pH value is adjusted to neutral, generally to 6.5~7.5, preferably 6.98~7.02.

[0031] In step (3), the stirring reaction time is generally 0.5~1.5 h.

[0032] The present invention also provides a high-loaded amorphous curcumin solution and a targeted sustained-release curcumin complex prepared by the above method, wherein the loading of amorphous curcumin is 60-70%.

[0033] This invention also provides the application of high-load amorphous curcumin solution and targeted sustained-release curcumin complex in the preparation of enteric-coated targeted sustained-release oral curcumin formulations.

[0034] This invention also provides the application of high-load amorphous curcumin solution and targeted sustained-release curcumin complex as food additives.

[0035] This invention also provides the application of high-load amorphous curcumin solution and targeted sustained-release curcumin complex in the preparation of liver-protecting foods or drugs.

[0036] This invention involves heating whey protein isolate under acidic conditions to prepare whey protein isolate fibers, which are then compounded with κ-carrageenan. Subsequently, the mixture is adjusted to alkaline conditions using a pH shifting method. Under these conditions, curcumin is added to fully dissolve and bind with the whey protein isolate fiber-κ-carrageenan composite system. Finally, the pH of the system is adjusted back to neutral.

[0037] This invention discovers that whey protein isolate fibers and κ-carrageenan self-assemble during pH cycling to form a stable composite network structure, possessing significant carrier potential. This invention investigated the loading capacity, stability, and delivery performance of curcumin at different mass ratios of whey protein isolate fibers to κ-carrageenan (1:1, 3:1, 5:1). Curcumin was successfully loaded onto the solid form of whey protein isolate fibers after self-assembly with κ-carrageenan, converting curcumin from a crystalline to an amorphous state with a loading capacity as high as 70 wt%, and significantly improving thermal stability and antioxidant properties. Furthermore, the in vitro release behavior of the amorphous curcumin solid formulation conformed to the Higuchi model, exhibiting pH-responsive sustained-release characteristics.

[0038] The method of this invention not only promotes the efficient embedding of curcumin in the composite carrier, but also effectively inhibits the crystallization of curcumin under neutral conditions, allowing it to exist stably in the particles in an amorphous state, thereby significantly increasing the loading of curcumin to 70 wt%, which is far higher than the level disclosed in the prior art.

[0039] The high-loading amorphous curcumin liquid formulation provided by this invention features a high loading capacity, making it suitable for use as a food additive. Furthermore, it exhibits enteric coating, targeting, and sustained-release properties, allowing for the preparation of enteric-coated, targeted, and sustained-release oral curcumin formulations. These oral formulations can be in various pharmaceutically common forms, such as liquids or capsules. The oral formulations can be used to prepare various hepatoprotective drugs or foods.

[0040] The beneficial effects of this invention are as follows: (1) For the first time, a composite carrier was constructed using whey protein isolate and κ-carrageenan via a pH-driven method, achieving a high loading of curcumin (up to 70 wt%). Both whey protein isolate and κ-carrageenan are food-grade raw materials of natural origin, possessing recognized safety and good edibility. All excipients meet food additive standards, are safe, non-toxic, and environmentally friendly, and the preparation process does not involve organic solvents.

[0041] (2) The study found that whey protein isolate fiber and κ-carrageenan can undergo synergistic self-assembly under specific pH treatment conditions to form a composite network structure dominated by hydrophobic interaction and stabilized by hydrogen bonding and electrostatic interaction. Curcumin is efficiently captured in the composite network structure formed by the two, achieving a loading of up to 70 wt% while stabilizing curcumin in an amorphous form, effectively inhibiting curcumin crystallization and promoting its high loading in the solid system in an amorphous form.

[0042] (3) By utilizing the structural responsiveness of κ-carrageenan under different pH conditions and the colonic fermentation potential of whey protein isolate fibers, the programmed release of curcumin in the gastrointestinal tract can be achieved, especially exhibiting sustained-release behavior in a simulated colonic environment.

[0043] (4) The solid formulation of the targeted sustained-release curcumin complex prepared by the present invention significantly improves the solubility, thermal stability and in vitro antioxidant activity of curcumin, and enhances its bioaccessibility and cellular uptake efficiency.

[0044] (5) The targeted sustained-release curcumin complex solid formulation prepared by the present invention achieves high loading capacity while having both sustained-release and targeted properties. Moreover, all components are raw materials permitted by food regulations, and it has broad application prospects in the fields of functional foods, special medical foods and oral preparations. Attached Figure Description

[0045] Figure 1 Transmission electron microscopy (TEM) of whey protein isolate (Figure A) and whey protein isolate fibers (Figure B).

[0046] Figure 2 This section presents DSC charts, encapsulation efficiency, and loading rates of curcumin and curcumin solid formulation powders. Chart A shows the DSC charts for WPIF / κ-CG-60, WPIF / κ-CG-70, and WPI / κ-CG of curcumin and curcumin solid formulation powders. Chart B shows the DSC charts for WPIF / κ-CG... 1:1 -Cur、WPIF / κ-CG 3:1 -Cur、WPIF / κ-CG 5:1 -Cur encapsulation and loading results graph.

[0047] Figure 3 XRD results for pure curcumin, κ-carrageenan and whey protein cellulose isolate complex (WPIF / κ-CG), and solid formulations of curcumin using whey protein cellulose isolate / κ-carrageenan complex WPIF / κ-CG-60 and WPIF / κ-CG-70.

[0048] Figure 4 The images show the appearance of pure curcumin and the amorphous curcumin liquid preparation prepared according to this invention dissolved in distilled water in equal amounts of curcumin. Image A is a front view, and image B is a rear view laid flat. The left side of images A and B shows pure curcumin, and the right side of images A and B shows the amorphous curcumin liquid preparation prepared according to this invention.

[0049] Figure 5 The images show the appearance and scanning electron microscope (SEM) images of curcumin powder and the solid curcumin preparation prepared according to the present invention, wherein image A shows curcumin powder and image B shows the solid curcumin preparation.

[0050] Figure 6 The diagrams show the functional properties of curcumin and the curcumin liquid preparation prepared according to the present invention, where Figure A is the in vitro antioxidant stability diagram, Figure B is the thermal stability diagram, Figure C is the cellular uptake diagram, and Figure D is the in vitro dissolution diagram. Detailed Implementation

[0051] The technical solution of the present invention will be further described below with reference to the accompanying drawings, but the scope of protection of the present invention is not limited thereto.

[0052] Example 1 High-load amorphous curcumin liquid formulation (1) Accurately weigh 20 g of whey protein isolate and dissolve it in 1 L of water to prepare a 2% whey protein isolate solution. Let it stand at 4℃ for 25 h.

[0053] (2) The fully hydrated whey protein isolate solution was adjusted to pH 2 with 6M hydrochloric acid and stirred in a 90 ℃ water bath for 6 h. It was then cooled to room temperature in an ice-water bath to obtain the whey protein cellulose isolate solution, as shown below. Figure 1 As shown in Figure B, and Figure 1 Compared to Figure A (whey protein isolate), whey protein isolate fibers appear as long, thin fibers.

[0054] (3) Dissolve 1g of κ-carrageenan in 1L of water to prepare a κ-carrageenan solution with a mass fraction of 0.1%, and adjust the pH to 7 with 1M NaOH; add 5.6L of water to dilute the whey protein cellulose solution to 0.3%, and adjust the pH to 7.

[0055] (4) 1 L of κ-carrageenan solution and 1 L of diluted whey protein cellulose isolate solution were mixed in a 1:1 volume ratio to obtain a mixed solution of 2 L of κ-carrageenan solution and whey protein cellulose isolate. After stirring and mixing, the pH was adjusted to 12 with 1M NaOH. The mass fraction of whey protein cellulose isolate in the mixed solution was 0.15%, and the mass fraction of κ-carrageenan was 0.05%.

[0056] (5) 6 g of curcumin powder was dissolved in 6 L of water, and the pH of the aqueous solution was adjusted to pH 12 with 1 M NaOH solution to prepare a 0.1% curcumin alkaline solution. The 6 L of curcumin alkaline solution was stirred evenly and then added to a 2 L mixed solution under constant stirring. After stirring for 1 h, the pH was adjusted to 7 to obtain a liquid curcumin formulation with high loading amorphous form. The solid formulation was obtained by freeze-drying and denoted as WPIF / κ-CG. 3:1 -Cur.

[0057] The mass ratio of whey protein isolate to carrageenan in the mixed solution was changed to 1:1 and 5:1, respectively, while the mass fraction of κ-carrageenan in the mixed solution remained constant at 0.05%. A liquid formulation with high loading of amorphous curcumin was prepared, and lyophilized to obtain a solid formulation, denoted as WPIF / κ-CG. 1:1 -Cur、WPIF / κ-CG 5:1-Cur. WPIF / κ-CG 1:1 -Cur、WPIF / κ-CG 3:1 During the preparation of -Cur, the proportions of curcumin added were 70% and 60%, respectively, and therefore they were also recorded as WPIF / κ-CG-70 and WPIF / κ-CG-60.

[0058] Detection of WPIF / κ-CG 1:1 -Cur、WPIF / κ-CG 3:1 -Cur、WPIF / κ-CG 5:1 -Cur's encapsulation efficiency and loading rate results are as follows Figure 2 As shown in Figure B, WPIF / κ-CG 3:1 -Cur exhibits the best load capacity, reaching a load rate of up to 70%, therefore, WPIF / κ-CG will be used in subsequent experiments. 3:1 -Cur, denoted as WPIF / κ-CG-Cur, was compared with pure curcumin in an analysis. WPIF / κ-CG 1:1 -Cur's load rate reaches 60%, which is also a relatively high load rate.

[0059] The load is calculated as follows: Load factor = m c / m a m c The mass (g) of curcumin in amorphous solid dosage forms, m a The total mass (g) of the amorphous solid dosage form.

[0060] Encapsulation rate = m c / m b m c The mass (g) of curcumin in amorphous solid dosage forms, m b The total mass (g) of curcumin added.

[0061] DSC charts of curcumin and curcumin solid formulation powders WPIF / κ-CG-60 and WPIF / κ-CG-70 are shown below. Figure 2 As shown in Figure A, WPIF / κ-CG-60 and WPIF / κ-CG-70 represent curcumin dosage ratios of 60 wt% and 70 wt%, respectively, corresponding to WPIF / κ-CG... 3:1 -Cur、WPIF / κ-CG 1:1 -Cur, meaning the loading rates were approximately 70% and 60%, respectively. The results showed that after loading curcumin onto whey protein isolate / κ-carrageenan, the sharp endothermic peak of crystalline curcumin disappeared, indicating that the curcumin in this product was likely amorphous rather than crystalline.

[0062] The XRD pattern of the κ-carrageenan and whey protein cellulose complex (denoted as WPIF / κ-CG) obtained by freeze-drying a mixed solution of WPIF / κ-CG-60, WPIF / κ-CG-70, curcumin Cur, κ-carrageenan solution, and whey protein cellulose isolate is shown in the figure. Figure 3 As shown.

[0063] Figure 3 The results showed that the solid curcumin formulation did not have the crystal diffraction peaks characteristic of curcumin, and was a typical amorphous form, indicating that the polysaccharide complex system in this method successfully and efficiently transported curcumin.

[0064] The appearance of 10 mg of pure curcumin dissolved in 10 mL of distilled water is shown in the figure below. Figure 4 As shown, Figure A is a front view, Figure B is a rear view laid flat, the left side of Figures A and B shows pure curcumin, and the right side of Figures A and B shows the amorphous curcumin liquid preparation prepared in this invention.

[0065] The appearance of 10 mg of pure curcumin dissolved in 10 mL of distilled water is shown in the figure below. Figure 4 As shown on the left side of Figures A and B, there is obvious curcumin precipitation; the appearance of the amorphous curcumin liquid preparation prepared in this invention is shown in the figure below. Figure 4 As shown on the right side of Figures A and B, curcumin is stable and uniformly suspended in the mixture. Figure 4 The results showed that curcumin has extremely low solubility in water, while the curcumin liquid preparation prepared by this invention is a yellow, homogeneous solution.

[0066] Appearance and scanning electron microscope images of curcumin powder and the curcumin solid preparation prepared in this invention are shown below. Figure 5 As shown, Figure A shows yellow curcumin powder, which appears as curcumin crystals in the electron microscope image; Figure B shows an orange-red solid curcumin preparation, which does not show curcumin crystals in the electron microscope image. Figure 5 The results showed that curcumin was successfully loaded into the whey protein isolate / κ-carrageenan composite carrier in an amorphous form.

[0067] The functional properties of the curcumin, κ-carrageenan, and whey protein isolate cellulose complex WPIF / κ-CG, and the curcumin solid formulation WPIF / κ-CG-Cur prepared in this invention are as follows: Figure 6As shown, Figure A shows the antioxidant activity of DPPH and ABTS; Figure B shows the thermal stability (the horizontal axis represents the sample name, and the vertical axis represents the retention rate of curcumin molecules after treatment at 90℃ for 30 min); Figure C shows the in vitro dissolution of the sample at pH 1.2 and 7.4 (the vertical axis represents the release rate of curcumin from the sample); and Figure D shows the cellular uptake (IPEC-1 cells were used for cellular uptake experiments. After the cells took up the sample, they were lysed, and the fluorescence intensity of curcumin in the cell lysate was measured by fluorescence spectroscopy. The change in uptake was characterized by the fluorescence intensity of curcumin). Figure 6 The results showed that, compared with pure curcumin, the solid curcumin formulation is in an amorphous form, which nearly doubled its thermal stability. It also showed significantly improved in vitro antioxidant activity and cellular uptake compared with curcumin, and achieved high loading capacity while also possessing intestinal sustained release and targeted properties.

[0068] Comparative Example 1 (1) Accurately weigh 20 g of whey protein isolate and dissolve it in 1 L of water to prepare a 2% whey protein isolate solution. Let it stand at 4℃ for 25 h.

[0069] (2) Dissolve 1g of κ-carrageenan in 1L of water to prepare a κ-carrageenan solution with a mass fraction of 0.1%, and adjust the pH to 7 with 1M NaOH; add 5.6L of water to dilute the whey protein isolate solution to 0.3%, and adjust the pH to 7.

[0070] (4) 1 L of κ-carrageenan solution and 1 L of diluted whey protein isolate solution were mixed in a 1:1 volume ratio to obtain 2 L of a mixed solution of κ-carrageenan solution and whey protein isolate. After stirring and mixing, the pH was adjusted to 12 with 1 M NaOH. The mass fraction of whey protein isolate in the mixed solution was 0.15%, and the mass fraction of κ-carrageenan was 0.05%.

[0071] (5) 6 g of curcumin powder was dissolved in 6 L of water, and the pH of the aqueous solution was adjusted to pH 12 with 1 M NaOH solution to prepare a curcumin alkaline solution with a mass fraction of 0.1%. The 6 L of curcumin alkaline solution was stirred evenly and then added to a 2 L mixed solution that was stirred at a constant speed. After stirring thoroughly for 0.5 h, the pH was adjusted to 7 to obtain a liquid curcumin preparation. The solid preparation was freeze-dried and denoted as WPI / κ-CG-60, with a curcumin feed ratio of 60%.

[0072] DSC of whey protein isolate and k-carrageenan complex loaded with curcumin, as shown in Figure 2 As shown by the WPI / κ-CG-60 curve in Figure A, curcumin still partially exists in a crystalline structure and is not completely encapsulated. Further measurements of its encapsulation efficiency and loading rate yielded the following results: Figure 2As shown in Figure B, the encapsulation efficiency of curcumin by WPI / κ-CG was 29.45%, with a loading rate of 9.8 wt%. Therefore, the direct complexation of whey protein isolate with κ-carrageenan resulted in low curcumin loading efficiency and a low loading rate, failing to completely encapsulate curcumin. However, the complexation of whey protein isolate with κ-carrageenan after acidification and heating to obtain whey protein isolate fibers showed a significantly improved curcumin loading rate.

[0073] Example 2 A high-content curcumin liquid formulation was prepared according to the method in Example 1, and after freeze-drying, a food-based curcumin solid formulation was obtained for the preparation of curcumin oral capsules.

[0074] X-ray diffraction analysis of the product powder showed no characteristic crystalline peaks of curcumin, indicating that curcumin had been successfully converted into an amorphous form.

[0075] Curcumin oral capsules can be obtained by placing 0.25 g of amorphous curcumin oral preparation into enteric-coated capsules.

Claims

1. A method for preparing a targeted sustained-release curcumin complex with auxiliary liver-protective function, characterized in that... The method includes the following steps: (1) The whey protein isolate solution was allowed to stand and hydrate at 0~4℃, the pH was adjusted to acidic, the reaction was heated and stirred, and then cooled to obtain the whey protein isolate fiber solution; (2) Adjust the pH of the κ-carrageenan aqueous solution to neutral, mix it with the diluted whey protein cellulose isolate solution, and then adjust the pH to alkaline to obtain a mixed solution; (3) Add curcumin alkaline aqueous solution to the mixed solution in step (2) under stirring. After stirring thoroughly, adjust the pH value to neutral to obtain a high-load amorphous curcumin solution. The targeted sustained-release curcumin complex is obtained by freeze drying.

2. The method as described in claim 1, characterized in that... In step (1), the whey protein isolate solution has a mass fraction of 1.5-3%, and after hydration, the pH is adjusted to 1.5-2.2 by adding acid; in step (1), the reaction is carried out at a temperature of 85-90°C for 5-8 hours.

3. The method as described in claim 1, characterized in that... In step (2), the mass concentration of the κ-carrageenan aqueous solution is 0.05~0.2%, and the pH value is 6.5~7.

5.

4. The method as described in claim 1, characterized in that... In the mixed solution of step (2), the mass fraction of whey protein isolate is 0.05-0.25%, the mass ratio of whey protein isolate to κ-carrageenan is 1-5:1, and the pH value of the mixed solution is 11.5-12.

5.

5. The method as described in claim 4, characterized in that... In step (2), the mass ratio of whey protein isolate to κ-carrageenan is 3:

1.

6. The method as described in claim 1, characterized in that... In step (3), the mass fraction of curcumin alkaline aqueous solution is 0.05-0.2%, and the pH value is 11.5-12.5; the volume ratio of curcumin alkaline aqueous solution to mixed solution is 1.5-4.5:

1.

7. The method as described in claim 1, characterized in that... In step (3), the mass ratio of curcumin in the curcumin alkaline aqueous solution to whey protein isolate fiber in the mixed solution is 6:0.5~5.

8. The high-loaded amorphous curcumin solution or targeted sustained-release curcumin complex preparation obtained by the method according to any one of claims 1 to 7, wherein the loading of amorphous curcumin is 60 to 70%.

9. The application of the high-load amorphous curcumin solution and targeted sustained-release curcumin complex as described in claim 8 in the preparation of enteric-coated targeted sustained-release oral curcumin formulations.

10. The high-load amorphous curcumin solution and targeted sustained-release curcumin complex as described in claim 8 are used in the preparation of liver-protecting foods or drugs.

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