Galactomannan-tangerine peel extract composite nanoparticles and their preparation and application

Abstract

Galactomannan-tangerine peel extract composite nanoparticles and their preparation and application. The preparation method comprises: stirring and dissolving galactomannan in warm water to obtain a saturated solution of galactomannan; completely dissolving the tangerine peel extract in distilled water to obtain a tangerine peel extract solution, wherein the tangerine peel original drug concentration is 15-25 mg / mL; heating the galactomannan saturated solution to 50-60°C, and fully stirring and adding the tangerine peel extract solution to obtain a mixed solution; centrifuging the obtained mixed solution at room temperature, separating the solid matter to obtain galactomannan-tangerine peel extract composite nanoparticles. The preparation method of the present invention is simple and fast, and is convenient for industrial implementation. The obtained composite nanobody can significantly improve the bioavailability of tangerine peel extract in vivo and enhance its biological activity.

Description

Technical Field

[0001] The invention relates to a tangerine peel extract preparation. Background Art

[0002] Tangerine peel is a medicinal and edible material made from mature citrus peels that have been stored and dried for a period of time. It is recorded in "Shennong's Herbal Classic", "Bencao Jing Jizhu" and "Shi Liao Ben Cao". It has the effects of regulating qi and digestion, promoting qi and resolving phlegm, appetizing and removing dampness, regulating qi and relieving depression, and resolving phlegm and relieving cough. Modern pharmacological studies have shown that tangerine peel has good medicinal value in the cardiovascular system, immunity, antioxidant and anti-tumor aspects. The chemical composition of tangerine peel is mainly flavonoid compounds. The 2020 edition of the "Chinese Pharmacopoeia" stipulates that hesperidin is an indicator component of tangerine peel. However, the solubility of hesperidin in water is only 6.63 µg / mL, resulting in low oral absorption bioavailability (about 3.51%), and its clinical application is subject to certain restrictions. Therefore, the use of more effective preparations to improve its bioavailability plays an important role in the clinical application of hesperidin (tangerine peel extract). Summary of the invention

[0003] The object of the present invention is to provide a tangerine peel extract preparation, which can effectively improve the bioavailability of the tangerine peel extract in vivo and enhance its biological activity.

[0004] According to one aspect of the present invention, a method for preparing galactomannan-tangerine peel extract composite nanoparticles is provided, comprising:

[0005] (1) stirring and dissolving galactomannan in warm water to obtain a saturated galactomannan solution;

[0006] (2) completely dissolving the tangerine peel extract in distilled water to obtain a tangerine peel extract solution, wherein the tangerine peel original drug concentration is 20-25 mg / mL;

[0007] (3) heating the saturated galactomannan solution to 50° C. to 60° C., and adding the tangerine peel extract solution after sufficient stirring to obtain a mixed solution;

[0008] (4) The obtained mixed solution is centrifuged at room temperature to separate the solid matter to obtain galactomannan-tangerine peel extract composite nanoparticles.

[0009] Galactomannan is a water-soluble dietary fiber and prebiotic widely found in beans, grains and some vegetables. In some Chinese medicine granules, oral solutions or oral suspensions, adding galactomannan can improve the solubility of the drug, enhance the efficacy and mask the bitterness of the preparation or improve the taste. At the same time, galactomannan can promote the growth of beneficial bacteria in the intestines, improve the balance of intestinal flora, and thus have a positive effect on intestinal health. It is suitable for the development of food or nutritional supplements for specific populations (such as patients with irritable bowel syndrome (IBS)). The present invention combines it with tangerine peel extract to prepare an inclusion compound, which can significantly improve the bioavailability of hesperidin (tangerine peel extract) while continuing to exert its nutritional value and functionality.

[0010] According to the preparation method of the present invention, the temperature of the warm water may be 20° C. to 25° C., and the concentration of the galactomannan saturated solution may be about 10 mg / mL.

[0011] According to the preparation method of the present invention, the tangerine peel extract can be an extract obtained by an ethanol reflux method.

[0012] According to the preparation method of the present invention, the mass ratio of tangerine peel to galactomannan is (0.5-2.5):1.

[0013] According to another aspect of the present invention, a galactomannan-tangerine peel extract composite nanoparticle is provided, which is prepared according to the above preparation method.

[0014] According to another aspect of the present invention, there is also provided the use of the galactomannan-tangerine peel extract composite nanoparticles in the preparation of medicines, health products or cosmetics.

[0015] The preparation method of the invention is simple and quick, and is convenient for industrial implementation. The prepared composite nanobody can significantly improve the bioavailability of the tangerine peel extract in a living body and enhance its biological activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 The figure is a SEM image of galactomannan-tangerine peel extract composite nanoparticles prepared according to the present invention.

[0017] Figure 2 The figure is a particle size distribution diagram of the galactomannan-tangerine peel extract composite nanoparticles prepared according to the present invention.

[0018] Figure 3 The graph shows the blood drug concentration of the treatment group and the control group. DETAILED DESCRIPTION

[0019] The present invention is described in detail below with reference to the accompanying drawings and specific embodiments.

[0020] Preparation of galactomannan-tangerine peel extract composite nanoparticles

[0021] (1) Dissolve galactomannan in warm water at 22°C under stirring (500 rpm) to obtain 100 mL of a 10 mg / mL galactomannan saturated solution;

[0022] (2) Take tangerine peel powder (500 g; provided by Guangzhou Chenliji Pharmaceutical Factory), extract it with 95% ethanol under reflux for 3 times, each time for 1.5 h, and finally concentrate the extract to an extract, and dry it to obtain tangerine peel extract;

[0023] (3) taking a portion of the tangerine peel extract and completely dissolving it in 100 mL of distilled water to obtain a tangerine peel extract solution having a tangerine peel content of 20 mg / mL (based on tangerine peel powder original drug);

[0024] (3) 100 ml of the saturated galactomannan solution obtained in step (1) was heated to 55° C., stirred thoroughly (500 rpm; 1 h), and added with the above-mentioned tangerine peel extract solution to obtain a mixed solution;

[0025] (4) The obtained mixed solution was centrifuged at room temperature, and the separated solid matter was washed with distilled water and further dried to obtain 1000 mg of galactomannan-tangerine peel extract composite nanoparticles.

[0026] Surface morphology and particle size distribution test of composite nanoparticles

[0027] The surface morphology of the prepared galactomannan-tangerine peel extract composite nanoparticles was observed using a scanning electron microscope (SEM): a drop of nanoparticle suspension was placed on a silicon wafer, dried in a fume hood overnight, and pre-treated with platinum spraying under vacuum (to increase sample conductivity) at a voltage of 10 kV for 90 s. The surface morphology of the MPs was observed and recorded using a scanning electron microscope, and photographed and recorded, such as Figure 1 shown.

[0028] The prepared galactomannan-tangerine peel extract composite nanoparticles were prepared into a galactomannan-tangerine peel extract composite nanoparticle aqueous solution with a concentration of 1 mg / mL, and the particle size distribution of the composite nanoparticles was detected using an Anton Paar nano laser particle size analyzer. Figure 2 shown.

[0029] Evaluation of bioavailability of composite nanoparticles

[0030] Wistar rats fasted for 12 hours were used as experimental subjects, and the dosage was calculated according to the rat body weight (50 mg / kg). The galactomannan-tangerine peel extract composite nanoparticles prepared above were orally administered as the administration group A, and the tangerine peel extract was orally administered as the control group B. After administration, blood was collected from the eye sockets of each group at 1, 4, 8, 12, and 24 hours, and the blood samples were placed in heparin-soaked centrifuge tubes and centrifuged at 4000 r / min for 10 minutes. The supernatant was aspirated and stored at -20°C for later use. The plasma samples were processed according to the following (1), and the blood drug mass concentration was determined according to the following (2) chromatographic conditions.

[0031] (1) Take 50 μL of the rat plasma to be tested and place it in a 1.5 mL EP tube. Add 10 μL of hesperidin solution with a mass concentration of 10 mg / mL, vortex for 60 s, add an appropriate amount of ethyl acetate for extraction, vortex for 5 min, centrifuge at 3500 r / min for 15 min, take 900 μL of the supernatant, place it in a 1.5 mL EP tube, blow dry with nitrogen at 37°C, re-dissolve the residue with 100 μL of methanol, vortex for 5 min, centrifuge at 15000 r / min for 15 min, take 20 μL of the supernatant and dilute it with 1 mL of methanol. The blood drug mass concentration is determined according to the chromatographic conditions under (2) and the mass concentration of hesperidin in the sample is calculated.

[0032] (2) Chromatographic conditions were as follows: Eclipse Plus C18 column (4.6 mm × 100 mm, 3.5 μm), mobile phase was acetonitrile-water (containing 0.1% phosphoric acid), isocratic elution, detection wavelength was 283 nm, flow rate was 1 mL / min, column temperature was 40 °C, injection volume was 10 μL.

[0033] The results of blood drug concentration determination in groups A and B are shown in Tables 1 and Figure 3 shown.

[0034]

[0035] like Figure 3 The results shown in the figure indicate that the peak blood drug concentration of the drug-administered group was significantly higher than that of the control group; the bioavailability at different time points increased by 16.7% (1h), 11.7% (4h), 21.0% (8h), 32.7% (12h), and 37.8% (24h), respectively; as the administration time increased, the bioavailability of the combination calculated as hesperidin gradually increased, indicating that the prepared galactomannan and tangerine peel nanocomplex or composite nanoparticles can significantly improve the bioavailability of tangerine peel extract.

[0036] In conclusion, the galactomannan-tangerine peel extract composite nanoparticle system constructed according to the present invention can significantly increase the water solubility of tangerine peel extract, thereby improving the bioavailability of tangerine peel extract in the field of medicine, health care products or cosmetics.

Claims

1. A method for preparing galactomannan-tangerine peel extract composite nanoparticles, comprising: (1) stirring and dissolving galactomannan in warm water to obtain a saturated galactomannan solution, wherein the temperature of the warm water is 20° C. to 25° C., and the concentration of the saturated galactomannan solution is about 10 mg / mL; (2) completely dissolving the tangerine peel extract in distilled water to obtain a tangerine peel extract solution, wherein the tangerine peel original drug concentration is 15-25 mg / mL; (3) heating the saturated galactomannan solution to 55° C., adding the tangerine peel extract solution after sufficient stirring to obtain a mixed solution, wherein the mass ratio of tangerine peel to galactomannan is (1.5-2.5):1; (4) The obtained mixed solution is centrifuged at room temperature to separate the solid matter to obtain galactomannan-tangerine peel extract composite nanoparticles.

2. The preparation method according to claim 1, wherein the tangerine peel extract is an extract obtained by an ethanol reflux method.

3. A galactomannan-tangerine peel extract composite nanoparticle, prepared according to the preparation method according to claim 1 or 2.

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