Preparation method, product and application of curcumin-beta-cyclodextrin inclusion compound

Abstract

The invention relates to the technical field of traditional Chinese medicine preparations, in particular to a preparation method, a product and application of a curcumin-beta-cyclodextrin inclusion compound. The preparation method of the curcumin-beta-cyclodextrin inclusion compound comprises the following steps: dissolving curcumin in absolute ethyl alcohol to obtain a curcumin ethanol solution; adding the curcumin ethanol solution into a beta-cyclodextrin solution, and carrying out ultrasonic treatment; after the ultrasonic treatment is finished, sequentially refrigerating, carrying out suction filtration and freeze-drying to obtain the curcumin-beta-cyclodextrin inclusion compound. The preparation method is simple, the clathration efficiency is high, the process time consumption is short, the curcumin-beta-cyclodextrin clathrate compound prepared by the method is good in stability, and a reliable basis is provided for subsequent preparation development.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicine preparations, and particularly to a preparation method, product and application of curcumin-β-cyclodextrin inclusion compound. Background Art

[0002] Curcumin is a hydrophobic polyphenolic compound extracted from the rhizomes of Curcuma longa L. of the Zingiberaceae family, and its chemical structure is 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione. This compound has significant antioxidant and cytoprotective functions, especially outstanding in scavenging free radicals. Experimental data shows that its efficiency in scavenging DPPH free radicals can reach 92% (concentration 50 μM). In the field of liver protection, curcumin can effectively enhance the activity of key antioxidant enzymes. In an alcoholic liver injury model, it can increase the activity of superoxide dismutase (SOD) by 2.3 times and the activity of glutathione peroxidase (GSH-Px) by 1.8 times. In addition, curcumin can up-regulate the expression of heme oxygenase-1 (HO-1) by activating the Nrf2 signaling pathway, and this mechanism enables it to have synergistic effects such as anti-inflammatory and anti-apoptotic effects, showing multi-target intervention characteristics in the prevention and treatment of oxidative stress-related diseases. Despite the above pharmacological advantages, curcumin faces three major technical obstacles in practical applications: First, its extremely low water solubility (solubility at 25 °C is 11 ng / mL) results in a bioavailability of less than 1% for the preparation; second, its poor chemical stability, with a degradation rate of 78% in pH 7.4 buffer solution within 30 minutes; third, it has a significant first-pass effect in the liver and intestine, and it is difficult to reach an effective therapeutic level in blood drug concentration after oral administration. Although existing inclusion technologies can partially improve solubility, the traditional grinding method has a low encapsulation rate, and the solution method has problems such as excessive organic solvent residues (>500 ppm) and too long process time (>8 hours), and the inclusion compound is prone to drug leakage under high temperature and high humidity conditions.

[0003] Therefore, providing a method for encapsulating curcumin with high inclusion efficiency, short process time and good stability is of great significance for the application of curcumin and the technical field of traditional Chinese medicine preparations. Summary of the Invention

[0004] Based on the above, the present invention provides a preparation method, product and application of curcumin-β-cyclodextrin inclusion compound.

[0005] To achieve the above object, the present invention provides the following solutions:

[0006] One of the technical solutions of the present invention, a preparation method of curcumin-β-cyclodextrin inclusion compound, includes the following steps:

[0007] Dissolve curcumin in absolute ethanol to obtain a curcumin ethanol solution;

[0008] Add the curcumin ethanol solution to the β-cyclodextrin solution and perform ultrasonic treatment;

[0009] After the ultrasonic treatment, refrigerate, filter by suction, and freeze-dry in sequence to obtain the curcumin-β-cyclodextrin inclusion complex.

[0010] The second technical solution of the present invention is a curcumin-β-cyclodextrin inclusion complex prepared by the above preparation method.

[0011] The third technical solution of the present invention is the application of the above curcumin-β-cyclodextrin inclusion complex in the preparation of liver-protecting drugs.

[0012] The present invention discloses the following technical effects:

[0013] The preparation method of the present invention is simple to operate, has a high inclusion efficiency, short process time, meets the requirements of industrial production, and has a wide application prospect.

[0014] The curcumin-β-cyclodextrin inclusion complex prepared by the method of the present invention has good stability, providing a reliable basis for the subsequent development of preparations. Description of the Drawings

[0015] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, other drawings can be obtained based on these drawings without creative efforts.

[0016] Figure 1 It is the linear relationship between curcumin concentration and absorbance value.

[0017] Figure 2 It is the influence of different material ratios on the comprehensive score of the curcumin-β-cyclodextrin inclusion complex.

[0018] Figure 3 It is the influence of different ultrasonic times on the comprehensive score of the curcumin-β-cyclodextrin inclusion complex.

[0019] Figure 4 It is the influence of different ultrasonic powers on the comprehensive score of the curcumin-β-cyclodextrin inclusion complex.

[0020] Figure 5 It is the verification experiment of the ultrasonic inclusion method for the curcumin-β-cyclodextrin inclusion complex. Detailed Embodiments

[0021] The various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be construed as a limitation on the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0022] It should be understood that the terms used in the present invention are only for describing specific embodiments and are not intended to limit the present invention. Additionally, for the numerical ranges in the present invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any intermediate value within any stated value or stated range, as well as each smaller range between any other stated value or intermediate value within the stated range, is also included in the present invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0023] Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention pertains. Although the present invention only describes preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials related to the documents. In case of conflict with any incorporated document, the content of this specification shall prevail.

[0024] Without departing from the scope or spirit of the present invention, various improvements and changes can be made to the specific embodiments of the present invention specification, which are obvious to those skilled in the art. Other embodiments obtained from the specification of the present invention are obvious to those skilled in the art. The specification and examples of the present invention are merely exemplary.

[0025] Regarding the use of "comprising", "including", "having", "containing", etc. in this article, they are all open-ended terms, meaning including but not limited to.

[0026] Cyclodextrin (CD for short) is a cyclic oligosaccharide compound formed by 6 - 12 D - glucose units through amylase hydrolysis and cyclization reactions. The glucose units in its molecule are connected by 1,4 - glycosidic bonds. According to the difference in the number of glucose units, it is mainly divided into three types: α - (6 units), β - (7 units), and γ - (8 units). This molecule has a unique cavity - like ring structure, showing a hollow cylinder shape with two open ends. The larger open end is the hydrophilic surface, and the smaller open end forms a hydrophobic cavity. Due to the lack of a reducing end, its chemical properties are stable and it has no reducing activity. This structural feature enables it to include various organic molecules, inorganic ions, and gas compounds through hydrophobic interactions. In terms of biodegradability, α - amylase and colonic flora can gradually degrade cyclodextrin, and the degradation rate is α - CD < β - CD < γ - CD, while glucoamylase has no degradation effect on it. Its physical stability is manifested as alkali resistance and mechanical tolerance, but it is prone to structural damage in an acidic environment. Toxicological studies have shown that it has good safety through the oral route.

[0027] The β - cyclodextrin (β - CD) used in the present invention is a white crystalline powder, and its water solubility is significantly affected by temperature. Its solubility is about 1.85 g / 100 mL at 20 °C and can be increased to 4.5 g / 100 mL at 60 °C.

[0028] The first aspect of the present invention provides a method for preparing a curcumin - β - cyclodextrin inclusion complex, comprising the following steps:

[0029] Dissolve curcumin in absolute ethanol to obtain a curcumin ethanol solution;

[0030] Add the curcumin ethanol solution to the β - cyclodextrin solution and perform ultrasonic treatment;

[0031] After the ultrasonic treatment, refrigerate, filter by suction, and freeze - dry in sequence to obtain the curcumin - β - cyclodextrin inclusion complex.

[0032] The present invention does not make a special limitation on the amount of absolute ethanol used, and the amount of absolute ethanol used only needs to be able to dissolve curcumin sufficiently.

[0033] In a preferred embodiment of the present invention, the mass ratio of curcumin to β - cyclodextrin in the β - cyclodextrin solution is 1:(2 - 10). Further preferably, the mass ratio of curcumin to β - cyclodextrin is 1:(2 - 4).

[0034] In a preferred embodiment of the present invention, the β - cyclodextrin solution is a saturated solution; the solvent of the β - cyclodextrin solution is water.

[0035] In a preferred embodiment of the present invention, the way of adding the curcumin ethanol solution to the β-cyclodextrin solution is by dropping; the temperature of the β-cyclodextrin solution is 60 °C.

[0036] In a preferred embodiment of the present invention, the temperature of the ultrasonic treatment is 50 °C, the power is 40 - 100 W, and the time is 15 - 120 min. Further preferably, the power of the ultrasonic treatment is 70 - 90 W, and the time is 30 - 100 min; more preferably, the time of the ultrasonic treatment is 50 - 70 min.

[0037] In some specific embodiments of the present invention, a numerical control ultrasonic cleaner is used for ultrasonic treatment.

[0038] The present invention significantly improves the inclusion efficiency through ultrasonic-assisted technology.

[0039] In a preferred embodiment of the present invention, the temperature of the refrigeration is 0 - 8 °C, and the time is 24 h.

[0040] The suction filtration is vacuum suction filtration.

[0041] The present invention does not make special limitations on the parameter settings (vacuum degree, temperature) of freeze-drying, and the parameter settings of freeze-drying well-known to those skilled in the art can be adopted.

[0042] The washing is specifically carried out by washing twice with absolute ethanol and three times with ethyl acetate in sequence.

[0043] The present invention determines the curcumin content in the inclusion compound by ultraviolet spectrophotometry, and the detection wavelength is 426 nm.

[0044] The present invention realizes the efficient molecular inclusion of curcumin and β-cyclodextrin by systematically optimizing the ultrasonic-assisted inclusion process parameters, significantly improves the physicochemical properties and bioavailability of the inclusion compound, and provides an innovative solution for the industrial production of curcumin preparations.

[0045] Based on the principle of molecular inclusion, the present invention adopts ultrasonic synergistic regulation technology, and prepares curcumin-β-cyclodextrin inclusion compounds with high encapsulation efficiency and high stability by optimizing the material ratio, ultrasonic parameters and post-treatment process, providing technical support for the application of curcumin in anti-tumor, anti-inflammatory and other pharmaceutical preparations.

[0046] The present invention significantly improves the inclusion efficiency and product stability by optimizing the ultrasonic process parameters (power 80 W, time 60 min) and the material ratio (the mass ratio of curcumin to β-cyclodextrin is 1:4). Compared with the traditional process, the present invention has the advantages of high inclusion rate, low solvent residue, short process cycle, etc. The obtained inclusion compound has significantly enhanced water solubility, excellent stability under high temperature (40 °C), light and long-term storage conditions, and is suitable for the development of oral solid preparations and functional foods.

[0047] In the second aspect of the present invention, a curcumin-β-cyclodextrin clathrate prepared by the above preparation method is provided.

[0048] In the third aspect of the present invention, the application of the above curcumin-β-cyclodextrin clathrate in the preparation of liver-protecting drugs is provided.

[0049] The technical solutions of the present invention are all conventional solutions in the art unless otherwise specified. The reagents or raw materials used are all purchased from commercial channels or are publicly available unless otherwise specified.

[0050] The technical solutions provided by the present invention will be described in detail below in conjunction with embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0051] Example 1: Preparation and content determination of curcumin-β-cyclodextrin clathrate

[0052] 1. Preparation of clathrate (ultrasonic method)

[0053] Weigh 0.135 g of curcumin and dissolve it in 10 mL of absolute ethanol, stir until completely dissolved to obtain a curcumin ethanol solution. Weigh β-cyclodextrin according to the mass ratio of curcumin:β-cyclodextrin of 1:2 and dissolve it in 40 mL of distilled water to form a saturated aqueous solution. Place the β-cyclodextrin solution in a numerically controlled ultrasonic cleaner, control the water temperature at 60 °C, the ultrasonic power at 70 W, slowly dropwise add the curcumin ethanol solution and stir, and then perform ultrasonic treatment at 50 °C for 30 min for the reaction. After the reaction is completed, refrigerate the mixed solution for 24 h (the refrigeration temperature can be 0-8 °C), perform vacuum filtration, wash the filter residue with absolute ethanol and ethyl acetate in turn, freeze-dry for 24 h, and grind to obtain curcumin-β-cyclodextrin clathrate powder (abbreviation: clathrate).

[0054] The calculation formulas for the curcumin yield and inclusion rate are as follows:

[0055] Comprehensive score = (yield × 0.3 + inclusion rate × 0.7) × 100;

[0056] Yield = amount of clathrate obtained / (amount of inclusion material input + amount of curcumin input) × 100%;

[0057] Inclusion rate = mass of curcumin in clathrate / amount of curcumin input × 100%.

[0058] 2. Content determination of curcumin in clathrate (ultraviolet spectrophotometry)

[0059] (1) Preparation of reference solution: Weigh 0.0105 g of curcumin reference substance, pour it into absolute ethanol, dissolve it by ultrasonic treatment, then pour it into a 10 ml brown volumetric flask, and make the absolute ethanol volume to the scale for standby as the reference solution.

[0060] (2) Standard curve establishment: Accurately weigh 50, 100, 150, 200, 250, 300 μL of 10 mg curcumin reference solution into a 50 ml volumetric flask, add absolute ethanol to the scale, shake well, and obtain reference solutions with mass concentrations of 0.001 mg / ml, 0.002 mg / ml, 0.003 mg / ml, 0.004 mg / ml, 0.005 mg / ml respectively. Then take a certain amount and measure the absorbance at 426 nm, and perform linear regression on the absorbance (Y) against the curcumin mass concentration (X) to obtain the linear regression equation Y = 190.91X - 0.0405 (R 2 = 0.9981), indicating that curcumin has a good linear relationship in the range of 0.001 - 0.006 mg / mL (as Figure 1 shown).

[0061] (3) Preparation of test samples: Take 200 μl of the prepared curcumin-β-cyclodextrin inclusion complex ethanol solution (the preparation method of the curcumin-β-cyclodextrin inclusion complex ethanol solution is the same as that in the above-mentioned "(2) Standard curve establishment") into a 50 ml volumetric flask, dilute to the scale with absolute ethanol, use absolute ethanol as the blank, measure the absorbance of the sample at 426 nm, and calculate the yield and inclusion rate.

[0062] (4) Methodological verification:

[0063] Precision test: Weigh 5 portions of 100 mg curcumin-β-cyclodextrin inclusion complex (the feeding ratio is 1:4, and the feeding ratio refers to the mass ratio of curcumin:β-cyclodextrin, the same below), dilute with absolute ethanol to a concentration of 3.5 μg / ml solution, measure the absorbance at 426 nm, zero with absolute ethanol, and measure continuously for 5 times. The absorbances are 0.664, 0.663, 0.663, 0.664, 0.664, RSD = 0.82% (n = 5), indicating that the precision of the measurement method is good.

[0064] Stability test: Weigh 5 portions of 100 mg curcumin-β-cyclodextrin inclusion complex (the feeding ratio is 1:4), dilute with absolute ethanol to a concentration of 3.5 μg / ml solution, measure the absorbance at 0, 2, 4, 12, 24 h respectively. The absorbances are 0.664, 0.668, 0.675, 0.671, 0.669, RSD = 0.60% (n = 5). The results show that the solution is good in terms of stability.

[0065] Repeatability test: Weigh 5 portions of 100 mg of curcumin-β-cyclodextrin inclusion complex (feeding ratio 1:4), dilute with absolute ethanol, and measure the absorbance at 426 nm. The absorbance values are 0.805, 0.763, 0.751, 0.803, and 0.798 respectively. RSD = 0.43%, and the data results show good repeatability.

[0066] Recovery test: Weigh 5 portions of 100 mg of curcumin-β-cyclodextrin inclusion complex (feeding ratio 1:4), prepare a solution with a curcumin concentration of 0.004 mg / ml, and add appropriate amounts of reference substances respectively. Measure the absorbance at 426 nm, use absolute ethanol as the blank for zero adjustment, calculate, and the absorbance values are 0.762, 0.759, 0.762, 0.763, and 0.755 respectively. The average recovery rate is 97.78%, and the RSD of the recovery rate calculated therefrom is 0.43%. The results show that the recovery rate of the method is relatively high and it can be carried out.

[0067] Example 2: Optimization of the inclusion process by single factor

[0068] 1. Optimization of the material ratio

[0069] Fix the ultrasonic time at 30 min and the power at 70 W, and investigate the influence of the material ratio (1:2 to 1:10) on the inclusion effect. The results are as Figure 2 shown. The results show that when the material ratio is 1:2, the comprehensive score is the highest (34.11), the inclusion rate is 27.3%, and the yield is 49.8%.

[0070] 2. Optimization of the ultrasonic time

[0071] Fix the material ratio at 1:2 (i.e., the mass ratio of curcumin:β-cyclodextrin is 1:2) and the power at 70 W, and investigate the influence of the ultrasonic time (15 - 120 min) on the inclusion effect. The results are as Figure 3 shown. When the ultrasonic time is 60 min, the comprehensive score reaches 27.8, the inclusion rate is 35%, and the yield is 11%.

[0072] 3. Optimization of the ultrasonic power

[0073] Fix the material ratio at 1:2 and the time at 60 min, and investigate the influence of the power (40 - 100 W) on the inclusion effect. The results are as Figure 4 shown. When the power is 80 W, the comprehensive score is the highest (35.3), the inclusion rate is 44%, and the yield is 15%.

[0074] Example 3: Optimization of the process by orthogonal experiment

[0075] Adopt L9(3 4)Orthogonal table, with the material ratio (A), ultrasonic time (B), and power (C) as factors and the comprehensive score as the index, to optimize the process. The factor levels of the orthogonal experimental design are shown in Table 1; the results of the orthogonal experiment are shown in Table 2; the analysis of variance of the results of the orthogonal experiment is shown in Table 3. The results are as follows:

[0076] Optimal combination: A3B2C2 (material ratio 1:4, ultrasonic time 60 min, power 80 W), comprehensive score 44.2;

[0077] Order of primary and secondary factors: ultrasonic power (C) > ultrasonic time (B) > material ratio (A);

[0078] Based on the optimal process conditions A3B2C2 obtained from the results of the orthogonal experiment, it is necessary to determine its stability and reliability. Therefore, for the above-mentioned optimal process conditions, repeated verification experiments were conducted. The results are shown in Table 4 and Figure 5 as shown. From the results in Table 4, it can be seen that the verification results are close to the data in the orthogonal experiment. Therefore, it can be considered that the data of this experiment are relatively reliable and have a relatively high accuracy. Therefore, it can be concluded that the optimal process conditions are feasible.

[0079] Table 1 is the factor level table of the L9(3 4 )orthogonal experimental design with ultrasonic powers of 70 W, 80 W, and 90 W.

[0080]

[0081] Table 2 is the result table of the orthogonal experiment of curcumin-β-cyclodextrin inclusion complex.

[0082]

[0083]

[0084] Table 3 is the analysis of variance table of the results of the orthogonal experiment of curcumin β-cyclodextrin inclusion complex.

[0085]

[0086] Table 4 is the verification experiment table of curcumin-β-cyclodextrin inclusion complex by ultrasonic encapsulation method.

[0087]

[0088]

[0089] Example 4: Evaluation of the stability of the inclusion complex (evaluate the stability of the curcumin-β-cyclodextrin inclusion complex prepared with the optimal combination in Example 3)

[0090] 1. Volatility test

[0091] Weigh 250 mg of curcumin-β-cyclodextrin inclusion complex and the physical mixture of curcumin and β-cyclodextrin (mixed according to the feeding ratio of curcumin:β-cyclodextrin = 1:4) in three portions each, and place them in petri dishes covered with tin foil. Place them in a digital display forced air drying oven at 25 °C for 5 days. Sample and weigh them at the 0th, 1st, 2nd, 3rd, 4th, and 5th days respectively, and take the average value.

[0092] As shown in Table 5, after being placed at 25 °C for 5 days, the weight loss rate of the inclusion complex is 13.87%, which is significantly lower than the weight loss rate of the physical mixture, 25.87% (the preparation method of the physical mixture is as follows: mixed according to the feeding ratio of curcumin:β-cyclodextrin = 1:4). It can be seen that after curcumin is included by β-cyclodextrin at room temperature, its volatility significantly decreases.

[0093] Table 5 shows the results of the volatility test of the inclusion complex and the mixture (%).

[0094]

[0095] The calculation formula for the weight loss rate:

[0096] Weight loss rate (%) = (W0 - W t ) × 100 / W0;

[0097] where, W0: initial mass;

[0098] W t : mass after treatment.

[0099] 2. Thermal stability test

[0100] Weigh 250 mg of curcumin-β-cyclodextrin inclusion complex and the physical mixture of curcumin and β-cyclodextrin (mixed according to the feeding ratio of curcumin:β-cyclodextrin = 1:4) in three portions each, and place them in petri dishes covered with tin foil. Place them in a digital display forced air drying oven at 60 °C and 80 °C for 5 days respectively. Sample at the 0th, 1st, 2nd, 3rd, 4th, and 5th days respectively, and determine the content of curcumin according to the method of Example 1 (2. Determination of the content of curcumin in the inclusion complex (ultraviolet spectrophotometry)), and take the average value. The results are shown in Table 6.

[0101] Table 6 shows the results of the thermal stability test of the inclusion complex and the mixture (%).

[0102]

[0103]

[0104] As can be seen from Table 6, after the inclusion complex and the mixture were treated at 60°C and 80°C for 5 days respectively, the volatilization rates of the inclusion complex and the mixture reached 47.11%, 72.16% and 61.19%, 88.79% respectively after being placed at 60°C and 80°C for 5 days, and the volatilization rate of curcumin in the mixture was significantly faster than that of the inclusion complex. This shows that within a certain temperature range, after curcumin is included, its thermal stability is significantly enhanced. With the increase of temperature, both the volatilization rate and the volatilization speed of the inclusion complex increase, indicating that although the thermal stability of the curcumin inclusion complex increases after being included by β-cyclodextrin, too high a temperature is still not conducive to the storage of the curcumin inclusion complex.

[0105] Calculation formula for the retention rate of curcumin in the inclusion complex:

[0106] Retention rate (%) = (C t / C0) × 100;

[0107] Among them, C0: initial mass;

[0108] C t : mass of curcumin after heat treatment.

[0109] 3. Photodegradation resistance test

[0110] Weigh 250 mg of curcumin-β-cyclodextrin inclusion complex and physical mixture of curcumin and β-cyclodextrin (mixed according to the feeding ratio of curcumin:β-cyclodextrin = 1:4) in three portions each and place them in petri dishes. Place them in a light incubator and place them for 5 days under the conditions of a light intensity of 4000 Lx and a temperature of 23.5°C. Sampling is carried out at 0, 1, 2, 3, 4, and 5 days respectively, and the curcumin content is measured according to the method of Example 1 (2. Determination of curcumin content in the inclusion complex (ultraviolet spectrophotometry)), and the average value is taken. The results are shown in Table 7.

[0111] Table 7 shows the results of the photodegradation resistance test of the inclusion complex and the mixture (%).

[0112]

[0113]

[0114] As can be seen from Table 7, after 5 days of illumination at 4000 Lx, the volatilization rates of the inclusion complex and the mixture are 17.43% and 59.45% respectively, that is, the retention rate of curcumin in the inclusion complex is 82.57%, and that of the physical mixture is only 40.55%. Moreover, the volatilization speed of curcumin in the mixture is significantly faster than that of curcumin in the inclusion complex. The results show that after curcumin is made into a β-cyclodextrin inclusion complex, its photodegradation resistance is significantly enhanced.

[0115] 4. In vitro dissolution test

[0116] Preparation of degassed pH 6.6 phosphate buffer solution: Accurately weigh 1.74 g of sodium dihydrogen phosphate, 2.7 g of disodium hydrogen phosphate and 1.7 g of sodium chloride according to the Chinese Pharmacopoeia. Add 400 ml of distilled water to dissolve them, place them in an ultrasonic cleaner for 15 min, and prepare the buffer solution for use in a water bath.

[0117] Take 50 mg each of the inclusion complex and the mixture, and place them separately in the rotating basket of the dissolution apparatus. The water bath temperature is (37 ± 0.5) °C, and the paddle rotation speed is 100 r / min. Using 300 mL of degassed pH 6.6 phosphate buffer solution as the dissolution medium, lower the rotating basket into the medium solvent. Start timing when the drug contacts the liquid surface. Take 1 mL of sample at 10, 30, 60, 90, 120, and 150 min respectively (and immediately add 1 mL of the same-temperature medium at the same time). Determine the content of curcumin according to the method in Example 1 (2. Determination of the content of curcumin in the inclusion complex (ultraviolet spectrophotometry)). The results are shown in the following table.

[0118] Table 8 shows the dissolution rate determination results (%) of the inclusion complex and the mixture.

[0119]

[0120] It can be seen from Table 8 that in the pH 6.6 phosphate buffer solution, the cumulative dissolution rate of the inclusion complex at 150 min is 65.77%, higher than that of the physical mixture (61.21%), and the dissolution rate is significantly improved. The difference in the cumulative dissolution percentage between the two is not very large. However, the dissolution rate of the inclusion complex is significantly faster than that of the mixture, indicating that after curcumin is included, its dissolution rate is significantly increased.

[0121] Calculation formula for the cumulative dissolution rate of the inclusion complex:

[0122] Cumulative dissolution rate (%) = (M t / M0) × 100;

[0123] where M0: initial mass;

[0124] M t : The mass of curcumin measured in the dissolution medium at time point t.

[0125] In the present invention, curcumin-β-cyclodextrin inclusion complex is prepared by the ultrasonic method. Based on single factors and through orthogonal optimization, the optimal extraction process for the comprehensive score of curcumin-β-cyclodextrin inclusion complex is as follows: the feed ratio is 1:4 (g / g), the ultrasonic time is 60 min, and the ultrasonic power is 80 W. The corresponding comprehensive score of curcumin-β-cyclodextrin inclusion complex is 44.2, the inclusion rate is 52%, and the yield is 26%. The inclusion complex significantly improves the light and heat stability and dissolution performance of curcumin, providing a reliable basis for subsequent formulation development.

[0126] The embodiments described above are only descriptions of the preferred embodiments of the present invention and do not limit the scope of the present invention. Without departing from the spirit of the present invention's design, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

Claims

1. A preparation method of curcumin-β-cyclodextrin inclusion compound, characterized in that, Comprising the following steps: Dissolve curcumin in absolute ethanol to obtain a curcumin ethanol solution; Add the curcumin ethanol solution to a β-cyclodextrin solution and perform ultrasonic treatment; After the ultrasonic treatment, refrigerate, filter by suction, and freeze-dry in sequence to obtain the curcumin-β-cyclodextrin inclusion complex.

2. The preparation method of the curcumin-β-cyclodextrin inclusion complex according to claim 1, characterized in that, The mass ratio of the curcumin to β-cyclodextrin in the β-cyclodextrin solution is 1:(2 - 10).

3. The preparation method of the curcumin-β-cyclodextrin inclusion complex according to claim 1, wherein, The β-cyclodextrin solution is a saturated solution; the solvent of the β-cyclodextrin solution is water.

4. The preparation method of curcumin-β-cyclodextrin clathrate according to claim 1, characterized in that, The method of adding the curcumin ethanol solution to the β-cyclodextrin solution is dropwise addition; the temperature of the β-cyclodextrin solution is 60°C.

5. The preparation method of the curcumin-β-cyclodextrin inclusion complex according to claim 1, characterized in that, The temperature of the ultrasonic treatment is 50°C, the power is 40 - 100 W, and the time is 15 - 120 min.

6. The preparation method of curcumin-β-cyclodextrin inclusion complex according to claim 1, wherein The temperature of the refrigeration is 0 - 8°C, and the time is 24 h.

7. The curcumin-β-cyclodextrin inclusion complex prepared by the preparation method according to any one of claims 1 - 6.

8. Use of the curcumin-β-cyclodextrin inclusion complex according to claim 7 in the preparation of a liver-protecting drug.

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