SOLID DISPERSION CONTAINING DESMODIUM STYRACIFOLIUM (OSB.) MERR. FLAVONOIDS, METHOD OF PREPARING SAME, AND USE THEREOF

Abstract

A solid dispersion containing Desmodium Styracifolium (Osb.) Merr. flavonoids, method of preparing same and use thereof. The Desmodium Styracifolium (Osb.) Merr. flavonoids are alcohol extract of Desmodium Styracifolium (Osb.) Merr., and the solid dispersion is used for preparing a drug for treating urinary tract calculi.

Claims

1-42. (canceled)

43. A method for preparing an oral solid formulation containing total flavonoids of Desmodium Styracifolium, comprising: heating and refluxing a raw material of Desmodium Styracifolium for extraction, 1 to 3 times with 1 to 3 hours for each time, with ethanol having a concentration ranging from 50% to 95% and a weight ranging from 8 to 14 times as heavy as the raw material of Desmodium styracifolium, to obtain an extracting solutions of Desmodium styracifolium followed by mixing; concentrating mixed extracting solutions of Desmodium Styracifolium, so as to remove ethanol; subjecting the mixed extracting solutions of Desmodium Styracifolium after concentrated to adsorption onto a macroporous resin column, so as to obtain alcohol extract of Desmodium Styracifolium; mixing the alcohol extract of Desmodium Styracifolium with a solid dispersion carrier and a surfactant, and preparing a solid dispersion containing total flavonoids of Desmodium Styracifolium via a solid dispersion technology; mixing the solid dispersion containing total flavonoids of Desmodium Styracifolium with a filler and a disintegrant followed by preparing a soft material, granulating and size stabilizing, and then mixing with a lubricant, so as to obtain a mixture; and capsulizing the mixture with an encapsulating machine so as to obtain a capsule containing total flavonoids of Desmodium Styracifolium, or tableting the mixture with a tableting machine so as to obtain a tablet containing total flavonoids of Desmodium Styracifolium.

44-46. (canceled)

47. The method according to claim 43, wherein the solid dispersion carrier is at least one of povidone K.sub.30 and poloxamer 188.

48. The method according to claim 43, wherein the surfactant is at least one of Tween 80, methoxypolyethylene glycol, and sodium dodecyl sulfate.

49. The method according to 43, wherein the filler is at least one of microcrystalline cellulose, lactose, and pregelatinized starch.

50. The method according to 43, wherein the disintegrant is at least one of sodium croscarmellose, cross-linked povidone, and sodium carboxymethyl starch.

51. The method according to 43, wherein the lubricant is at least one of magnesium stearate, aerosil, and sodium stearyl fumarate.

52. The method according to claim 43, further comprising: weighing a raw material of Desmodium Styracifolium, heating and refluxing the raw material for extraction, 1 to 3 times with 1 to 3 hours for each time, at a temperature of 50 C. to 60 C. with ethanol having a concentration ranging from 50% to 95% and a weight ranging from 8 to 14 times as heavy as the raw material, so as to obtain alcohol extracting solutions of Desmodium Styracifolium followed by mixing; concentrating the alcohol extracting solution to be of a volume 2 to 8 times the weight of the raw material followed by still standing and filtering to obtain a filtrate; subjecting the filtrate to adsorption onto an AB-8 macroporous resin column at a flow rate ranging from 1 to 3 column bed volumes per hour, eluting and purifying with water having a volume ranging from 8 to 12 times the weight of filled resin, and eluting with ethanol having a concentration of 40% to 95% and a volume ranging from 6 to 10 column bed volumes at a flow rate ranging from 2 to 4 column bed volumes per hour, to obtain an eluted solution; and concentrating the eluted solution into a concentrated solution with a relative density ranging from 1.10 to 1.30 followed by drying and then smashing, so as to obtain the alcohol extract of Desmodium Styracifolium.

53. The method according to claim 43, further comprising: dissolving the total flavonoids of Desmodium Styracifolium, a solid dispersion carrier and a surfactant in respective formula dosage, sieved at 40 to 200 meshes in advance respectively, with ethanol having a concentration ranging from 20% to 75% under stirring and at a temperature of 50 C. to 75 C., followed by removing the solvent via evaporation under reduced pressure at a temperature of 30 C. to 75 C., vacuum drying at a temperature of 30 C. to 60 C., smashing and sieving at 40 to 200 meshes, so as to obtain the solid dispersion containing total flavonoids of Desmodium Styracifolium; mixing a filler and a disintegrant, sieved at 40 to 100 meshes in advance, respectively, with the solid dispersion containing total flavonoids of Desmodium Styracifolium, followed by preparing a soften material, granulating at 10 to 30 meshes, drying at a temperature of 30 C. to 75 C., size stabilizing, and mixing with a lubricant, then capsulizing the mixture obtained with an encapsulating machine so as to obtain the capsule containing total flavonoids of Desmodium Styracifolium.

54. The method according to claim 43, further comprising: dissolving the total flavonoids of Desmodium Styracifolium, a solid dispersion carrier and a surfactant in respective formula dosage, sieved at 40 to 200 meshes in advance respectively, with ethanol having a concentration ranging from 20% to 75% under stirring and at a temperature of 50 C. to 75 C., followed by removing the solvent via evaporation under reduced pressure at a temperature of 30 C. to 75 C., vacuum drying at a temperature of 30 C. to 60 C., smashing and sieving at 40 to 200 meshes, so as to obtain the solid dispersion containing total flavonoids of Desmodium Styracifolium; mixing a filler and a disintegrant, sieved at 40 to 100 meshes in advance, respectively, with the solid dispersion containing total flavonoids of Desmodium Styracifolium, followed by preparing a soften material, granulating at 10 to 30 meshes, drying at a temperature of 30 C. to 75 C., size stabilizing, and mixing with a lubricant, then tableting the mixture obtained with a tableting machine so as to obtain the tablet containing total flavonoids of Desmodium Styracifolium.

55. The method according to claim 43, comprising: a. preparing the total flavonoids of Desmodium Styracifolium: weighing a raw material of Desmodium Styracifolium in a formula dosage, heating and refluxing at a temperature of 55 C. for 2 hours for first extraction with ethanol having a concentration of 80% and a weight 12 times as heavy as the raw material, heating and refluxing at a temperature of 55 C. for 1.5 hours for second extraction with ethanol having a concentration of 80% and a weight 10 times as heavy as the raw material, so as to obtain alcohol extracting solutions of Desmodium Styracifolium followed by mixing; concentrating the alcohol extracting solution to be of a volume 5 times the weight of the raw material followed by still standing and filtering, to obtain a filtrate; subjecting the filtrate to adsorption onto an AB-8 macroporous resin column at a flow rate of 2 column bed volumes per hour, eluting and purifying with water having a volume 10 times the weight of filled resin, and eluting with ethanol having a concentration of 60% and a volume of 8 column bed volumes at a flow rate of 2 column bed volumes per hour, to obtain an eluted solution; and concentrating the eluted solution into a concentrated solution with a relative density of 1.22, followed by drying under reduced pressure at a temperature of 75 C. and then smashing to obtain the total flavonoids of Desmodium Styracifolium; b. preparing a solid dispersion containing total flavonoids of Desmodium Styracifolium: dissolving the total flavonoids of Desmodium Styracifolium, povidone K.sub.30, poloxamer 188 and sodium dodecyl sulfate in respective formula dosage, sieved at 80 meshes in advance respectively, with ethanol having a concentration of 50% under stirring and at a temperature of 65 C., followed by removing the solvent via evaporation under reduced pressure at a temperature of 50 C., vacuum drying at a temperature of 40 C., smashing and sieving at 80 meshes, so as to obtain the solid dispersion containing total flavonoids of Desmodium Styracifolium; c. preparing granules containing total flavonoids of Desmodium Styracifolium: mixing lactose and sodium croscarmellose, sieved at 80 meshes in advance respectively, with the solid dispersion containing the total flavonoids of Desmodium Styracifolium to be uniform, followed by preparing a soften material, granulating at 20 meshes, drying at a temperature of 55 C., size stabilizing, and mixing with aerosil to be uniform, so as to obtain the granules containing total flavonoids of Desmodium Styracifolium; d. capsulizing: capsulizing the granules containing total flavonoids of Desmodium Styracifolium with an encapsulating machine so as to obtain the capsule containing total flavonoids of Desmodium Styracifolium.

56. The method according to claim 43, comprising: a. preparing the total flavonoids of Desmodium Styracifolium: weighing a raw material of Desmodium Styracifolium in a formula dosage, heating and refluxing at a temperature of 55 C. for 2 hours for first extraction with ethanol having a concentration of 80% and a weight 12 times as heavy as the raw material, heating and refluxing at a temperature of 55 C. for 1.5 hours for second extraction with ethanol having a concentration of 80% and a weight 10 times as heavy as the raw material, so as to obtain alcohol extracting solutions of Desmodium Styracifolium followed by mixing; concentrating the alcohol extracting solution to be of a volume 5 times the weight of the raw material followed by still standing and filtering, to obtain a filtrate; subjecting the filtrate to adsorption onto an AB-8 macroporous resin column at a flow rate of 2 column bed volumes per hour, eluting and purifying with water having a volume 10 times the weight of filled resin, and eluting with ethanol having a concentration of 60% and a volume of 8 column bed volumes at a flow rate of 2 column bed volumes per hour, to obtain an eluted solution; and concentrating the eluted solution into a concentrated solution with a relative density of 1.22, followed by drying under reduced pressure at a temperature of 75 C. and then smashing to obtain the total flavonoids of Desmodium Styracifolium; b. preparing a solid dispersion containing total flavonoids of Desmodium Styracifolium: dissolving the total flavonoids of Desmodium Styracifolium, povidone K.sub.30, poloxamer 188 and sodium dodecyl sulfate in respective formula dosage, sieved at 80 meshes in advance respectively, with ethanol having a concentration of 50% under stirring and at a temperature of 65 C., followed by removing the solvent via evaporation under reduced pressure at a temperature of 50 C., vacuum drying at a temperature of 40 C., smashing and sieving at 80 meshes, so as to obtain the solid dispersion containing total flavonoids of Desmodium Styracifolium; c. preparing granules containing total flavonoids of Desmodium Styracifolium: mixing lactose and sodium croscarmellose, sieved at 80 meshes in advance respectively, with the solid dispersion containing the total flavonoids of Desmodium Styracifolium to be uniform, followed by preparing a soften material, granulating at 20 meshes, drying at a temperature of 55 C., size stabilizing, and mixing with aerosil to be uniform, so as to obtain the granules containing total flavonoids of Desmodium Styracifolium; d. tableting: tableting the granules containing total flavonoids of Desmodium Styracifolium with a tableting machine to obtain the tablet containing total flavonoids of Desmodium Styracifolium.

57. The method according to claim 43, wherein 33 to 133 weight parts of total flavonoids of Desmodium Styracifolium, 198 to 798 weight parts of the solid dispersion carrier, 6.6 to 133 weight parts of the surfactant, 1 to 50 weight parts of the filler, 1 to 50 weight parts of the disintegrant, and 1 to 10 weight parts of the lubricant are used.

58. The method according to claim 57, wherein a formula is used which is at least one selected from: 33 weight parts of total flavonoids of Desmodium Styracifolium, 132 weight parts of povidone K.sub.30, 66 weight parts of poloxamer 188, 6.6 weight parts of sodium dodecyl sulfate, 50 weight parts of lactose, 20 weight parts of cross-linked povidone, and 1 weight part of aerosil; 33 weight parts of total flavonoids of Desmodium Styracifolium, 132 weight parts of povidone K.sub.30, 66 weight parts of poloxamer 188, 19.8 weight parts of sodium dodecyl sulfate, 30 weight parts of lactose, 20 weight parts of sodium croscarmellose, and 3 weight parts of sodium stearyl fumarate; 33 weight parts of total flavonoids of Desmodium Styracifolium, 132 weight parts of povidone K.sub.30, 66 weight parts of poloxamer 188, 33 weight parts of sodium dodecyl sulfate, 10 weight parts of microcrystalline cellulose, 20 weight parts of sodium croscarmellose, and 2 weight parts of magnesium stearate; 33 weight parts of total flavonoids of Desmodium Styracifolium, 132 weight parts of povidone K.sub.30, 66 weight parts of poloxamer 188, 19.8 weight parts of Tween 80, 40 weight parts of lactose, 5 weight parts of sodium carboxymethyl starch, and 4 weight parts of sodium stearyl fumarate; 33 weight parts of total flavonoids of Desmodium Styracifolium, 132 weight parts of povidone K.sub.30, 66 weight parts of poloxamer 188, 19.8 weight parts of methoxypolyethylene glycol, 20 weight parts of microcrystalline cellulose, 15 weight parts of sodium carboxymethyl starch, and 3 weight parts of sodium stearyl fumarate; 50 weight parts of total flavonoids of Desmodium Styracifolium, 200 weight parts of povidone K.sub.30, 100 weight parts of poloxamer 188, 10 weight parts of sodium dodecyl sulfate, 50 weight parts of lactose, 20 weight parts of sodium croscarmellose, and 5 weight parts of sodium stearyl fumarat; 50 weight parts of total flavonoids of Desmodium Styracifolium, 200 weight parts of povidone K.sub.30, 100 weight parts of poloxamer 188, 30 weight parts of sodium dodecyl sulfate, 50 weight parts of lactose, 20 weight parts of sodium croscarmellose, and 5 weight parts of sodium stearyl fumarate; 50 weight parts of total flavonoids of Desmodium Styracifolium, 200 weight parts of povidone K.sub.30, 100 weight parts of poloxamer 188, 50 weight parts of sodium dodecyl sulfate, 50 weight parts of lactose, 20 weight parts of sodium croscarmellose, and 5 weight parts of sodium stearyl fumarate; 50 weight parts of total flavonoids of Desmodium Styracifolium, 200 weight parts of povidone K.sub.30, 100 weight parts of poloxamer 188, 30 weight parts of Tween 80, 50 weight parts of lactose, 20 weight parts of sodium croscarmellose, and 5 weight parts of sodium stearyl fumarate; 50 weight parts of total flavonoids of Desmodium Styracifolium, 200 weight parts of povidone K.sub.30, 100 weight parts of poloxamer 188, 30 weight parts of methoxypolyethylene glycol, 50 weight parts of lactose, 20 weight parts of sodium croscarmellose, and 5 weight parts of sodium stearyl fumarate; 50 weight parts of total flavonoids of Desmodium Styracifolium, 200 weight parts of povidone K.sub.30, 100 weight parts of poloxamer 188, 30 weight parts of sodium dodecyl sulfate, 50 weight parts of pregelatinized starch, 20 weight parts of sodium croscarmellose, and 5 weight parts of sodium stearyl fumarate; 50 weight parts of total flavonoids of Desmodium Styracifolium, 200 weight parts of povidone K.sub.30, 100 weight parts of poloxamer 188, 50 weight parts of sodium dodecyl sulfate, 50 weight parts of cross-linked povidone, 20 weight parts of sodium croscarmellose, and 5 weight parts of sodium stearyl fumarate; 50 weight parts of total flavonoids of Desmodium Styracifolium, 200 weight parts of povidone K.sub.30, 100 weight parts of poloxamer 188, 30 weight parts of methoxypolyethylene glycol, 50 weight parts of microcrystalline cellulose, 20 weight parts of sodium croscarmellose, and 5 weight parts of aerosol; 66.5 weight parts of total flavonoids of Desmodium Styracifolium, 266 weight parts of povidone K.sub.30, 133 weight parts of poloxamer 188, 13.3 weight parts of sodium dodecyl sulfate, 20 weight parts of microcrystalline cellulose, 10 weight parts of sodium carboxymethyl starch, and 8 weight parts of sodium stearyl fumarate; 66.5 weight parts of total flavonoids of Desmodium Styracifolium, 266 weight parts of povidone K.sub.30, 133 weight parts of poloxamer 188, 39.9 weight parts of sodium dodecyl sulfate, 10 weight parts of lactose, 15 weight parts of sodium croscarmellose, and 6 weight parts of sodium stearyl fumarate; 66.5 weight parts of total flavonoids of Desmodium Styracifolium, 266 weight parts of povidone K.sub.30, 133 weight parts of poloxamer 188, 66.5 weight parts of sodium dodecyl sulfate, 1 weight part of lactose, 10 weight parts of cross-linked povidone, and 10 weight parts of magnesium stearate; 66.5 weight parts of total flavonoids of Desmodium Styracifolium, 266 weight parts of povidone K.sub.30, 133 weight parts of poloxamer 188, 39.9 weight parts of Tween 80, 10 weight parts of lactose, 50 weight parts of sodium croscarmellose, and 1 weight part of sodium stearyl fumarate; 66.5 weight parts of total flavonoids of Desmodium Styracifolium, 266 weight parts of povidone K.sub.30, 133 weight parts of poloxamer 188, 39.9 weight parts of methoxypolyethylene glycol, 15 weight parts of pregelatinized starch, 30 weight parts of sodium croscarmellose, and 5 weight parts of sodium stearyl fumarate; 100 weight parts of total flavonoids of Desmodium Styracifolium, 400 weight parts of povidone K.sub.30, 200 weight parts of poloxamer 188, 20 weight parts of sodium dodecyl sulfate, 50 weight parts of pregelatinized starch, 20 weight parts of sodium croscarmellose, and 5 weight parts of sodium stearyl fumarate; 100 weight parts of total flavonoids of Desmodium Styracifolium, 400 weight parts of povidone K.sub.30, 200 weight parts of poloxamer 188, 60 weight parts of sodium dodecyl sulfate, 50 weight parts of lactose, 40 weight parts of cross-linked povidone, and 8 weight parts of sodium stearyl fumarate; 100 weight parts of total flavonoids of Desmodium Styracifolium, 400 weight parts of povidone K.sub.30, 200 weight parts of poloxamer 188, 100 weight parts of sodium dodecyl sulfate, 10 weight parts of microcrystalline cellulose, 20 weight parts of sodium carboxymethyl starch, and 10 weight parts of sodium stearyl fumarate; 100 weight parts of total flavonoids of Desmodium Styracifolium, 400 weight parts of povidone K.sub.30, 200 weight parts of poloxamer 188, 60 weight parts of Tween 80, 10 weight parts of lactose, 15 weight parts of sodium croscarmellose, and 8 weight parts of sodium stearyl fumarate; 100 weight parts of total flavonoids of Desmodium Styracifolium, 400 weight parts of povidone K.sub.30, 200 weight parts of poloxamer 188, 60 weight parts of methoxypolyethylene glycol, 15 weight parts of lactose, 10 weight parts of sodium croscarmellose, and 8 weight parts of sodium stearyl fumarate; 133 weight parts of total flavonoids of Desmodium Styracifolium, 532 weight parts of povidone K.sub.30, 266 weight parts of poloxamer 188, 26.6 weight parts of sodium dodecyl sulfate, 20 weight parts of lactose, 20 weight parts of sodium croscarmellose, and 8 weight parts of sodium stearyl fumarate; 133 weight parts of total flavonoids of Desmodium Styracifolium, 532 weight parts of povidone K.sub.30, 266 weight parts of poloxamer 188, 79.8 weight parts of sodium dodecyl sulfate, 20 weight parts of lactose, 25 weight parts of cross-linked povidone, and 9 weight parts of sodium stearyl fumarate; 133 weight parts of total flavonoids of Desmodium Styracifolium, 532 weight parts of povidone K.sub.30, 266 weight parts of poloxamer 188, 133 weight parts of sodium dodecyl sulfate, 1 weight part of microcrystalline cellulose, 1 weight part of sodium carboxymethyl starch, and 10 weight parts of sodium stearyl fumarate; 133 weight parts of total flavonoids of Desmodium Styracifolium, 532 weight parts of povidone K.sub.30, 266 weight parts of poloxamer 188, 79.8 weight parts of Tween 80, 10 weight parts of lactose, 10 weight parts of sodium croscarmellose, and 8 weight parts of magnesium stearate; 133 weight parts of total flavonoids of Desmodium Styracifolium, 532 weight parts of povidone K.sub.30, 266 weight parts of poloxamer 188, 79.8 weight parts of methoxypolyethylene glycol, 5 weight parts of pregelatinized starch, 5 weight parts of cross-linked povidone, and 5 weight parts of magnesium stearate;

59-85. (canceled)

86. A solid dispersion formulation containing total flavonoids of Desmodium Styracifolium prepared by the method according to claim 43.

87. A method for treating urinary stone, comprising administrating a solid dispersion formulation containing total flavonoids of Desmodium Styracifolium prepared by the method according to claim 43 to a patient in need thereof.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0168] These and other aspects and advantages of embodiments of the present disclosure will become apparent and more readily appreciated from the following descriptions made with reference to the drawings, in which:

[0169] FIG. 1 is a leaking curve showing an amount of total flavonoids of Desmodium Styracifolium in a sample solution adsorbed by an AB-8 macroporous resin column according to an embodiment of the present disclosure;

[0170] FIG. 2 is an eluting curve showing an amount of total flavonoids of Desmodium Styracifolium eluted by the resin column with 60% ethanol as an eluent according to an embodiment of the present disclosure; and

[0171] FIG. 3 is a curve for comparing the dissolutions in vitro of a tablet containing total flavonoids of Desmodium Styracifolium prepared with the solid dispersion process (embodiment 20) and that prepared with a common wet granulation process (formula 1) according to a comparative embodiment.

DETAILED DESCRIPTION

[0172] In the following, embodiments of the present disclosure will be described in detail, whose examples will be shown in drawings. Embodiments described in the following with reference to drawings are explanatory, illustrative, and used to generally understand the present disclosure, and shall not be construed to limit the present disclosure.

Embodiment 1

Preparation of Total Flavonoids of Desmodium Styracifolium

[0173] (1) Extracting method: free flavonoids and flavonoid glycosides generally can be extracted with an organic solvent according to the solubility of flavonoids, for example, ethanol with relative high concentration is commonly used in industrial production. Based on common industrialized method for extracting flavonoids, the extraction in the present study is performed with ethanol having a concentration of 60% to 95% (as an extraction solvent) twice, which is more economical and practical according to conventional production method.

[0174] Study on extraction process of refluxing with ethanol: Parameters for the extraction process, including ethanol concentration, ethanol weight (with respect to the weight of raw material of Desmodium Styracifolium), and extraction period, were determined by L9 (34) orthogonal tests, which took the total flavonoids of Desmodium Styracifolium as index. A content of the total flavonoids in an extract is measured by UV-visible spectrophotometry, and comparative analysis was performed with the content of total flavonoids and a net weight of total flavonoids in a dry extract as evaluation indexes. Factors and levels of experiments were designed as shown in Table 1, and analysis results are shown in Table 2.

Table 1 Factors and Levels of Experiments

[0175]

TABLE-US-00001 Factors B Ethanol amount (with A respect to the weight of raw Ethanol material of Desmodium D concentration Styracifolium) C extraction period (h) Levels (%) 1.sup.st time 2.sup.nd time Control 1.sup.st time 2.sup.nd time 1 60 8 6 1.0 1.0 2 80 10 8 1.5 1.0 3 95 12 10 2.0 1.5

Table 2 Orthogonal Tests and Analysis Results

[0176]

TABLE-US-00002 Content Net weight of total of total Experiment flavonoids flavonoids No. A B C D (%) (g) 1 1 1 1 1 19.0 0.67 2 1 2 2 2 23.8 1.01 3 1 3 3 3 23.0 1.11 4 2 1 2 3 27.4 1.05 5 2 2 3 1 25.5 1.03 6 2 3 1 2 30.7 1.15 7 3 1 3 2 15.0 0.45 8 3 2 1 3 16.0 0.48 9 3 3 2 1 16.8 0.49 K1 2.790 2.170 2.300 2.190 K2 3.230 2.520 2.550 2.610 K3 1.420 2.750 2.590 2.640 k1 0.930 0.723 0.767 0.730 k2 1.077 0.840 0.850 0.870 k3 0.473 0.917 0.863 0.880 R 0.604 0.194 0.096 0.150

[0177] Visual analysis: As can be seen from R values shown in Table 2, R.sub.A>R.sub.B>R.sub.D, which shows that an order of factors is A>B>D. And as can be seen from k values, A2>A1>A3, B3>B2>B1, D3>D2>D1, therefore, an optimal level combination of factors is A2B3D3. That is, an optimum extraction process for total flavonoids of Desmodium Styracifolium is: extracting twice with 80% ethanol, having a weight of 12 times as heavy as the raw material of Desmodium styracifolium for 2 hours for the first time, and having a weight of 10 times as heavy as the raw material of Desmodium styracifolium for 1.5 hours for the second time.

[0178] (2) Study on Purification Process with an Extracting Solution of Desmodium Styracifolium Obtained Through Above Optimized Extraction Conditions by Adsorption onto a Macroporous Resin Column:

[0179] 1) Study on Screening Macroporous Resins

[0180] Resin: AB-8 resin (Nankai University), D101 resin (Shandong Lukang), HPD100 resin (Hebei Baocang Co., Ltd).

[0181] a) Studies on Static Saturated Adsorption and Desorption Elution with Total Flavonoids in the Sample Solution Using Different Macroporous Adsorption Resins

[0182] 2 g well-treated (pumping filtrated till without water drop) macroporous resin was weighted precisely, and added into 100 mL ground erlenmeyer flask, followed by precisely added with 50 mL sample solution and then continuously shaken 24 hours on an oscillator for fully adsorption. The resulting supernatants was measured with the concentrations of total flavonoids therein. The saturated adsorption capacity of the resin was calculated by the following formula: saturated adsorption capacity=[(initial concentration-concentration after adsorption)volume of adsorption solution]/resin weight], elution rate=(eluent concentrationelution volume)/saturated adsorption capacity100%, and the results are shown in Table 3.

[0183] Table 3 results of static saturated adsorption and desorption as for three types of resin

TABLE-US-00003 Total flavonoids Saturated adsorption Elution rate Resin type capacity (mg/g) (%) AB-8 58.36 89.75 D101 49.27 81.23 HPD100 52.41 85.35

[0184] The results show that, saturated adsorption capacities, elution volumes and elution rates of AB-8, D101, HPD 100 types of macroporous resins for total flavonoids in the sample solution are relatively close in the static adsorption and desorption tests, and static adsorption and desorption properties of the three types of macroporous resins were further investigated.

[0185] b) Study on Static Saturated Adsorption and Desorption Properties with Total Flavonoids in the Sample Solution Using the Three Types of Macroporous Adsorption Resins

[0186] For three types of macroporous resins, 2 g each type of macroporous resins was weighed precisely and packed into a column for use. 100 mL loading sample was subjected to adsorption onto respective macroporous resin column at a flow rate of 1 mL/min thereby obtaining first effluents, which was subjected to adsorption again with the same column thereby obtaining second effluents. Each macroporous resin column adsorbed with loading sample was eluted with a certain volume of water to obtain an eluted solution, which was used for measuring the content of total flavonoids in the eluted solution. The adsorption ratio of respective macroporous resin was calculated based on the following formula: adsorption ratio=[(a substance content in the loading samplea substance content in the second effluenta substance content in the eluted solution)]/filled resin weight], elution ratio=[concentration of the eluted solutionvolume of the eluted solution/filled resin weight], and the results are shown in Table 4.

[0187] Table 4 results of saturated adsorption on and desorption on of three types of resin

TABLE-US-00004 Total flavonoids Resin type Adsorption ratio (mg/g) Elution ratio (%) AB-8 50.24 86.52 D101 40.78 78.34 HPD100 45.02 80.19

[0188] The results show that, the AB-8 macroporous resin is of good adsorption ratio and the elution ratio of total flavonoids of Desmodium Styracifolium, and high safety, which has been most applied in domestic pharmaceutical manufacturing industry, therefore, the present study selected AB-8 macroporous resin to purify the total flavonoids of Desmodium Styracifolium.

[0189] 2) Study on Purification Process with AB-8 Macroporous Resin

[0190] a) Optimization to Adsorption Conditions

[0191] L9 (34) orthogonal table was used to design levels and factors including a concentration of the loading sample (by the weight of raw material contained in the loading sample), an adsorption velocity and a ratio of diameter to height, as shown in Table 5. Contents of the total flavonoids were measured for the following 9 testing groups, adsorption ratios were calculated, and comprehensive evaluation was performed. Analysis results are shown in Table 6.

TABLE-US-00005 TABLE 5 Table of factors and levels B A adsorption concentration velocity of (multiples D loading sample of column C ratio of diameter Levels\Factors (g/mL) volume/h) Control to height 1 0.1 2 1:4 2 0.2 4 1:8 3 0.4 6 1:12

Table 6 Orthogonal Design and Analysis Results

[0192]

TABLE-US-00006 Content Net weight of total of total Experiment flavonoids flavonoids NO. A B C D (%) (g) 1 1 1 1 1 70.35 0.28 2 1 2 2 2 66.75 0.22 3 1 3 3 3 63.08 0.26 4 2 1 2 3 69.21 0.25 5 2 2 3 1 66.06 0.24 6 2 3 1 2 68.54 0.28 7 3 1 3 2 60.97 0.27 8 3 2 1 3 61.21 0.24 9 3 3 2 1 66.09 0.20 K1 0.760 0.800 0.800 0.720 K2 0.770 0.700 0.670 0.770 K3 0.710 0.740 0.770 0.750 k1 0.253 0.267 0.267 0.240 k2 0.257 0.233 0.223 0.257 k3 0.237 0.247 0.257 0.250 R 0.020 0.034 0.044 0.017

[0193] Result analysis: As can be seen from R values shown in Table 2, RB>RA>RD, which shows that an order of factors was B>A>D. And as can be seen from k values, A2>A1>A3, B1>B2>B2, D2>D3>D1, therefore, an optimal level combination of factors was A2B13D2. Therefore, an optimum adsorption condition of total flavonoids alternatively is: 0.2 g/ml of loading sample, 2 BV/h of adsorption velocity, and 1:8 of ratio of diameter to height.

[0194] b) Investigation in a Volume of Loading Sample

[0195] 0.2 g/mL loading sample was applied onto 20 g AB-8 resin column (400 mm20 mm) at the flow rate of 2 Bv/h. 10 mL was collected from each fraction. Concentrations of total flavonoids in each fraction were measured and calculated, and a leaking curve was plotted, the results are shown in FIG. 1. As can be seen from the figure, total flavonoids begin to leak when the volume of the loading sample was 50 mL (i.e. 10 g raw material of Desmodium Styracifolium), and an adsorption saturation state was reached when the volume of the loading sample was 600 mL (about 30 times the weight of filled resin).

[0196] c) Investigation in Washing Condition

[0197] 50 mL loading sample was subjected to adsorption in accordance above optimum adsorption condition, purified with water, with every 20 mL of effluent for one fraction, inspection was performed through -naphthol reaction, at the same time, weight of dry extract was determined, -naphthol reaction was negative and the weight of dry extract does not change anymore after washing with 300 mL water, indicating that sugars adsorbed by the resin column can be substantially removed after washing with 300 mL water (about 15 times the weight of resin).

[0198] d) Investigation in Ethanol Concentration for Elution

[0199] Another five copies of resin (with 20 g for each copy) each were subjected to adsorptions, purified in accordance above adsorption condition and washing condition followed by separately eluted with 400 mL ethanol each having a concentration of 30%, 45%, 60%, 75%, 90% at same flow rate, the content and desorption rate of total flavonoids were determined and calculated, results are shown in Table 7.

Table 7 Results of Ethanol Concentration for Elution of Total Flavonoids of Desmodium Styracifolium

[0200]

TABLE-US-00007 Ethanol concentration (%) 30 45 60 75 90 Desorption rate (%) 38.16 59.25 85.63 81.56 79.21 Weight of dry extract (mg) 87.23 178.5 231.6 216.2 209.3 Content of total flavonoids 35.21 42.06 58.63 55.45 56.82 (%)

[0201] The above results show that, both the desorption rate and content of total flavonoids are high when the ethanol concentration is 60% or more, and desorption capacities are considerable when the ethanol concentrations separately are 60%, 75% and 90%, the present test chose 60% ethanol as the elution solvent for the sake of manufacturing cost.

[0202] e) Investigation in Elution Velocity

[0203] Dynamic adsorption was performed with 60% ethanol as the elution solvent at flow rate of 1, 3, 5 column bed volumes per hour, respectively, according to above conditions, ethanol eluents were collected, the content and desorption rate of total flavonoids were determined and calculated, results are shown in Table 8.

Table 8 Results of Elution Velocity of Ethanol for Elution of Total Flavonoids of Desmodium Styracifolium

[0204]

TABLE-US-00008 Content of total flavonoids in Elution velocity Desorption rate (%) dry extract (%) 1BV/h 88.31 57.92 3BV/h 87.45 56.37 5BV/h 80.16 50.08

[0205] Results show that, there was no big difference between elution velocity of 1 column bed volume per hour and elution velocity of 3 column bed volumes per hour, and choosing elution velocity of 3 BV/h was more reasonable, considering the production efficiency.

[0206] f) Investigation in Elution Volume

[0207] Dynamic adsorption was performed with 60% ethanol as elution solvent according to above conditions, the effluent was quantitative collected and in which the content of total flavonoids were determined. Results are shown in FIG. 2. Results show that, flavonoids adsorbed by 20 g resin can be completely eluted with 240 mL (8 times the resin column volume) of 60% ethanol. Therefore, flavonoids adsorbed by 20 g resin can be completely eluted with 240 mL (8 times the resin column volume) of 60% ethanol at 3 BV/h of elution velocity.

Embodiment 2

Preparation of Total Flavonoids of Desmodium Styracifolium

[0208] 50 g raw material of Desmodium Styracifolium was weighted, heated and refluxed at a temperature of 55 C. for 2 hours for first extraction with 80% ethanol having a weight of 12 times as heavy as the raw material, and then heated and refluxed at a temperature of 55 C. for 1.5 hours for second extraction with 80% ethanol having a weight of 10 times as heavy as the raw material followed by mixing. The alcohol extraction solution was concentrated to be of a volume 5 times the weight of the raw material followed by still standing and filtering, thereby obtaining a filtrate (i.e., loading sample) for use. 100 g AB-8 macroporous resin (in pharmaceutical grade) was immersed into a suitable amount of ethanol, and then packed into a column via a wet method followed by treatment for use. The filtrate (the loading sample) was subjected to adsorption onto an AB-8 macroporous resin column at a flow rate of 2 column bed volumes per hour, eluted and purified with water having a volume of 10 times the weight of filled resin, then eluted with 60% ethanol having a volume of 8 column bed volumes at a flow rate of 2 column bed volumes per hour, to obtain an eluted solution. The eluted solution was concentrated to recycle ethanol and to obtain a concentrated solution with a relative density of 1.22, then dried under reduced pressure at a temperature of 75 C. and smashing to obtain 1.10 g total flavonoids extract of Desmodium Styracifolium.

Embodiment 3

Preparation of Total Flavonoids of Desmodium Styracifolium

[0209] 200 g raw material of Desmodium Styracifolium was weighted, heated and refluxed at a temperature of 55 C. for 2 hours for first extraction with 80% ethanol having a weight of 12 times as heavy as the raw material, and then heated and refluxed at a temperature of 55 C. for 1.5 hours for second extraction with 80% ethanol having a weight of 10 times as heavy as the raw material followed by mixing. The alcohol extraction solution was concentrated to be of a volume 5 times the weight of the raw material followed by still standing and filtering, thereby obtaining a filtrate (i.e., loading sample) for use. 400 g AB-8 macroporous resin (in pharmaceutical grade) was immersed into a suitable amount of ethanol, and then packed into a column via a wet method followed by treatment for use. The filtrate (the loading sample) was subjected to adsorption onto an AB-8 macroporous resin column at a flow rate of 2 column bed volumes per hour, eluted and purified with water having a volume of 10 times the weight of filled resin, then eluted with 60% ethanol having a volume of 8 column bed volumes at a flow rate of 2 column bed volumes per hour, to obtain an eluted solution. The eluted solution was concentrated to recycle ethanol and to obtain a concentrated solution with a relative density of 1.22, then dried under reduced pressure at a temperature of 75 C. and smashing to obtain 4.03 g total flavonoids extract of Desmodium Styracifolium (placed in a shady and cool place).

[0210] By means of UV-visible spectrophotometry, the content of the total flavonoids was measured to be of 63.31% (by dried product, %), the content of schaftoside was 5.38% (by dried product, %).

Embodiment 4

Preparation of Total Flavonoids of Desmodium Styracifolium

[0211] 200 g raw material of Desmodium Styracifolium was weighted, heated and refluxed at a temperature of 60 C. for 3 hours for first extraction with 95% ethanol having a weight of 14 times as heavy as the raw material, and heated and refluxed at a temperature of 50 C. for 2 hours for second extraction with 95% ethanol having a weight of 12 times as heavy as the raw material, then heated and refluxed at a temperature of 50 C. for 1 hour for third extraction with 80% ethanol having a weight of 8 times as heavy as the raw material followed by mixing. The alcohol extraction solution was concentrated to be of a volume 8 times the weight of the raw material followed by still standing and filtering, thereby obtaining a filtrate (i.e., loading sample) for use. 400 g AB-8 macroporous resin (in pharmaceutical grade) was immersed into a suitable amount of ethanol, and then packed into a column via a wet method followed by treatment for use.

[0212] The filtrate (the loading sample) was subjected to adsorption onto an AB-8 macroporous resin column at a flow rate of 2 column bed volumes per hour, eluted and purified with water having a volume of 12 times the weight of filled resin, then eluted with 95% ethanol having a volume of 10 column bed volumes at a flow rate of 2 column bed volumes per hour, to obtain an eluted solution. The eluted solution was concentrated to recycle ethanol and to obtain a concentrated solution with a relative density of 1.10, then dried under reduced pressure at a temperature of 75 C. and smashing to obtain 4.03 g total flavonoids extract of Desmodium Styracifolium (placed in a shady and cool place). By means of UV-visible spectrophotometry, the content of the total flavonoids was measured to be of 71.65% (by dried product, %), and the content of schaftoside was 10.30% (by dried product, %).

Embodiment 5

Preparation of Total Flavonoids of Desmodium Styracifolium

[0213] 200 g raw material of Desmodium Styracifolium was weighted, heated and refluxed at a temperature of 55 C. for 2 hours for first extraction with 70% ethanol having a weight of 12 times as heavy as the raw material, and then heated and refluxed at a temperature of 55 C. for 1.5 hours for second extraction with 70% ethanol having a weight of 10 times as heavy as the raw material followed by mixing. The alcohol extraction solution was concentrated to be of a volume 5 times the weight of the raw material followed by still standing and filtering, thereby obtaining a filtrate (i.e., loading sample) for use. 400 g AB-8 macroporous resin (in pharmaceutical grade) was immersed into a suitable amount of ethanol, and then packed into a column via a wet method followed by treatment for use.

[0214] The filtrate (the loading sample) was subjected to adsorption onto an AB-8 macroporous resin column at a flow rate of 1 column bed volumes per hour, eluted and purified with water having a volume of 10 times the weight of filled resin, then eluted with 60% ethanol having a volume of 8 column bed volumes at a flow rate of 2 column bed volumes per hour, to obtain an eluted solution. The eluted solution was concentrated to recycle ethanol and to obtain a concentrated solution with a relative density of 1.22, then dried under reduced pressure at a temperature of 75 C. and smashing to obtain 4.68 g total flavonoids extract of Desmodium Styracifolium (placed in a shady and cool place). By means of UV-visible spectrophotometry, the content of the total flavonoids was measured to be of 60.07% (by dried product, %), the content of schaftoside was 4.45% (by dried product, %).

Embodiment 6

Preparation of Total Flavonoids of Desmodium Styracifolium

[0215] 200 g raw material of Desmodium Styracifolium was weighted, heated and refluxed for extraction at a temperature of 60 C. for 3 hours with 50% ethanol having a weight of 12 times as heavy as the raw material to obtain an alcohol extraction solution. The alcohol extraction solution was concentrated to be of a volume 2 times the weight of the raw material followed by still standing and filtering, thereby obtaining a filtrate (i.e., loading sample) for use. 400 g AB-8 macroporous resin (in pharmaceutical grade) was immersed into a suitable amount of ethanol, and then packed into a column via a wet method followed by treatment for use.

[0216] The filtrate (the loading sample) was subjected to adsorption onto an AB-8 macroporous resin column at a flow rate of 2 column bed volumes per hour, eluted and purified with water having a volume of 8 times the weight of filled resin, then eluted with 40% ethanol having a volume of 6 column bed volumes at a flow rate of 2 column bed volumes per hour, to obtain an eluted solution. The eluted solution was concentrated to recycle ethanol and to obtain a concentrated solution with a relative density of 1.30, then dried under reduced pressure at a temperature of 75 C. and smashing to obtain 3.89 g total flavonoids extract of Desmodium Styracifolium (placed in a shady and cool place). By means of UV-visible spectrophotometry, the content of the total flavonoids was measured to be of 52.64% (by dried product, %), the content of schaftoside was 4.17% (by dried product, %).

Embodiment 7

Preparation of Total Flavonoids of Desmodium Styracifolium

[0217] 50 kg raw material of Desmodium Styracifolium was weighted, heated and refluxed at a temperature of 55 C. for 2 hours for first extraction with 80% ethanol having a weight of 12 times as heavy as the raw material, and then heated and refluxed at a temperature of 55 C. for 1.5 hours for second extraction with 80% ethanol having a weight of 10 times as heavy as the raw material followed by mixing. The alcohol extraction solution was concentrated to be of a volume 5 times the weight of the raw material followed by still standing and filtering, thereby obtaining a filtrate (i.e., loading sample) for use. 100 kg AB-8 macroporous resin (in pharmaceutical grade) was immersed into a suitable amount of ethanol, and then packed into a column via a wet method followed by treatment for use.

[0218] The filtrate (the loading sample) was subjected to adsorption onto an AB-8 macroporous resin column at a flow rate of 2 column bed volumes per hour, eluted and purified with water having a volume of 10 times the weight of filled resin, then eluted with 60% ethanol having a volume of 8 column bed volumes at a flow rate of 2 column bed volumes per hour, to obtain an eluted solution. The eluted solution was concentrated to recycle ethanol and to obtain a concentrated solution with a relative density of 1.22, then dried under reduced pressure at a temperature of 75 C. and smashing to obtain 1.12 kg total flavonoids extract of Desmodium Styracifolium (placed in a shady and cool place). By means of UV-visible spectrophotometry, the content of the total flavonoids was measured to be of 59.49% (by dried product, %), the content of schaftoside was 5.10% (by dried product, %).

Embodiment 8

Preparation of Total Flavonoids of Desmodium Styracifolium

[0219] 50 kg raw material of Desmodium Styracifolium was weighted, heated and refluxed at a temperature of 55 C. for 2 hours for first extraction with 80% ethanol having a weight of 12 times as heavy as the raw material, and then heated and refluxed at a temperature of 55 C. for 1.5 hours for second extraction with 80% ethanol having a weight of 10 times as heavy as the raw material followed by mixing. The alcohol extraction solution was concentrated to be of a volume 5 times the weight of the raw material followed by still standing and filtering, thereby obtaining a filtrate (i.e., loading sample) for use. 100 kg AB-8 macroporous resin (in pharmaceutical grade) was immersed into a suitable amount of ethanol, and then packed into a column via a wet method followed by treatment for use.

[0220] The filtrate (the loading sample) was subjected to adsorption onto an AB-8 macroporous resin column at a flow rate of 2 column bed volumes per hour, eluted and purified with water having a volume of 10 times the weight of filled resin, then eluted with 60% ethanol having a volume of 8 column bed volumes at a flow rate of 2 column bed volumes per hour, to obtain an eluted solution. The eluted solution was concentrated to recycle ethanol and to obtain a concentrated solution with a relative density of 1.22, then dried under reduced pressure at a temperature of 75 C. and smashing to obtain 1.14 kg total flavonoids extract of Desmodium Styracifolium (placed in a shady and cool place). By means of UV-visible spectrophotometry, the content of the total flavonoids was measured to be of 59.37% (by dried product, %), the content of schaftoside was 5.01% (by dried product, %).

[0221] Results show that: the process parameters studied by the present experiments was feasible and can be used in industrial production.

Embodiment 9

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0222] Formula:

TABLE-US-00009 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Sodium dodecyl sulfate 30 g Lactose 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 tablets

[0223] Preparation was performed by the following steps:

[0224] a. preparing total flavonoids of Desmodium Styracifolium according to Embodiment 8;

[0225] b. preparing a solid dispersion containing total flavonoids of Desmodium Styracifolium: dissolving 50 g total flavonoids of Desmodium Styracifolium, 200 g povidone K.sub.30, 100 g poloxamer 188 and 30 g sodium dodecyl sulfate in respective formula dosage, sieved at 80 meshes in advance respectively, with 50% ethanol under stirring and at a temperature of 65 C., followed by removing the solvent via evaporation under reduced pressure at a temperature of 50 C., vacuum drying at a temperature of 40 C., smashing and sieving at 80 meshes, so as to obtain the solid dispersion containing total flavonoids of Desmodium Styracifolium;

[0226] c. preparing granules containing total flavonoids of Desmodium Styracifolium: mixing 50 g lactose and 20 g sodium croscarmellose, sieved at 80 meshes in advance respectively, with the solid dispersion containing the total flavonoids of Desmodium Styracifolium obtained in step (b) to be uniform, followed by preparing a soften material with suitable amount of water, granulating at 20 meshes, drying at a temperature of 55 C., size stabilizing, and mixing with 5 g sodium stearyl fumarate to be uniform, so as to obtain the granules containing total flavonoids of Desmodium Styracifolium;

[0227] d. tableting: tableting the granules containing total flavonoids of Desmodium Styracifolium with a tableting machine to obtain a tablet containing total flavonoids of Desmodium Styracifolium with a dissolution rate measured to be 90.7%.

[0228] Method for Determining the Dissolution Rate:

[0229] Dissolution rate was measured in accordance with the First Method in appendix XC, part II, Chinese Pharmacopoeia, 2010 edition.

[0230] Testing sample solutions were obtained by the following steps: dissolving the above-obtained tablet in 1000 ml water (as a dissolution medium) contained in a beaker; setting a rotation rate of dissolution rate analysis instruments to be 100 rpm per min; taking 10 ml from the beaker after 5, 15, 25, 35, 45 and 60 min from operations specified in the First Method, followed by filtration; taking 1 ml secondary filtrate precisely each into a 5 ml volumetric flask and adding 0.1 M hydrochloric acid up to graduation on the volumetric flask, followed by shaken to be uniform, thereby obtaining the testing sample solutions.

[0231] Reference sample solutions were obtained by the following steps: weighing a certain amount of schaftosides precisely as a reference sample; dissolving the reference sample with an appropriate volume of ethanol in a volumetric flask; adding 0.1 M hydrochloric acid up to graduation on the volumetric flask, thereby obtaining the reference sample solutions each having a schaftoside concentration of 15 g/ml.

[0232] The testing sample solutions and the reference sample solutions were subjected to ultraviolet spectrophotometry (appendix IV A) at 270 nm, for calculating the dissolution rate of each tablet.

Embodiment 10

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0233] Formula:

TABLE-US-00010 Total flavonoids of Desmodium Styracifolium 33 g Povidone K.sub.30 132 g Poloxamer 188 66 g Sodium dodecyl sulfate 6.6 g Lactose 50 g Cross-linked povidone 20 g Aerosil 1 g Total 1000 tablets

[0234] Preparation: identical to Embodiment 9.

Embodiment 11

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0235] Formula:

TABLE-US-00011 Total flavonoids of Desmodium Styracifolium 33 g Povidone K.sub.30 132 g Poloxamer 188 66 g Sodium dodecyl sulfate 19.8 g Lactose 30 g Sodium croscarmellose 20 g Sodium stearyl fumarate 3 g Total 1000 tablets

[0236] Preparation: identical to Embodiment 9.

Embodiment 12

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0237] Formula:

TABLE-US-00012 Total flavonoids of Desmodium Styracifolium 33 g Povidone K.sub.30 132 g Poloxamer 188 66 g Sodium dodecyl sulfate 33 g Microcrystalline cellulose 10 g Sodium croscarmellose 20 g Magnesium stearate 2 g Total 1000 tablets

[0238] Preparation: identical to Embodiment 9

Embodiment 13

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0239] Formula:

TABLE-US-00013 Total flavonoids of Desmodium Styracifolium 33 g Povidone K.sub.30 132 g Poloxamer 188 66 g Tween 80 19.8 g Lactose 40 g Sodium carboxymethyl starch 5 g Sodium stearyl fumarate 4 g Total 1000 tablets

[0240] Preparation: identical to Embodiment 9. Dissolution ratio is determined to be 90.4%.

Embodiment 14

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0241] Formula:

TABLE-US-00014 Total flavonoids of Desmodium Styracifolium 33 g Povidone K.sub.30 132 g Poloxamer 188 66 g Methoxypolyethylene glycol 19.8 g Microcrystalline cellulose 20 g Sodium carboxymethyl starch 15 g Sodium stearyl fumarate 3 g Total 1000 tablets

[0242] Preparation: identical to Embodiment 9.

Embodiment 15

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0243] Formula:

TABLE-US-00015 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Sodium dodecyl sulfate 10 g Lactose 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 tablets

[0244] Preparation: identical to Embodiment 9

Embodiment 16

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0245] Formula:

TABLE-US-00016 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Sodium dodecyl sulfate 50 g Lactose 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 tablets

[0246] Preparation: identical to Embodiment 9

Embodiment 17

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0247] Formula:

TABLE-US-00017 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Tween 80 30 g Lactose 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 tablets

[0248] Preparation: identical to Embodiment 9

Embodiment 18

Preparation of tablets containing total flavonoids of Desmodium Styracifolium

[0249] Formula

TABLE-US-00018 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Methoxypolyethylene glycol 30 g Lactose 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 tablets

[0250] Preparation: identical to Embodiment 9. Dissolution ratio is determined to be 91.1%.

Embodiment 19

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0251] Formula:

TABLE-US-00019 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Sodium dodecyl sulfate 30 g Pregelatinized starch 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 tablets

[0252] Preparation: identical to Embodiment 9

Embodiment 20

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0253] Formula:

TABLE-US-00020 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Sodium dodecyl sulfate 50 g Cross-linked povidone 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 tablets

[0254] Preparation: identical to Embodiment 9

Embodiment 21

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0255] Formula:

TABLE-US-00021 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Methoxypolyethylene glycol 30 g Microcrystalline cellulose 50 g Sodium croscarmellose 20 g Aerosil 5 g Total 1000 tablets

[0256] Preparation: identical to Embodiment 9

Embodiment 22

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0257] Formula:

TABLE-US-00022 Total flavonoids of Desmodium Styracifolium 66.5 g Povidone K.sub.30 266 g Poloxamer 188 133 g Sodium dodecyl sulfate 13.3 g Microcrystalline cellulose 20 g Sodium carboxymethyl starch 10 g Sodium stearyl fumarate 8 g Total 1000 tablets

[0258] Preparation: identical to Embodiment 9

Embodiment 23

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0259] Formula:

TABLE-US-00023 Total flavonoids of Desmodium Styracifolium 66.5 g Povidone K.sub.30 266 g Poloxamer 188 133 g Sodium dodecyl sulfate 39.9 g Lactose 10 g Sodium croscarmellose 15 g Sodium stearyl fumarate 6 g Total 1000 tablets

[0260] Preparation: identical to Embodiment 9. Dissolution ratio is determined to be 91.5%.

Embodiment 24

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0261] Formula:

TABLE-US-00024 Total flavonoids of Desmodium Styracifolium 66.5 g Povidone K.sub.30 266 g Poloxamer 188 133 g Sodium dodecyl sulfate 66.5 g Lactose 1 g Cross-linked povidone 10 g Magnesium stearate 10 g Total 1000 tablets

[0262] Preparation: identical to Embodiment 9

Embodiment 25

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0263] Formula:

TABLE-US-00025 Total flavonoids of Desmodium Styracifolium 66.5 g Povidone K.sub.30 266 g Poloxamer 188 133 g Tween 80 39.9 g Lactose 10 g Sodium croscarmellose 50 g Sodium stearyl fumarate 1 g Total 1000 tablets

[0264] Preparation: identical to Embodiment 9

Embodiment 26

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0265] Formula:

TABLE-US-00026 Total flavonoids of Desmodium Styracifolium 66.5 g Povidone K.sub.30 266 g Poloxamer 188 133 g Methoxypolyethylene glycol 39.9 g Pregelatinized starch 15 g Sodium croscarmellose 30 g Sodium stearyl fumarate 5 g Total 1000 tablets

[0266] Preparation: identical to Embodiment 9.

Embodiment 27

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0267] Formula:

TABLE-US-00027 Total flavonoids of Desmodium Styracifolium 100 g Povidone K.sub.30 400 g Poloxamer 188 200 g Sodium dodecyl sulfate 20 g Pregelatinized starch 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 tablets

[0268] Preparation: identical to Embodiment 9

Embodiment 28

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0269] Formula:

TABLE-US-00028 Total flavonoids of Desmodium Styracifolium 100 g Povidone K.sub.30 400 g Poloxamer 188 200 g Sodium dodecyl sulfate 60 g Lactose 50 g Cross-linked povidone 40 g Sodium stearyl fumarate 8 g Total 1000 tablets

[0270] Preparation: identical to Embodiment 9

Embodiment 29

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0271] Formula:

TABLE-US-00029 Total flavonoids of Desmodium Styracifolium 100 g Povidone K.sub.30 400 g Poloxamer 188 200 g Sodium dodecyl sulfate 100 g Microcrystalline cellulose 10 g Sodium carboxymethyl starch 20 g Sodium stearyl fumarate 10 g Total 1000 tablets

[0272] Preparation: identical to Embodiment 9

Embodiment 30

Preparation of tablets containing total flavonoids of Desmodium Styracifolium

[0273] Formula:

TABLE-US-00030 Total flavonoids of Desmodium Styracifolium 100 g Povidone K.sub.30 400 g Poloxamer 188 200 g Tween 80 60 g Lactose 10 g Sodium croscarmellose 15 g Sodium stearyl fumarate 8 g Total 1000 tablets

[0274] Preparation: identical to Embodiment 9

Embodiment 31

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0275] Formula:

TABLE-US-00031 Total flavonoids of Desmodium Styracifolium 100 g Povidone K.sub.30 400 g Poloxamer 188 200 g Methoxypolyethylene glycol 60 g Lactose 15 g Sodium croscarmellose 10 g Sodium stearyl fumarate 8 g Total 1000 tablets

[0276] Preparation: identical to Embodiment 9

Embodiment 32

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0277] Formula:

TABLE-US-00032 Total flavonoids of Desmodium Styracifolium 133 g Povidone K.sub.30 532 g Poloxamer 188 266 g Sodium dodecyl sulfate 26.6 g Lactose 20 g Sodium croscarmellose 20 g Sodium stearyl fumarate 8 g Total 1000 tablets

[0278] Preparation: identical to Embodiment 9

Embodiment 33

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0279] Formula:

TABLE-US-00033 Total flavonoids of Desmodium Styracifolium 133 g Povidone K.sub.30 532 g Poloxamer 188 266 g Sodium dodecyl sulfate 79.8 g Lactose 20 g Cross-linked povidone 25 g Sodium stearyl fumarate 9 g Total 1000 tablets

[0280] Preparation: identical to Embodiment 9

Embodiment 34

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0281] Formula:

TABLE-US-00034 Total flavonoids of Desmodium Styracifolium 133 g Povidone K.sub.30 532 g Poloxamer 188 266 g Sodium dodecyl sulfate 133 g Microcrystalline cellulose 1 g Sodium carboxymethyl starch 1 g Sodium stearyl fumarate 10 g Total 1000 tablets

[0282] Preparation: identical to Embodiment 9

Embodiment 35

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0283] Formula:

TABLE-US-00035 Total flavonoids of Desmodium Styracifolium 133 g Povidone K.sub.30 532 g Poloxamer 188 266 g Tween 80 79.8 g Lactose 10 g Sodium croscarmellose 10 g Magnesium stearate 8 g Total 1000 tablets

[0284] Preparation: identical to Embodiment 9

Embodiment 36

Preparation of Tablets Containing Total Flavonoids of Desmodium Styracifolium

[0285] Formula:

TABLE-US-00036 Total flavonoids of Desmodium Styracifolium 133 g Povidone K.sub.30 532 g Poloxamer 188 266 g Methoxypolyethylene glycol 79.8 g Pregelatinized starch 5 g Cross-linked povidone 5 g Magnesium stearate 5 g Total 1000 tablets

[0286] Preparation: identical to Embodiment 9

Embodiment 37

Preparation of Capsules Containing Total Flavonoids of Desmodium Styracifolium

[0287] Formula:

TABLE-US-00037 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Sodium dodecyl sulfate 30 g Lactose 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 capsules

[0288] Preparation was performed by the following steps:

[0289] a. preparing total flavonoids of Desmodium Styracifolium according to Embodiment 8;

[0290] b. preparing a solid dispersion containing total flavonoids of Desmodium Styracifolium: dissolving 50 g total flavonoids of Desmodium Styracifolium, 200 g povidone K.sub.30, 100 g poloxamer 188 and 30 g sodium dodecyl sulfate in respective formula dosage, sieved at 80 meshes in advance respectively, with 50% ethanol under stirring and at a temperature of 65 C., followed by removing the solvent via evaporation under reduced pressure at a temperature of 50 C., vacuum drying at a temperature of 40 C., smashing and sieving at 80 meshes, so as to obtain the solid dispersion containing total flavonoids of Desmodium Styracifolium;

[0291] c. preparing granules containing total flavonoids of Desmodium Styracifolium: mixing 50 g lactose and 20 g sodium croscarmellose, sieved at 80 meshes in advance respectively, with the solid dispersion containing the total flavonoids of Desmodium Styracifolium obtained in step (b) to be uniform, followed by preparing a soften material with suitable amount of water, granulating at 20 meshes, drying at a temperature of 55 C., size stabilizing, and mixing with 5 g sodium stearyl fumarate to be uniform, so as to obtain the granules containing total flavonoids of Desmodium Styracifolium;

[0292] d. capsulizing: capsulizing the granules containing total flavonoids of Desmodium Styracifolium with an encapsulating machine to obtain a capsule containing total flavonoids of Desmodium Styracifolium with a dissolution rate measured to be 91.1%.

Embodiment 38

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0293] Formula:

TABLE-US-00038 Total flavonoids of Desmodium Styracifolium 33 g Povidone K.sub.30 132 g Poloxamer 188 66 g Sodium dodecyl sulfate 6.6 g Lactose 50 g Cross-linked povidone 20 g Aerosil 1 g Total 1000 capsules

[0294] Preparation: identical to Embodiment 37.

Embodiment 39

Preparation of Capsules Containing a Capsule Containing Total Flavonoids of Desmodium Styracifolium

[0295] Formula:

TABLE-US-00039 Total flavonoids of Desmodium Styracifolium 33 g Povidone K.sub.30 132 g Poloxamer 188 66 g Sodium dodecyl sulfate 19.8 g Lactose 30 g Sodium croscarmellose 20 g Sodium stearyl fumarate 3 g Total 1000 capsules

[0296] Preparation: identical to Embodiment 37.

Embodiment 40

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0297] Formula:

TABLE-US-00040 Total flavonoids of Desmodium Styracifolium 33 g Povidone K.sub.30 132 g Poloxamer 188 66 g Sodium dodecyl sulfate 33 g Microcrystalline cellulose 10 g Sodium croscarmellose 20 g Magnesium stearate 2 g Total 1000 capsules

[0298] Preparation: identical to Embodiment 37.

Embodiment 41

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0299] Formula:

TABLE-US-00041 Total flavonoids of Desmodium Styracifolium 33 g Povidone K.sub.30 132 g Poloxamer 188 66 g Tween 80 19.8 g Lactose 40 g Sodium carboxymethyl starch 5 g Sodium stearyl fumarate 4 g Total 1000 capsules

[0300] Preparation: identical to Embodiment 37. Dissolution ratio is determined to be 91.5%.

Embodiment 42

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0301] Formula:

TABLE-US-00042 Total flavonoids of Desmodium Styracifolium 33 g Povidone K.sub.30 132 g Poloxamer 188 66 g Methoxypolyethylene glycol 19.8 g Microcrystalline cellulose 20 g Sodium carboxymethyl starch 15 g Sodium stearyl fumarate 3 g Total 1000 capsules

[0302] Preparation: identical to Embodiment 37.

Embodiment 43

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0303] Formula:

TABLE-US-00043 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Sodium dodecyl sulfate 10 g Lactose 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 capsules

[0304] Preparation: identical to Embodiment 37.

Embodiment 44

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0305] Formula:

TABLE-US-00044 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Sodium dodecyl sulfate 50 g Lactose 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 capsules

[0306] Preparation: identical to Embodiment 37.

Embodiment 45

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0307] Formula:

TABLE-US-00045 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Tween 80 30 g Lactose 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 capsules

[0308] Preparation: identical to Embodiment 37.

Embodiment 46

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0309] Formula:

TABLE-US-00046 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Methoxypolyethylene glycol 30 g Lactose 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 capsules

[0310] Preparation: identical to Embodiment 37. Dissolution ratio is determined to be 91.0%.

Embodiment 47

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0311] Formula:

TABLE-US-00047 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Sodium dodecyl sulfate 30 g Pregelatinized starch 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 capsules

[0312] Preparation: identical to Embodiment 37.

Embodiment 48

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0313] Formula:

TABLE-US-00048 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Sodium dodecyl sulfate 50 g Cross-linked povidone 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 capsules

[0314] Preparation: identical to Embodiment 37.

Embodiment 49

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0315] Formula:

TABLE-US-00049 Total flavonoids of Desmodium Styracifolium 50 g Povidone K.sub.30 200 g Poloxamer 188 100 g Methoxypolyethylene glycol 30 g Microcrystalline cellulose 50 g Sodium croscarmellose 20 g Aerosil 5 g Total 1000 capsules

[0316] Preparation: identical to Embodiment 37.

Embodiment 50

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0317] Formula:

TABLE-US-00050 Total flavonoids of Desmodium Styracifolium 66.5 g Povidone K.sub.30 266 g Poloxamer 188 133 g Sodium dodecyl sulfate 13.3 g Microcrystalline cellulose 20 g Sodium carboxymethyl starch 10 g Sodium stearyl fumarate 8 g Total 1000 capsules

[0318] Preparation: identical to Embodiment 37.

Embodiment 51

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0319] Formula:

TABLE-US-00051 Total flavonoids of Desmodium Styracifolium 66.5 g Povidone K.sub.30 266 g Poloxamer 188 133 g Sodium dodecyl sulfate 39.9 g Lactose 10 g Sodium croscarmellose 15 g Sodium stearyl fumarate 6 g Total 1000 capsules

[0320] Preparation: identical to Embodiment 37. Dissolution ratio is determined to be 91.3%.

Embodiment 52

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0321] Formula:

TABLE-US-00052 Total flavonoids of Desmodium Styracifolium 66.5 g Povidone K.sub.30 266 g Poloxamer 188 133 g Sodium dodecyl sulfate 66.5 g Lactose 1 g Cross-linked povidone 10 g Magnesium stearate 10 g Total 1000 capsules

[0322] Preparation: identical to Embodiment 37.

Embodiment 53

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0323] Formula:

TABLE-US-00053 Total flavonoids of Desmodium Styracifolium 66.5 g Povidone K.sub.30 266 g Poloxamer 188 133 g Tween 80 39.9 g Lactose 10 g Sodium croscarmellose 50 g Sodium stearyl fumarate 1 g Total 1000 capsules

[0324] Preparation: identical to Embodiment 37.

Embodiment 54

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0325] Formula:

TABLE-US-00054 Total flavonoids of Desmodium Styracifolium 66.5 g Povidone K.sub.30 266 g Poloxamer 188 133 g Methoxypolyethylene glycol 39.9 g Pregelatinized starch 15 g Sodium croscarmellose 30 g Sodium stearyl fumarate 5 g Total 1000 capsules

[0326] Preparation: identical to Embodiment 37.

Embodiment 55

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0327] Formula:

TABLE-US-00055 Total flavonoids of 100 g Desmodium Styracifolium Povidone K.sub.30 400 g Poloxamer 188 200 g Sodium dodecyl sulfate 20 g Pregelatinized starch 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 5 g Total 1000 capsules

[0328] Preparation: identical to Embodiment 37.

Embodiment 56

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0329] Formula:

TABLE-US-00056 Total flavonoids of 100 g Desmodium Styracifolium Povidone K.sub.30 400 g Poloxamer 188 200 g Sodium dodecyl sulfate 60 g Lactose 50 g Cross-linked povidone 40 g Sodium stearyl fumarate 8 g Total 1000 capsules

[0330] Preparation: identical to Embodiment 37.

Embodiment 57

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0331] Formula:

TABLE-US-00057 Total flavonoids of 100 g Desmodium Styracifolium Povidone K.sub.30 400 g Poloxamer 188 200 g Sodium dodecyl sulfate 100 g Microcrystalline cellulose 10 g Sodium carboxymethyl starch 20 g Sodium stearyl fumarate 10 g Total 1000 capsules

[0332] Preparation: identical to Embodiment 37.

Embodiment 58

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0333] Formula:

TABLE-US-00058 Total flavonoids of 100 g Desmodium Styracifolium Povidone K.sub.30 400 g Poloxamer 188 200 g Tween 80 60 g Lactose 10 g Sodium croscarmellose 15 g Sodium stearyl fumarate 8 g Total 1000 capsules

[0334] Preparation: identical to Embodiment 37.

Embodiment 59

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0335] Formula:

TABLE-US-00059 Total flavonoids of 100 g Desmodium Styracifolium Povidone K.sub.30 400 g Poloxamer 188 200 g Methoxypolyethylene glycol 60 g Lactose 15 g Sodium croscarmellose 10 g Sodium stearyl fumarate 8 g Total 1000 capsules

[0336] Preparation: identical to Embodiment 37.

Embodiment 60

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0337] Formula:

TABLE-US-00060 Total flavonoids of 133 g Desmodium Styracifolium Povidone K.sub.30 532 g Poloxamer 188 266 g Sodium dodecyl sulfate 26.6 g Lactose 20 g Sodium croscarmellose 20 g Sodium stearyl fumarate 8 g Total 1000 capsules

[0338] Preparation: identical to Embodiment 37.

Embodiment 61

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0339] Formula:

TABLE-US-00061 Total flavonoids of 133 g Desmodium Styracifolium Povidone K.sub.30 532 g Poloxamer 188 266 g Sodium dodecyl sulfate 79.8 g Lactose 20 g Cross-linked povidone 25 g Sodium stearyl fumarate 9 g Total 1000 capsules

[0340] Preparation: identical to Embodiment 37.

Embodiment 62

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0341] Formula:

TABLE-US-00062 Total flavonoids of 133 g Desmodium Styracifolium Povidone K.sub.30 532 g Poloxamer 188 266 g Sodium dodecyl sulfate 133 g Microcrystalline cellulose 1 g Sodium carboxymethyl starch 1 g Sodium stearyl fumarate 10 g Total 1000 capsules

[0342] Preparation: identical to Embodiment 37.

Embodiment 63

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0343] Formula:

TABLE-US-00063 Total flavonoids of 133 g Desmodium Styracifolium Povidone K.sub.30 532 g Poloxamer 188 266 g Tween 80 79.8 g Lactose 10 g Sodium croscarmellose 10 g Magnesium stearate 8 g Total 1000 capsules

[0344] Preparation: identical to Embodiment 37.

Embodiment 64

Preparation of Capsules Containing Containing Total Flavonoids of Desmodium Styracifolium

[0345] Formula:

TABLE-US-00064 Total flavonoids of 133 g Desmodium Styracifolium Povidone K.sub.30 532 g Poloxamer 188 266 g Methoxypolyethylene glycol 79.8 g Pregelatinized starch 5 g Cross-linked povidone 5 g Magnesium stearate 5 g Total 1000 capsules

[0346] Preparation: identical to Embodiment 37.

Embodiment 65

General Pharmacological Experiments of Total Flavonoids of Desmodium Styracifolium

[0347] Experiment object: to observe the pharmacological effect of total flavonoids of Desmodium Styracifolium on general behaviour, state, central nervous system and digestive system of an animal.

[0348] Experiment animals and administration: Kunming mice, female, having a weight ranging from 18 g to 22 g, provided by Animal Center of Academy of Military Medical Science with a permit number of experiment animal quality: SOCK (Military) 2002-001, were raised in a mice experiment room of the center with an experiment proved facility number: SYXK (Military) 2002-001.

[0349] Experiment grouping: all mice were randomly divided into four groups, i.e., a reference group (administrated with 0.5% sodium carboxymethyl cellulose via gavage), a low-dosage group of total flavonoids of Desmodium Styracifolium (75 mg/kg), a middle-dosage group of total flavonoids of Desmodium Styracifolium (150 mg/kg) and a high-dosage group of total flavonoids of Desmodium Styracifolium (300 mg/kg). Each group contained 10 to 20 mice.

[0350] Single gavage was chosen to be the administration route with an administration volume of 0.6 ml/mouse.

[0351] Indicators and Results:

[0352] 1.1 Effects of Total Flavonoids of Desmodium Styracifolium on General Behaviour of Mouse

[0353] The general behaviour of mice was observed according to Bastian classification. Each group contained 10 mice, and the observation started after 15 min from gavage for continuous 60 min, which was performed once again after 24 hours. The observation was made to mental, gait, eye, tail, skin, hair and faeces.

[0354] After the observation to the general behaviour of the mice, the total flavonoids of Desmodium Styracifolium in the low-, middle- or high-dosage group (75 mg/kg, 150 mg/kg and 300 mg/kg) had little effects on the animal behaviour, action, activity, emotion and gait, with non-significant difference as compared with the reference group.

[0355] 1.2 Effects of Total Flavonoids of Desmodium Styracifolium on Spontaneous Activity

[0356] The results, recorded by a photoelectric method, showed that the spontaneous activities of the mice administrated with different dosages of total flavonoids of Desmodium Styracifolium via gavage had non-significant difference as compared with the reference group, and specific data was shown in Table 9.

TABLE-US-00065 TABLE 9 Effect on spontaneous activity of the mice adminitrated with total flavonoids of Desmodium Styracifolium via gavage before animal dosage administration after administration (times/3 min) number (mg/kg) (times/3 min) 30 min 60 min 120 min 20 0 43.5 7.2 41.8 3.3 40.3 3.1 37.8 2.2 20 75 43.8 5.0 41.3 3.1 39.8 3.3 38.5 1.3 20 150 44.8 5.0 39.8 2.2 39.3 1.7 39.5 1.3 20 300 43.5 4.2 40.5 1.9 39.8 2.2 39.5 1.9

[0357] 1.3 Effects of Total Flavonoids of Desmodium Styracifolium on Activating Central Nervous System of Mice

[0358] After administrated with total flavonoids of Desmodium Styracifolium via gavage, seizure lasting duration of mouse was observed by subjecting ear tips, applied with an appropriate amount of saline and clamped by a fish-mouth clamp at both sides, to electricity stimulation at a voltage of 110 V for 0.3 second.

[0359] As can be seen from obtaining result that the seizure lasting duration caused by the electricity stimulation was not significantly prolonged or shortened by total flavonoids of Desmodium Styracifolium in the low-, middle- or high-dosage group (75 mg/kg, 150 mg/kg and 300 mg/kg) as compared with the reference group; while the seizure occurrence was not changed significantly either (see the specific data shown in Table 10), thus indicating that the total flavonoids had no obvious activating effect on central nervous system via gavage administration.

TABLE-US-00066 TABLE 10 Effects on activating central nervous system of the mice administrated with total flavonoids of Desmodium Styracifolium via gavage animal dosage seizure lasting number weight (g) (mg/kg) duration (sec) 10 21.1 0.6 0 32.8 5.3 10 20.9 0.8 75 37.1 8.1 10 20.3 0.7 150 37.7 6.0 10 21.0 0.9 300 35.5 8.7

[0360] 1.4 Effects of Total Flavonoids of Desmodium Styracifolium on Digestive System of Mice

[0361] All mice were randomly grouped such that each group contained 10 mice, all of which were fasten for 12 hours before starting experiment. After 1 hour from administration with total flavonoids of Desmodium Styracifolium, the experiment mice were administrated with a suspending solution made from 5% carbon powder and 10% Arabic gum, with administration volume of 0.2 ml per mouse. All experiment mice were sacrificed after 20 minutes from the administration with the suspending solution for gastrointestinal tract harvest. The gastrointestinal tract was straighten on a glass plate for measuring a distance from pylorus to where the carbon powder headed with a ruler, then a percentage of such the distance to the total length of the gastrointestinal tract was calculated. Obtaining results showed that total flavonoids of Desmodium Styracifolium had no obvious effects on gastrointestinal movement. Specific data was shown in Table 11.

TABLE-US-00067 TABLE 11 Effects on propelling rate of the mice administrated with total flavonoids of Desmodium Styracifolium via gavage total length of distance from pylorus to where dosage gastrointestinal the carbon powder headed propelling (mg/kg) tract (cm) (cm) rate (%) 0 52.2 1.9 30.2 2.4 57.8 4.2 75 52.5 1.7 31.6 2.4 58.1 3.5 150 52.3 2.3 28.8 3.5 56.8 5.0 300 52.0 1.9 29.8 2.9 58.0 3.4

Example 66

Pharmacodynamic Experiments of Total Flavonoids of Desmodium Styracifolium in Animals

[0362] 1.1 Experiment of Therapeutic Effects of Total Flavonoids of Desmodium Styracifolium on Ethylene Glycol Calcium Oxalate Kidney Stones in Rats

[0363] As compared with the reference group (administrated with 0.5% sodium carboxymethyl cellulose via gavage), the total flavonoids of Desmodium Styracifolium in four dosage groups (50 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, 400 mg/kg/day) inhibited amount of calcium oxalate crystalline polymer in kidney with a significant dose-effect relationship (P<0.05-0.01); reduced the formation rate of kidney stones (P<0.05-0.01); decreased creatinine content (P<0.05-0.01) and uric acid content (P<0.05-0.01) in serum, and improved kidney function of rats.

[0364] 1.2 Experiment of Preventing Effects of Total Flavonoids of Desmodium Styracifolium on Ethylene Glycol-Induced Toxic Calcium Oxalate Kidney Stones in Rats

[0365] As compared with the reference group (administrated with 0.5% sodium carboxymethyl cellulose via gavage), the total flavonoids of Desmodium Styracifolium in three dosage groups (50 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day) alleviated pyclectasis, reduced the formation rate of kidney stones, decreased the amount of the calcium oxalate crystalline polymer (P<0.01-0.001) and decreased the creatinine content and the uric acid content in serum (P<0.05-0.01).

[0366] 1.3 Experiment of Dissolving Effect of Total Flavonoids of Desmodium Styracifolium on Implanted Human Bladder Stones in Rats

[0367] As compared with the reference group (administrated with 0.5% sodium carboxymethyl cellulose via gavage), total flavonoids of Desmodium Styracifolium in three dosage groups (100 mg/kg/day, 200 mg/kg/day, 400 mg/kg/day) had effects of dissolving stones and reducing the formation of new stones. The total flavonoids of Desmodium Styracifolium in 100 mg/kg/day group lightened the stone weight (P<0.05). The total flavonoids of Desmodium Styracifolium in 200 gm/kg/day group lightened the stone weight (P<0.05) and dissolved 20% stones. The total flavonoids of Desmodium Styracifolium in 400 gm/kg/day group lightened the stone weigh (P<0.01) and dissolved 30% stones.

[0368] 1.4 Experiment of Diuretic Effects of Total Flavonoids of Desmodium Styracifolium on Rats Suffering Ethylene Glycol-Induced Kidney Stones and Normal Rats

[0369] As compared with a reference group (administrated with 0.5% sodium carboxymethyl cellulose via gavage), rats in three dosage groups (50 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day) had a total urine output ranging from 76.4 to 89.5 ml, which was more than that of rats in the normal group (48.1 ml) by 29-36 ml after 6 hours from single administration. After 4 weeks treatment with administration to those rats suffering stones, the urine output within 12 hours was increased significantly, more than that in the model group by 12-36%.

[0370] 1.5 Experiment of Inhibition Effects of Total Flavonoids of Desmodium Styracifolium on Swelling Degree and Rate Swelling in Rat Toe Injected with Fresh Albumen

[0371] As compared with the reference group (administrated with 0.5% sodium carboxymethyl cellulose via gavage), total flavonoids of Desmodium Styracifolium in three dosage groups (100 mg/kg/day, 200 mg/kg/day, 400 mg/kg/day) alleviated the swelling degree and the rate swelling in rat toe injected with fresh albumen, indicating that total flavonoids of Desmodium Styracifolium has a certain anti-inflammatory effect and has an obvious inhibiting effect on proliferation of granulation tissue.

Example 67

Acute Toxicity Test of Total Flavonoids of Desmodium Styracifolium in Animals

[0372] 1.1 Acute Toxicity Tests of Total Flavonoids of Desmodium Styracifolium in Mice

[0373] All mice were randomly divided into 6 groups, each containing 20 mice with 10 male and 10 female, with 0.85 distances between groups. After administration, decreased activities, unstable gait, weakened breaths appeared in animals. Most mice died within an hour after the administration, and a few of mice died within 1 to 6 hours after the administration. After calculation by Bliss, LD50 for female was 18.162 g/kg with an upper limit of 20.199 g/kg and a lower limit of 16.326 g/kg under a confidence limit of 95%; LD50 for male was 17.084 g/kg with an upper limit of 18.975 g/kg and a lower limit of 15.301 g/kg under a confidence limit of 95%, with no obvious difference as for LD50 between female and male. According to the results described above, total flavonoids of Desmodium Styracifolium could be recognized as a substantially nontoxic medicament.

[0374] 1.2 Acute Toxicity Tests of Total Flavonoids of Desmodium Styracifolium in Rats

[0375] The test was performed according to fixed dosage by single oral administration. Rats were administrated with 2000 mg/kg total flavonoids of Desmodium Styracifolium for preliminary tests, resulting in nonobvious acute toxic reaction; accordingly, 2000 mg/kg was taken as the fixed dosage for formal tests.

[0376] Rats for the test were randomly divided into a reference group and an administration group, each containing 10 animals with 5 female and 5 male. Rats in the administration group were administrated with 2000 mg/kg total flavonoids of Desmodium Styracifolium by single gavage, with an administration volume of 2.0 ml/100 g body weight. Rats in the reference group were administrated with 0.5% sodium carboxymethyl cellulose by single gavage, with an administration volume of 2.0 ml/100 g body weight.

[0377] Rats in the administration group became lazy to move within 3 hours from the administration; excreted faeces in an ash black color after 1 day from the administration; consumed slightly reduced amount of food, had mildly inhibited increasement in body weight, which recovered to those in the reference group. According to the results described above, total flavonoids of Desmodium Styracifolium could be regarded as a tested medicament without severe and acute toxicity.

Embodiment 68

[0378] In this embodiment, tablets containing total flavonoids of Desmodium Styracifolium prepared by a common wet granulation process without solid dispersion carrier material were used as a control to compare with that prepared by the present method.

[0379] The formula (formula 1) used in comparative embodiment was as follows:

TABLE-US-00068 Total flavonoids of 50 g Desmodium Styracifolium Lactose 50 g Sodium croscarmellose 20 g Sodium stearyl fumarate 1 g Water suitable amount Total 1000 tablets

[0380] Preparation method of the comparative embodiment was performed by the following steps:

[0381] a. preparing the total flavonoids of Desmodium Styracifolium according to Embodiment 8;

[0382] b. sieving 50 g total flavonoids of Desmodium Styracifolium, 50 g lactose, and 20 g sodium croscarmellose in respective formula dosage at 80 meshes, respectively;

[0383] c. evenly mixing total flavonoids of Desmodium Styracifolium with lactose and sodium croscarmellose and, followed by preparing a soften material with suitable amount of water, granulating at 20 meshes, drying at a temperature of 55 C., size stabilizing, uniformly mixing with sodium stearyl fumarate, and tableting, to obtain a tablet containing total flavonoids of Desmodium Styracifolium.

[0384] Method for determining the dissolution rate:

[0385] Dissolution rate was measured in accordance with the First Method in appendix XC, part II, Chinese Pharmacopoeia, 2010 edition.

[0386] Testing sample solutions were obtained by the following steps: dissolving the above-obtained tablet in 1000 ml water (as a dissolution medium) contained in a beaker; setting a rotation rate of dissolution rate analysis instruments to be 100 rpm per min; taking 10 ml from the beaker after 5, 15, 25, 35, 45 and 60 min from operations specified in the First Method, followed by filtration; taking 1 ml secondary filtrate precisely each into a 5 ml volumetric flask and adding 0.1 M hydrochloric acid up to graduation on the volumetric flask, followed by shaken to be uniform, thereby obtaining the testing sample solutions.

[0387] Reference sample solutions were obtained by the following steps: weighing a certain amount of schaftosides precisely as a reference sample; dissolving the reference sample with an appropriate volume of ethanol in a volumetric flask; adding 0.1 M hydrochloric acid up to graduation on the volumetric flask, thereby obtaining the reference sample solutions each having a schaftoside concentration of 15 g/ml.

[0388] The testing sample solutions and the reference sample solutions were subjected to ultraviolet spectrophotometry (appendix IV A) at 270 nm, for calculating the dissolution rate of each tablet and the dissolution rate of each tablet was calculated. The dissolution rate was measured to be 75.0%.

[0389] Through researching tests, the solid dispersion containing total flavonoids of Desmodium Styracifolium was obtained to use as follow: dissolving the total flavonoids of Desmodium Styracifolium and povidone K.sub.30 used as a hydrophilic carrier of solid dispersion with a weight of 1:5 to 12, with 50% ethanol under stirring and at a temperature of 65 C., followed by removing the solvent via evaporation under reduced pressure at a temperature of 50 C., vacuum drying at a temperature of 50 C., smashing and sieving at 80 meshes.

[0390] Screening on Formula 2 to Formula 7 with povidone K.sub.30 used as solid dispersion carrier are shown in Table 12.

[0391] Preparation process was performed by the following steps: mixing lactose and sodium croscarmellose with the solid dispersion containing total flavonoids of Desmodium Styracifolium, sieved at 80 meshes in advance, respectively, to be uniform, followed by preparing a soften material with suitable amount of water, granulating at 20 meshes, drying at a temperature of 55 C., size stabilizing, and mixing with sodium stearyl fumarate to be uniform, then tableting, so as to obtain tablets.

[0392] The dissolution rates of total flavonoids of Desmodium Styracifolium were determined, and the determination results are shown in Table 12.

[0393] Table 12 screening on Formula of the comparative embodiment and Formulas of the present disclosure

TABLE-US-00069 Formula No. Formula 1 Formula 2 Formula 3 Formula 4 Formula 5 Formula 6 Formula 7 total flavonoids of 50 g / / / / / / Desmodium Styracifolium solid dispersion: total / 300 g 0 / / / / flavonoids of Desmodium Styracifolium:povidone K.sub.30 (1:5) solid dispersion: total / / 325 g / / / / flavonoids of Desmodium Styracifolium:povidone K.sub.30 (1:5.5) solid dispersion: total / / / 350 g / / / flavonoids of Desmodium Styracifolium:povidone K.sub.30 (1:6) solid dispersion: total / / / / 400 g / / flavonoids of Desmodium Styracifolium:povidone K.sub.30 (1:7) solid dispersion: total / / / / / 450 g / flavonoids of Desmodium solid dispersion: Styracifolium:povidone K.sub.30 (1:8) solid dispersion: total / / / / / / 650 g flavonoids of Desmodium Styracifolium:povidone K.sub.30 (1:12) lactose 50 50 50 50 50 50 50 sodium croscarmellose 20 20 20 20 20 20 20 sodium stearyl fumarate 1 5 5 5 5 5 5 water suitable suitable suitable suitable suitable suitable suitable amount amount amount amount amount amount amount determination result of 75.0 79.3 79.9 82.0 79.1 79.3 78.8 dissolution rate (%)

[0394] As can be seen from the experimental results shown in Table 12: the dissolution rate of the total flavonoids of Desmodium Styracifolium can be significantly increased by adding povidone K.sub.30 with the solid dispersion technology, and the dissolution rate of a tablet prepared according to Formula 4 with a weight ratio of total flavonoids of Desmodium Styracifolium: povidone K.sub.30 being 1:6 is higher than that of other tablets under the same testing condition. It has been found from the testing results that, although the dissolution rate has been improved to a certain degree, it still needs to be further improved by optimizing the Formula, so screening is further preformed by adding a certain amount of poloxamer 188 on above basis, i.e. the weight ratio of total flavonoids of Desmodium Styracifolium: povidone K.sub.30 is 1:6. FIG. 3 shows a curve for comparing the dissolutions in vitro of a table containing total flavonoids of Desmodium Styracifolium prepared with a solid dispersion process (prepared according to Embodiment 20) and that prepared with a common wet granulation process (Formula 1) according to a comparative embodiment.

[0395] Through researching tests, hydrophilic carriers of different solid dispersions, such as povidone K.sub.30, poloxamer 188 and polyethylene glycol 6000, are screened, the solid dispersions containing total flavonoids of Desmodium Styracifolium were obtained to use as follow: dissolving 50 g total flavonoids of Desmodium Styracifolium and hydrophilic carriers of solid dispersions with a weight of 1:6, with 50% ethanol under stirring and at a temperature of 65 C., followed by removing the solvent via evaporation under reduced pressure at a temperature of 50 C., vacuum drying at a temperature of 40 C., smashing and sieving at 80 meshes.

[0396] Screening on Formula 8 to Formula 14 with the solid dispersion materials are shown in Table 13.

[0397] Preparation process was performed by the following steps: mixing lactose and sodium croscarmellose with the solid dispersion containing total flavonoids of Desmodium Styracifolium, sieved at 80 meshes in advance, respectively, to be uniform, followed by preparing a soften material with suitable amount of water, granulating at 20 meshes, drying at a temperature of 55 C., size stabilizing, and mixing with sodium stearyl fumarate to be uniform, then tableting, so as to obtain tablets.

[0398] The dissolution rates of total flavonoids of Desmodium Styracifolium were determined, and the determination results are shown in Table 13.

[0399] Table 13 further screening on Formulas of the present disclosure

TABLE-US-00070 Formula Formula Formula Formula Formula Formula Formula Formula No. 8 9 10 11 12 13 14 solid dispersion: total 350 g / / / / / / flavonoids of Desmodium Styracifolium:poloxamer 188 (1:6) solid dispersion: total / 350 g / / / / / flavonoids of Desmodium Styracifolium: polyethylene glycol 6000 (1:6) solid dispersion: total / / 350 g / / / / flavonoids of Desmodium Styracifolium:povidone K.sub.30:poloxamer 188 (1:5:1) solid dispersion: total / / / 350 g / / / flavonoids of Desmodium Styracifolium:povidone K.sub.30:poloxamer 188 (1:4:2) solid dispersion: total / / / / 350 g / / flavonoids of Desmodium Styracifolium:povidone K.sub.30:poloxamer 188 (1:3:3) solid dispersion: total / / / / / 350 g / flavonoids of Desmodium Styracifolium:povidone K.sub.30:poloxamer 188 (1:2:4) solid dispersion: total / / / / / / 350 g flavonoids of Desmodium Styracifolium:povidone K.sub.30:poloxamer 188 (1:1:5) lactose 50 50 50 50 50 50 50 sodium croscarmellose 20 20 20 20 20 20 20 sodium stearyl fumarate 5 5 5 5 5 5 5 water suitable suitable suitable suitable suitable suitable suitable amount amount amount amount amount amount amount determination result of 81.3 80.1 83.6 86.9 85.3 84.0 82.9 dissolution rate (%)

[0400] As can be seen from the experimental results shown in Table 13: the dissolution rate of total flavonoids of Desmodium Styracifolium can be significantly increased with the solid dispersion technology, and the dissolution rate of a tablet prepared according to Formula 11 with a weight ratio of total flavonoids of Desmodium Styracifolium: povidone poloxamer 188 being 1:4:2 is higher than that of other tablets under the same testing condition. It has been found from the testing results that, although the dissolution rate has been improved to a certain degree, it still needs to be further improved by optimizing the Formula, so screening is further preformed by adding a certain amount of surfactant on above basis, i.e. the weight ratio of total flavonoids of Desmodium Styracifolium: povidone K.sub.30: poloxamer 188 is 1:4:2.

[0401] Screening on Formula 15 to Formula 19 which were performed by adding a suitable amount of surfactant on the basis of the solid dispersion, i.e. adding sodium dodecyl sulfate, Tween 80, and methoxypolyethylene glycol, respectively, with different weight ratios on the basis of original different Formulas, are shown in Table 14.

[0402] Preparation process was performed by the following steps: mixing lactose and sodium croscarmellose with the solid dispersion containing total flavonoids of Desmodium Styracifolium, sieved at 80 meshes in advance, respectively, to be uniform, followed by preparing a soften material with suitable amount of water, granulating at 20 meshes, drying at a temperature of 55 C., size stabilizing, and mixing with sodium stearyl fumarate to be uniform, then tableting, so as to obtain tablets.

[0403] The dissolution rates of total flavonoids of Desmodium Styracifolium were determined, and the determination results are shown in Table 14.

[0404] Table 14 screening on Formulas of the present disclosure with surfactant on the basis of solid dispersion

TABLE-US-00071 Formula No. Formula Formula Formula Formula Formula 15 16 17 18 19 solid dispersion: total flavonoids of 360 g 0 / / / Desmodium Styracifolium:povidone K.sub.30:poloxamer 188:sodium dodecyl sulfate (1:4:2:0.2) solid dispersion: total flavonoids of / 380 g / / / Desmodium Styracifolium:povidone K.sub.30:poloxamer 188:sodium dodecyl sulfate (1:4:2:0.6) solid dispersion: total flavonoids of / / 400 g / / Desmodium Styracifolium:povidone K.sub.30:poloxamer 188:sodium dodecyl sulfate (1:4:2:1.0) solid dispersion: total flavonoids of / / / 380 g / Desmodium Styracifolium:povidone K.sub.30:poloxamer 188:Tween 80 (1:4:2:0.6) solid dispersion: total flavonoids of / / / / 380 g Desmodium Styracifolium:povidone K.sub.30:poloxamer 188:methoxypolyethylene glycol (1:4:2:0.6) lactose 50 50 50 50 50 sodium croscarmellose 20 20 20 20 20 sodium stearyl fumarate 5 5 5 5 5 water suitable suitable suitable suitable suitable amount amount amount amount amount determination result of dissolution rate (%) 89.1 90.7 88.9 88.1 88.6

[0405] As can be seen from the experimental results shown in Table 14: all the dissolution rates of Formula 15 to Formula 19 are significantly increased and can reach more than 88% by adding sodium dodecyl sulfate, Tween 80, and methoxypolyethylene glycol, respectively, with different weight ratios on the basis of original different Formulas, and in which the improvement of Formula 16 is most obvious. Therefore, the optimal Formula to prepare the solid dispersion containing total flavonoids of Desmodium Styracifolium is determined to be: total flavonoids of Desmodium Styracifolium: povidone K.sub.30: poloxamer 188: sodium dodecyl sulfate is 1:4:2:0.6 (by weight).

[0406] Reference throughout this specification to an embodiment, some embodiments, one embodiment, another example, an example, a specific example, or some examples, means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present disclosure. Thus, the appearances of the phrases such as in some embodiments, in one embodiment, in an embodiment, in another example, in an example, in a specific example, or in some examples, in various places throughout this specification are not necessarily referring to the same embodiment or example of the present disclosure. Furthermore, the particular features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments or examples.

[0407] Although explanatory embodiments have been shown and described, it would be appreciated by those skilled in the art that the above embodiments cannot be construed to limit the present disclosure, and changes, alternatives, and modifications can be made in the embodiments without departing from spirit, principles and scope of the present disclosure, and the scope of the present disclosure is defined by claims and equivalents thereof.