Capsule containing total flavonoids of desmodium styracifolium, method for preparing the same and use

Abstract

A capsule containing total flavonoids of Desmodium styracifolium, a method for preparing the same and a use of the capsule containing total flavonoids of Desmodium styracifolium are provided. Specifically, the capsule includes total flavonoids of Desmodium Styracifolium provided in a form of alcohol extract of Desmodium Styracifolium and a pharmaceutically acceptable excipient.

Claims

1. A capsule, comprising total flavonoids of Desmodium Styracifolium, as an active ingredient, provided in a form of alcohol extract of Desmodium Styracifolium, and a pharmaceutically acceptable excipient, wherein the pharmaceutically acceptable excipient comprises a filling agent, an adhesion agent, a wetting agent, a disintegrating agent and a lubricating agent, and the alcohol extract of Desmodium Styracifolium is obtained by the following steps: heating and refluxing a raw material of Desmodium Styracifolium with ethanol, so as to obtain an extracting solution of Desmodium Styracifolium, the ethanol being of a concentration ranging from 50% to 95% and a weight ranging from 8 to 14 times than that of the raw material of Desmodium styracifolium; concentrating the extracting solution of Desmodium Styracifolium, so as to remove ethanol; and subjecting the extracting solution of Desmodium Styracifolium after concentrated to adsorption onto a macroporous resin column, so as to obtain the alcohol extract of Desmodium Styracifolium.

2. The capsule according to claim 1, wherein the extracting solution of Desmodium Styracifolium is obtained by: heating and refluxing the raw material of Desmodium Styracifolium, for 1 to 3 times with 1 to 3 hours for each time, with ethanol having the concentration ranging from 50% to 95% and the weight ranging from 8 to 14 times than that of Desmodium Styracifolium for extraction, and mixing the ethanol extracting solutions.

3. The capsule according to claim 1, wherein the filling agent is at least one selected from corn starch, dextrin, lactose, pregelatinized starch, saccharose, microcrystalline cellulose, mannitol, sorbitol, xylitol, calcium hydrophosphate and calcium carbonate.

4. The capsule according to claim 1, wherein the adhesion agent is at least one selected from starch paste, hydroxypropyl methylcellulose, povidone K.sub.30, povidone K.sub.25, polyethylene glycol 6000, methylcellulose and ethanol.

5. The capsule according to claim 1, wherein the wetting agent is at least one selected from water and ethanol.

6. The capsule according to claim 1, wherein the disintegrating agent is at least one selected from sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, cross-linked povidone, dry starch, cross-linked sodium carboxymethyl cellulose and calcium carboxymethyl cellulose.

7. The capsule according to claim 1, wherein the lubricating agent is at least one selected from magnesium stearate, talc, aerosol, magnesium dodecyl sulfate, sodium dodecyl sulfate, sodium benzoate and sodium stearyl fumarate.

8. The capsule according to claim 1, comprising 33 to 400 weight parts of the total flavonoids of Desmodium Styracifolium, 30 to 120 weight parts of the filling agent, 0.1 to 10 weight parts of the adhesion agent, 1 to 80 weight parts of the disintegrating agent, 1 to 10 weight parts of the lubricating agent, and 80 to 210 weight parts of the wetting agent.

9. The capsule according to claim 8, comprising 33 weight parts of the total flavonoids of Desmodium Styracifolium, 66 weight parts of microcrystalline cellulose, 66 weight parts of lactose, 1 weight part of povidone K.sub.30, 10 weight parts of cross-linked sodium carboxymethyl cellulose, 1 weight part of sodium stearyl fumarate, and 120 weight parts of water; or 33 weight parts of the total flavonoids of Desmodium Styracifolium, 33 weight parts of microcrystalline cellulose, 33 weight parts of lactose, 60 weight parts of cross-linked povidone, 5 weight parts of polyethylene glycol 6000, 5 weight parts of sodium stearyl fumarate, and 120 weight parts of water; or 50 weight parts of the total flavonoids of Desmodium Styracifolium, 50 weight parts of microcrystalline cellulose, 50 weight parts of lactose, 2 weight parts of polyethylene glycol 6000, 2 weight parts of magnesium stearate, 120 weight parts of ethanol, and 40 weight parts of water; or 66.5 weight parts of the total flavonoids of Desmodium Styracifolium, 40 weight parts of microcrystalline cellulose, 40 weight parts of cross-linked sodium carboxymethyl cellulose, 30 weight parts of cross-linked povidone, 10 weight parts of polyethylene glycol 6000, 5 weight parts of magnesium stearate, and 200 weight parts of water; or 66.5 weight parts of the total flavonoids of Desmodium Styracifolium, 50 weight parts of microcrystalline cellulose, 50 weight parts of lactose, 30 weight parts of calcium carboxymethyl cellulose, 2 weight parts of povidone K.sub.30, 5 weight parts of magnesium stearate, and 180 weight parts of water; or 80 weight parts of the total flavonoids of Desmodium Styracifolium, 35 weight parts of microcrystalline cellulose, 30 weight parts of lactose, 0.1 weight parts of povidone K.sub.30, 5 weight parts of magnesium stearate, and 80 weight parts of water; or 100 weight parts of the total flavonoids of Desmodium Styracifolium, 60 weight parts of lactose, 35 weight parts of cross-linked sodium carboxymethyl cellulose, 0.1 weight parts of hydroxypropyl methylcellulose, 2 weight parts of aerosol, 100 weight parts of ethanol, and 10 weight parts of water; or 100 weight parts of the total flavonoids of Desmodium Styracifolium, 40 weight parts of microcrystalline cellulose, 20 weight parts of cross-linked sodium carboxymethyl cellulose, 40 weight parts of cross-linked povidone, 10 weight parts of polyethylene glycol 6000, 10 weight parts of magnesium stearate, and 210 weight parts of water; or 120 weight parts of the total flavonoids of Desmodium Styracifolium, 40 weight parts of microcrystalline cellulose, 40 weight parts of lactose, 2 weight parts of polyethylene glycol 6000, 2 weight parts of magnesium stearate, and 120 weight parts of water; or 120 weight parts of the total flavonoids of Desmodium Styracifolium, 120 weight parts of lactose, 1 weight part of hydroxypropyl methylcellulose, 1 weight part of magnesium stearate, 100 weight parts of ethanol, and 20 weight parts of water; or 120 weight parts of the total flavonoids of Desmodium Styracifolium, 40 weight parts of microcrystalline cellulose, 40 weight parts of lactose, 1 weight part of polyethylene glycol 6000, 1 weight part of povidone K.sub.30, 2 weight parts of aerosol, 96 weight parts of ethanol, and 24 weight parts of water; or 133 weight parts of the total flavonoids of Desmodium Styracifolium, 30 weight parts of microcrystalline cellulose, 37 weight parts of lactose, 1 weight part of povidone K.sub.30, and 120 weight parts of water; or 133 weight parts of the total flavonoids of Desmodium Styracifolium, 30 weight parts of microcrystalline cellulose, 37 weight parts of lactose, 1 weight part of povidone K.sub.30, 20 weight parts of cross-linked sodium carboxymethyl cellulose, 1 weight part of aerosol, and 120 weight parts of water; or 133 weight parts of the total flavonoids of Desmodium Styracifolium, 33 weight parts of microcrystalline cellulose, 33 weight parts of lactose, 1 weight part of povidone K.sub.30, 15 weight parts of cross-linked sodium carboxymethyl cellulose, 1 weight part of aerosol, and 120 weight parts of water; or 150 weight parts of the total flavonoids of Desmodium Styracifolium, 30 weight parts of microcrystalline cellulose, 30 weight parts of lactose, 80 weight parts of cross-linked povidone, 5 weight parts of polyethylene glycol 6000, 5 weight parts of sodium stearyl fumarate, 130 weight parts of ethanol, and 45 weight parts of water; or 150 weight parts of the total flavonoids of Desmodium Styracifolium, 30 weight parts of microcrystalline cellulose, 20 weight parts of lactose, 1.2 weight parts of povidone K.sub.30, 2 weight parts of aerosol, and 80 weight parts of water; or 200 weight parts of the total flavonoids of Desmodium Styracifolium, 30 weight parts of microcrystalline cellulose, 30 weight parts of lactose, 2 weight parts of povidone K.sub.30, 2 weight parts of aerosol, and 120 weight parts of water; or 400 weight parts of the total flavonoids of Desmodium Styracifolium, 50 weight parts of microcrystalline cellulose, 50 weight parts of lactose, 2 weight parts of povidone K.sub.30, 4 weight parts of aerosol, and 200 weight parts of water.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) 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:

(2) FIG. 1 is an in vitro dissolution curve of a capsule containing total flavonoids of Desmodium Styracifolium (example 7) prepared according to an embodiment of the present disclosure;

(3) FIG. 2 is a comparison of in vitro dissolution curves of capsules containing total flavonoids of Desmodium Styracifolium respectively prepared by a granulation process with fluidized bed and a common wet granulation process (a comparable example) according to an embodiment of the present disclosure.

DETAILED DESCRIPTION

(4) Reference will be made in detail to embodiments of the present disclosure. The same or similar elements and the elements having same or similar functions are denoted by like reference numerals throughout the descriptions. The embodiments described herein with reference to drawings are explanatory, illustrative, and used to generally understand the present disclosure. The embodiments shall not be construed to limit the present disclosure.

Example 1 Preparation of Total Flavonoids Extract of Desmodium Styracifolium

(5) 200 g raw material of Desmodium Styracifolium was weighed, added with 95% ethanol having a weight of 14 times than that of the raw material, followed by heated and refluxed for 3 hours at a temperature of 60° C. for first extraction. The raw material was added with 95% ethanol having a weight of 12 times than that of the raw material, followed by heated and refluxed for 2 hours at a temperature of 50° C. for second extraction. The raw material was added with 80% ethanol having a weight of 8 times than that of the raw material followed by heated and refluxed for 1 hour at a temperature of 50° C. for third extraction. After mixed, resulting alcohol extracting solutions as a whole were concentrated to be of a volume 8 times than the weight of the raw material followed by still standing and filtration, thereby obtaining filtrate (a loading sample) for use. 400 g pharmaceutical-grade AB-8 type macroporous resin, after immersed in an appropriate amount of ethanol, was packed into a column by a wet method, followed by dealt for use.

(6) The filtrate (the loading sample) was subjected to adsorption onto an AB-8 macroporous resin column at a flow rate of 3 column bed volumes per hour, followed by eluted and purified with water having a volume of 12 times than the weight of macroporous resin, and then eluted with 95% ethanol having a volume of 10 column bed volumes at a flow rate of 3 column bed volumes per hour, to obtain an eluted solution. The ethanol was recycled from the eluted solution and the eluted solution was concentrated to a concentrated solution with a relative density of 1.10. 4.03 g extract of Desmodium Styracifolium was obtained after dried under reduced pressure at 75° C. and smashed, which was preserved at shady and cool place. After measured by ultraviolet-visible spectrophotometry, the resulting extract of Desmodium Styracifolium was of a total flavonoids content of 71.65% (by dried extract, %), and a schaftoside content of 10.30% (by dried extract, %).

Example 2 Preparation of Total Flavonoids Extract of Desmodium Styracifolium

(7) 200 g raw material of Desmodium Styracifolium was weighed, added with 70% ethanol having a weight of 12 times than that of the raw material, followed by heated and refluxed for 2 hours at a temperature of 55° C. for first extraction. The raw material was added with 70% ethanol having a weight of 10 times than that of the raw material, followed by heated and refluxed for 1.5 hours at a temperature of 55° C. for second extraction. After mixed, resulting alcohol extracting solutions as a whole were concentrated to be of a volume 5 times than the weight of the raw material followed by still standing and filtration, thereby obtaining filtrate (a loading sample) for use. 400 g pharmaceutical-grade AB-8 type macroporous resin, after immersed in an appropriate amount of ethanol, was packed into a column by a wet method, followed by dealt for use.

(8) The filtrate (the loading sample) was subjected to adsorption onto an AB-8 macroporous resin column at a flow rate of 1 column bed volume per hour, followed by eluted and purified with water having a volume of 10 times than the weight of macroporous resin, and 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 ethanol was recycled from the eluted solution and the eluted solution was concentrated to a concentrated solution with a relative density of 1.22. 4.68 g extract of Desmodium Styracifolium was obtained after dried under reduced pressure at 75° C. and smashed, which was preserved at shady and cool place. After measured by ultraviolet-visible spectrophotometry, the resulting extract of Desmodium Styracifolium was of a total flavonoids content of 63.31% (by dried extract, %), and a schaftoside content of 5.38% (by dried extract, %).

Example 3 Preparation of Total Flavonoids Extract of Desmodium Styracifolium

(9) 50 kg raw material of Desmodium Styracifolium was weighed, added with 80% ethanol having a weight of 12 times than that of the raw material, followed by heated and refluxed for 2 hours at a temperature of 55° C. for first extraction. The raw material was added with 80% ethanol having a weight of 10 times than that of the raw material, followed by heated and refluxed for 1.5 hours at a temperature of 55° C. for second extraction. After mixed, resulting alcohol extracting solutions as a whole were concentrated to be of a volume 5 times than the weight of the raw material followed by still standing and filtration, thereby obtaining filtrate (a loading sample) for use. 100 kg pharmaceutical-grade AB-8 type macroporous resin, after immersed in an appropriate amount of ethanol, was packed into a column by a wet method, followed by dealt for use.

(10) 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, followed by eluted and purified with water having a volume of 10 times than the weight of macroporous resin, and 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 ethanol was recycled from the eluted solution and the eluted solution was concentrated to a concentrated solution with a relative density of 1.22. 1.12 kg extract of Desmodium Styracifolium was obtained after dried under reduced pressure at 75° C. and smashed, which was preserved at shady and cool place. After measured by ultraviolet-visible spectrophotometry, the resulting extract of Desmodium Styracifolium was of a total flavonoids content of 59.49% (by dried extract, %), and a schaftoside content of 5.10% (by dried extract, %).

Example 4 Preparation of Total Flavonoids Extract of Desmodium Styracifolium

(11) 50 kg raw material of Desmodium Styracifolium was weighed, added with 80% ethanol having a weight of 12 times than that of the raw material, followed by heated and refluxed for 2 hours at a temperature of 55° C. for first extraction. The raw material was added with 80% ethanol having a weight of 10 times than that of the raw material, followed by heated and refluxed for 1.5 hours at a temperature of 55° C. for second extraction. After mixed, resulting alcohol extracting solutions as a whole were concentrated to be of a volume 5 times than the weight of the raw material followed by still standing and filtration, thereby obtaining filtrate (a loading sample) for use. 100 kg pharmaceutical-grade AB-8 type macroporous resin, after immersed in an appropriate amount of ethanol, was packed into a column by a wet method, followed by dealt for use.

(12) 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, followed by eluted and purified with water having a volume of 10 times than the weight of macroporous resin, and 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 ethanol was recycled from the eluted solution and the eluted solution was concentrated to a concentrated solution with a relative density of 1.22. 1.14 kg extract of Desmodium Styracifolium was obtained after dried under reduced pressure at 75° C. and smashed, which was preserved at shady and cool place. After measured by ultraviolet-visible spectrophotometry, the resulting extract of Desmodium Styracifolium was of a total flavonoids content of 59.37% (by dried extract, %), and a schaftoside content of 5.01% (by dried extract, %).

(13) The above results show that processing parameters used in embodiments of the present disclosure are workable and able to be smoothly transited into industrial production after further adjusted during a pilot test.

Example 5 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(14) Formula:

(15) TABLE-US-00001 total flavonoids of Desmodium Styracifolium 133 g microcrystalline cellulose 30 g lactose 37 g povidone K.sub.30 1 g water 120 g total 1000 capsules

(16) Method for Preparing:

(17) a. The total flavonoids extract of Desmodium Styracifolium was prepared according to Example 4.

(18) b. 1 g povidone K.sub.30 was dissolved in 120 g water, thus obtaining a solution of the adhesion agent after stirring, for use.

(19) c. After mixed, 133 g total flavonoids of Desmodium Styracifolium, 30 g microcrystalline cellulose, 37 g lactose were added into a fluidized bed, followed by preheated to 45° C. for 20 min. The solution of the adhesion agent was then granulated by spraying, with gunjet under an atomizing pressure of 0.9 bar and a spraying speed of 20 rpm/min, into the fluidized bed (after adjusted with suitable parameters). Such the solution of the adhesion agent was completely sprayed within 15 min, during which a material temperature was held at 45° C. by adjusting air inlet temperature to 55° C.

(20) d. After the granulation, drying was performed by adjusting parameters. In specific, the material temperature was held at 45° C. by adjusting air inlet temperature to 65° C., for 10 min drying.

(21) e. Those granules after dried, were cooled, discharged, and subjected to size stabilization by sieving at 60 meshes, and then capsulized to obtain 1000 capsules containing total flavonoids of Desmodium Styracifolium.

(22) Dissolution rate was measured in accordance with the First Method in appendix XC, part II, Chinese Pharmacopoeia, 2010 edition.

(23) Testing sample solutions were obtained by the following steps: dissolving the above-obtained capsule 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.

(24) 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 μg/ml.

(25) 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 capsule. The dissolution rate curve (as shown in FIG. 1) was plotted by taking time as X-coordinate and accumulative release as Y-coordinate.

Example 6 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(26) Formula:

(27) TABLE-US-00002 total flavonoids of Desmodium Styracifolium 133 g microcrystalline cellulose 30 g lactose 37 g povidone K.sub.30 1 g cross-linked sodium carboxymethyl cellulose 20 g aerosil 1 g water 120 g total 1000 capsules

(28) Method for Preparing:

(29) a. The total flavonoids extract of Desmodium Styracifolium was prepared according to Example 4.

(30) b. The formula dosages of 133 g total flavonoids of Desmodium Styracifolium, 30 g microcrystalline cellulose, 37 g lactose, 1 g povidone K.sub.30, 20 g cross-linked sodium carboxymethyl cellulose were separately sieved at 80 meshes for use. 1 g povidone K.sub.30 as the adhesion agent was dissolved in 120 g water, thereby obtaining the aqueous solution containing povidone K.sub.30 after stirred to be uniform for use.

(31) c. The materials in respective formula dosage were preheated to 45° C. for 20 min in a fluidized bed. The solution of the adhesion agent was then granulated by spraying, with gunjet under an atomizing pressure of 0.9 bar and a spraying speed of 20 rpm/min, into the fluidized bed (after adjusted with suitable parameters). Such the solution of the adhesion agent was completely sprayed within 15 min, during which a material temperature was held at 45° C. by adjusting air inlet temperature to 55° C.

(32) d. After the granulation, drying was performed by adjusting parameters. In specific, the material temperature was held at 45° C. by adjusting air inlet temperature to 65° C., for 10 min drying.

(33) e. Those granules after dried, were cooled, discharged, mixed with the cross-linked sodium carboxymethyl cellulose in a mixer, and then subjected to size stabilization by sieving at 60 meshes, after which 1 g aerosil was added and mixed to be uniform, for further capsulization, thereby obtaining 1000 capsules containing total flavonoids of Desmodium Styracifolium.

(34) The dissolution rate was measured, same as Example 5, to be 89.9%.

Example 7 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(35) Formula:

(36) TABLE-US-00003 total flavonoids of Desmodium Styracifolium 133 g microcrystalline cellulose 33 g lactose 33 g povidone K.sub.30 1 g cross-linked sodium carboxymethyl cellulose 15 g aerosil 1 g water 120 g total 1000 capsules

(37) Method for preparing is same as Example 6.

(38) The dissolution rate was measured, same as Example 5, to be 90.5%. Example 8 Preparation of a capsule containing total flavonoids of Desmodium Styracifolium

(39) Formula:

(40) TABLE-US-00004 total flavonoids of Desmodium Styracifolium 33 g microcrystalline cellulose 66 g lactose 66 g povidone K.sub.30 1 g cross-linked sodium carboxymethyl cellulose 10 g sodium stearyl fumarate 1 g water 120 g total 1000 capsules

(41) Method for preparing is same as Example 6.

Example 9 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(42) Formula:

(43) TABLE-US-00005 total flavonoids of Desmodium Styracifolium 33 g microcrystalline cellulose 33 g lactose 33 g cross-linked povidone 60 g polyethylene glycol 6000 5 g sodium stearyl fumarate 5 g water 120 g total 1000 capsules

(44) Method for preparing is same as Example 6.

Example 10 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(45) Formula:

(46) TABLE-US-00006 total flavonoids of Desmodium Styracifolium 50 g microcrystalline cellulose 50 g lactose 50 g polyethylene glycol 6000 2 g magnesium stearate 2 g ethanol 120 g water 40 g total 1000 capsules

(47) Method for preparing is same as Example 6.

Example 11 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(48) Formula:

(49) TABLE-US-00007 total flavonoids of Desmodium Styracifolium 66.5 g microcrystalline cellulose 40 g cross-linked sodium carboxymethyl cellulose 40 g cross-linked povidone 30 g polyethylene glycol 6000 10 g magnesium stearate 5 g water 200 g total 1000 capsules

(50) Method for preparing is same as Example 6.

(51) The dissolution rate was measured, same as Example 5, to be 90.0%.

Example 12 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(52) Formula:

(53) TABLE-US-00008 total flavonoids of Desmodium Styracifolium 66.5 g microcrystalline cellulose 50 g lactose 50 g calcium carboxymethyl cellulose 30 g povidone K.sub.30 2 g magnesium stearate 5 g water 180 g total 1000 capsules

(54) Method for preparing is same as Example 6.

Example 13 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(55) Formula:

(56) TABLE-US-00009 total flavonoids of Desmodium Styracifolium 80 g microcrystalline cellulose 35 g lactose 30 g povidone K.sub.30 0.1 g magnesium stearate 5 g water 80 g total 1000 capsules

(57) Method for preparing is same as Example 5.

Example 14 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(58) Formula:

(59) TABLE-US-00010 total flavonoids of Desmodium Styracifolium 100 g microcrystalline cellulose 40 g cross-linked sodium carboxymethyl cellulose 20 g cross-linked povidone 40 g polyethylene glycol 6000 10 g magnesium stearate 10 g water 210 g total 1000 capsules

(60) Method for preparing is same as Example 6.

Example 15 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(61) Formula:

(62) TABLE-US-00011 total flavonoids of Desmodium Styracifolium 100 g lactose 60 g cross-linked sodium carboxymethyl cellulose 35 g hydroxypropyl methylcellulose 0.1 g aerosil 2 g ethanol 100 g water 10 g total 1000 capsules

(63) Method for preparing is same as Example 6.

Example 16 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(64) Formula:

(65) TABLE-US-00012 total flavonoids of Desmodium Styracifolium 120 g microcrystalline cellulose 40 g lactose 40 g povidone K.sub.30 1 g polyethylene glycol 6000 1 g aerosil 2 g ethanol 96 g water 24 g total 1000 capsules

(66) Method for preparing is same as Example 6.

Example 17 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(67) Formula:

(68) TABLE-US-00013 total flavonoids of Desmodium Styracifolium 120 g hydroxypropyl methylcellulose 1 g lactose 120 g povidone K.sub.30 1 g magnesium stearate 1 g ethanol 100 g water 20 g total 1000 capsules

(69) Method for preparing is same as Example 6.

Example 18 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(70) Formula:

(71) TABLE-US-00014 total flavonoids of Desmodium Styracifolium 120 g microcrystalline cellulose 40 g lactose 40 g polyethylene glycol 6000 2 g magnesium stearate 1 g water 120 g total 1000 capsules

(72) Method for preparing is same as Example 6.

Example 19 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(73) Formula:

(74) TABLE-US-00015 total flavonoids of Desmodium Styracifolium 150 g microcrystalline cellulose 30 g lactose 30 g cross-linked povidone 80 g polyethylene glycol 6000 5 g sodium stearyl fumarate 5 g polyethylene glycol 6000 2 g ethanol 130 g water 45 g total 1000 capsules

(75) Method for preparing is same as Example 6.

Example 20 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(76) Formula:

(77) TABLE-US-00016 total flavonoids of Desmodium Styracifolium 150 g microcrystalline cellulose 30 g lactose 20 g povidone K.sub.30 1.2 g aerosil 2 g water 80 g total 1000 capsules

(78) Method for preparing is same as Example 5.

(79) The dissolution rate was measured, same as Example 5, to be 88.9%.

Example 21 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(80) Formula:

(81) TABLE-US-00017 total flavonoids of Desmodium Styracifolium 200 g microcrystalline cellulose 30 g lactose 30 g povidone K.sub.30 2 g aerosil 2 g water 120 g total 1000 capsules

(82) Method for preparing is same as Example 5.

Example 22 Preparation of a Capsule Containing Total Flavonoids of Desmodium Styracifolium

(83) Formula:

(84) TABLE-US-00018 total flavonoids of Desmodium Styracifolium 400 g microcrystalline cellulose 50 g lactose 50 g povidone K.sub.30 2 g aerosil 4 g water 200 g total 1000 capsules

(85) Method for preparing is same as Example 5.

Example 23 Measurement to the Dissolution Rate of the Capsule Containing Total Flavonoids of Desmodium Styracifolium

(86) As for the comparable example, the formula was same as Example 6, and the total flavonoids of Desmodium Styracifolium was prepared according to Example 4 with a differences in that the capsule containing total flavonoids of Desmodium Styracifolium of Inventive Example was obtained by a fluidized bed granulation process; whilst the capsule containing total flavonoids of Desmodium Styracifolium of Comparable Example was obtained by a common wet granulation process.

(87) Formula of Comparable Example:

(88) TABLE-US-00019 total flavonoids of Desmodium Styracifolium 133 g microcrystalline cellulose 30 g lactose 37 g povidone K.sub.30 1 g cross-linked sodium carboxymethyl cellulose 20 g aerosil 1 g water 120 g total 1000 capsules

(89) Method for Preparing of Comparable Example:

(90) a. The total flavonoids extract of Desmodium Styracifolium was prepared in accordance with example 4.

(91) b. The formula dosages of 133 g total flavonoids of Desmodium Styracifolium, 30 g microcrystalline cellulose, 37 g lactose, 1 g povidone K.sub.30, and 20 g cross-linked sodium carboxymethyl cellulose were separately sieved at 80 meshes for use. The povidone K.sub.30 as the adhesion agent was dissolved in 120 g water, thereby obtaining the aqueous solution containing povidone K.sub.30 after stirred to be uniform for use.

(92) c. The lactose and the microcrystalline cellulose were mixed to be uniform at first, and then added and mixed with the total flavonoids extract of Desmodium Styracifolium to be uniform, followed by added with the aqueous solution containing povidone K.sub.30. After stirred to be uniform, the resulting mixture was then formed into a soft material, followed by granulation. After dried at 55° C., resulting granules were subjected to size stabilization, and then the microcrystalline cellulose was added thereto. After sieved at 80 meshes, those granules having a particle size between 40 and 80 meshes were added with the aerosil, followed by mixed to be uniform for further capsulization.

(93) Dissolution rate was measured in accordance with the First Method in appendix XC, part II, Chinese Pharmacopoeia, 2010 edition, as mentioned in Example 5. The in vitro dissolution rate curve was plotted by taking time as X-coordinate and accumulative release as Y-coordinate.

(94) The dissolution rates of capsules containing total flavonoids of Desmodium Styracifolium obtained in the Comparable Example and the Example 6 were measured, and obtaining results of the dissolution rates were shown in Table 1 and the in vitro dissolution rate curve was shown as FIG. 2.

(95) TABLE-US-00020 TABLE 1 Dissolution rates of capsules containing total flavonoids of Desmodium Styracifolium prepared by two different processes Dissolution rate Example Preparation process (%) Comparable Example wet granulation 73.6 Example 6 fluidized bed granulation 89.9

Example 24 General Pharmacological Experiments of Total Flavonoids of Desmodium Styracifolium

(96) 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.

(97) 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.

(98) 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.

(99) Single gavage was chosen to be the administration route with an administration volume of 0.6 ml/mouse.

(100) Indicators and Results:

(101) 1.1 Effects of Total Flavonoids of Desmodium Styracifolium on General Behaviour of Mouse

(102) 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.

(103) 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.

(104) 1.2 Effects of Total Flavonoids of Desmodium Styracifolium on Spontaneous Activity

(105) 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 2.

(106) TABLE-US-00021 TABLE 2 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

(107) 1.3 Effects of Total Flavonoids of Desmodium Styracifolium on Activating Central Nervous System of Mice

(108) 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.

(109) 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 3), thus indicating that the total flavonoids had no obvious activating effect on central nervous system via gavage administration.

(110) TABLE-US-00022 TABLE 3 Effects on activating central nervous system of the mice administrated with total flavonoids of Desmodium Styracifolium via gavage animal weight dosage seizure lasting duration number (g) (mg/kg) (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

(111) 1.4 Effects of Total Flavonoids of Desmodium Styracifolium on Digestive System of Mice

(112) 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 4.

(113) TABLE-US-00023 TABLE 4 Effects on propelling rate of the mice administrated with total flavonoids of Desmodium Styracifolium via gavage total length distance from pylorus of gastro- to where the carbon dosage intestinal tract powder headed propelling rate (mg/kg) (cm) (cm) (%) 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 25 Pharmacodynamic Experiments of Total Flavonoids of Desmodium Styracifolium in Animals

(114) 1.1 Experiment of Therapeutic Effects of Total Flavonoids of Desmodium Styracifolium on Ethylene Glycol Calcium Oxalate Kidney Stones in Rats

(115) 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.

(116) 1.2 Experiment of Preventing Effects of Total Flavonoids of Desmodium Styracifolium on Ethylene Glycol-Induced Toxic Calcium Oxalate Kidney Stones in Rats

(117) 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).

(118) 1.3 Experiment of Dissolving Effect of Total Flavonoids of Desmodium Styracifolium on Implanted Human Bladder Stones in Rats

(119) 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.

(120) 1.4 Experiment of Diuretic Effects of Total Flavonoids of Desmodium Styracifolium on Rats Suffering Ethylene Glycol-Induced Kidney Stones and Normal Rats

(121) As compared with a model group, 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 29-36 ml more than that of rats in the normal group (48.1 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, 12-36% more than that in the model group.

(122) 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

(123) 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 26 Acute Toxicity Test of Total Flavonoids of Desmodium Styracifolium in Animals

(124) 1.1 Acute Toxicity Tests of Total Flavonoids of Desmodium Styracifolium in Mice

(125) 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.

(126) 1.2 Acute Toxicity Tests of Total Flavonoids of Desmodium Styracifolium in Rats

(127) 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.

(128) 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.

(129) 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.

Example 27 Long Term Toxicity Tests of Total Flavonoids of Desmodium Styracifolium in Animals

(130) 1.1 Long Term Toxicity Tests in Rats Administrated with Total Flavonoids of Desmodium Styracifolium by Gavage

(131) Three dosage groups were designed to be a low dosage group of 200 mg/kg/day, a middle dosage group of 600 mg/kg/day, a high dosage group 1800 mg/kg/day, which were equivalent to 11.7, 35.1 and 105.3 times of the dosage for human respectively, along with a reference group in which rats were administrated with 0.5% sodium carboxymethyl cellulose. The rats were administrated 6 times per week for 26 continuous weeks by gavage. Rats were observed in terms of general drug reaction, biochemical indicators in urine, visible components in peripheral blood, clotting time, biochemical indicators in serum, organ weight, and histopathology.

(132) All rats in every group were survived until predetermined sacrificing time. Rats in the reference group, the low dosage group and the middle dosage group behaved lively, had soft and polish hair, excreted faeces in a granule shape. A few rats in the high dosage group were in a slight emaciation shape with slightly yellow and unruly hair after 14 to 26 weeks from the administration. During 26 weeks after the administration, increasements of body weights were mildly inhibited by the high dosage group after 15 to 26 weeks from the administration for female and after 21 weeks from the administration to 2 weeks subsequent to administration withdraw for male, without statistical difference as compared with the reference group. Increasements of body weights in the high dosage group recovered to that in the reference group after 4 weeks after administration withdraw. Male rats in the high dosage group exhibited an aspartate aminotransferase level obviously higher than that in the reference group (P<0.05) after 26 weeks from the administration. Male and female rats in the middle dosage group all exhibited a total serum bilirubin content significantly lower than that in the reference group (P<0.05) after 13 weeks from the administration. Male rats in the high dosage group exhibited a total cholesterol content in serum obviously lower than that in the reference group (P<0.01) after 26 weeks from the administration. Rats in the middle dosage group still exhibited the total cholesterol content in serum obviously lower than that in the reference group after 4 weeks from the administration withdraw. All these changes could be related to the pharmacological effect of total flavonoids of Desmodium Styracifolium. Other indicators had no significant difference among groups. After 4 weeks from the administration withdraw, all of indicated mentioned above which had been changed recovered to that in the reference group.

(133) According to histological examination, no pathological alteration related to the administration of total flavonoids of Desmodium Styracifolium has been found in each group with different dosages.

(134) 1.2 Long Term Toxicity Tests in Beagles Administrated with Total Flavonoids of Desmodium Styracifolium by Gavage

(135) Three dosage groups were designed to be a low dosage group of 100 mg/kg/day, a middle dosage group of 300 mg/kg/day, a high dosage group 900 mg/kg/day, along with a reference group in which beagles were administrated with 0.5% sodium carboxymethyl cellulose, there were 6 beagles in each group. Beagles having normal state were selected to be subjected to various of indexes two or three times, and the beagles were subsequently selected to be evenly and randomly divided into groups, each containing 3 male and 3 female.

(136) All beagles were survived until predetermined time. During the test, beagles in each group had polish hair, good appetite and a normal temperature. A few beagles in the high dosage group were in a slight poor appetite after 4.5 to 6.0 months from the administration. After 1 month from the administration withdraw, all of indicated mentioned above which had been changed recovered to that in the reference group. During the administration, increasements of body weights were obviously inhibited by the high dosage group during the administration, and after 6.0 months from the administration, there was an obvious difference compared with the reference group after 6 months from the administration. After 1 month from the administration withdraw, all of indicated mentioned above which had been changed recovered to that in the reference group. Beagles in the high dosage group exhibited an aspartate aminotransferase level and an urea nitrogen level obviously higher than those in the reference group after 6.0 months from the administration. During the administration, beagle in each group all exhibited improved total serum bilirubin level and total cholesterol level. After 1 month from the administration withdraw, all of indicated mentioned above had been changed recovered to normal.

(137) According to histological examination, no pathological alteration related to the administration of total flavonoids of Desmodium Styracifolium has been found in each group with different dosages.

(138) Example 28 random, double-blind, multi-dosage parallel-controlled and multi-centered II phase clinical trial about effectivity and safety of the capsule containing total flavonoids of Desmodium Styracifolium for treating urinary stone (stagnation of dampness-heat)

(139) Approval Document of Medicament Clinical Trial: 2007L04844

(140) inclusion criteria of the clinical trial: (1) renal pelvic stones and ureteral stones; (2) having an age ranging from 18 to 65 years old; (3) 0.4 cm<stone diameter≦1.0 cm; (4) good kidney function, in particularly in a kidney suffering from the stones (if the patient has hydronephrosis, it should be less than moderate level); (5) a good body condition with life-independent ability; (6) well-known about the study and a consent to sign the paper.

(141) exclusion criteria of the clinical trial: (1) malformation, stenosis, obstruction and surgery scar synechia are present at a connection portion between the kidney and the ureter or at distal ureter; (2) severe hydronephrosis (type III); (3) continuous severe hematuria or even shock; (4) acute obstruction oliguria or anuria; (5) pregnancy or lactation female; (6) heart and cerebral vessels, liver, kidney and hemopoietic system-combined severe idiopathic diseases, or fatal diseases endangering life (such as tumor or AIDs), or mentally or legally disabled patient; (7) having liver function ALT and/or AST value beyond a normal range; (8) urolithiasis patient intervened with surgery treatment in the past month; (9) other diseases with reduced possibilities of assignment or complicating assignment determined by researcher, such as loss to follow-up caused by job changing; (10) participant in other clinical trials in last three months; (11) allergy to the medicament or ingredients therein.

(142) Tests were performed in random, double-blind, multi-dosage parallel-controlled and multi-centered ways.

(143) A group (high dosage group): the capsule containing total flavonoids of Desmodium Styracifolium×5

(144) B group (middle dosage group): the capsule containing total flavonoids of Desmodium Styracifolium×3+capsule containing a simulant agent×2

(145) C group (low dosage group): capsule containing a simulant agent×5

(146) Subjects: patients diagnosed with renal pelvic stones or ureteral stones, fitted in the pattern of dampness-heat brewing and binding, 18 to 65 years old, willing to sign a consent paper.

(147) Administration scheme: 5 capsules containing the simulant agent/3 capsules containing total flavonoids of Desmodium Styracifolium+2 capsules containing the simulant agent/5 capsules containing total flavonoids of Desmodium Styracifolium were taken orally each time and three times one day (the capsule containing total flavonoids of Desmodium Styracifolium and the capsule containing the simulant agent each are of a quality of 0.02 g/capsule. Each capsule containing total flavonoids of Desmodium Styracifolium is of a total flavonoids content of 133 mg. Each capsule containing the simulant agent is of a total flavonoids content of 1.33 mg). The administration period is 4 weeks.

(148) The indicators for evaluating effectivity include: (1) X-ray examination (KUB, IVP, Ctu/Mru/CT); (2) single examination: symptoms and signs; (3) symptoms integrals.

(149) The indicators for evaluating safety include: (1) physical examination: body temperature, breath, heartbeat and resting blood pressure; (2) blood routine examination, urine routine examination, liver function (ALT, AST, Tbil, ALP, γ-GT), kidney function (Cr, Bun), coagulation tests, total cholesterol; (3) electrocardiogram; (4) adverse event.

(150) All statistical tests were two-sided, P value was smaller than or equal to a standard with a statistical significance (unless specified).

(151) Statistical Analysis Population:

(152) Full Analysis Set (FAS): refers to a set of ideal subjects having a trend to intentional analysis principle

(153) Per Protocol Set (PPS): all the files accorded with experimental treatment, a good compliance, amount of tested medicament between 80% and 120% and a completely filled content by CRF standard, the major variable may be measured, the baseline variable has no deficiency and there is no large contrary to the experimental design.

(154) Safety Analysis Set (SS): the subject at least treated once after randomization.

(155) The full analysis set and the per protocol set were selected by the analyses of the major variable and the comprehensive curative effect, respectively. The full analysis set was selected by demography and other baseline variable and the per protocol set was selected by other analyses of curative effect indexes. The safety analysis set was selected by a safety index analysis.

(156) The test has 68 patients, and there are 22 patients, 24 patients and 22 patients in the large dosage group, the middle dosage group and the small dosage group. The FAS includes 22 from the large dosage group, 23 from the middle dosage group and 22 from the small dosage group. The PPS includes 20 from the large dosage group, 22 from the middle dosage group and 22 from the small dosage group. The SS includes 22 from the large dosage group, 23 from the middle dosage group and 22 from the small dosage group. Two from the large dosage group and two from the middle dosage group were taken off, and one from the middle dosage was eliminated. The difference of elimination rates among three groups had no statistical significance (P=0.3652). Three from the large dosage group and two from the middle dosage group had poor compliances and the difference of occurrence rates of poor compliance among three groups had no statistical significance (P=0.2220). The distributions of demography characteristic, vital signs and accompanied diseases of the patients of three groups were similar and the difference had no statistical significance. The differences of stone conditions at the baselines of three groups and primary symptom of traditional Chinese symptom classification both had no statistical significance.

(157) 1. Primary Curative Effect: Effective Rate of Discharging Stones

(158) Result of the FAS: the effective rate of discharging stones of the large dosage group was 63.64%, the effective rate of discharging stones of the middle dosage group was 69.57%, and the effective rate of discharging stones of the small dosage group was 50.00%. Analyzed by a logistic regression of the control center effect, the difference between the large dosage group and the middle dosage group had no statistical significance (P=0.6857), the difference between the large dosage group and the small dosage group had no statistical significance (P=0.3476), the difference between the middle dosage group and the small dosage group had no statistical significance (P=0.1806).

(159) Result of the PPS: the effective rate of discharging stones of the large dosage group was 70%, the effective rate of discharging stones of the middle dosage group was 72.73%, and the effective rate of discharging stones of the small dosage group was 50.00%. Analyzed by a logistic regression of the control center effect, the difference between the large dosage group and the middle dosage group had no statistical significance (P=0.9168), the difference between the large dosage group and the small dosage group had no statistical significance (P=0.1764), the difference between the middle dosage group and the small dosage group had no statistical significance (P=0.1366).

(160) 2. Secondary Curative Effect

(161) 2.1 Discharging Time

(162) Result of the FAS: after 14 and 28 days from the treatment, the discharging rates of the large dosage group were 35.00% and 35.00%, respectively, the discharging rates of the middle dosage group were 43.48% and 26.09%, respectively, and the discharging rates of the small dosage group were 36.36% and 13.64%, respectively. Analyzed by CMH.sub.χ.sup.2 test, the difference among the discharging time of three groups had no statistical significance (P=0.4489).

(163) 2.2 Traditional Chinese Medicine Syndrome

(164) Result of the FAS: effective rates of three groups were 85% of the large dosage group, 95.65% of middle dosage group and 77.27% of small dosage group. Analyzed by a Kruskal-Wallis test, the difference among three groups had no statistical significance (P=0.5841).

(165) Result of the random, double-blind, multi-dosage parallel-controlled and multi-centered II phase clinical trial about efficacy and safety of capsule containing total flavonoids of Desmodium Styracifolium for treating urinary stone (stagnation of dampness-heat) shows that the effective rate of treating urinary stone (stagnation of dampness-heat) with the capsule containing total flavonoids of Desmodium Styracifolium is 95.65% (each capsule includes 133 mg of the total flavonoids extract of Desmodium Styracifolium, orally taken for 3 times per day, 3 capsules for each time, administrated for 4 weeks).

(166) 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.

(167) 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.