Preparation method of curcumin dispersion for medicinal and edible purposes

Abstract

The invention belongs to the fields of biomedical technology and food technology, and specifically relates to a method for preparing a curcumin dispersion liquid for both medicinal and edible purposes, wherein soybean lecithin, propylene glycol and curcumin are dissolved in a mixed solvent, and then the mixed solvent is removed by rotary evaporation to form a film, and then an aqueous dispersion liquid containing an emulsifier is added to the film, and the film is hydrated and dispersed. In this scheme, propylene glycol is used instead of cholesterol to prepare liposomes in combination with lecithin, and the film-forming uniformity of the liposomes is improved by the selection of a mixed solvent, thereby further promoting the stability of the dispersion after hydration.

Description

Technical Field

[0001] The invention belongs to the fields of biomedicine technology and food technology, and specifically relates to a method for preparing a curcumin dispersion liquid for both medicinal and edible purposes. Background Art

[0002] Among the many functional raw materials derived from plants, curcumin has emerged in the plant-based trend due to its multiple functions and has received more and more attention. Studies have shown that curcumin has multiple pharmacological activities such as anti-oxidation, lipid regulation, hypolipidemic, hypoglycemic, anti-ulcer, inhibition of liver fat accumulation and fibrosis, and anti-tumor, and has broad application prospects in the field of disease treatment and health care.

[0003] However, curcumin has defects such as poor water solubility and low oral bioavailability, which limits its application. Liposomes are a commonly used solubilization measure, in which cholesterol is one of the main components of liposome preparations and plays an important role in maintaining the liposome membrane structure and stability. However, when used as an oral agent, excessive cholesterol intake may lead to the occurrence of diseases such as atherosclerosis.

[0004] Therefore, how to develop a green and safe curcumin solubilization method based on approved food additives is still a technical challenge faced by the development of curcumin medicinal or edible products such as curcumin oral liquid preparations or curcumin functional beverages. Summary of the invention

[0005] In order to solve the above technical problems, the present invention provides a method for preparing a curcumin dispersion for both medicinal and edible purposes, and the steps are as follows:

[0006] (1) dissolving soybean lecithin, propylene glycol and curcumin in a mixed solvent, and then removing the mixed solvent by rotary evaporation to form a film,

[0007] The mass ratio of soybean lecithin, propylene glycol, curcumin and mixed solvent is 1:0.01-2:0.01-0.3:10-300, preferably 1:1:0.15:150.

[0008] The mixed solvent is a mixture of ethanol and ethyl acetate, and the volume ratio of ethanol to ethyl acetate is 1:1.

[0009] Ethyl acetate is more conducive to the dissolution of curcumin, and ethanol is more conducive to the dissolution of lecithin. At the same time, ethanol and ethyl acetate are relatively close in boiling point. Therefore, in this scheme, ethanol and ethyl acetate are mixed for use, which not only has strong solubility, but also is conducive to synchronous volatilization, ensuring that the effective ingredients will not precipitate during the rotary evaporation concentration film forming process, making the prepared film more uniform, and also making the subsequent hydration effect better.

[0010] The rotary evaporation temperature is 45-65°C, preferably 60°C;

[0011] (2) adding an aqueous dispersion containing an emulsifier to the film obtained in step (1) to hydrate and disperse the film,

[0012] Among them, the emulsifier is preferably Tween, such as Tween-40, Tween-60, Tween-80,

[0013] The mass ratio of emulsifier to soybean lecithin is 0.15-0.3:1.

[0014] In the aqueous dispersion containing an emulsifier, the mass concentration of the emulsifier is 0.05 to 0.2%, preferably 0.2%.

[0015] The membrane is hydrated and dispersed by water bath ultrasonic measures, the water bath ultrasonic time is 5 to 30 minutes, preferably 30 minutes, and the water bath ultrasonic temperature is 45 to 65°C, preferably 60°C.

[0016] The advantages of the present invention are: in this scheme, propylene glycol replaces cholesterol well to prepare curcumin liposome preparation with lecithin, avoiding cholesterol from being ingested as an oral medicament component, and can also play an emulsifying effect in the emulsified state, which is more conducive to dispersion stability; at the same time, the film-forming uniformity of the liposome is improved by the selection of a mixed solvent, thereby further promoting the stability of dispersion after hydration; the materials used in the preparation method of the curcumin dispersion provided by the present invention are all food additives, and the preparation process is green and safe. The method provided by the present invention can be directly used for the development of curcumin medicinal or edible products such as curcumin oral liquid preparations or curcumin functional beverages. DETAILED DESCRIPTION

[0017] Example 1: Preparation of 1 mg / mL Curcumin Dispersion (Containing Neither Propylene Glycol nor Cholesterol)

[0018] (1) 30 mg of curcumin, 200 mg of soy lecithin, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45°C for 30 min, leaving a thin film on the wall of the flask.

[0019] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0020] After testing, the average particle size of the obtained dispersion was 655.7 nm and the average potential was 14.3 mV.

[0021] Example 2: Preparation of 1 mg / mL Curcumin Dispersion (Propylene glycol added during liposome preparation)

[0022] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45 °C for 30 min, leaving a thin film on the wall of the flask.

[0023] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0024] After testing, the average particle size of the obtained dispersion was 146.8 nm and the average potential was 23.6 mV.

[0025] Example 3: Preparation of 1 mg / mL Curcumin Dispersion (Propylene glycol is added during the hydration and dispersion stage of step 2)

[0026] (1) 30 mg of curcumin, 200 mg of soy lecithin, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45°C for 30 min, leaving a thin film on the wall of the flask.

[0027] (2) 60 mg of Tween-80 and 100 mg of 1,2-propylene glycol were dissolved in 30 mL of distilled water, heated to 45° C., added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0028] After testing, the average particle size of the obtained dispersion was 347.6 nm and the average potential was 18.1 mV.

[0029] Example 4: Preparation of 1 mg / mL Curcumin Dispersion (Propylene glycol replaced by cholesterol in traditional liposome preparation)

[0030] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of cholesterol, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and ultrasonically dissolved in an ultrasonic cleaner until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45°C for 30 min, leaving a thin film on the wall of the flask.

[0031] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0032] After testing, the average particle size of the obtained dispersion was 152.4 nm and the average potential was 25.6 mV.

[0033] Example 5: Preparation of 1 mg / mL Curcumin Dispersion (Based on Propylene Glycol, a Small Amount of Cholesterol Was Added)

[0034] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, 30 mg of cholesterol, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and ultrasonically dissolved in an ultrasonic cleaner until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45 °C for 30 min, leaving a thin film on the wall of the flask.

[0035] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0036] Example 6: Preparation of 1 mg / mL Curcumin Dispersion (Tween-80 is added during liposome film formation)

[0037] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, 60 mg of Tween-80, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45 °C for 30 min, leaving a thin film on the wall of the flask.

[0038] (2) Take 30 mL of distilled water, heat it to 45° C., add it to the flask dried in step (1), and ultrasonically disperse it in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0039] Example 7: Preparation of 1 mg / mL Curcumin Dispersion

[0040] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,3-propylene glycol, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and ultrasonically dissolved in an ultrasonic cleaner until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45°C for 30 min, leaving a thin film on the wall of the flask.

[0041] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0042] Example 8: Preparation of 1 mg / mL Curcumin Dispersion (using only anhydrous ethanol as solvent in liposome film-forming operation)

[0043] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, and 20 mL of anhydrous ethanol were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45°C for 30 min, leaving a thin film on the wall of the flask.

[0044] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0045] Example 9: Preparation of 1 mg / mL Curcumin Dispersion (Ethyl acetate is used as solvent only in liposome film formation operation)

[0046] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, and 20 mL of ethyl acetate were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45°C for 30 min, leaving a thin film on the wall of the flask.

[0047] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0048] Example 10: Preparation of 1 mg / mL Curcumin Dispersion (Methanol and Ethyl Acetate as Mixed Solvents in Liposome Film Formation Operation)

[0049] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, 10 mL of methanol, and 10 mL of ethyl acetate were added to a round-bottom flask and placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45°C for 30 min, leaving a thin film on the wall of the flask.

[0050] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0051] Example 11: Preparation of 1 mg / mL Curcumin Dispersion (Ethanol and Acetone Are Used as Mixed Solvents in Liposome Film Formation)

[0052] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, 10 mL of ethanol, and 10 mL of acetone were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45 °C for 30 min, leaving a thin film on the wall of the flask.

[0053] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0054] Example 12: Preparation of 1 mg / mL Curcumin Dispersion (using Sodium Carboxymethyl Cellulose instead of Tween-80)

[0055] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45 °C for 30 min, leaving a thin film on the wall of the flask.

[0056] (2) 30 mg of sodium carboxymethyl cellulose was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0057] Example 13: Preparation of 1 mg / mL Curcumin Dispersion (using Sodium Carboxymethyl Cellulose instead of Tween-80)

[0058] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,3-propylene glycol, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and ultrasonically dissolved in an ultrasonic cleaner until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45°C for 30 min, leaving a thin film on the wall of the flask.

[0059] (2) 60 mg of sodium carboxymethyl cellulose was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0060] Example 14: Preparation of 1 mg / mL Curcumin Dispersion (using Sodium Carboxymethyl Cellulose instead of Tween-80)

[0061] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45 °C for 30 min, leaving a thin film on the wall of the flask.

[0062] (2) 90 mg of sodium carboxymethyl cellulose was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0063] Example 15: Preparation of 1 mg / mL Curcumin Dispersion (Based on Tween-80, a small amount of sodium carboxymethyl cellulose was added)

[0064] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45 °C for 30 min, leaving a thin film on the wall of the flask.

[0065] (2) 60 mg of Tween-80 and 20 mg of sodium carboxymethyl cellulose were dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0066] Example 16: Preparation of 1 mg / mL Curcumin Dispersion (Preparation Temperature Increased)

[0067] (1) 30 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 60 °C for 30 min, leaving a thin film on the wall of the flask.

[0068] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 65° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 65° C. water bath for 30 min to obtain a 1 mg / mL curcumin dispersion.

[0069] Example 17: Preparation of 1.33 mg / mL Curcumin Dispersion

[0070] (1) 40 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,2-propylene glycol, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45°C for 30 min, leaving a thin film on the wall of the flask.

[0071] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1.33 mg / mL curcumin dispersion.

[0072] Example 18: Preparation of 1.66 mg / mL Curcumin Dispersion

[0073] (1) 50 mg of curcumin, 200 mg of soy lecithin, 100 mg of 1,3-propylene glycol, 10 mL of anhydrous ethanol, and 10 mL of ethyl acetate were added to a round-bottom flask, and the mixture was placed in an ultrasonic cleaner for ultrasonic dissolution until no particles were present. The organic solvent was evaporated on a rotary evaporator at 45 °C for 30 min, leaving a thin film on the wall of the flask.

[0074] (2) 60 mg of Tween-80 was dissolved in 30 mL of distilled water, heated to 45° C., and added to the flask dried in step (1), and ultrasonically dispersed in a 45° C. water bath for 30 min to obtain a 1.66 mg / mL curcumin dispersion.

[0075] 3 mL of each of the curcumin dispersions prepared in the above embodiments was taken in triplicate and allowed to stand at room temperature (25° C., the same below) for 10 days. The supernatant was taken every day, diluted 10 times with distilled water, and the absorbance at 425 nm was measured. The absorbance measured on the first day was taken as 100%, and the absorbance values ​​measured at different times were normalized. The relative absorbance values ​​of three parallel samples of the same sample were averaged to obtain the change of relative absorbance over time, as shown in Table 1:

[0076] Table 1

[0077]

[0078]

[0079] Compared with Example 1, relatively complete and stable liposomes were formed in Examples 2 and 4.

[0080] Comparison between Examples 1 and 4 shows that cholesterol is one of the main components of liposome preparations and plays an important role in the stability and dispersibility of liposomes.

[0081] Comparing Example 2 with Examples 1, 3, and 4, it can be seen that the propylene glycol used in this solution can not only replace cholesterol as one of the liposome preparations to form a film with curcumin, but also play an emulsification role after emulsification and dispersion, making the dispersion of poorly soluble curcumin more stable.

[0082] By comparing Examples 2 and 5, it can be seen that the amount of propylene glycol used as one of the liposome preparations in Example 2 is already substantially saturated, and the addition of traditional cholesterol does not improve the dispersion stability of the liposomes, which again illustrates that propylene glycol fully replaces cholesterol in the liposome preparation of this solution.

[0083] By comparing Examples 2, 8, 9, 10, and 11, it can be seen that the mixed solvent in this scheme not only satisfies the dissolution of curcumin and soybean lecithin at the same time in terms of solubility, but also because the boiling points of the components of the mixed solvent are close, it is beneficial to the synchronization during rotary evaporation and volatilization, and it is avoided as much as possible that curcumin or soybean lecithin is first precipitated during rotary evaporation film formation. Synchronous film formation is more conducive to the uniformity of the film, thereby further promoting the stability of hydrated dispersion.

[0084] It can be seen from Examples 12, 13, and 14 that when sodium carboxymethyl cellulose is used to disperse and emulsify the liposome system of this scheme, the short-term stability is improved with the increase in the amount of sodium carboxymethyl cellulose used, but long-term stability cannot be achieved at all.

[0085] Comparison between Examples 2 and 15 shows that, in the present solution of soy lecithin, propylene glycol and Tween-80, the addition of sodium carboxymethyl cellulose can improve the stability of the dispersion in the first few days, but as time goes by, its stability is worse than that without the addition of sodium carboxymethyl cellulose, indicating that the addition of sodium carboxymethyl cellulose to the solubilization combination of soy lecithin, propylene glycol and Tween-80 does not have a beneficial effect.

Claims

1. A method for preparing a curcumin dispersion for both medicinal and edible purposes, comprising the following steps: (1) dissolving soybean lecithin, propylene glycol and curcumin in a mixed solvent, and then removing the mixed solvent by rotary evaporation to form a film; (2) adding an aqueous dispersion containing an emulsifier to the film obtained in step (1) to hydrate and disperse the film; wherein: In the step (1), the mass ratio of soybean lecithin, propylene glycol, curcumin and mixed solvent is 1:0.01-2:0.01-0.3:10-300, and the mixed solvent is a mixture of ethanol and ethyl acetate; in the step (2), the emulsifier includes Tween-40, Tween-60 and Tween-80.

2. The method for preparing the edible and medicinal curcumin dispersion according to claim 1, wherein: The rotary evaporation temperature in step (1) is 45-65°C.

3. The method for preparing the edible and medicinal curcumin dispersion according to claim 1, wherein: The mass ratio of the emulsifier to the soybean lecithin in step (2) is 0.15-0.3:

1.

4. The method for preparing the edible and medicinal curcumin dispersion according to claim 1, wherein: The mass concentration of the emulsifier in the aqueous dispersion in step (2) is 0.05-0.2%.

5. The method for preparing the edible and medicinal curcumin dispersion according to claim 1, characterized in that: In step (2), the membrane is hydrated and dispersed by water bath ultrasonication, the water bath ultrasonication time is 5 to 30 minutes, and the water bath ultrasonication temperature is 45 to 65°C.

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