CN112190554B

CN112190554B - Curcumin preparation for improving curcumin dissolution characteristic and preparation method thereof

Info

Publication number: CN112190554B
Application number: CN202010947197.5A
Authority: CN
Inventors: 樊金玲; 韩兴曼; 张晓宇; 任国艳; 朱文学
Original assignee: Henan University of Science and Technology
Current assignee: Zaozuo Technology Co ltd
Priority date: 2020-09-10
Filing date: 2020-09-10
Publication date: 2022-04-26
Anticipated expiration: 2040-09-10
Also published as: CN112190554A

Abstract

The invention relates to a curcumin preparation for improving curcumin dissolution characteristics and a preparation method thereof, belonging to the technical field of functional foods and dietary nutritional supplements, wherein PGOS is adopted to load CCM to obtain PGOS-CCM nanoparticle negative carrier liquid, and the PGOS-CCM nanoparticle negative carrier liquid is combined with a CS solution within the pH range of 2.5-6.5 to obtain a PGOS-CCM/CS compound; when the PGOS-CCM nanoparticle negative carrier liquid is combined with the CS solution, the mass ratio of CS to PGOS is 1: 10-1: 50. Through the electrostatic interaction between PGOS and CS, CS film coating treatment is carried out on the PGOS-CCM nanoparticles to prepare core-shell type novel nanoparticles PGOS-CCM/CS, and the dissolution rate of CCM in vitro simulated gastrointestinal fluids is improved.

Description

Curcumin preparation for improving curcumin dissolution characteristic and preparation method thereof

Technical Field

The invention relates to a curcumin preparation, in particular to a curcumin preparation for improving the dissolution property of curcumin in human gastrointestinal tracts, which can be applied to functional foods, dietary nutritional supplements and medicines.

Background

Curcumin (CCM) has various biological activities of resisting oxidation, resisting inflammation, preventing and resisting cancer, protecting nerves, repairing and protecting liver function, and the like. Curcumin needs to be dissolved into free flavone molecules in the gastrointestinal tract firstly, and then is taken up and transported by small intestinal epithelial cells in a transmembrane transport mode taking passive diffusion as a main mode. Curcumin belongs to the fourth category of biological pharmaceutical classification systems (BCS), has low solubility and small permeability coefficient, is two main factors influencing the dissolution rate and the passive diffusion rate of curcumin, and is the main reasons of low curcumin absorption rate and poor bioavailability. Seriously restricts the exertion of the biological activity of the vitamin C and influences the application of the vitamin C in foods, nutritional health-care products and pharmaceutical preparations.

Phytoglycogen (PG) is prepared fromα-1,4 andα-1,6 glycosidically linked, highly branched, solubleα-D-glucan. Octenyl succinic acid esterified Phytoglycogen (PGOS) is an amphiphilic molecule formed by phytoglycogen substituted by Octenyl Succinic Anhydride (OSA), namely: the PG molecules have certain hydrophobicity due to the introduction of C8 clusters on the PG molecules while maintaining good water solubility. Besides the inner core which is relatively hydrophobic with PG molecules, the hydrophobic group carried by PGOS molecules can also interact with hydrophobic small molecule substances, and the outer shell still has the advantages of aqueous phase dispersion, biocompatibility and the like. Thus, PGOS can act as a vehicle to increase the solubility of hydrophobic molecules. Meanwhile, the carboxylic acid groups can be protonated to enable PGOS molecules to be negatively charged, and can generate electrostatic interaction with positively charged molecules to form a novel compound carrier system.

Chitosan (Chitson, CS) is a high molecular aminopolysaccharide prepared by deacetylation of chitin, and has pKa value of 6.5-6.8. The amino groups of the chitosan molecule can be protonated to take positive charge under acidic conditions. The chitosan can adsorb mucin on intestinal mucosa through electrostatic action, so that the chitosan has good mucosa adhesion. Meanwhile, chitosan also has the functions of opening the tight connection between epithelial cells of small intestine mucosa and assisting the drugs to enter the systemic circulation through intestinal mucosa by paracellular route. Therefore, chitosan can be bonded with negatively charged molecules such as protein, ionic polysaccharide, ionic surfactant and the like on the surface through electrostatic interaction to carry insoluble substances, so that the bioavailability of the insoluble substances is improved. The chitosan has the advantages of no toxicity, good biocompatibility and degradability, and the degradation product of the chitosan generally has no toxic or side effect on human bodies, does not accumulate in the human bodies and has no immunogenicity. Meanwhile, the chitosan and the derivatives thereof have the functions of reducing blood pressure, blood fat and blood sugar, resisting tumors, acids and ulcers and the like; therefore, CS and the derivatives thereof have extremely wide application prospects in the biomedical field and the pharmaceutical field.

Disclosure of Invention

In response to the problem of low dissolution rate of curcumin, the present invention describes a complex for improving the dissolution profile of curcumin in the human gastrointestinal tract. More specifically, complexes comprising octenyl succinylated phytoglycogen, chitosan and curcumin are described, which are useful for improving the dissolution rate of curcumin in the stomach and intestinal tract in foods, functional foods, dietary nutritional supplements, and pharmaceutical products, and for increasing the bioavailability of curcumin. The invention aims at providing a method for improving the dissolution rate of curcumin in the stomach and intestinal tracts, aims at providing a curcumin preparation, and aims at providing a method for preparing the curcumin preparation.

In order to achieve the purpose, the invention adopts the specific scheme that:

a curcumin preparation comprises octenyl succinylated phytoglycogen, chitosan and curcumin; the octenyl succinated phytoglycogen loads curcumin to obtain PGOS-CCM; obtaining PGOS-CCM/CS by the chitosan coating PGOS-CCM; the mass ratio of the chitosan to the octenyl succinate phytoglycogen is 1: 10-1: 50.

The invention also provides a method for improving the dissolution characteristic of curcumin, which comprises the steps of firstly preparing the PGOS-CCM/CS compound loaded with curcumin, and then placing the PGOS-CCM/CS compound in a gastrointestinal fluid environment for dissolution;

the PGOS-CCM/CS compound is prepared according to the following steps: loading CCM on PGOS to obtain PGOS-CCM nanoparticle negative carrier liquid, and mixing the PGOS-CCM nanoparticle negative carrier liquid with a CS solution within the pH range of 2.5-6.5 to obtain a PGOS-CCM/CS compound; when the PGOS-CCM nanoparticle negative carrier liquid is combined with the CS solution, the mass ratio of CS to PGOS is 1: 10-1: 50.

As a further optimization of the above method for improving curcumin dissolution characteristics, the process of loading PGOS with CCM is as follows: firstly, CCM is dissolved in ethanol solution to prepare CCM/ethanol solution; then mixing the CCM/ethanol solution with a PGOS aqueous solution, centrifuging, and taking the supernatant to obtain the final product.

The invention also provides a preparation method of the curcumin preparation, which comprises the following steps:

step one, preparing a PGOS-CCM nanoparticle negative carrier liquid by adopting PGOS loaded CCM, and adjusting the pH of the PGOS-CCM nanoparticle negative carrier liquid to 2.5-6.5;

dissolving CS in an acetic acid aqueous solution to prepare a CS/acetic acid solution, and adjusting the pH of the CS/acetic acid solution to be the same as the pH of the PGOS-CCM nanoparticle negative carrier liquid;

step three, mixing the PGOS-CCM nanoparticle negative carrier liquid obtained in the step one and the CS/acetic acid solution obtained in the step two, wherein the mixing ratio is as follows: the mass ratio of CS to PGOS is 1: 10-1: 50, and a PGOS-CCM/CS compound is obtained;

and step four, freeze-drying the PGOS-CCM/CS compound obtained in the step three to prepare a compound freeze-dried powder, namely the curcumin preparation.

As a further optimization of the preparation method, the preparation method of the PGOS-CCM nanoparticle negative carrier fluid of step one comprises: preparing a PGOS aqueous solution with the mass percent of 1.19%; preparing CCM/ethanol solution with the concentration of 4 mg/mL; mixing the PGOS aqueous solution and the CCM/ethanol solution according to the volume ratio of 99:1, shaking the table for 30min, centrifuging for 10min at 5000g, and sucking the supernatant to obtain the PGOS-CCM nanoparticle negative carrier liquid.

As a further optimization of the preparation method, the volume percentage of the acetic acid aqueous solution in the second step is 0.5%; the mass percentage of CS in the CS/acetic acid solution is 0.0238%.

As a further optimization of the preparation method, the pH value of the PGOS-CCM nanoparticle negative carrier liquid is adjusted to be 2.5, 3.5, 4.5, 5.5 or 6.5 in the step one. Further, the pH of the PGOS-CCM nanoparticle negative carrier liquid is adjusted to 2.5 or 6.5, at which the cumulative dissolution rate is higher.

And as a further optimization of the preparation method, the mass ratio of the CS to the PGOS in the third step is 1: 30.

Has the advantages that:

according to the invention, octenyl succinated phytoglycogen PGOS is adopted as a carrier to load curcumin to obtain octenyl succinated phytoglycogen-curcumin complex PGOS-CCM, and then the octenyl succinated phytoglycogen-curcumin complex PGOS-CCM is subjected to chitosan CS coating treatment by utilizing the electrostatic interaction between the octenyl succinated phytoglycogen PGOS and chitosan CS to prepare the octenyl succinated phytoglycogen-curcumin/chitosan complex PGOS-CCM/CS. Compared with the CCM, the PGOS-CCM and the PG-CCM, the dissolution rate of the octenyl succinated phytoglycogen-curcumin/chitosan compound PGOS-CCM/CS in a gastrointestinal fluid environment is remarkably increased, and particularly in an intestinal fluid environment, when the pH value is 2.5 or 6.5, the dissolution rate of the PGOS-CCM/CS compound is up to 64%, and the continuous dissolution rate of gastric and intestinal fluids is also higher and is about 87%. Therefore, the curcumin preparation prepared by the method can obviously improve the dissolution rate of CCM in gastrointestinal fluid.

Drawings

FIG. 1 is a graph of the effect of NaOH usage on pH and Δ pH of PGOS (A) solutions of various concentrations;

FIG. 2 is a graph of the effect of NaOH usage on pH and Δ pH of CS (B) solutions of varying concentrations;

FIG. 3 is a graph showing the effect of pH on OD values of a mixture of PGOS/CS complex (CS: PGOS at a mass ratio of 1: 10) and a supernatant;

FIG. 4 is a graph showing the effect of the OD value of the mixture of PGOS/CS complex (CS: PGOS at a mass ratio of 1: 20) and the supernatant;

FIG. 5 is a graph showing the effect of the OD value of the mixture of PGOS/CS complex (CS: PGOS at a mass ratio of 1: 30) and the supernatant;

FIG. 6 is a graph showing the effect of the OD value of the mixture of PGOS/CS complex (CS: PGOS at a mass ratio of 1: 40) and the supernatant;

FIG. 7 is a graph of the effect of pH on the PGOS-CCM dissolution profile in a gastric fluid environment;

FIG. 8 is a graph of the effect of pH on the PGOS-CCM dissolution profile in an intestinal fluid environment;

FIG. 9 is a graph of the effect of pH on the PGOS-CCM dissolution profile in a continuous environment of gastrointestinal fluid;

FIG. 10 is a graph of the effect of pH on the PGOS-CCM/CS dissolution profile in a gastric fluid environment;

FIG. 11 is a graph of the effect of pH on the PGOS-CCM/CS dissolution profile in an intestinal fluid environment;

FIG. 12 is a graph of the effect of pH on the PGOS-CCM/CS dissolution profile in a continuous environment of gastrointestinal fluid;

FIG. 13 is a graph comparing the dissolution rates of CCM, PG-CCM, PGOS-CCM, and PGOS-CCM/CS.

Detailed Description

A preparation for improving curcumin in vitro dissolution characteristics is prepared by loading PGOS with CCM to obtain PGOS-CCM nanoparticle negative carrier liquid, and combining with CS under different pH conditions to obtain PGOS-CCM/CS compound prepared under different pH conditions. The dissolution characteristics of the complex in vitro under conditions simulating gastrointestinal fluids were investigated.

The octenylsuccinylated Phytoglycogen (PGOS) is obtained by substituting PG (CAS registry number: 42482-06-4, molecular formula: C12H18O3, molecular weight: 210.27) with 6% (g/g) of OSA.

The chitosan (chitson, CS) CAS registry number 9012-76-4.

The steps for preparing the PGOS-CCM/CS complex are as follows:

the method comprises the following steps: dissolving the CCM in an ethanol solution to prepare a CCM/ethanol solution; then mixing the CCM/ethanol solution with a PGOS aqueous solution, centrifuging, and taking the supernatant to prepare a PGOS-CCM negative carrier liquid;

step two, regulating the pH of the PGOS-CCM loading solution prepared in the step one to 2.5, 3.5, 4.5, 5.5 or 6.5 respectively by hydrochloric acid, regulating the pH of the CS solution to the same pH, and mixing the two solutions according to the mass ratio of CS to PGOS of 1: 10-1: 50, and obtaining PGOS-CCM/CS compound prepared under different pH conditions.

The dissolution characteristics of the PGOS-CCM/CS complex in vitro under simulated gastrointestinal fluid conditions were studied: preparing in vitro simulated gastrointestinal fluid, adding 3mL of sample in a dialysis bag, wherein the concentration of the gastric and intestinal/ethanol solution is 50% 60 mL outside the bag, carrying out water bath at 37 ℃, taking 1mL of the solution outside the bag at intervals, and supplementing 1mL of the 50% gastric and intestinal ethanol solution. Dissolution experiments are respectively carried out under three conditions of gastric juice (2 h), intestinal juice (4 h) and gastrointestinal continuity (2 h of gastric juice and 4h of intestinal juice). The dissolution rate of CCM was measured.

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention.

Example 1: preparation of PGOS/CS Complex (Complex resulting from interaction of PGOS and CS)

(1) Determination of PGOS/CS quality ratio

The equivalent point of the change of the pH of the PGOS solution and the CS solution is determined by a potentiometric titration method, the NaOH solution is continuously and equivalently dripped, the changes of the pH of the PGOS solution and the CS solution with different concentrations along with the change of the NaOH dosage are respectively monitored until the pH reaches a stable value, the delta pH is calculated, the NaOH dosage consumed at the position with the maximum delta pH of each solution is determined, and the results are shown in figures 1 and 2.

From FIG. 1A₁It can be seen that the amount of NaOH used has little effect on the pH change of PGOS at different concentrations, and the change of Δ pH with the amount of NaOH was plotted below pH7, considering that CS can only be dissolved under acidic conditions (FIG. 1A)₂) And NaOH consumed at the position with the maximum delta pH is 3.5-3.7 mEq. For the CS solution (B of FIG. 2)₁And B₂) As the concentration increased, the NaOH consumed at the maximum Δ pH decreased gradually, and when the CS concentration was 0.05%, the NaOH consumed at the maximum Δ pH was 3.6 mEq. In this study, when NaOH was titrated into the PGOS and CS solutions, it was completely dissociated and produced Na + and OH-neutralizing the COO-of the PGOS molecule and the NH3 of the CS molecule, respectively⁺When the two NaOH equivalent weight consumed at the position with the maximum delta pH value under certain concentration condition is the same, the mass ratio of the two groups generating the maximum coagulation amount can be calculated. Therefore, the mass ratio of CS to PGOS is 1:10 ~ 1:50。

(2) Effect of pH on PGOS/CS Complex formation

After the two macromolecules with opposite charges are mixed, the absorbance of the mixed solution or the supernatant is very small, which indicates that the two macromolecules have no interaction; when the mixed solution is turbid, the absorbance value is very large, but the absorbance of the supernatant after centrifugation is still large, two possibilities exist, namely the two possibilities are explained to begin to interact to form a soluble compound, and the two possibilities are also explained to begin to reject or become insoluble under the influence of pH or other factors; when the mixture is turbid, the absorbance value is large, and the absorbance of the supernatant liquid is almost reduced to 0, which indicates that the two completely interact with each other and the maximum condensation is generated.

According to the research, the influence of pH on the formation of a PGOS/CS compound is researched by measuring the absorbance values of a mixed solution of PGOS and CS under different pH conditions and a supernatant obtained by mixing and centrifuging, the mass ratio of CS to PGOS is selected to be 1: 10-1: 40, and the result is shown in figures 3-6. When CS: PGOS is 1:30 (FIG. 5): when the pH value is 2-3.5, the absorbance of the mixed solution starts to increase, and the absorbance of the supernatant liquid rapidly increases to the maximum value, which shows that: PGOS interacts with CS to form soluble complexes. When the pH value is 3.5-4.5, the absorbance of the mixed solution enters a flash increasing stage, and the absorbance of the supernatant enters a flash decreasing stage, which shows that: the interaction between PGOS and CS is increasingly strengthened and soluble complexes begin to aggregate with each other to form insoluble aggregates. At pH4.5, the absorbance of the mixture increased to a maximum value, while the absorbance of the supernatant decreased to 0, indicating that: PGOS and CS are fully functional, forming the largest insoluble aggregates. The absorbance of the mixed solution is continuously reduced at the pH of 4.5-6.5, and the absorbance of the supernatant is rapidly increased from 0 when the pH is 4.5-5, is maintained at a higher level at the pH of 5-6, and is reduced at the pH of 6-6.5, which shows that: the interaction between PGOS and CS is continuously reduced and the insoluble aggregates are gradually disaggregated to form soluble complexes. When the pH value is 6.5-8, the absorbance of the mixed solution is continuously reduced until the minimum value; the absorbance of the supernatant also fluctuated within the minimum range, with no significant change, indicating that: the interaction of PGOS with CS gradually disappeared and the soluble complex was dissociated. The ratio of CS to PGOS (1: 10, 1: 20: 1:30, 1: 40) is changed, and the above rule is basically obeyed; at the same time, the amount of CS was reduced and the pH at which the formation of insoluble aggregates was completed was gradually reduced to 6, 5, 4.5 and 4, respectively.

Example 2:

a method for preparing curcumin preparation for improving in vitro dissolution characteristics of curcumin comprises the following steps:

the method comprises the following steps: preparing a PGOS aqueous solution with the concentration of 1.19 percent and a CCM/ethanol solution with the concentration of 4 mg/mL; mixing the PGOS aqueous solution and the CCM/ethanol solution according to a volume ratio of 99:1, shaking for 30min, centrifuging for 10min at 5000g, and sucking the supernatant to obtain the PGOS-CCM negative carrier liquid.

Step two: a CS/acetic acid solution was prepared at a concentration of 0.0238%, wherein the concentration of the acetic acid solution as a solvent was 0.5%.

Step three: and (3) respectively adjusting the pH of the two liquids obtained in the first step and the second step to 2.5, 3.5, 4.5, 5.5 and 6.5 by using hydrochloric acid and sodium hydroxide, and mixing the two liquids in a volume ratio of the CS/acetic acid solution to the PGOS-CCM negative carrier liquid of 1:4 to obtain PGOS-CCM/CS compounds under different preparation pH conditions.

Step four: and (3) mixing the solution prepared in the first step with 0.5% acetic acid solution in a volume ratio of 4:1 to obtain PGOS-CCM solutions with different preparation pH values, wherein the PGOS-CCM solutions are used as a control group of the compound prepared in the third step.

Step five: and (4) freeze-drying all the compound liquid to obtain the compound freeze-dried powder.

Example 3:

studying the dissolution characteristics of the complex in vitro under simulated gastrointestinal fluid conditions, comprising the steps of:

the method comprises the following steps: preparing in vitro simulated gastrointestinal fluid. 2.0 g NaCl was added to 100 mL deionized water and the pH was adjusted to 1.2 with concentrated HCl to give a simulated gastric fluid. Weighing 6.8 g of monopotassium phosphate, and dissolving in 650 mL of deionized water; the pH value is adjusted to 6.9 by 0.2M sodium hydroxide, and the simulated intestinal fluid is obtained.

Step two: respectively re-dissolving the prepared PGOS-CCM and PG-CCM/CS freeze-dried powders with different pH values into water, measuring OD values, and calculating CCM concentration according to a standard curve to ensure that the CCM concentration is 100 mu g/mL.

Step three: 3mL of sample is added into the dialysis bag, 60 mL of 50% gastric and intestinal/ethanol solution is added outside the bag, water bath is carried out at 37 ℃, 1mL of solution outside the bag is taken at intervals, and 1mL of 50% gastric and intestinal ethanol solution is supplemented. Dissolution experiments are respectively carried out under three conditions of gastric juice (2 h), intestinal juice (4 h) and gastrointestinal continuity (2 h of gastric juice and 4h of intestinal juice).

Step four: and (5) measuring the dissolution rate. The absorbance of the withdrawn liquid at 425nm was measured, and the dissolution rate was calculated by the following formula:

in the formula: a is CCM concentration (mu g/mL) outside a dialysis bag at a certain time point;

b is the CCM concentration in 1mL taken at all previous time points (μ g/mL).

The results are shown in FIGS. 7-12.

When PGOS-CCM is independently dissolved out in gastric juice and intestinal juice, the dissolution rate is hardly influenced by the preparation pH; the dissolution rate of all samples in intestinal fluid is about 51-55%, which is higher than the dissolution rate in gastric fluid (33-45%) (fig. 7, fig. 8). When PGOS-CCM/CS is dissolved out in gastric juice, the dissolution rates of samples prepared by different pH values are similar; however, when dissolved in intestinal fluids, the preparation pH significantly affects the sample dissolution rate: the dissolution rate is small and is about 46% -50% when the pH value is 4.5 and 5.5; the dissolution rate is higher and is about 64 percent when the pH is 2.5 and 6.5; the dissolution rate at pH3.5 was centered at about 58% (FIGS. 10, 11).

The continuous elution of the PGOS-CCM and PGOS-CCM/CS samples was matched with the results of the elution alone (FIGS. 9, 12), i.e.: in a continuous dissolution experiment, the dissolution rates of PGOS-CCM samples prepared at different pH values are similar in the whole experiment stage; the dissolution curves have no significant difference, namely the preparation pH has no significant influence on the dissolution of PGOS-CCM. The dissolution curves of PGOS-CCM/CS samples prepared at different pH values are greatly different: wherein, the accumulative dissolution rate is lower at pH4.5 and 5.5, which is about 63%; the dissolution curves of the two are not obviously different. The cumulative dissolution rates at pH2.5 and 6.5 were high, about 87%; the dissolution curves of the two have no obvious difference; but the difference was significant compared to pH4.5 and 5.5. The cumulative dissolution rate at pH3.5 was centered at about 74%.

When the pH value of the PGOS-CCM/CS and the PGOS-CCM is 2.5 and 6.5, the dissolution curve difference of the PGOS-CCM and the PGOS-CCM is obvious, namely the dissolution rate of the PGOS-CCM is obviously increased after the PGOS-CCM is subjected to CS film coating; under other pH conditions, the dissolution curves of the two have no significant difference.

The results of comparison of the dissolution rate curves with time for CCM, PG-CCM, PGOS-CCM and PGOS-CCM/CS (preparation pH 2.5) samples were obtained under the conditions for continuous dissolution of gastric and intestinal fluids, and are shown in FIG. 13. Since the pH of the preparation had no significant effect on the dissolution curves of the PG-CCM and PGOS-CCM samples, deionized water was used for the preparation of these two samples, and the pH was not adjusted. The dissolution rate and dissolution rate of the PGOS-CCM/CS composite sample are significantly higher than those of free CCM, and also significantly higher than those of PGOS-CCM and PG-CCM.

It should be noted that the above-mentioned embodiments illustrate rather than limit the scope of the invention, which is defined by the appended claims. It will be apparent to those skilled in the art that certain insubstantial modifications and adaptations of the present invention can be made without departing from the spirit and scope of the invention.

Claims

1. A curcumin formulation characterized by: including octenyl succinate phytoglycogen, chitosan and curcumin; the octenyl succinated phytoglycogen loads curcumin to obtain PGOS-CCM; coating the chitosan on PGOS-CCM to obtain PGOS-CCM/CS within the pH range of 2.5-6.5; the mass ratio of the chitosan to the octenyl succinate phytoglycogen is 1: 10-1: 50.

2. A method for improving curcumin in vitro dissolution characteristics is characterized in that: firstly, preparing a PGOS-CCM/CS compound loaded with curcumin, and then placing the PGOS-CCM/CS compound in a gastrointestinal fluid environment for dissolution;

3. The method for improving in vitro dissolution characteristics of curcumin as claimed in claim 2, wherein: the process of loading CCM by the PGOS is as follows: firstly, CCM is dissolved in ethanol solution to prepare CCM/ethanol solution; then mixing the CCM/ethanol solution with a PGOS aqueous solution, centrifuging, and taking the supernatant to obtain the final product.

4. A method for preparing curcumin preparation is characterized by comprising the following steps: the method comprises the following steps:

5. The method for preparing a curcumin preparation according to claim 4, wherein: step one, the preparation method of the PGOS-CCM nanoparticle negative carrier liquid comprises the following steps: preparing a PGOS aqueous solution with the mass percent of 1.19%; preparing CCM/ethanol solution with the concentration of 4 mg/mL; mixing the PGOS aqueous solution and the CCM/ethanol solution according to the volume ratio of 99:1, shaking the table for 30min, centrifuging for 10min at 5000g, and sucking the supernatant to obtain the PGOS-CCM nanoparticle negative carrier liquid.

6. The method for preparing a curcumin preparation according to claim 4, wherein: the volume percentage of the acetic acid aqueous solution in the second step is 0.5 percent; the mass percentage of CS in the CS/acetic acid solution is 0.0238%.

7. The method for preparing a curcumin preparation according to claim 4, wherein: step one, the pH value of the PGOS-CCM nanoparticle negative carrier liquid is adjusted to be 2.5, 3.5, 4.5, 5.5 or 6.5.

8. The method for preparing a curcumin preparation according to claim 7, wherein: the pH of the PGOS-CCM nanoparticle negative carrier fluid is adjusted to 2.5 or 6.5.

9. The method for preparing a curcumin preparation according to claim 4, wherein: and step three, the mass ratio of the CS to the PGOS is 1: 30.