Liquidambaric acid or ursolic acid nano-granule and preparation method thereof

[0065] Example 1

[0066] A Passepartout acid nanocapsule particle, which uses Passepartout acid as a core material and rubusoside as a wall material. The amounts of the core material and the wall material are calculated according to the mass ratio, and the core material: wall material is 1:10.

[0067] The above-mentioned preparation method of Passepartout acid nanocapsule particles is prepared by high-energy ball milling, and the steps are as follows:

[0068] Accurately weigh 1g of BEA and 10g of rubusoside, put them in an 80ml grinding bowl, use a planetary high-energy enhanced ball mill (FRITSCH premium line Planetary Mills, PULVERISETTE 7, Germany), select parameters: 80ml embedded grinding bowl with self-locking function, dry Grinding method, 3mm grinding ball, 20g steel ball, rotating speed 1100 rpm, reaction time 7min, drug loading = 1:10, finally got Passepartout acid nanocapsules.

[0069] The particle diameter of the above-mentioned obtained Passepartout acid nanocapsule particles is tested, and the test results are as follows: figure 1 shown, from figure 1 It can be seen that the average particle size is 4.5±0.6nm.

[0070] The solubility of the Passepartout acid nanocapsule particles obtained above was measured in water, and the results showed that its solubility in water was 740 μg/mL. Passepartout acid nanocapsule particles in water to obtain a transparent aqueous solution, compared with the solubility of BEA itself 1.6μg/mL, the solubility of Passepartout acid nanocapsule particles in water is 450 times higher than the intrinsic solubility of Passepartout acid, the reason may be due to The selected wall material can increase the concentration of BEA in the aqueous solution.

[0071] Determination of the effect of the above-mentioned Passepartout acid nanocapsule particles on inhibiting the growth of cancer cells, the IC of Passepartout acid nanocapsule particles calculated by concentration-inhibition rate 50 For HT-29 (intestinal cancer cells), MDA-MB-231 (breast cancer) and DU145 (prostate cancer) cells, they were 31.5, 30.6 and 26.4 μg/mL, and the experimental data of Passepartout acid dissolved in DMSO was 42.6 , 28.8 and 38.7 μg/mL for comparison; IC of Passepartout acid nanoparticles and Passepartout acid dissolved in DMSO on MDA-MB-231 cells 50 The values ​​are similar, which shows that the solubility of Passepartout acid is increased but not reduced after being prepared into nanoparticles;

[0072] IC of Passepartout acid nanoparticles on HT-29 and DU145 cells 50 Value ratio of Passepartout acid dissolved in DMSO to IC of HT-29 and DU145 cells 50 The value is low, which further shows that the solubility of Passepartout acid is increased but not reduced after being prepared into nanoparticles. Inhibition rate has enhanced effect.

[0073] Measure the permeability of the Passepartout acid nanocapsule particles obtained above, and the Passepartout acid permeability coefficient is 4.30×10 -6.cm.s –1 , Passepartout acid nanocapsules showed a permeability coefficient of 13.77×10 - 6.cm.s -1 , the permeability of Passepartout acid nanocapsule particles is 3.2 times that of Passepartout acid, which shows that Passepartout acid nanocapsule particles have a higher permeability than the ordinary system of Passepartout acid through monolayer cells .

[0074] Example 2

[0075] A ursolic acid nanocapsule particle, which uses ursolic acid as a core material and stevioside as a wall material. The amounts of the core material and the wall material are calculated by mass ratio, and the core material: wall material is 1:20.

[0076] The preparation method of above-mentioned a kind of ursolic acid nanocapsule particle adopts high-energy ball milling method to prepare ursolic acid nanoparticle, specifically as follows:

[0077] Accurately weigh 0.5g of URA and 10g of stevioside, and place them in an 80ml grinding bowl, using a planetary high-energy enhanced ball mill (FRITSCH premium line Planetary Mills, PULVERISETTE 7, Germany), selection parameters: 80ml embedded grinding bowl with self-locking function , Dry grinding, 3mm grinding ball, 20g steel ball, rotating speed 900rpm, reaction time 9min, drug loading = 1:20, and finally ursolic acid nanocapsule particles were obtained.

[0078] The particle diameter of the ursolic acid nanocapsule particle of above-mentioned gained is tested, test result is as follows figure 2 shown, from figure 2 It can be seen that the average particle size is 4.2±0.7nm.

[0079] The solubility of the obtained ursolic acid nanocapsule particles in water was measured, and the results showed that the solubility was 690 μg/mL. Ursolic acid nanocapsule particles in water to obtain a transparent aqueous solution, compared with the solubility of ursolic acid itself 1.7μg/mL, the solubility of ursolic acid nanocapsule particles in water is 405 times higher than the intrinsic solubility of ursolic acid, the reason is due to the selection of The wall material can increase the concentration of ursolic acid in the aqueous solution.

[0080] Measure the ursolic acid nanocapsule particle of above-mentioned gained to inhibiting cancer cell growth effect, the ursolic acid nanocapsule particle IC calculated by concentration-inhibition rate 50 For HT-29 (intestinal cancer cells), MDA-MB-231 (breast cancer) and DU145 (prostate cancer) cells were 19.37, 28.17 and 32.60 μg/mL, IC 50 The values ​​show that ursolic acid nanocapsules have inhibitory activity on the three selected cancer cell lines. The selected wall material has no effect on the viability of cell line culture at the current concentration.

[0081] Measure the permeability of the ursolic acid nanocapsule particle of above-mentioned gained, and the ursolic acid permeability coefficient is 3.09 * 10 -6.cm.s -1 , ursolic acid nanocapsules showed a permeability coefficient of 10.91×10 -6.cm.s -1 , the permeability of ursolic acid nanocapsules is 3.5 times that of ursolic acid, which shows that the permeability of ursolic acid nanocapsules through monolayer cells is higher than that of ursolic acid common system.

[0082] Example 3

[0083] A Passepartout acid nanocapsule particle, which uses Passepartout acid as a core material and tea saponin as a wall material. The amounts of the core material and the wall material are calculated by mass ratio, and the core material: wall material is 1:30.

[0084] The above-mentioned preparation method of Passepartout acid nanocapsule particles is prepared by an ultrasonic high-speed homogenizer method, which specifically includes the following steps:

[0085] (1) The core material Passepartout acid was added to ethanol, and after ultrasonic treatment and mixing evenly, an ethanol solution of Passepartout acid with a mass percentage concentration of 25% was obtained;

[0086] (2) Dissolving the wall material tea saponin in distilled water, and after ultrasonic treatment and mixing evenly, an aqueous solution of tea saponin with a concentration of 25% by mass is obtained;

[0087] (3), the Passepartout acid ethanol solution obtained in step (1) and the tea saponin aqueous solution obtained in step (2) are calculated according to the mass ratio, the Passepartout acid in the Passepartout acid ethanol solution: the tea saponin aqueous solution The ratio of tea saponin is 1:30. After mixing Passepartout acid ethanol solution and tea saponin aqueous solution, the ultrasonic high-speed homogenizer controls the speed of 13000-18000rpm to homogenize for 15min, and then uses a rotary evaporator (R210, BUCHI ,Switzerland) Ethanol is evaporated to remove ethanol under the conditions of controlling the rotation speed of 120-200rpm, vacuum degree of 180-250 mbar, and temperature of 50-75°C to obtain a nano-scale solution, and then use a small spray dryer (B-191, Buchi) to obtain a nano-scale solution company, Switzerland) to spray-dry to get Passepartout acid nanoparticles;

[0088] In the above spray drying process, the inlet temperature is controlled at 160-185°C, the feed flow rate is 10-30 mL/min, and the spray pressure is 150-190KPa.

[0089] The particle diameter of the above-mentioned obtained Passepartout acid nanocapsule particles is tested, and the test results are as follows: image 3 As shown, its average particle size is 13.5±0.7nm.

[0090] The solubility in water of the Passepartout acid nanocapsule particles obtained above was measured, and the result showed that its solubility in water was 729 μg/mL. Passepartout acid nanocapsule particles obtain transparent aqueous solution in water, and the solubility of Passepartout acid nanocapsule particles in water increases more than 430 times than the intrinsic solubility of Passepartout acid. The effect of increasing the concentration of Passepartout acid in aqueous solution.

[0091] Determination of the effect of the above-mentioned Passepartout acid nanocapsule particles on inhibiting the growth of cancer cells, the IC of Passepartout acid nanocapsule particles calculated by concentration-inhibition rate 50 For HT-29 (intestinal cancer cells), MDA-MB-231 (breast cancer) and DU145 (prostate cancer) cells were 30.2, 31.7 and 28.3 μg/mL, that is, the effect of Passepartout acid nanocapsules on the above three cancer cells cells are inhibited.

[0092] Measure the permeability of the Passepartout acid nanocapsule particles obtained above, and the Passepartout acid permeability coefficient is 4.20×10 -6.cm.s –1 , Passepartout acid nanocapsules showed a permeability coefficient of 12.94×10 - 6.cm.s -1 , the permeability of Passepartout acid nanocapsules is 3.1 times that of Passepartout acid, which shows that Passepartout acid nanocapsules have a higher permeability than the ordinary system of Passepartout acid through monolayer cells .

[0093] In summary, a kind of Passepartout acid nanocapsule particle or ursolic acid nanocapsule particle of the present invention, the average particle diameter of gained Passepartout acid nanocapsule particle or ursolic acid nanoparticle is all less than 100 nanometers; Compared with the original compound Passepartout acid or ursolic acid, the water solubility of Passepartout acid nanoparticles or ursolic acid nanocapsule particles has been improved by more than 400 times; The compound Passepartout acid or ursolic acid increased the cell permeability by more than 3 times; and the Passepartout acid nanoparticles or ursolic acid nanoparticles have the ability to inhibit HT-29, MDA-MB-231 and DU145 tumor cells Proliferation.