CN101530591A - A Chinese medicine capsule having functions of tonify Qi, enliven the spleen and quiet the spirit and its preparation method - Google Patents

Abstract

The present invention provides a capsule having functions of tonify Qi, enliven the spleen and quiet the spirit, including ginseng, deer antler, dog kidneys, cinnamon, Amomum villosum, Taurus grass, Fructus arctii, cherokee rose, Eucommia, Cyathula copies, honeysuckle, forsythia, oneself, yams, Polygalaceae, Suanzaoren, Chinese angelica, keel, oysters, Poria, Atractylodes, cassia twig, licorice copies, peony root, cardamom; this invention also provides a preparation method of the capsule preparation; the preparation can improve product stability and simultaneously reduce its negative effects to a minimum.

Description

Has Chinese medicinal capsule of replenishing QI to invigorate the spleen, tranquilizing the mind effect and preparation method thereof

Technical field

The invention provides a kind of extract oral capsule preparations and preparation method thereof, each preparation unit contains glycyrrhizic acid must not be lower than 0.15mg.

Background technology

The dosage form of the brain-tonifying and kidney-nourishing Chinese patent medicine of clinical practice at present mainly provides medicinal with the form of oral liquid or traditional pill.But for many years production and clinical practice prove that existing brain-tonifying and kidney-nourishing oral liquid (brain-tonifying and kidney-nourishing oral liquid is that the 16th in Chinese traditional patent formulation preparation records) and traditional pill exist a lot of conspicuous defectives.Oral liquid quality instability, for example: precipitation and variable color very easily take place; In order to regulate oral a large amount of sugar part that needs to add, not only inconvenient diabetes patient takes medicine, and the adding of a large amount of sugar parts makes troubles for storing again, and temperature is crossed low can separating out influences outward appearance, the too high meeting of temperature increases the probability of preparation microbiological contamination greatly, comes controlling microbial so add a large amount of antibacterial again; The production of oral liquid, store, carry equal inconvenience; The useful life is short or the like.And the defective of traditional pill is well-known especially, and pill is the conventional dosage forms of China's Chinese medicine preparation, and its disintegrate in gastrointestinal tract is slow, and it is slow to absorb; Dose is big and taste is not good, very bitter usually, uses very inconvenient; Dosage can't accurately be controlled; Produce lack of standardization and long flow path, if easily influence is molten diffusing for misoperation in the production process, microorganism is not easy control in the operating process, microbiological contamination easily, and usually in the adhesion that increases pill, improve mouthfeel, in preparation, need to add a large amount of Mel and sugar part, this more XXL the probability of microbiological contamination.Only all be herein incorporated at this with the mode of quoting above-mentioned dosage form content with prior art.

Among numerous peroral dosage forms, capsule have bioavailability height, good airproof performance, content accurately, good looking appearance, cover characteristics such as bad smell.As everyone knows, the physicochemical property of brain-tonifying and kidney-nourishing extract makes it to be not easy to make very much capsule, though have relevant instruction is arranged in the relevant patented technology.But inventor back after deliberation finds, is made into soft capsule, though dosage form has improved, need overcome a lot of difficulties, for example the capsule of prior art become defective, the moisture absorption and content caking equistability problem of disintegrate in storage period.And affected by environment in actual use big, often promptly lost efficacy before the deadline or defective or the like the problems of character.To those skilled in the art, these problems are difficult to expect.Up to now, in view of the problem that occurs in the complexity of brain-tonifying and kidney-nourishing physicochemical property and the clinical practice thereof, also have no talent and the beneficial effect of the capsule that comprises brain-tonifying and kidney-nourishing is provided the prediction of science.

Therefore, this area presses for the brain-tonifying and kidney-nourishing oral Pharmaceutical dosage forms that exploitation makes new advances, and said preparation should be reduced to bottom line with its negative effect when effectively improving product stability.This pharmaceutical dosage form can improve patient's treatment compliance, and must be safe.

Summary of the invention

The purpose of this invention is to provide a kind of extract with 25 flavor Chinese medicines such as Radix Ginseng, Cornu Cervi Pantotrichum, Testis et Pentis Canis is the capsule capsule preparations with replenishing QI to invigorate the spleen, tranquilizing the mind effect of raw material, said preparation is reduced to bottom line with its negative effect when can improving product stability.

The present invention also aims to provide a kind of capsule with replenishing QI to invigorate the spleen, tranquilizing the mind effect, this capsular each preparation unit contains glycyrrhizic acid must not be lower than 0.15mg.

The present invention also aims to provide a kind of capsular preparation method with replenishing QI to invigorate the spleen, tranquilizing the mind effect.

For achieving the above object, technical scheme provided by the invention is as follows:

A kind of capsule with replenishing QI to invigorate the spleen, tranquilizing the mind effect comprises the component of following weight proportion:

45～65 parts of Radix Ginsengs, 7～18 parts in Cornu Cervi Pantotrichum, 18～24 parts of Testis et Pentis Canis, 45～65 parts of Cortex Cinnamomis, 65～85 parts of Fructus Amomis, 15～30 parts of Herba Polygalae Telephioidis, 52～40 parts of Fructus Arctiis, 15～30 parts of Fructus Rosae Laevigatae, 55～78 parts of the Cortexs Eucommiae, 55～78 parts of Radix Cyathulaes, 40～55 parts of Flos Loniceraes, 35～53 parts of Fructus Forsythiaes, 35～53 parts of Periostracum Cicadaes, 75～100 parts of Rhizoma Dioscoreaes, 65～85 parts of Radix Polygalaes, 65～85 parts of Semen Ziziphi Spinosaes, 55～78 parts of g of Radix Angelicae Sinensis, 55～78 parts of Os Draconis, 65～85 parts of Concha Ostreaes, 120～180 parts in Poria, 65～85 parts of the Rhizoma Atractylodis Macrocephalaes, 55～78 parts of Ramulus Cinnamomi, 45～60 parts in Radix Glycyrrhizae, 55～78 parts of the Radix Paeoniae Albas, 55～78 parts in Fructus Amomi Rotundus;

Wherein, this capsule makes via following method:

Get Radix Ginseng, Cornu Cervi Pantotrichum, Testis et Pentis Canis, Cortex Cinnamomi, Fructus Amomi, the alcohol reflux with 10%～80%, extracting liquid filtering obtains ethanol extract;

Herba Polygalae Telephioidis, Fructus Arctii, Fructus Rosae Laevigatae, the Cortex Eucommiae, Radix Cyathulae, Flos Lonicerae, Fructus Forsythiae, Periostracum Cicadae, Rhizoma Dioscoreae, Radix Polygalae, Semen Ziziphi Spinosae, Radix Angelicae Sinensis, Os Draconis, Concha Ostreae, Poria, the Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Radix Glycyrrhizae, the Radix Paeoniae Alba, Fructus Amomi Rotundus decoct with water, decocting liquid filters, filtrate concentrates, merge with above-mentioned ethanol extract, obtain amalgamation liquid;

Add ethanol and make that to contain alcohol amount be 60%～80% in amalgamation liquid, get supernatant, reclaim ethanol, add water to 3500 parts, stir evenly, leave standstill, get supernatant and filter, filtrate is condensed into thick paste, and crushed after being dried adds auxiliary materials and mixing, granulates, and drying incapsulates, promptly.

The above-mentioned capsule with replenishing QI to invigorate the spleen, tranquilizing the mind effect, wherein, each preparation unit contains glycyrrhizic acid and is not less than 0.15mg～0.6mg.

In a preferred embodiment of the invention, provided by the invention have a replenishing QI to invigorate the spleen, the capsule of tranquilizing the mind effect wherein preferably includes the component of following weight proportion: 55 parts of Radix Ginsengs, 13 parts in Cornu Cervi Pantotrichum, 26 parts of Testis et Pentis Canis, 55.5 parts of Cortex Cinnamomis, 77 parts of Fructus Amomis, 22 parts of Herba Polygalae Telephioidis, 33.0 parts of Fructus Arctiis, 22.5 parts of Fructus Rosae Laevigatae, 66.5 parts of the Cortexs Eucommiae, 66.5 parts of Radix Cyathulaes, 48.0 parts of Flos Loniceraes, 44.0 parts of Fructus Forsythiaes, 44.0 parts of Periostracum Cicadaes, 88.0 parts of Rhizoma Dioscoreaes, 77.0 parts of Radix Polygalaes, 77.5 parts of Semen Ziziphi Spinosaes, 66.0 parts of g of Radix Angelicae Sinensis, 64.5 parts of Os Draconis, 77.5 parts of Concha Ostreaes, 154.5 parts in Poria, 77.5 parts of the Rhizoma Atractylodis Macrocephalaes, 64.5 parts of Ramulus Cinnamomi, 51.5 parts in Radix Glycyrrhizae, 64.5 parts of the Radix Paeoniae Albas, 64.0 parts in Fructus Amomi Rotundus.

In above-mentioned composition preparation of the present invention (capsule), the Chinese crude drug of some component need be through concocting, the method of concocting is listed in medical material title back with abbreviation and is marked with bracket, that is, described " Fructus Arctii " is " Fructus Arctii (stir-fry) ", for getting clean Fructus Arctii, put in the heat pot, with slow fire fry to slightly heave, little when fragrance is arranged, taking-up cools, and promptly gets Fructus Arctii (stir-fry); Described " Cortex Eucommiae " is " Cortex Eucommiae (charcoal) ", for getting the clean Cortex Eucommiae, put in the heat pot, when frying with high heat to surperficial coke black, inner coke yellow, the spray clear water a little, extinguish Mars, take out, dry, promptly get the Cortex Eucommiae (charcoal); Described " Radix Polygalae " is " Radix Polygalae (liquorice beverage system) ", is extracting liquorice, adds an amount of decocting soup, removes slag, and adds clean Radix Polygalae, simmers in water to the soup exhaustion, takes out, and drying promptly gets Radix Polygalae (liquorice beverage system); Described " Semen Ziziphi Spinosae " is " Semen Ziziphi Spinosae (stir-fry) ", for getting clean Semen Ziziphi Spinosae, put in the heat pot, with slow fire fry to slightly heave, color is little when deepening, taking-up cools, and promptly gets Semen Ziziphi Spinosae (stir-fry); Described " Os Draconis " are " Os Draconis (forging) ", for getting clean Os Draconis, pound into fritter, put on the smokeless stove fire or put in the suitable container, forge when being popular in, and cool, and taking-up is pulverized, and promptly gets Os Draconis (forging); Described " Rhizoma Atractylodis Macrocephalae " is " Rhizoma Atractylodis Macrocephalae (parched with bran) ", for getting bran, removes in heat pot, is heated to when smoldering, and adds the clean Rhizoma Atractylodis Macrocephalae, stirs rapidly, fries to be yellow or complexion changed to the medical material surface when dark, takes out, and sieves and removes wheat bran, cools, and promptly gets the Rhizoma Atractylodis Macrocephalae (parched with bran).

In sum, in another preferred embodiment of the present invention, described have a replenishing QI to invigorate the spleen, the capsule of tranquilizing the mind effect is comprising the component of following weight proportion: 55 parts of Radix Ginsengs, 13 parts in Cornu Cervi Pantotrichum, 26 parts of Testis et Pentis Canis, 55.5 parts of Cortex Cinnamomis, 77 parts of Fructus Amomis, 22 parts of Herba Polygalae Telephioidis, 33.0 parts of Fructus Arctiis (stir-fry), 22.5 parts of Fructus Rosae Laevigatae, 66.5 parts of the Cortexs Eucommiae (charcoal), 66.5 parts of Radix Cyathulaes, 48.0 parts of Flos Loniceraes, 44.0 parts of Fructus Forsythiaes, 44.0 parts of Periostracum Cicadaes, 88.0 parts of Rhizoma Dioscoreaes, 77.0 parts of Radix Polygalaes (liquorice beverage system), 77.5 parts of Semen Ziziphi Spinosaes (stir-fry), 66.0 parts of g of Radix Angelicae Sinensis, 64.5 parts of Os Draconis (forging), 77.5 parts of Concha Ostreaes, 154.5 parts in Poria, 77.5 parts of the Rhizoma Atractylodis Macrocephalaes (parched with bran), 64.5 parts of Ramulus Cinnamomi, 51.5 parts in Radix Glycyrrhizae, 64.5 parts of the Radix Paeoniae Albas, 64.0 parts in Fructus Amomi Rotundus.

The present invention also provides the above-mentioned capsular preparation method with replenishing QI to invigorate the spleen, tranquilizing the mind effect, and wherein, this method comprises:

Get Radix Ginseng, Cornu Cervi Pantotrichum, Testis et Pentis Canis, Cortex Cinnamomi, Fructus Amomi, the alcohol reflux with 10%～80%, extracting liquid filtering obtains ethanol extract;

Herba Polygalae Telephioidis, Fructus Arctii, Fructus Rosae Laevigatae, the Cortex Eucommiae, Radix Cyathulae, Flos Lonicerae, Fructus Forsythiae, Periostracum Cicadae, Rhizoma Dioscoreae, Radix Polygalae, Semen Ziziphi Spinosae, Radix Angelicae Sinensis, Os Draconis, Concha Ostreae, Poria, the Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Radix Glycyrrhizae, the Radix Paeoniae Alba, Fructus Amomi Rotundus decoct with water, decocting liquid filters, filtrate concentrates, merge with above-mentioned ethanol extract, obtain amalgamation liquid;

Add ethanol and make that to contain alcohol amount be 60%～80% in amalgamation liquid, get supernatant, reclaim ethanol, add water to 3500 parts, stir evenly, leave standstill, get supernatant and filter, filtrate is condensed into thick paste, and crushed after being dried adds auxiliary materials and mixing, granulates, and drying incapsulates.

In developing capsular process of the present invention, the inventor finds that determining of extracting parameter is very important, and it is concerning whether product forms (capsule) conforms with the requirement of be correlated with qualitative and quantitative and capsular physico-chemical parameter.

The present invention is as follows for the screening experiment of the parameter of extraction process:

1, the ethanol extraction method is investigated

1.1, the investigation of ethanol extraction water absorption rate

Take by weighing Radix Ginseng 55g, Cornu Cervi Pantotrichum 13g, Testis et Pentis Canis 26g, Cortex Cinnamomi 55.5g, Fructus Amomi 77g, take by weighing 2 parts respectively, add 50% soak with ethanol of 10 times of amounts respectively, observe medical material simultaneously and run through phenomenon, medical material runs through fully after 1 hour as a result; After the soaked overnight (about 15 hours), calculate the suction multiple and be about 1 times.The results are shown in Table 1.

The medical material water absorption rate experimental result of table 1, ethanol extraction technology

The experiment label	Take by weighing medical material weight (g)	Soak medical material weight (g) after 15 hours	Absorbance (%)
				1	227	476	109.7％
2	227	464	104.4％

The meansigma methods of above-mentioned 2 parts of experimental datas is 107%, and water absorption rate is about 1 times.Contain a large amount of ethanol owing to extract solution, and medical material is rhizome, do not contain careless class, so the medical material water absorption rate is not high

1.2, the determining of optimum extraction counterflow condition

Extraction conditions is most important to the quality influence of extracting solution, comprises that the factor of the each amount that adds of solvent, solvent of use, each soak time to medical material, extraction time, each extraction time or the like each side all can produce beyond thought or even diametrically opposite effect to the quality of the pharmaceutical preparations and effect of drugs.For example:

Select water different fully with the composition that ethanol extraction comes out; Different concentration of alcohol not only influences the quality of extracting solution, also can make things convenient for production greatly, if adopt the ethanol more than 50%, each equipment and workshop all will be carried out explosion-proof processing separately, increase production cost and danger greatly.

What of ethanol consumption have significant impact to the extraction of active ingredient: ethanol adds few, and then the amount extracted of active ingredient just reduces relatively, and this influences the quality of product, and finally has influence on the final curative effect of product; And ethanol has been added, and causes the increasing of production cost on the one hand, and it is also many that the product that obtains on the other hand contains impurity, causes the toxic and side effects of final products to strengthen, and causes the treatment consequence that can't estimate to the patient; Moreover, add amount of alcohol and make that too much the extraction liquid measure that finally obtains is also many, not only prolong concentration time and strengthened production cost, and concentrated for a long time heating makes medicinal liquid for the condition of high temperature, not only can cause the loss of some volatile effective therapeutic components, and bigger to heat-labile chemical constituent influence, the final quality that directly influences preparation.

Contain the effective ingredient that to measure in a large number in the capsular ethanol extraction of brain-tonifying and kidney-nourishing, for example: the ginsenoside in the Radix Ginseng, the cinnamic aldehyde in the Cortex Cinnamomi.In experimentation of the present invention, the screening with experiment condition is groped in a large amount of creative experiment of process, the final index of investigating as extraction conditions with the content of the cinnamic aldehyde in the alcohol extraction extract, on the one hand because cinnamic aldehyde is the volatilization oily matter, special Cortex Cinnamomi virtue abnormal smells from the patient is arranged, and is the effective ingredient of ethanol extraction; Cinnamic aldehyde can part decompose under the continuous high temperature state on the other hand, and whether this more helps the selected extraction conditions of check test desirable.

The cinnamic aldehyde assay method:

Chromatographic condition and system suitability test are filler with octadecyl or octyl silane group silica gel; Acetonitrile-0.1% phosphoric acid (48:52) is mobile phase; The detection wavelength is 288nm.Number of theoretical plate should be not less than 2000 by the cinnamic aldehyde peak.

The preparation precision of reference substance solution takes by weighing the cinnamic aldehyde reference substance and puts in right amount in the brown volumetric flask, adds methanol and makes the solution that contains the about 10 μ g of cinnamic aldehyde among every 1ml.

The preparation precision of need testing solution takes by weighing the about 0.5g of extracting solution, puts in the 100ml measuring bottle, and it is an amount of to add 70% methanol, and ultrasonic 30 minutes, put coldly, be diluted to scale with 70% methanol, shake up, filter, promptly.

Respectively accurate reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject high performance liquid chromatograph and measure, and calculate the content that promptly gets cinnamic aldehyde according to the external standard method of regulation in the Chinese Pharmacopoeia 2005 editions.

1.2.1, the selection of ethanol extraction technology

Take by weighing Radix Ginseng 110g, Cornu Cervi Pantotrichum 26g, Testis et Pentis Canis 52g, Cortex Cinnamomi 111g, Fructus Amomi 154g, take by weighing 2 parts respectively, add 10 times of amount 50% ethanol respectively, a direct heating extracts, and another part adopts reflux, extract; After the extracting solution that obtains filtered respectively, measure the content of cinnamic aldehyde then respectively.The results are shown in Table 2

The selection of table 2, ethanol extraction technology

The experiment label	Inventory (g)	Cinnamic aldehyde content (mg)
			1	455	985.6
2	455	897.1

Conclusion: reflux, extract, can guarantee the maximum level of volatile ingredient cinnamic aldehyde, so select reflux, extract, technology.

1.2.2, the selection of concentration of alcohol investigates

Take by weighing Radix Ginseng 55g, Cornu Cervi Pantotrichum 13g, Testis et Pentis Canis 26g, Cortex Cinnamomi 55.5g, Fructus Amomi 77g, take by weighing 6 parts respectively, the alcoholic solution that adds 10 times of amounts of variable concentrations, carry out the reflux, extract, experiment respectively, after the extracting solution that obtains filtered respectively, concentrating under reduced pressure, vacuum drying get extract powder, measure the content of cinnamic aldehyde then respectively.The results are shown in Table 3.

Table 3, concentration of alcohol are selected experiment

The experiment label	Concentration of alcohol (%)	Extract powder (g)	Cinnamic aldehyde content (mg/g)
				1	75％	87.6	6.09
2	60％	83.1	6.25
				3	50％	76.2	6.46
4	40％	75.1	6.51
				5	30％	69.6	6.11
6	20％	57.7	4.39

Conclusion: from the absolute magnitude of cinnamic aldehyde extraction, concentration is that 75% the extract powder that ethanol obtained is maximum, but the impurity of Ti Quing is also many simultaneously, therefore the percentage composition of its cinnamic aldehyde reduces on the contrary, in conjunction with two parts data analysis, concentration of alcohol from 50% to 40%, cinnamic aldehyde content does not almost have significant difference, considers to select the ethanol of 40% concentration from saving production cost.

1.2.3, the reflux, extract, number of times influences extracting solution

Take by weighing Radix Ginseng 55g, Cornu Cervi Pantotrichum 13g, Testis et Pentis Canis 26g, Cortex Cinnamomi 55.5g, Fructus Amomi 77g, take by weighing 6 parts respectively, add 10 times of amount 40% alcoholic solution, carry out the reflux, extract, experiment respectively, the backflow number of times is respectively 1 time, 2 times, 3 times, after the extracting solution that obtains filtered respectively, measure the content of cinnamic aldehyde then, the results are shown in Table 4.

Table 4, the experiment of ethanol extract backflow selection of times

The experiment label	The reflux, extract, number of times	Cinnamic aldehyde content (mg)
			1	1	311.4
2	2	491.2
			3	3	496.3

Conclusion: reflux, extract, 2 times and 3 times, cinnamic aldehyde content does not almost have significant difference, considers to select 40% alcohol reflux 2 times from saving production cost.

1.2.4, the investigation of extracting return time

Take by weighing Radix Ginseng 55g, Cornu Cervi Pantotrichum 13g, Testis et Pentis Canis 26g, Cortex Cinnamomi 55.5g, Fructus Amomi 77g, take by weighing 7 parts respectively, add the alcoholic solution of 10 times of amounts 40%, carry out reflux, extract, respectively 2 times, return time is as follows, after the extracting solution that obtains is filtered respectively, measures the content of cinnamic aldehyde then respectively.The results are shown in Table 5.

Table 5, extraction return time are investigated experiment

The experiment label	For the first time return time (hour)	For the second time return time (hour)	Cinnamic aldehyde content (mg)
				1	3	1	451.3
2	3	2	490.5
				3	3	3	487.9
4	2	1	398.2
				5	2	2	423.1
6	1	1	365.2
				7	1	2	387.1

Conclusion: reflux, extract, 3 hours for the first time and 2 hours for the second time, the content of cinnamic aldehyde is best.

1.2.5, add of the influence of alcoholic acid amount to extracting solution

Take by weighing Radix Ginseng 55g, Cornu Cervi Pantotrichum 13g, Testis et Pentis Canis 26g, Cortex Cinnamomi 55.5g, Fructus Amomi 77g, take by weighing 6 parts respectively, each alcoholic solution of 40% that adds different doubly amounts, carry out reflux, extract, respectively 2 times, 3 hours for the first time, 2 hours for the second time, after the extracting solution that obtains filtered respectively, concentrating under reduced pressure, vacuum drying get extract powder, measure the content of cinnamic aldehyde then respectively.The results are shown in Table 6.

The investigation experiment of table 6, adding amount of alcohol

The experiment label	Add for the first time 40% amount of alcohol	Add for the second time 40% amount of alcohol	Extract powder (g)	Cinnamic aldehyde content (mg/g)
					1	10	10	76.5	6.46
2	8	8	75.8	6.44
					3	6	6	70.4	6.85
4	4	4	53.1	4.88
					5	8	6	71.9	6.78
6	6	4	67.8	6.63

Conclusion: add 4 times of amount ethanol, because it is few to extract solvent, so the amount of cinnamic aldehyde is also low in the gained extracting solution.And add the ethanol of 10 and 8 times of amounts, and the first, owing to extract the increase of quantity of solvent, it is many that impurity level also extracts, so the amount of extracting solution is also many, so cinnamic aldehyde content reduces relatively; On the other hand,, prolonged concentration time owing to extract the increase of quantity of solvent, cinnamic aldehyde under continuous high temperature, also some decomposition.

Above experimental result shows that the optimised process of this product alcohol extraction is: gets recipe quantity Radix Ginseng, Cornu Cervi Pantotrichum, Testis et Pentis Canis, Cortex Cinnamomi, Fructus Amomi,, adds 6 times of amounts at every turn with 40% alcohol reflux secondary, and 3 hours for the first time, 2 hours for the second time.

2, water extracting method is investigated

2.1, the investigation of water extraction water absorption rate

Take by weighing 20 flavor medical materials such as Herba Polygalae Telephioidis, Fructus Arctii (stir-fry), Fructus Rosae Laevigatae, the Cortex Eucommiae (charcoal), Radix Cyathulae, Flos Lonicerae, Fructus Forsythiae, Periostracum Cicadae, Rhizoma Dioscoreae by 1/3 recipe quantity, take by weighing 2 parts respectively, adding water 5kg soaks, observe medical material simultaneously and run through phenomenon, medical material runs through fully after 2 hours as a result, after the soaked overnight, calculate the suction multiple and be about 2 times.The results are shown in Table 7.

The medical material water absorption rate experimental result of table 7, water extraction process

The experiment label	Take by weighing medical material weight (g)	Soak medical material weight (g) after 13 hours	Absorbance (%)
				1	425	1263	197.2％
2	425	1307	207.5％

The meansigma methods of above-mentioned 2 parts of experimental datas is 202.35%, and water absorption rate is about 2 times.

2.2, the determining of optimum extraction condition

Extraction conditions is most important to the quality influence of extracting solution, comprises that the factor of the each amount that adds of solvent, solvent of use, each soak time to medical material, extraction time, each extraction time or the like each side all can produce beyond thought or even diametrically opposite effect to the quality of the pharmaceutical preparations and effect of drugs.For example:

What of water consumption have significant impact to the extraction of active ingredient: water adds few, and then the amount extracted of active ingredient just reduces relatively, and this influences the quality of product, and finally has influence on the final curative effect of product; And water has been added, and causes the increasing of production cost on the one hand, and it is also many that the product that obtains on the other hand contains impurity, causes the toxic and side effects of final products to strengthen, and causes the treatment consequence that can't estimate to the patient; Moreover, add hypervolia and make that the extraction liquid measure that finally obtains is also many, not only prolonged concentration time and strengthened production cost, and concentrated for a long time heating makes medicinal liquid for the condition of high temperature, can be bigger to heat-labile chemical constituent influence, finally directly influence the quality of preparation.

Contain the effective ingredient that to measure in a large number in the capsular water extract of brain-tonifying and kidney-nourishing, for example: the chlorogenic acid in the Flos Lonicerae, peoniflorin in the Radix Paeoniae Alba, phillyrin in the Fructus Forsythiae etc., but because various mensuration compositions or content can't detect very little, perhaps the rate of transform is crossed the low requirement that can't reach detection sensitivity; Grope screening with experiment condition through a large amount of experiments, finally selected the investigation index of the content of the content of n-butanol extract and glycyrrhizic acid as extraction process by water; Use n-butanol extract content to control whole extraction situation, and glycyrrhizic acid can reach every requirement of detection on the one hand, glycyrrhizic acid hydrolysis easily under continuous high temperature on the other hand, reasonability, science that like this can the final extraction conditions of more effective investigation, thus filter out best water extraction condition.

Assay method:

A, n-butanol extract: the about 3g of sample thief, accurate claim surely, put in the 250ml conical flask, precision adds positive fourth 50ml, close plug is weighed, leave standstill 1 hour after, connect reflux condensing tube, be heated to boiling, and keep little and boiled 1 hour.Put cold after, claim, supply the weight that subtracts mistake with n-butyl alcohol, shake up, filter with dry filter, precision is measured subsequent filtrate 25ml, puts in the evaporating dish that is dried to constant weight, behind evaporate to dryness in the water-bath, in 105 ℃ of dryings 3 hours, in the dislocation exsiccator, cooled off 30 minutes, accurately rapidly claim to decide weight.

B, glycyrrhizic acid:

Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; Methanol-0.2mol/L Spirit of Mindererus .-glacial acetic acid (63:37:2) is a mobile phase; The detection wavelength is 250nm.Number of theoretical plate calculates by the glycyrrhizic acid peak should be not less than 1500.

The preparation precision of reference substance solution takes by weighing ammonium glycyrrhizinate reference substance an amount of (being equivalent to glycyrrhizic acid 12.5mg approximately), puts in the 25ml measuring bottle, adds the mobile phase dissolving and is diluted to scale, shake up, precision pipettes 5ml and puts in the 50ml measuring bottle, adds mobile phase and is diluted to scale, shake up, promptly.

The preparation sample thief of need testing solution, porphyrize, precision takes by weighing about 0.5g, put in the tool plug conical flask, accurate methanol-36% acetic acid (25:5) the solution 25ml that adds weighs supersound process 40 minutes, put cold, weigh again, supply the amount of loss, shake up with methanol-36% acetic acid (25: 5) solution, filter, promptly.

Respectively accurate reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject high performance liquid chromatograph and measure, and calculate the content that promptly gets glycyrrhizic acid according to the external standard method of regulation in the Chinese Pharmacopoeia 2005 editions.

2.2.1, the water extraction number of times influences extracting solution

Take by weighing 20 flavor medical materials such as Herba Polygalae Telephioidis, Fructus Arctii (stir-fry), Fructus Rosae Laevigatae, the Cortex Eucommiae (charcoal), Radix Cyathulae, Flos Lonicerae, Fructus Forsythiae, Periostracum Cicadae, Rhizoma Dioscoreae by recipe quantity, take by weighing 3 parts respectively, the aqueous solution that adds 10 times of amounts, extract experiment respectively, extraction time is respectively 1 time, 2 times, 3 times, and the extracting solution that obtains is merged, filter, it is 1.2～1.4 thick paste that filtrate is concentrated into relative density, crushed after being dried, extract powder.Measure the content of n-butanol extract and glycyrrhizic acid then respectively.The results are shown in Table 8.

Table 8, the experiment of water extraction selection of times

The experiment label	Extraction time	Extract powder (g)	Glycyrrhizic acid content (mg/g)	N-butanol extract (%)
					1	1	345	0.413	6.1
2	2	598	0.733	6.7
					3	3	609	0.735	6.4

Conclusion: water extraction 2 times and 3 times, glycyrrhizic acid content does not almost have significant difference, considers to select water extraction 2 times from saving production cost.

2.2.2, the investigation of extraction time-

Take by weighing 20 flavor medical materials such as Herba Polygalae Telephioidis, Fructus Arctii (stir-fry), Fructus Rosae Laevigatae, the Cortex Eucommiae (charcoal), Radix Cyathulae, Flos Lonicerae, Fructus Forsythiae, Periostracum Cicadae, Rhizoma Dioscoreae by recipe quantity, take by weighing 6 parts respectively, add the aqueous solution of 10 times of amounts, extract experiment respectively, extract 2 times, each decocting time is as follows, the extracting solution that obtains is merged, filter, it is 1.2～1.4 thick paste that filtrate is concentrated into relative density, crushed after being dried gets extract powder.Measure the content of n-butanol extract and glycyrrhizic acid then respectively, the results are shown in Table 9.

Table 9, extraction time are investigated experiment

The experiment label	For the first time decocting time (hour)	For the second time decocting time (hour)	Extract powder (g)	Glycyrrhizic acid content (mg/g)	N-butanol extract (%)
						1	3	2	623	7.17	6.0
2	2	1	559	7.40	6.4
						3	2	1.5	568	7.39	6.7

4	2	2	584	7.29	6.5
						6	1	1	309	5.95	6.2

Conclusion: water extraction 2 times, 2 hours for the first time and 1.5 hours for the second time, n-butanol extract was maximum, and the content of glycyrrhizic acid is best.

2.2.3, amount of water is to the influence of extracting solution

Take by weighing 20 flavor medical materials such as Herba Polygalae Telephioidis, Fructus Arctii (stir-fry), Fructus Rosae Laevigatae, the Cortex Eucommiae (charcoal), Radix Cyathulae, Flos Lonicerae, Fructus Forsythiae, Periostracum Cicadae, Rhizoma Dioscoreae by recipe quantity, take by weighing 6 parts respectively, amount of water following (numeral in the chart is the multiple weight of medical material weight) extracts experiment respectively, decoct and extract 2 times, decocting time is 2 hours for the first time, 1.5 hours for the second time, the extracting solution that obtains is merged, filter, it is 1.2～1.4 thick paste that filtrate is concentrated into relative density, crushed after being dried, extract powder.Measure the content of n-butanol extract and glycyrrhizic acid then respectively.The results are shown in Table 10.

The investigation experiment of table 10, amount of water

The experiment label	Amount of water (doubly) for the first time	Amount of water (doubly) for the second time	Extract powder (g)	Glycyrrhizic acid content (mg/g)	N-butanol extract (%)
						1	10	10	607	7.29	6.6
2	10	8	602	7.33	6.5
						3	10	6	589	7.18	6.5
4	8	8	533	6.85	6.2
						5	8	6	528	6.79	6.2

Conclusion: add 6 times of water gagings, because it is few to extract solvent, therefore the amount of extract obtained glycyrrhizic acid is also low.Do not have significant difference and test 1 and 2 extractive contents that obtained,, decocted 2 hours, add 8 times of water gagings for the second time, decocted 1.5 hours so select to add 10 times of water gagings for the first time.

Above experimental result shows that this product water extraction optimised process is: get 20 flavors such as recipe quantity Herba Polygalae Telephioidis and decoct with water secondary, add 10 times of water gagings for the first time, decocted 2 hours, add 8 times of water gagings the second time, decocted 1.5 hours.

3, impurity removal process is investigated

Alcohol reflux liquid merging with 5 flavor medical materials such as the concentrated thick paste of the water extracted immersing paste of Herba Polygalae Telephioidis, Fructus Arctii (stir-fry), Fructus Rosae Laevigatae, the Cortex Eucommiae (charcoal), Radix Cyathulae, Flos Lonicerae, Fructus Forsythiae, Periostracum Cicadae, Rhizoma Dioscoreae etc. 20 flavor medical materials and Radix Ginsengs adds ethanol and carries out remove impurity.Select glycyrrhizic acid as testing index.

3.1, the screening of concentration of alcohol

Get above-mentioned united extraction thing solution, add not commensurability alcoholic solution respectively, remove the impurity experiment screening, left standstill 24 hours, after liquid filters respectively with leaving standstill of obtaining, concentrating under reduced pressure, vacuum drying, extract powder, measure the content of glycyrrhizic acid.Measurement result sees Table 11.

The screening of table 11, remove impurity experiment concentration of alcohol

The experiment label	United extraction liquid measure (ml)	Contain concentration of alcohol (%)	Amount of alcohol added (ml)	Extract powder (g)	Glycyrrhizic acid total content (mg)
						1	500	85	4250	267	98.6
2	500	80	2667	289	100.2
						3	500	70	1400	345	135.5
4	500	60	860	375	136.9
						5	500	50	556	411	136.1

Conclusion: the supernatant hypervolia more than 80%, but glycyrrhizic acid content is but few relatively, because concentration of alcohol is too high, remove amounts of protein, tannin, and adsorbed part glycyrrhizic acid in the solution, so that the glycyrrhizic acid total amount reduces greatly, illustrate in the ethanol of high concentration and contain a lot of impurity, removal impurity weak effect; And 60%, 50% the alcohol amount that contains because concentration of alcohol is low excessively, can't effectively keep compositions such as glycyrrhizic acid, does not reach the effect of remove impurity; The ethanol of comprehensive screening 70% concentration is as the solvent of removing impurity.

3.2, the screening of time of repose

Get above-mentioned united extraction thing solution, add ethanol and make solution contain the alcohol amount in right amount to reach 70%, remove the impurity experiment screening, leave standstill different time, get the content that supernatant is measured glycyrrhizic acid.Measurement result sees Table 12.

The screening of time of repose in table 12, the remove impurity experiment

The experiment label	United extraction liquid measure (ml)	Amount of alcohol added (ml)	Time of repose (hour)	Extract powder (g)	Glycyrrhizic acid total content (mg)
						1	500	1400	6	359	134.1
2	500	1400	12	339	135.2
						3	500	1400	24	337	133.9
4	500	1400	36	329	134.7

Conclusion: the content that leaves standstill 6 hours glycyrrhizic acids is obviously on the low side, because the time is short, wafing in the solution has flocculent deposit, causes filtration difficulty, from final measurement result, remove impurity is incomplete; And 12,24 and 36 hours basically identicals.Final selection 12 hours, spending the night of just saying on the ordinary meaning gets final product.

3.3, obtain the screening of supernatant method

Get above-mentioned united extraction thing solution, it is an amount of to add ethanol, make contain the alcohol amount reach 70%, remove the impurity experiment screening, after the standing over night, adopt distinct methods to obtain supernatant, measure the content of glycyrrhizic acid.Measurement result sees Table 13.

Obtain the screening of supernatant method in table 13, the remove impurity experiment

The experiment label	United extraction liquid measure (ml)	Amount of alcohol added (ml)	The method of the supernatant of crossing	Extract powder (g)	Glycyrrhizic acid total content (mg)
						1	500	1400	Directly get supernatant	311	127.1
2	500	1400	Get supernatant and partially mixed liquid after-filtration	335	133.5
						3	500	1400	Get behind supernatant and the partially mixed liquid centrifugal	341	134.2

Conclusion: directly get supernatant because the loss of part solution causes glycyrrhizic acid content on the low side, though and centrifugal content is constant, but cause partial impurities to enter and cause final extract powder on the high side in the solution.So method that the supernatant after-filtration is got in final selection.

4, the preparation stability craft screening is investigated

4.1, the selection of binding agent

Find that by testing us this product extract powder has very strong hygroscopicity, and become sticky after the moisture absorption, be difficult for granulating, therefore select non-aqueous solution ethanol preparation soft material for use, concentration of alcohol screening experiment and result such as table 14 select the better starch of resistance to water soak commonly used to make filler.

The screening of the binding agent concentration of alcohol of table 14, preparation soft material

Sequence number	1	2	3
				Extract powder amount (g)	58.4	58.4	58.4

Starch (g)	41.6	41.6	41.6
				75% ethanol	In right amount	---	---
85% ethanol	---	In right amount	---
				95% ethanol	---	---	In right amount
The granulation situation	Difficult	Easily	Easily
				The fill situation	Easily	Easily	Easily
Qualified capsule (grain)	154	318	319
				Pre-output (grain)	333	333	333
Yield rate (%)	46.2	95.5	95.8

Conclusion: as seen from the above table, No. 1 technology granulation is difficult, and it is more to produce the chieftain, and yield rate is too low, because its operation is wayward, so 85% following ethanol preparation soft material technology is infeasible; 95% and 85% effect that is produced is suitable, finally selects the binding agent of 85% alcoholic solution as the preparation soft material.

4.2, supplementary product kind screening and the experiment of preparation hygroscopicity

Find that by testing us this product extract powder has very strong hygroscopicity, and become sticky after the moisture absorption, be difficult for granulating, although select for use the high concentration ethanol of non-aqueous solution to prepare soft material as binding agent, filler is most important for the drying regime that keeps preparation, and the constant product quality on each link that can guarantee to be in storage, to transport and to sell is qualified, therefore, resist hygroscopic adjuvant and screen, carried out hygroscopicity at moisture simultaneously and quickened influence factor's experiment, the results are shown in Table 15.

Table 15, supplementary product kind screening and the experiment of preparation hygroscopicity

Unit (g)	1	2	3	4	5	6	7	8
									The extract powder amount	175	175	175	175	175	175	175	175
Starch	125	---	---	---	---	---	---	---
									Pre-paying starch	---	125	---	---	---	---	---	--
Dextrin	---	---	125	---	---	---	---	---
									Microcrystalline Cellulose	---	---	---	125	---	---	---	---
Lactose	---	---	---	---	125	---	---	---
									Calcium carbonate	---	---	---	---	---	125	---	---
Calcium hydrogen phosphate	---	---	---	---	---	---	125	---

Magnesium oxide	---	---	---	---	---	---	---	125
									85% ethanol	In right amount	In right amount	In right amount	In right amount	In right amount	In right amount	In right amount	In right amount
High humidity 75%, weightening finish in 10 days	2.1％	3.7％	7.6％	2.4％	4.3％	1.9％	5.2％	1.1％
									High humidity 75%, weightening finish in 30 days	9.4％	11.5％	22.9％	10.3％	10.7％	6.2％	17.8％	4.6％
High humidity 92.5%, weightening finish in 30 days behind the damp-prrof packing	1.8％	2.2％	4.0％	2.4％	2.3％	1.4％	3.6％	0.7％

Conclusion: can filter out the filler that is fit to this product from above-mentioned table, comprise starch, pre-paying starch, microcrystalline Cellulose, calcium carbonate and magnesium oxide, wherein calcium carbonate and magnesium oxide effect are best; Factors such as comprehensive production cost, preferred starch, calcium carbonate and magnesium oxide.

5, brain-tonifying and kidney-nourishing capsule amplification technique confirmatory experiment

Get 10 times of recipe quantity medical materials, operate according to said extracted technology, the extract powder of acquisition and appropriate amount of starch mixing are granulated with crossing 16 mesh sieves behind the 85% ethanol system soft material, and dry back granulate dress capsule the results are shown in Table 16

Table 16, three batches of pilot process checking amplification tests

Batch	Extract powder amount (kg)	Starch (kg)	85% ethanol (L)	Finished product number (grain)	Every glycyrrhizic acid content (mg)
						1	1.71	1.29	1.17	9163	0.39
2	1.86	1.14	1.05	9422	0.33
						3	1.64	1.36	1.23	9516	0.36

In sum, in a preferred embodiment of the invention, capsular preparation method of the present invention preferably includes:

Get Radix Ginseng, Cornu Cervi Pantotrichum, Testis et Pentis Canis, Cortex Cinnamomi, Fructus Amomi, with 40% alcohol reflux at least 2 times, add 6 times of amounts at every turn, each 2～3 hours, merge extractive liquid, filtered, and obtains ethanol extract; Herba Polygalae Telephioidis, Fructus Arctii, Fructus Rosae Laevigatae, the Cortex Eucommiae, Radix Cyathulae, Flos Lonicerae, Fructus Forsythiae, Periostracum Cicadae, Rhizoma Dioscoreae, Radix Polygalae, Semen Ziziphi Spinosae, Radix Angelicae Sinensis, Os Draconis, Concha Ostreae, Poria, the Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Radix Glycyrrhizae, the Radix Paeoniae Alba, Fructus Amomi Rotundus decoct with water 2 times at least, adding 10 times of water gagings for the 1st time soaked 1 hour, decocted 1～3 hour, the 2nd time and add 8 times of water gagings later at every turn, decocted 1～2 hour, collecting decoction filters, filtrate concentrates, and merges with above-mentioned ethanol extract, adds ethanol and makes that to contain the alcohol amount be 70%, leave standstill, get supernatant, reclaim ethanol, add water to 3500ml part, stir evenly, leave standstill; Get supernatant and filter, filtrate is condensed into thick paste, and crushed after being dried adds auxiliary materials and mixing, granulates, and drying incapsulates, promptly.

The invention provides the brain-tonifying and kidney-nourishing capsule, it is characterized in that this capsular each preparation unit contains glycyrrhizic acid and must not be lower than 0.15mg.

In brain-tonifying and kidney-nourishing capsule 's content of the present invention, every capsules contains glycyrrhizic acid and must not be lower than 0.15mg and can reach beneficial effect of the present invention and purpose.

The assay method of glycyrrhizic acid is as follows among the present invention:

At first prepare described brain-tonifying and kidney-nourishing capsule, the extract of this capsular content is prepared according to following step method:

Get Radix Ginseng 55g, Cornu Cervi Pantotrichum 13g, Testis et Pentis Canis 26g, Cortex Cinnamomi 55.5g, Fructus Amomi 77g, with 40% alcohol reflux secondary, add 6 times of amounts at every turn, each 2～3 hours, merge extractive liquid, filters, and was standby; All the other Herba Polygalae Telephioidis 22g, Fructus Arctii (stir-fry) 33.0g, Fructus Rosae Laevigatae 22.5g, the Cortex Eucommiae (charcoal) 66.5g, Radix Cyathulae 66.5g, Flos Lonicerae 48.0g, Fructus Forsythiae 44.0g, Periostracum Cicadae 44.0g, Rhizoma Dioscoreae 88.0g, Radix Polygalae (liquorice beverage system) 77.0g, Semen Ziziphi Spinosae (stir-fry) 77.5g, Radix Angelicae Sinensis 66.0g, Os Draconis (forging) 64.5g, Concha Ostreae 77.5g, Poria 154.5g, the Rhizoma Atractylodis Macrocephalae (parched with bran) 77.5g, Ramulus Cinnamomi 64.5g, Radix Glycyrrhizae 51.5g, Radix Paeoniae Alba 64.5g, Fructus Amomi Rotundus 64.0g totally 20 flavors decocts with water 2 times, adding 10 times of water gagings for the 1st time soaked 1 hour, decocted 1～3 hour, add 8 times of water gagings the 2nd time, decocted 1～2 hour, collecting decoction, filter, filtrate concentrates, merge with above-mentioned standby extracting solution, add ethanol and make that to contain alcohol amount be 70%, leave standstill, get supernatant, reclaim ethanol, add water to 3500ml, stir evenly, leave standstill.Get supernatant and filter, filtrate is condensed into thick paste, and crushed after being dried adds the appropriate amount of auxiliary materials mixing, granulates, and drying incapsulates, and makes 1000, promptly.

Chromatographic condition and system suitability test are filler with octadecyl or octyl silane group silica gel; Methanol-0.2mol/L Spirit of Mindererus .-glacial acetic acid (63:37:2) is a mobile phase; The detection wavelength is 250nm.Number of theoretical plate calculates by the glycyrrhizic acid peak should be not less than 1500.

The preparation precision of reference substance solution takes by weighing ammonium glycyrrhizinate reference substance an amount of (being equivalent to glycyrrhizic acid 12.5mg approximately), puts in the 25ml measuring bottle, adds the mobile phase dissolving and is diluted to scale, shake up, precision pipettes 5ml and puts in the 50ml measuring bottle, adds mobile phase and is diluted to scale, shake up, promptly.

It is an amount of that capsule 's content is got in the preparation of need testing solution, porphyrize, and precision takes by weighing about 0.5g, put in the tool plug conical flask, accurate methanol-36% acetic acid (25:5) the solution 25ml that adds weighs supersound process 40 minutes, put cold, weigh again, supply the amount of loss, shake up with methanol-36% acetic acid (25:5) solution, filter, promptly.

Respectively accurate reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject high performance liquid chromatograph and measure, and calculate the content that promptly gets glycyrrhizic acid according to the external standard method of regulation in the Chinese Pharmacopoeia 2005 editions.

The invention provides the brain-tonifying and kidney-nourishing capsule, it can significantly strengthen its beneficial effect, than present commercially available prod remarkable stability and treatment advantage is arranged.Simultaneously, the invention provides a kind of selection, it provides a kind of new safety product as the substituting of prior art, and this dosage form will be the approval that the doctor recommends to use and obtain doctor and patient.

The object of the present invention is to provide a kind of brain-tonifying and kidney-nourishing pharmaceutical capsules preparation, it has overcome the defective of existing brain-tonifying and kidney-nourishing oral formulations, and overcome color variable color that oral liquid usually occurs, the effective ingredient precipitation separates out and microbiological contamination, effect duration short equistability difference problem, and strengthened the beneficial effect of said preparation.

In a preferred embodiment of the invention, described brain-tonifying and kidney-nourishing capsule, every capsules contains glycyrrhizic acid must not be lower than 0.15mg.

6, brain-tonifying and kidney-nourishing capsule pharmacodynamic experiment

Experiment purpose: observe senile forgetful, the dull-witted curative effect of brain-tonifying and kidney-nourishing capsule for treating.

The foundation of experimental model: the mode of subcutaneous injection D-galactose, set up the mouse model of senile dementia.

Experimental technique: after model group, test group and the administration of matched group difference, observe mouse brain neuronal cell apoptosis rate.Model group is a mice Model of Dementia group, and test group is for giving the brain-tonifying and kidney-nourishing Capsules group, and matched group is for giving the brain-tonifying and kidney-nourishing oral liquid group.

Assay method: adopt copolymerization Jiao, Flow Cytometry to detect the quantity of neuronal cell apoptosis.

The result: the mouse brain neuronal cell apoptosis rate of model group is 58.2 ± 10.8, and test group mouse brain neuronal cell apoptosis rate is 10.2 ± 9.3, and matched group is 29.3 ± 7.6.

Conclusion: the brain neuron of senile dementia animal model has tangible apoptosis to take place, and the reliability of this model is described; And the experimental data of test group and matched group illustrates simultaneously that also the brain-tonifying and kidney-nourishing capsule has more significant inhibition senile dementia than oral liquid, improves effects such as the old people is forgetful.

The specific embodiment

Below describe the present invention in detail, but do not limit practical range of the present invention.

Embodiment 1. capsules with replenishing QI to invigorate the spleen, tranquilizing the mind effect of the present invention

Form and proportioning:

55 parts of Radix Ginsengs, 13 parts in Cornu Cervi Pantotrichum, 26 parts of Testis et Pentis Canis, 55.5 parts of Cortex Cinnamomis, 77 parts of Fructus Amomis, 22 parts of Herba Polygalae Telephioidis, 33.0 parts of Fructus Arctiis (stir-fry), 22.5 parts of Fructus Rosae Laevigatae, 66.5 parts of the Cortexs Eucommiae (charcoal), 66.5 parts of Radix Cyathulaes, 48.0 parts of Flos Loniceraes, 44.0 parts of Fructus Forsythiaes, 44.0 parts of Periostracum Cicadaes, 88.0 parts of Rhizoma Dioscoreaes, 77.0 parts of Radix Polygalaes (liquorice beverage system), 77.5 parts of Semen Ziziphi Spinosaes (stir-fry), 66.0 parts of g of Radix Angelicae Sinensis, 64.5 parts of Os Draconis (forging), 77.5 parts of Concha Ostreaes, 154.5 parts in Poria, 77.5 parts of the Rhizoma Atractylodis Macrocephalaes (parched with bran), 64.5 parts of Ramulus Cinnamomi, 51.5 parts in Radix Glycyrrhizae, 64.5 parts of the Radix Paeoniae Albas, 64.0 parts in Fructus Amomi Rotundus.

Preparation method:

Get Radix Ginseng 55g, Cornu Cervi Pantotrichum 13g, Testis et Pentis Canis 26g, Cortex Cinnamomi 55.5g, Fructus Amomi 77g, with 40% alcohol reflux secondary, add 6 times of amounts at every turn, each 2～3 hours, merge extractive liquid, filters, and was standby; All the other Herba Polygalae Telephioidis 22g, Fructus Arctii (stir-fry) 33.0g, Fructus Rosae Laevigatae 22.5g, the Cortex Eucommiae (charcoal) 66.5g, Radix Cyathulae 66.5g, Flos Lonicerae 48.0g, Fructus Forsythiae 44.0g, Periostracum Cicadae 44.0g, Rhizoma Dioscoreae 88.0g, Radix Polygalae (liquorice beverage system) 77.0g, Semen Ziziphi Spinosae (stir-fry) 77.5g, Radix Angelicae Sinensis 66.0g, Os Draconis (forging) 64.5g, Concha Ostreae 77.5g, Poria 154.5g, the Rhizoma Atractylodis Macrocephalae (parched with bran) 77.5g, Ramulus Cinnamomi 64.5g, Radix Glycyrrhizae 51.5g, Radix Paeoniae Alba 64.5g, Fructus Amomi Rotundus 64.0g totally 20 flavors decocts with water 2 times, adding 10 times of water gagings for the 1st time soaked 1 hour, decocted 1～3 hour, add 8 times of water gagings the 2nd time, decocted 1～2 hour, collecting decoction, filter, filtrate concentrates, merge with above-mentioned standby extracting solution, add ethanol and make that to contain alcohol amount be 70%, leave standstill, get supernatant, reclaim ethanol, add water to 3500ml, stir evenly, leave standstill.Get supernatant and filter, filtrate is condensed into thick paste, and crushed after being dried adds the appropriate amount of auxiliary materials mixing, granulates, and drying incapsulates, and makes 1000, promptly.

Wherein:

Fructus Arctii (stir-fry) for getting clean Fructus Arctii, is put in the heat pot, with slow fire fry to slightly heave, little when fragrance is arranged, taking-up cools, promptly.

The Cortex Eucommiae (charcoal) is for getting the clean Cortex Eucommiae, put in the heat pot, when frying with high heat to surperficial coke black, inner coke yellow, the spray clear water a little, extinguish Mars, take out, dry, promptly

Radix Polygalae (liquorice beverage system) (be extracting liquorice, add an amount of decocting soup, remove slag, add clean Radix Polygalae, simmer in water, take out to the soup exhaustion, drying, promptly

Semen Ziziphi Spinosae (stir-fry) is for getting clean Semen Ziziphi Spinosae, put in the heat pot, with slow fire fry to slightly heave, color is little when deepening, taking-up cools, promptly

Os Draconis (forging) are pounded into fritter for getting clean Os Draconis, put on the smokeless stove fire or put in the suitable container, forge when being popular in, and cool, and taking-up is pulverized

The Rhizoma Atractylodis Macrocephalae (parched with bran) is for getting bran, removes in the heat pot, is heated to when smoldering, and adds the clean Rhizoma Atractylodis Macrocephalae, stirs rapidly, fries to be yellow or complexion changed to the medical material surface when dark, takes out, and sieves and removes wheat bran, cools, promptly.

Test 1, glycyrrhizic acid content are measured

Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; Methanol-0.2mol/L Spirit of Mindererus .-glacial acetic acid (63:37:2) is a mobile phase; The detection wavelength is 250nm.Number of theoretical plate calculates by the glycyrrhizic acid peak should be not less than 1500.

The preparation precision of reference substance solution takes by weighing ammonium glycyrrhizinate reference substance an amount of (being equivalent to glycyrrhizic acid 12.5mg approximately), puts in the 25ml measuring bottle, adds the mobile phase dissolving and is diluted to scale, shake up, precision pipettes 5ml and puts in the 50ml measuring bottle, adds mobile phase and is diluted to scale, shake up, promptly.

It is an amount of that capsule 's content is got in the preparation of need testing solution, porphyrize, and precision takes by weighing about 0.5g, put in the tool plug conical flask, accurate methanol-36% acetic acid (25:5) the solution 25ml that adds weighs supersound process 40 minutes, put cold, weigh again, supply the amount of loss, shake up with methanol-36% acetic acid (25:5) solution, filter, promptly.

Respectively accurate reference substance solution and each 10ul of need testing solution of drawing of algoscopy injects high performance liquid chromatograph and measures, and calculates according to the external standard method of regulation in the Chinese Pharmacopoeia 2005 editions, and the result is 0.35mg for the content of glycyrrhizic acid in every capsules.

Claims (8)

1. capsule with replenishing QI to invigorate the spleen, tranquilizing the mind effect comprises the component of following weight proportion:

45～65 parts of Radix Ginsengs, 7～18 parts in Cornu Cervi Pantotrichum, 18～24 parts of Testis et Pentis Canis, 45～65 parts of Cortex Cinnamomis, 65～85 parts of Fructus Amomis, 15～30 parts of Herba Polygalae Telephioidis, 52～40 parts of Fructus Arctiis, 15～30 parts of Fructus Rosae Laevigatae, 55～78 parts of the Cortexs Eucommiae, 55～78 parts of Radix Cyathulaes, 40～55 parts of Flos Loniceraes, 35～53 parts of Fructus Forsythiaes, 35～53 parts of Periostracum Cicadaes, 75～100 parts of Rhizoma Dioscoreaes, 65～85 parts of Radix Polygalaes, 65～85 parts of Semen Ziziphi Spinosaes, 55～78 parts of g of Radix Angelicae Sinensis, 55～78 parts of Os Draconis, 65～85 parts of Concha Ostreaes, 120～180 parts in Poria, 65～85 parts of the Rhizoma Atractylodis Macrocephalaes, 55～78 parts of Ramulus Cinnamomi, 45～60 parts in Radix Glycyrrhizae, 55～78 parts of the Radix Paeoniae Albas, 55～78 parts in Fructus Amomi Rotundus;

Wherein, this capsule makes via following method,

Get Radix Ginseng, Cornu Cervi Pantotrichum, Testis et Pentis Canis, Cortex Cinnamomi, Fructus Amomi, the alcohol reflux with 10%～80%, extracting liquid filtering obtains ethanol extract;

Herba Polygalae Telephioidis, Fructus Arctii, Fructus Rosae Laevigatae, the Cortex Eucommiae, Radix Cyathulae, Flos Lonicerae, Fructus Forsythiae, Periostracum Cicadae, Rhizoma Dioscoreae, Radix Polygalae, Semen Ziziphi Spinosae, Radix Angelicae Sinensis, Os Draconis, Concha Ostreae, Poria, the Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Radix Glycyrrhizae, the Radix Paeoniae Alba, Fructus Amomi Rotundus decoct with water, decocting liquid filters, filtrate concentrates, merge with above-mentioned ethanol extract, obtain amalgamation liquid;

Add ethanol and make that to contain alcohol amount be 60%～80% in amalgamation liquid, get supernatant, reclaim ethanol, add water to 3500 parts, stir evenly, leave standstill, get supernatant and filter, filtrate is condensed into thick paste, and crushed after being dried adds auxiliary materials and mixing, granulates, and drying incapsulates, promptly.

2. the capsule with replenishing QI to invigorate the spleen, tranquilizing the mind effect as claimed in claim 1, wherein, this capsular each preparation unit contains glycyrrhizic acid 0.15mg～0.6mg.

3. as claimed in claim 1 have a replenishing QI to invigorate the spleen, the capsule of tranquilizing the mind effect is comprising the component of following weight proportion: 55 parts of Radix Ginsengs, 13 parts in Cornu Cervi Pantotrichum, 26 parts of Testis et Pentis Canis, 55.5 parts of Cortex Cinnamomis, 77 parts of Fructus Amomis, 22 parts of Herba Polygalae Telephioidis, 33.0 parts of Fructus Arctiis, 22.5 parts of Fructus Rosae Laevigatae, 66.5 parts of the Cortexs Eucommiae, 66.5 parts of Radix Cyathulaes, 48.0 parts of Flos Loniceraes, 44.0 parts of Fructus Forsythiaes, 44.0 parts of Periostracum Cicadaes, 88.0 parts of Rhizoma Dioscoreaes, 77.0 parts of Radix Polygalaes, 77.5 parts of Semen Ziziphi Spinosaes, 66.0 parts of g of Radix Angelicae Sinensis, 64.5 parts of Os Draconis, 77.5 parts of Concha Ostreaes, 154.5 parts in Poria, 77.5 parts of the Rhizoma Atractylodis Macrocephalaes, 64.5 parts of Ramulus Cinnamomi, 51.5 parts in Radix Glycyrrhizae, 64.5 parts of the Radix Paeoniae Albas, 64.0 parts in Fructus Amomi Rotundus.

4. the capsule with replenishing QI to invigorate the spleen, tranquilizing the mind effect as claimed in claim 1, wherein, Fructus Arctii is the Fructus Arctii of parch, the Cortex Eucommiae is the Cortex Eucommiae of charcoal system, and Radix Polygalae is the Radix Polygalae with liquorice beverage system, and Semen Ziziphi Spinosae is the Semen Ziziphi Spinosae of parch, Os Draconis are the Os Draconis of calcine, and the Rhizoma Atractylodis Macrocephalae is the Rhizoma Atractylodis Macrocephalae of wheat bran parch.

5. as claimed in claim 4 have a replenishing QI to invigorate the spleen, the capsule of tranquilizing the mind effect is comprising the component of following weight proportion: 55 parts of Radix Ginsengs, 13 parts in Cornu Cervi Pantotrichum, 26 parts of Testis et Pentis Canis, 55.5 parts of Cortex Cinnamomis, 77 parts of Fructus Amomis, 22 parts of Herba Polygalae Telephioidis, 33.0 parts of Fructus Arctiis (stir-fry), 22.5 parts of Fructus Rosae Laevigatae, 66.5 parts of the Cortexs Eucommiae (charcoal), 66.5 parts of Radix Cyathulaes, 48.0 parts of Flos Loniceraes, 44.0 parts of Fructus Forsythiaes, 44.0 parts of Periostracum Cicadaes, 88.0 parts of Rhizoma Dioscoreaes, 77.0 parts of Radix Polygalaes (liquorice beverage system), 77.5 parts of Semen Ziziphi Spinosaes (stir-fry), 66.0 parts of g of Radix Angelicae Sinensis, 64.5 parts of Os Draconis (forging), 77.5 parts of Concha Ostreaes, 154.5 parts in Poria, 77.5 parts of the Rhizoma Atractylodis Macrocephalaes (parched with bran), 64.5 parts of Ramulus Cinnamomi, 51.5 parts in Radix Glycyrrhizae, 64.5 parts of the Radix Paeoniae Albas, 64.0 parts in Fructus Amomi Rotundus.

6. the described capsular preparation method of claim 1 with replenishing QI to invigorate the spleen, tranquilizing the mind effect, wherein, this method comprises:

Get Radix Ginseng, Cornu Cervi Pantotrichum, Testis et Pentis Canis, Cortex Cinnamomi, Fructus Amomi, the alcohol reflux with 10%～80%, extracting liquid filtering obtains ethanol extract;

Herba Polygalae Telephioidis, Fructus Arctii, Fructus Rosae Laevigatae, the Cortex Eucommiae, Radix Cyathulae, Flos Lonicerae, Fructus Forsythiae, Periostracum Cicadae, Rhizoma Dioscoreae, Radix Polygalae, Semen Ziziphi Spinosae, Radix Angelicae Sinensis, Os Draconis, Concha Ostreae, Poria, the Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Radix Glycyrrhizae, the Radix Paeoniae Alba, Fructus Amomi Rotundus decoct with water, decocting liquid filters, filtrate concentrates, merge with above-mentioned ethanol extract, obtain amalgamation liquid;

Add ethanol and make that to contain alcohol amount be 60%～80% in amalgamation liquid, get supernatant, reclaim ethanol, add water to 3500 parts, stir evenly, leave standstill, get supernatant and filter, filtrate is condensed into thick paste, and crushed after being dried adds auxiliary materials and mixing, granulates, and drying incapsulates.

7. preparation method as claimed in claim 6, wherein, this method comprises:

Get Radix Ginseng, Cornu Cervi Pantotrichum, Testis et Pentis Canis, Cortex Cinnamomi, Fructus Amomi, with 40% alcohol reflux at least 2 times, add 6 times of amounts at every turn, each 2～3 hours, merge extractive liquid, filtered, and obtains ethanol extract; Herba Polygalae Telephioidis, Fructus Arctii, Fructus Rosae Laevigatae, the Cortex Eucommiae, Radix Cyathulae, Flos Lonicerae, Fructus Forsythiae, Periostracum Cicadae, Rhizoma Dioscoreae, Radix Polygalae, Semen Ziziphi Spinosae, Radix Angelicae Sinensis, Os Draconis, Concha Ostreae, Poria, the Rhizoma Atractylodis Macrocephalae, Ramulus Cinnamomi, Radix Glycyrrhizae, the Radix Paeoniae Alba, Fructus Amomi Rotundus decoct with water 2 times at least, adding 10 times of water gagings for the 1st time soaked 1 hour, decocted 1～3 hour, the 2nd time and add 8 times of water gagings later at every turn, decocted 1～2 hour, collecting decoction filters, filtrate concentrates, and merges with above-mentioned ethanol extract, adds ethanol and makes that to contain the alcohol amount be 70%, leave standstill, get supernatant, reclaim ethanol, add water to 3500 parts, stir evenly, leave standstill; Get supernatant and filter, filtrate is condensed into thick paste, and crushed after being dried adds auxiliary materials and mixing, granulates, and drying incapsulates, promptly.

8. as claim 6 or 7 described preparation methoies, wherein, Fructus Arctii is the Fructus Arctii of parch, and the Cortex Eucommiae is the Cortex Eucommiae of charcoal system, and Radix Polygalae is the Radix Polygalae with liquorice beverage system, and Semen Ziziphi Spinosae is the Semen Ziziphi Spinosae of parch, and Os Draconis are the Os Draconis of calcine, and the Rhizoma Atractylodis Macrocephalae is the Rhizoma Atractylodis Macrocephalae of wheat bran parch.