A method for preparing a sulfobutyl-beta cyclodextrin / coenzyme Q10 inclusion compound

Abstract

The application discloses a sulfobutyl-beta-cyclodextrin / coenzyme Q10 inclusion compound and an ultrasonic preparation method thereof. The sulfobutyl-beta-cyclodextrin is used as a main inclusion material, the coenzyme Q10 is used as an active component, and an ultrasonic auxiliary process is used to complete molecular inclusion. In the prepared inclusion compound, the quinone nucleus structure of the coenzyme Q10 is embedded in the hydrophobic cavity of the sulfobutyl-beta-cyclodextrin, and the molecules are combined stably. The test shows that the inclusion rate of the inclusion compound can reach 31%, the drug loading amount is 16%, and the average particle size of the water dispersion system formed after the dispersion in water is only 64 nm. Compared with the free coenzyme Q10, the water solubility of the prepared inclusion compound is greatly improved; the improved water solubility can effectively retain and significantly enhance the antioxidant activity of the coenzyme Q10 in removing DPPH free radicals. The preparation process is simple and easy to operate, the inclusion efficiency is excellent, the prepared inclusion compound can effectively improve the defects of the coenzyme Q10, such as poor water solubility and low in-vivo bioavailability, and has a good industrial application prospect in the fields of medical preparations, functional health foods, skin care cosmetics and the like.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical and health product formulation technology, specifically to a method for preparing a sulfobutyl-β-cyclodextrin / coenzyme Q10 inclusion complex. Background Technology

[0002] Coenzyme Q10 (CoQ10), also known as ubiquinone, is a naturally occurring, lipid-soluble quinone compound that acts as a key electron transporter in the human cellular respiratory chain. Coenzyme Q10 possesses significant antioxidant activity, capable of scavenging free radicals, protecting cell membrane structure, and delaying aging, making it important in cardiovascular diseases, functional health foods, and anti-aging cosmetics. However, due to its long alkyl side chains and high hydrophobicity, Coenzyme Q10 has extremely low solubility in water (<0.005 μg / mL) and poor oral bioavailability, severely limiting its widespread application. Cyclodextrins and their derivatives possess a "hydrophilic on the outside, hydrophobic on the inside" cavity structure, enabling them to form inclusion complexes with hydrophobic drugs, thereby improving drug solubility and bioavailability.

[0003] Sulfobutyl-β-cyclodextrin (SBE-β-CD), as an anionic, highly water-soluble cyclodextrin derivative, exhibits superior water solubility, low nephrotoxicity, and strong drug inclusion capacity. While some studies have reported on the inclusion of coenzyme Q10 with cyclodextrin, research on the optimization of the systematic inclusion process of sulfobutyl-β-cyclodextrin with coenzyme Q10 and its impact on antioxidant properties is limited. Summary of the Invention

[0004] The purpose of this invention is to overcome the shortcomings of the prior art and provide a coenzyme Q10 inclusion complex with good water solubility, high inclusion rate and enhanced antioxidant activity, as well as a method for its preparation.

[0005] To achieve the above objectives, the present invention adopts the following technical solution: 1. Weigh an appropriate amount of sulfobutyl-β-cyclodextrin and dissolve it in deionized water. Sonicate the solution until it is completely dissolved to obtain an aqueous solution of sulfobutyl-β-cyclodextrin. 2. Weigh out coenzyme Q10 and dissolve it in anhydrous ethanol to prepare a coenzyme Q10 ethanol solution; 3. The sulfobutyl-β-cyclodextrin aqueous solution was slowly added dropwise to the coenzyme Q10 ethanol solution for ultrasonic inclusion; 4. After ultrasound treatment, freeze-dry the mixture to obtain a pale yellow inclusion complex.

[0006] Detailed implementation plan: The present invention will be further described in detail below with reference to specific embodiments, but the scope of protection of the present invention is not limited thereto. Example

[0007] Preparation of Coenzyme Q10 Inclusion Complex under Optimal Processing.

[0008] 1. Accurately weigh 0.0863 g (approximately 0.0001 mol) of coenzyme Q10, transfer it to a 100 mL round-bottom flask, and dissolve it in 50 mL of anhydrous ethanol for later use.

[0009] 2. Weigh the corresponding sulfobutyl-β-cyclodextrin according to the host-guest molar ratio of 1:1, dissolve it in 10 mL of deionized water, and sonicate until it is completely dissolved.

[0010] 3. The above-mentioned sulfobutyl-β-cyclodextrin aqueous solution was slowly added dropwise to the ethanol solution of coenzyme Q10, and ultrasonic encapsulation was performed at 30°C for 2 hours.

[0011] 4. After the reaction is complete, transfer the mixture and dry it thoroughly to obtain a pale yellow coenzyme Q10 inclusion complex.

[0012] 5. According to the determination and calculation, under the optimal process conditions of 1:1 molar ratio, the inclusion rate of the obtained coenzyme Q10 inclusion complex is 31%, the drug loading is 16%, and the water solubility of the coenzyme Q10 inclusion complex is 160 μM / L, which is 10 times the solubility of free coenzyme Q10. Example

[0013] Antioxidant performance evaluation experiment.

[0014] Prepare coenzyme Q10 sample solutions (0.02-1.0 mg / mL) and inclusion complex sample solutions (0.002-1.0 mg / mL) at different concentration gradients. Mix 2 mL of DPPH working solution (0.04 mg / mL) with 2 mL of sample solutions, react at room temperature in the dark for 30 minutes, and then measure the absorbance at 517 nm. Calculate the DPPH free radical scavenging rate using the following formula:

[0015] The results showed that the scavenging rates of DPPH free radicals by both the coenzyme Q10 sample and its inclusion complex were concentration-dependent, and at the same concentration, the scavenging rate of the coenzyme Q10 inclusion complex was significantly higher than that of the coenzyme Q10 sample. The half-maximal inhibitory concentration (IC50) of the coenzyme Q10 sample was also measured. 50 The concentration was 78.6 μmol / L, while the IC50 of the coenzyme Q10 inclusion complex was... 50 The value decreased to 52.3 μmol / L, indicating that the coenzyme Q10 inclusion complex has a better ability to scavenge DPPH free radicals than free coenzyme Q10.

Claims

1. A method for preparing a sulfobutyl-β-cyclodextrin / coenzyme Q10 inclusion complex, characterized by, Includes the following steps: (1) Add sulfobutyl-β-cyclodextrin to deionized water and sonicate at 25-35℃ for 10-20 min until completely dissolved to prepare an aqueous solution of sulfobutyl-β-cyclodextrin with a concentration of 0.05-0.15 mol / L; (2) Dissolve coenzyme Q10 in anhydrous ethanol, stir in the dark until completely dissolved, and prepare a coenzyme Q10 ethanol solution with a concentration of 0.05-0.15 mol / L; (3) The sulfobutyl-β-cyclodextrin aqueous solution is slowly added to the coenzyme Q10 ethanol solution at a dropping rate of 0.5-1.0 mL / min. During the dropping process, continuous sonication is performed. After the dropping is completed, sonication is continued for 1.5-2.5 h. The sonication power is controlled at 200-400 W and the sonication temperature is maintained at 25-35℃. (4) The mixture after the inclusion reaction is pre-frozen at -40 to -50°C for 6 to 8 h, and then freeze-dried for 24 to 36 h to obtain the sulfobutyl-β-cyclodextrin / coenzyme Q10 inclusion complex.

2. The method of claim 1, wherein: The molar ratio of sulfobutyl-β-cyclodextrin to coenzyme Q10 is (1~10):

1. ​ 3. The sulfonyl-β-cyclodextrin / coenzyme Q10 inclusion complex prepared by the method according to claim 1, characterized in that: The inclusion complex contains a quinone nucleus structure of coenzyme Q10 embedded within the hydrophobic cavity of sulfobutyl-β-cyclodextrin to form a host-guest inclusion structure with an inclusion rate of 30%–32% and a drug loading of 15%–17%.

4. The sulfobutyl-beta-cyclodextrin / coenzyme Q10 inclusion complex of claim 3, characterized by: The inclusion complex dispersed in an aqueous phase forms a nano-dispersion system with an average particle size of 60–70 nm and a polydispersity index (PDI) < 0.

3.

5. The sulfobutyl-beta-cyclodextrin / coenzyme Q10 inclusion complex of claim 3, characterized by: The inclusion complex has 8-12 times higher solubility in water at 25°C than free coenzyme Q10, and its scavenging rate of DPPH free radicals is more than 20% higher than that of free coenzyme Q10.

6. The use of the sulfobutyl-β-cyclodextrin / coenzyme Q10 inclusion complex according to claim 3 in the preparation of pharmaceuticals, functional health foods or cosmetics containing coenzyme Q10.

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