CN101461903A - Chinese medicinal composition for treating painful swelling of throat and constipation, and preparation method thereof - Google Patents

Abstract

The invention belongs to the technical field of traditional Chinese medicine preparation, and relates to a traditional Chinese medicine composition for treating sore throat and constipation and a preparation method thereof, in particular to a medicament prepared from the raw material medicine with effective components such as silkworm excrement, rhubarb, figwort, Chinese honeylocust fruit, red paeony root, dwarf lilyturf turber, forsythia, radix isatidis, rehmannia, honeysuckle, rhizome imperatae, tree peony bark, natural indigo, fritillaria cirrhosa, mint, and licorice and used for clearing away heat and toxic materials, relieving sore throat and pain, and treating diseases such as sore throat caused by pneumogastric intrinsic heat, fever and fidget, constipation, children acute pharyngitis, acute tonsillitis, and the like and a preparation method thereof. The invention also discloses a recipe for gelata prepared by extracting and mixing sixteen medicinal materials such as silkworm excrement, rhubarb and the like, quality standard, and a quality inspection method. The dosage form has the advantages of convenience for taking and carrying, good mouth feel, and easy acceptance by children, overcomes the defect that pills and tablets are difficult for the children to take, and is remarkably superior to cleaning pills.

Description

A kind of Chinese medicine composition for the treatment of painful swelling of throat and constipation and preparation method thereof

Technical field

The invention belongs to the Chinese medicine preparation technical field, particularly relate to and the present invention relates to a kind of heat-clearing and toxic substances removing, relieving sore throat and pain, be used for laryngopharynx swelling and pain due to the accumulated heat in the lung and stomach, fever and irritability, constipation, infantile acute pharyngitis, medicine of illness such as acute tonsillitis and preparation method thereof the invention still further relates to prescription, quality standard and the quality inspection method of this clear pour point depression glue.

Background technology

Acute pharyngitis (acute pharyngitis) is a pharyngeal mucous membrane, and involves under the mucosa and adenoid acute inflammation, often is secondary to after acute rhinitis or the acute tonsil or is the part of upper respiratory tract infection.Also often be the topical manifestations of general disease or be the prodrome of acute infectious disease.Chang Yin suffers from cold, and is overtired, and tobacco and wine excessively wait and cause whole body and the decline of local resistance, and pathogenic microorganism is taken advantage of a weak point and caused primary disease.Malnutrition is suffered from the chronic heart, kidney, joint disease, and life and working environment are not good, often contact high temperature, dust, destructive stimulus gas etc. and all easily suffer from primary disease, and be the inducement of numerous disease.The patient is of all ages, sex, occupation and regional, and all can fall ill the whole year, the winter-spring season pilosity, and people can have morbidity for several times in 1 year, and can cause severe complication.

China's infantile acute pharyngitis prevalence is 0.5-2.0%, report is arranged up to 5.2%, and because of the air pollution reason, the trend of increase is arranged in recent years.Serious harm human physical and mental health, so patient's wide material sources.Pathogenic microorganism is mainly Hemolytic streptococcus, Diplococcus pneumoniae, hemophilus influenzae and virus.Clinical manifestation onset urgency, the pharyngeal drying of first time-out, scorching hot, the pain that continues increase the weight of when swallowing, and can be radiated to ear.Sometimes general malaise, joint aches, headache, inappetence, and in various degree heating is arranged.Body temperature can be increased to 38 ℃, modern medicine is mainly with antibiotics etc., to throat do, itch, symptom such as pain is rapid-action, change the pharyngeal mucosa tissue but can not repair, just normal " curing the symptoms, not the disease " of saying, after being subjected to extraneous virus, antibacterial or chemical stimulation once more, subinfection very easily again.And antibiotic is destructive strong to human tissue cell, and antibiotic also has very strong Drug resistance simultaneously, uses for a long time, repeatedly to produce abortive response.Though antibiotic is obtained certain curative effect, toxicity, side effect is big.As use collutory, and buccal cydiodine, Anji buccal tablet etc., these medicine life-time service can cause the internal environment of oral cavity disorder.

Falling ball clearly is a kind of classical Chinese patent medicine, Ministry of Public Health standard WS ₃-B-3679-98 puts down in writing prescription: silkworm excrement, Radix Et Rhizoma Rhei, Indigo Naturalis, Radix Scrophulariae, Semen Gleditsiae, Radix Paeoniae Rubra, Radix Isatidis, Radix Ophiopogonis, Fructus Forsythiae, Cortex Moutan, Radix Rehmanniae, Radix Glycyrrhizae, Rhizoma Imperatae, Flos Lonicerae, Herba Menthae, Bulbus Fritillariae Cirrhosae

Method for making: above ten Six-elements, be ground into fine powder, mixing sieves.Every 100g powder adds to practice sweet 50g～60g and add an amount of water makes small honey pill or big honeyed pills promptly.

Function with cure mainly: heat-clearing and toxic substances removing, relieving sore throat and pain is used for laryngopharynx swelling and pain due to the accumulated heat in the lung and stomach, fever and irritability, constipation, infantile acute pharyngitis, illness such as acute tonsillitis.

Other has applying date 2003.6.4, the patent record prescription of patent No. ZL03129980.6 " heat-clearing and detoxic medicine and preparation method thereof ": silkworm excrement 20.84g Radix Et Rhizoma Rhei 20.84g Indigo Naturalis 10.42g Radix Scrophulariae 20.84g Semen Gleditsiae 20.84g Radix Paeoniae Rubra 20.84g Radix Isatidis 20.84g 20.84g Radix Ophiopogonis Fructus Forsythiae 20.84g Cortex Moutan 13.54g Radix Rehmanniae 20.84g Radix Glycyrrhizae 6.88g goldenseal 20.84g Flos Lonicerae 20.84g Mentholum 0.052g Bulbus Fritillariae Cirrhosae 2.60g

Function with cure mainly: heat-clearing and toxic substances removing, relieving sore throat and pain is used for laryngopharynx swelling and pain due to the accumulated heat in the lung and stomach, fever and irritability, constipation, infantile acute pharyngitis, Qingjiangpian tablets agent medicine of illness such as acute tonsillitis and preparation method thereof.

Ball falls clearly, Qingjiangpian tablets is a kind of pure Chinese medicinal preparation, evident in efficacy, major function is a heat-clearing and toxic substances removing, relieving sore throat and pain, but traditional ball, Qingjiangpian tablets volume of swallowing that falls clearly is big, mouthfeel is poor, absorb not exclusively, bioavailability is not high, particularly is not suitable for the child and swallows, so developing efficient, low toxicity, heat-clearing and toxic substances removing, relieving sore throat and pain is that one is suitable for the preparation that the child swallows, significant.

Summary of the invention

The object of the present invention is to provide a kind of reasonable recipe, select YAOJING good, the bioavailability height, disintegrate is fast, scattered, mouthfeel is suitable, absorbs fully, a kind of heat-clearing and toxic substances removing that is used for of increase evident in efficacy, the quality standard and the quality inspection method of clear pour point depression glue of relieving sore throat and pain and preparation method thereof and this clear pour point depression glue.

To achieve these goals, carried out etiology and pathogenesis method of treatment and compatibility analysis: acute pharyngitis is because exopathogen invasion and attack, injure pharyngeal so that qi depression to blood stasis, institute causes red swelling of the pharynx pain illness through the BI-syndrome involved the blood vessels resistance.With pharyngalgia or odynophagia, pharyngeal red slightly or scarlet, edema, heating, dry pharynx are scorching hot, aversion to cold is main performance.Chang Yin suffers from cold, overtired, tobacco and wine excessively wait and cause whole body and the decline of local resistance, pathogenic microorganism is taken advantage of a weak point and is caused primary disease, malnutrition is suffered from the chronic heart, kidney, joint disease, and life and working environment are not good, often contact high temperature, dust, destructive stimulus gas etc. are all easily suffered from primary disease, and are the inducements of numerous disease.Because pathogenic heat stop up to be contained, steam the throat that burns, so it is acute to have sore throat, the intenseness of heat impairment of body fluid, so thirsty polydipsia, the evil lung gold of violating, lung qi a surname falls not normal, and body fluid fried in shallow oil and be smelt expectorant, stores in the lung key, then cough, the sticking difficulty of expectorant goes out, interior-heat is contained in interior, and be full of in outside, so generate heat.Stomach internal organs intenseness of heat, FU QI being obstructed, thus big dry stool, red tongue, tongue fur BOHUANG, rapid pulse are strong, are all resembling of excess-heat, thus the legislation heat-clearing and toxic substances removing, relieving sore throat and pain.Be intended to drive straight on to latibulum, just middle pathogenesis, pyretic toxicity is clear, the throat profit, pain is ended and is recovered.

Acute pharyngitis traditional Chinese medical science basic pathology is because exopathogen invasion and attack, injure pharyngeal so that qi depression to blood stasis, institute causes red swelling of the pharynx pain through the BI-syndrome involved the blood vessels resistance.We are with silkworm excrement, Radix Et Rhizoma Rhei, Semen Gleditsiae, the fire of the clear eliminating the pathogens from the lung stomach of Rhizoma Imperatae, removing heat by catharsis expells the pathogenic heat.The silkworm excrement expelling wind and removing dampness, regulating the function of the stomach to resolve the turbidity; The Radix Et Rhizoma Rhei poison that purges heat, removing mass stagnates; The Semen Gleditsiae moistening dryness for relaxing bowels, the detumescence of dispeling the wind; The clear eliminating the pathogens from the lung stomach of Rhizoma Imperatae is treated the rotten all cards of the strongly fragrant pharyngalgia of stopping up of lung-heat.Fructus Forsythiae, Radix Isatidis, Indigo Naturalis, Flos Lonicerae heat-clearing and toxic substances removing, saturating flesh induces sweat, and heat clearing away is by wind.Radix Ophiopogonis, Radix Rehmanniae, Radix Paeoniae Rubra, Radix Scrophulariae removing pathogenic heat from blood and toxic substance from the body, nourishing YIN and moistening the lung, reinforcing stomach reg fluid.The Herba Menthae wind-dispelling heat-dissipating is evacuated pathogenic factor in the exterior, Cortex Moutan heat clearing away, removing heat from blood, and promoting the circulation of blood stagnates, and stagnates to go and hot and suffocating explaining by oneself, so also bring down a fever.Bulbus Fritillariae Cirrhosae lung moistening eliminating stagnation, antitussive reduces phlegm.Radix Glycyrrhizae and middle emergency, the pathogenic factor in the exterior that looses, throat, detoxifcation, lung moistening removes the long-pending heat of stomach, coordinating the actions of various ingredients in a prescription.This Fang Qing goes up diarrhea, induce sweat dredge in and based on removing heat by catharsis expells the pathogenic heat, make pyretic toxicity be able to removing summer-heat, heresy has outlet, thereby the throat tonneau.All medicines share, and play heat-clearing and toxic substances removing altogether, and the effect of relieving sore throat and pain is applicable to the caused infantile acute pharyngitis of lung sthenia gastropyrexia.So at the former ball that falls clearly, the medicine that the national drug standards are recorded, the number of recording is: WS ₃The suitable consumption proportion of screening changes dosage form on the basis of-B-3680-98, change technology, the formulation standard, studies on acute toxicity, long term toxicity test, Pharmacodynamic test of active extract have been carried out, finally the invention provides a kind of Chinese medicine composition for the treatment of painful swelling of throat and constipation of following technical scheme, it is characterized in that making the raw materials of effective components medicine and consist of:

400 Radix Ophiopogonis 400 of silkworm excrement 400 Radix Et Rhizoma Rhei 400 Radix Scrophulariaes 400 Semen Gleditsiae 400 Radix Paeoniae Rubra

Fructus Forsythiae 400 Radix Isatidis 400 Radix Rehmanniae 400 Flos Loniceraes 400 Rhizoma Imperataes 400

Cortex Moutan 260 Indigo Naturaliss 200 Bulbus Fritillariae Cirrhosaes 200 Herba Menthaes 200 Radix Glycyrrhizaes 132;

Its preparation method is:

More than ten Six-elements, Radix Et Rhizoma Rhei powder is made coarse powder and is mixed with Indigo Naturalis, Radix Scrophulariae, Bulbus Fritillariae Cirrhosae, adds 8 times of amount 80% ethanol extractions twice, each 1.5 hours, merge alcohol extract, reclaim ethanol and be condensed into cream, relative density 1.30～11.35,60 ℃;

Cortex Moutan is made coarse powder, mix with silkworm excrement, Semen Gleditsiae, Radix Paeoniae Rubra, Radix Ophiopogonis, Fructus Forsythiae, Flos Lonicerae, Radix Isatidis, Radix Rehmanniae, Rhizoma Imperatae, Herba Menthae, Radix Glycyrrhizae, adding 10 times of water gagings decocts twice, each 1.5 hours, collect volatile oil, the gradation of water extract filters, merging filtrate, be concentrated into relative density 1.05～11.08,60 ℃; , put to room temperature, add ethanol and make that to contain alcohol amount be 70%, standing over night, filter, filtrate recycling ethanol is concentrated into relative density 1.25～11.35,60 ℃, thick paste, make plain sheet or coated tablet or thin membrane coated tablet according to appendix rules of preparations of Chinese Pharmacopoeia version in 2000.

The Chinese medicine composition of described treatment painful swelling of throat and constipation is characterized in that described Chinese medicine composition is a pour point depression glue clearly, and it is prepared from by following processing step:

1) prescription: the water extract 0.703kg of Cortex Moutan, silkworm excrement, Semen Gleditsiae, Radix Paeoniae Rubra, Radix Ophiopogonis, Fructus Forsythiae, Flos Lonicerae, Radix Isatidis, Radix Rehmanniae, Rhizoma Imperatae, Herba Menthae, Radix Glycyrrhizae

The ethanol extract 0.37kg of Radix Et Rhizoma Rhei, Indigo Naturalis, Radix Scrophulariae, Bulbus Fritillariae Cirrhosae

The extraction volatile oil 5.5ml of Fructus Forsythiae, Cortex Moutan, Herba Menthae, Flos Lonicerae

Carrageenan 0.3774kg

Rhizoma amorphophalli powder 0.3774kg

Potassium chloride 0.0943kg

Sucrose 3.774kg

Citric acid 0.0566kg

Cyclamate 0.1132kg

Antiseptic 0.0321kg

Water 58.3kg

2) preparation method: feed intake according to the described raw materials of effective components medicine composition that makes of claim 1:

Radix Et Rhizoma Rhei powder is made coarse powder and is mixed with Indigo Naturalis, Radix Scrophulariae, Bulbus Fritillariae Cirrhosae, adds 8 times of amount 80% ethanol extractions twice, and each 1.5 hours, merge alcohol extract, reclaim ethanol and be condensed into cream, relative density 1.30～11.35,60 ℃;

Cortex Moutan is made coarse powder, mix with silkworm excrement, Semen Gleditsiae, Radix Paeoniae Rubra, Radix Ophiopogonis, Fructus Forsythiae, Flos Lonicerae, Radix Isatidis, Radix Rehmanniae, Rhizoma Imperatae, Herba Menthae, Radix Glycyrrhizae, adding 10 times of water gagings decocts twice, each 1.5 hours, collect volatile oil, the gradation of water extract filters, merging filtrate, be concentrated into relative density 1.05～11.08,60 ℃; Put to room temperature, add ethanol and make that to contain alcohol amount be 70%, standing over night filters, and filtrate recycling ethanol is concentrated into relative density 1.25～11.35,, 60 ℃ thick paste,

Water is proposed thick paste, alcohol extraction thick paste, citric acid, potassium chloride, white sugar, cyclamate, antiseptic mixing, add the water stirring and dissolving; With carrageenan, Rhizoma amorphophalli powder aqueous solution mixing, heating for dissolving in 70 ℃ of water-baths, add volatile oil, essence, add water to 64.2Kg, mixing, packing, sealing is behind the pasteurization, promptly.

The clear pour point depression glue that the preparation method of the Chinese medicine composition of described treatment painful swelling of throat and constipation makes is characterized in that every glass contains emodin (C ₁₅H ₁₀O ₅), chrysophanol (C ₁₅H ₁₀O ₄) total amount must not be less than the quantitative target of 0.50mg.

The clear pour point depression glue that the preparation method of the Chinese medicine composition of described treatment painful swelling of throat and constipation makes is characterized in that being provided with in the quality standard diagnostic test project of emodin in Radix Paeoniae, Radix Scrophulariae, Flos Lonicerae, Indigo Naturalis and the Radix Et Rhizoma Rhei, chrysophanol assay:

(1) identification of test method of wherein set Radix Paeoniae is: get 1 glass of this product, be cut into small pieces, put in the round-bottomed flask, add 100ml methanol, water-bath backflow 30min filters, water bath method, residue add water 40ml makes dissolving, filters, by the AB-8 macroporous resin column, internal diameter 10～112mm, long 100mm, earlier with water 100ml eluting, discard water lotion, reuse 30% alcoholic solution 100ml eluting continues with 70% alcoholic solution 80ml eluting; 30% ethanol elution evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution; Other gets the peoniflorin reference substance, adds methanol and makes dissolving, makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin layer chromatography, draw above-mentioned two kinds of solution, 5 μ l respectively, put respectively on same silica gel g thin-layer plate, with chloroform: ethyl acetate: methanol: formic acid=45:5:10:0.2 is developing solvent, launch, take out, dry, spray is with 10 ℅ ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing at 105 ℃; In the test sample chromatograph, with the corresponding position of peoniflorin reference substance chromatograph on, show the speckle of same color;

(2) identification of test method of wherein set Radix Scrophulariae is: get 70% ethanol elution of using of discriminating (1), water bath method, residue add methanol 2ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material powder 2g, adds methanol 10ml, soaks 1 hour, and supersound process 15 minutes filters, and filtrate is product solution in contrast; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned two kinds of solution, 3 μ l respectively, put respectively on same silica gel g thin-layer plate, with n-butyl alcohol: glacial acetic acid: water=7:1:2 is developing solvent, and lamellae launches with developing solvent presaturation 15 minutes, take out, dry, spray is with vanillin sulphuric acid test solution, and hot blast blows to clear spot; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

(3) identification of test method of wherein set Flos Lonicerae is: get the need testing solution of discriminating (1), be need testing solution; Other gets the chlorogenic acid reference substance, adds dissolve with methanol, makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin layer chromatography, draw above-mentioned two kinds of solution, 5 μ l respectively, put respectively on same silica gel g thin-layer plate, with butyl acetate: formic acid: water=7:2.5:2.5 is developing solvent, launches, take out, dry, put under the uviol lamp 365nm and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;

(4) identification of test method of wherein set Indigo Naturalis is: get one glass of this product, shred, put in the round-bottomed flask, add chloroform 20ml, water-bath refluxed 10 minutes, filtered, and filtrate is as need testing solution; Other gets the indirubin reference substance, adds chloroform, makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 5 ~ 10ul of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: chloroform: acetone=5:4:1 is developing solvent, launches, and takes out, and dries; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of identical redness;

(5) emodin in the wherein set Radix Et Rhizoma Rhei, the method for chrysophanol assay are: according to one one of Chinese Pharmacopoeia version in 2005, and appendix VI D high effective liquid chromatography for measuring,

Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; Methanol: 0.1% phosphoric acid solution=85:15 is a mobile phase; Flow velocity 1.0ml/min; Detect wavelength 254nm; Column temperature is a room temperature; Number of theoretical plate calculates by the emodin peak should be not less than 2000;

Precision takes by weighing emodin respectively, the chrysophanol reference substance is an amount of in the preparation of reference substance solution, makes the solution that every 1ml contains 6 μ g, 10 μ g, promptly;

One glass of this product is got in the preparation of need testing solution, and accurate the title decides, chopping, put in the apparatus,Soxhlet's, added the methanol reflux 3 hours, put cold, be transferred in the 100ml measuring bottle, add methanol and be diluted to scale, shake up, precision is measured 25ml, puts in the flask, flings to solvent and adds 8% hydrochloric acid solution 10ml, supersound process 2 minutes adds chloroform 10ml again, reflux 1 hour, put coldly, put in the separatory funnel, with a small amount of chloroform washing container, incorporate in the separatory funnel, divide and get chloroform layer, acid solution reuse chloroform extraction 3 times, each 10ml, merge chloroform liquid, decompression and solvent recovery is to doing, and residue adds methanol makes dissolving, be transferred in the 10ml measuring bottle, add methanol to scale, shake up, filter, get subsequent filtrate, promptly;

Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

Carried out the pharmacodynamics test of clear pour point depression glue: the function according to clear pour point depression glue cures mainly, and main pharmacodynamics is studied from the detoxifcation of dispeling the wind, antiinflammatory, analgesic, analgesic activity four aspects.

1. the Detoxication of dispeling the wind

1.1. the extracorporeal antivirus effect test shows that clear pour point depression glue is 46.8TCID in external virus attack amount ₅₀(promptly 10 ^-3.6In the time of doubly), clear pour point depression glue has the obvious suppression effect to influenza virus FM1.

1.2. bacteriostatic test shows that clear pour point depression glue can obviously reduce the mortality rate of mice lethal dose infection of staphylococcus aureus.It is 15 * 10 through lumbar injection concentration that matched group is tried mice ⁸Staphylococcus aureus solution 0.5ml/ only, animal is all dead in 48 hours.Clear pour point depression glue is subjected to the injection of examination group mouse peritoneal to be starkly lower than matched group with animal dead number in the dosage staphylococcus aureus solution 48 hours.

2. antiinflammatory action

2.1. 3.2, the clear pour point depression glue of 1.6g/kg xylol induced mice ear swelling has the obvious suppression effect.

2.2. the clear pour point depression glue of 2.2g/kg can suppress the rat carrageenan foot swelling effectively, sustainable 4 hours of action time; 1.1g/kg rat paw edema also has the obvious suppression effect, sustainable 3 hours of action time due to the clear pour point depression glue on Carrageenan; 0.55g/kg rat paw edema also has certain inhibitory action due to the clear pour point depression glue on Carrageenan, but only 1 hour effectively.

2.3. the clear pour point depression glue of 2.2g/kg not only can reduce the volume of inflammatory exudate but also can reduce leukocyte count; 1.1g/kg clear pour point depression glue can reduce the volume of inflammatory exudate, but statistical significance is not obvious, but can obviously reduce leukocyte count.

3. rat fever all has tangible refrigeration function due to the clear pour point depression rubber powder of refrigeration function: the 2.2.1.1g/kg foot couple dry yeast.

4. analgesic activity

But 4.1. 3.2, time of licking metapedes first in the clear pour point depression glue of the 1.6g/kg significant prolongation mice 1min, promptly hot plate induced mice pain there is the obvious suppression effect.

4.2. what 3.2, the clear pour point depression glue of 1.6g/kg can reduce acetic acid induced mice writhing response turns round the body number of times.

Experimental result shows: adopting the test effective dose of mice is 1.6g/kg, is equivalent to 12.5 times of clinical consumption, (child body weight 25kg per capita calculates the dried cream of 1.5993g and adjuvant/cup, 2 times/day, 1 glass/time); Adopting the test effective dose of rat is 1.1g/kg, is equivalent to 8.6 times of clinical consumption, (child body weight 25kg per capita calculates the dried cream of 1.5993g and adjuvant/cup, 2 times/day, 1 glass/time).

Clear pour point depression glue has certain antiviral, antibacterial action; Clear pour point depression glue can effectively suppress leukoplania and swelling, and has the exudation effect, shows that it has significant inhibitory effect to acute inflammation; Clear pour point depression glue has tangible refrigeration function to rat fever due to the dry yeast, and its analgesic activity is also more obvious.This results of pharmacodynamic test has shown that this product has heat-clearing and toxic substances removing, relieving sore throat and pain effect, has certain curative effect to infantile acute pharyngitis, acute tonsillitis.

The acute toxicity test of clear pour point depression glue: test objective: observe in one day at interval that certain hour repeatedly gives the empty stomach mice acute toxic reaction that this product is produced, and record its maximum dosage-feeding.

With maximum administration concentration (0.45g/ml, 45%), maximum dosage 40ml/kg, irritate stomach with 18.18g/kg interval 5h in one day and give the clear pour point depression rubber powder of empty stomach mice end 3 times, observed record dead mouse and body surface situation 14 days, mice shows that all are normal after the administration, none death.The maximum dosage of clear pour point depression glue is about 54.54g/kg, and 426 times (the equal body weight of child is calculated by 25kg) being equivalent to clinical child's consumption every day show that this product toxicity is low, clinical drug safety.

The long term toxicity test of clear pour point depression glue: test objective is observed continuous repeated multiple times and is irritated stomach and give issuable toxic reaction and recovery and development behind the clear pour point depression glue of rat, for human safe dose clinically provides with reference to evidence.

Give the clear pour point depression glue of rat 5,3,1.5g/kg. time (10,6,3g/kg. day) 1 month by irritating 20ml/kg every day stomach for 2 times, the behavior of observation rat outward appearance, ingest, drinking-water situation, body weight gain, blood, liver, kidney, coagulation function and multiple organs and tissues pathology.Through comparing its general performance as a result, blood, liver, kidney, the equal zero difference of coagulation function with matched group.Main organs naked eyes no abnormality seen, pathomorphology inspection do not see obviously, clocklike with the medicine relevant diseases.Convalescent period is observed identical with it every index, with the more equal zero difference of matched group.Conclusion: rat 10g/kg/ day, clear pour point depression glue was equivalent to about 78.16 times of child's consumption every day (by 25 kilograms of calculating of child's body weight per capita).Rat gives clearly for a long time, and pour point depression glue does not have overt toxicity and toxic and side effects generation.

We develop, and the pour point depression colloid is through pharmacodynamics test, acute toxicity test, long term toxicity test clearly, and the result has shown that this product has heat-clearing and toxic substances removing, relieving sore throat and pain effect, has certain curative effect to infantile acute pharyngitis, acute tonsillitis.This dosage form has taking convenience simultaneously, carrying convenience, and mouthfeel is good, and the acceptable advantage of child has overcome the problem of children taking difficulties such as pill and tablet, and this side significantly is better than falling clearly ball.

Key problem in technology of the present invention is the rational proportion of above-mentioned 16 flavor Chinese medicines, and combination traditional and high-new preparation method, the extraction means that in preparation process, adopted, make extremely refinement of drug particles, form particle volume and dwindle several times than pill, be convenient to swallow, compliance is good, help the absorption of human body, and then improve bioavailability medicine.

The specific embodiment

Embodiment 1: the Chinese medicine composition of treatment painful swelling of throat and constipation prepares clear pour point depression glue:

1) preparation prescription:

2) preparation method: feed intake according to the described raw materials of effective components medicine composition that makes of claim 1:

Radix Et Rhizoma Rhei powder is made coarse powder and is mixed with Indigo Naturalis, Radix Scrophulariae, Bulbus Fritillariae Cirrhosae, adds 8 times of amount 80% ethanol extractions twice, and each 1.5 hours, merge alcohol extract, reclaim ethanol and be condensed into cream, relative density 1.30～1.35,60 ℃;

Cortex Moutan is made coarse powder, mix with silkworm excrement, Semen Gleditsiae, Radix Paeoniae Rubra, Radix Ophiopogonis, Fructus Forsythiae, Flos Lonicerae, Radix Isatidis, Radix Rehmanniae, Rhizoma Imperatae, Herba Menthae, Radix Glycyrrhizae, adding 10 times of water gagings decocts twice, each 1.5 hours, collect volatile oil, the gradation of water extract filters, merging filtrate, be concentrated into relative density 1.05～1.08,60 ℃; Put to room temperature, add ethanol and make that to contain alcohol amount be 70%, standing over night filters, and filtrate recycling ethanol is concentrated into relative density 1.25～1.35,60 ℃, thick paste,

Water is proposed thick paste, alcohol extraction thick paste, citric acid, potassium chloride, white sugar, cyclamate, antiseptic mixing, add the water stirring and dissolving; With carrageenan, Rhizoma amorphophalli powder aqueous solution mixing, heating for dissolving in 70 ℃ of water-baths, add volatile oil, essence, add water to 64.2Kg, mixing, packing, sealing behind the pasteurization, promptly gets clear pour point depression glue, clear pour point depression glue 17g/ cup, 1.4287g crude drug/cup, clinical each half cup below 3 years old, 3～7 years old each 1 glass, 7～12 years old each 1.5 glasss, be one day twice, be two weeks the course of treatment.

Embodiment 2: clear pour point depression colloid amount standard

[prescription] silkworm excrement 400 Radix Et Rhizoma Rhei 400 Radix Scrophulariaes 400 Semen Gleditsiae 400 Radix Paeoniae Rubra 400 Fructus Forsythiaes, 400 Radix Isatidiss, 400 Radix Ophiopogonis 400 Radix Rehmanniae 400 Flos Loniceraes 400 Rhizoma Imperataes 400 Cortex Moutans 260 Indigo Naturaliss 200 Bulbus Fritillariae Cirrhosaes 200 Herba Menthaes 200 Radix Glycyrrhizaes 132

[method for making] above ten Six-elements, Radix Et Rhizoma Rhei powder become coarse powder to mix with Indigo Naturalis, Radix Scrophulariae, Bulbus Fritillariae Cirrhosae, add 8 times of amount 80% ethanol extractions twice, and each 1.5 hours, the merging alcohol extract, recovery ethanol is condensed into cream (relative density 1.30～1.35,60 ℃).The Paeonia suffruticosa corium farinosum becomes coarse powder, with silkworm excrement, Semen Gleditsiae, Radix Paeoniae Rubra, Radix Ophiopogonis, Fructus Forsythiae, Flos Lonicerae, Radix Isatidis, Radix Rehmanniae, Rhizoma Imperatae, Herba Menthae, Radix Glycyrrhizae mixes, adding 10 times of water gagings decocts twice, each 1.5 hours, collect volatile oil, the gradation of water extract filters, and merging filtrate is concentrated into relative density 1.05～11.08 (60 ℃), put to room temperature, add ethanol and make that to contain alcohol amount be 70%, standing over night filters, filtrate recycling ethanol, be concentrated into the thick paste of relative density 1.25～11.35 (60 ℃), with the alcohol extraction thick paste, citric acid, potassium chloride, white sugar, cyclamate mixes, and adds the water stirring and dissolving; With carrageenan, Rhizoma amorphophalli powder aqueous solution mixing, heating for dissolving in 70 ℃ of water-baths, add volatile oil, essence, add water to 64.2Kg, mixing, packing, sealing, promptly.

[character] this product is brown to tan translucent soft solid shape gel, feeble QI perfume (or spice), and it is sweet to distinguish the flavor of.

1 glass of this product is got in [discriminating] (1), is cut into small pieces, and puts in the round-bottomed flask, add 100ml methanol, water-bath backflow 30min filters, water bath method, residue add water 40ml makes dissolving, filters, by AB-8 macroporous resin column (internal diameter 10～112mm, long 100mm), earlier with water 100ml eluting, discard water lotion, reuse 30% alcoholic solution 100ml eluting continues with 70% alcoholic solution 80ml eluting.30% ethanol elution evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution.Other gets the peoniflorin reference substance, adds methanol and makes dissolving, makes the solution that every 1ml contains 1mg, in contrast product solution.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned two kinds of solution, 5 μ l respectively, put respectively on same silica gel g thin-layer plate, with chloroform: ethyl acetate: methanol: formic acid (45:5:10:0.2) is developing solvent, launch, take out, dry, spray is with 10 ℅ ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing at 105 ℃.In the test sample chromatograph, with the corresponding position of peoniflorin reference substance chromatograph on, show the speckle of same color.

(2) get 70% ethanol elution of using of discriminating (1), water bath method, residue add methanol 2ml makes dissolving, as need testing solution.Other gets Radix Scrophulariae control medicinal material powder 2g, adds methanol 10ml, soaks 1 hour, and supersound process 15 minutes filters, and filtrate is product solution in contrast.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned two kinds of solution, 3 μ l respectively, put respectively on same silica gel g thin-layer plate, with n-butyl alcohol-glacial acetic acid-water (7:1:2) is developing solvent, and lamellae launches with developing solvent presaturation 15 minutes, take out, dry, spray is with vanillin sulphuric acid test solution, and hot blast blows to clear spot.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color.

(3) get the need testing solution of discriminating (1), be need testing solution.Other gets the chlorogenic acid reference substance, adds dissolve with methanol, makes the solution that every 1ml contains 1mg, in contrast product solution.According to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005) test, draw above-mentioned two kinds of solution, 5 μ l respectively, put respectively on same silica gel g thin-layer plate, with butyl acetate-formic acid-water (7:2.5:2.5) is developing solvent, launches, and takes out, dry, put under the uviol lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color.

(4) get one glass of this product, shred, put in the round-bottomed flask, add chloroform 20ml, water-bath refluxed 10 minutes, filtered, and filtrate is as need testing solution.Other gets the indirubin reference substance, adds chloroform, makes the solution that every 1ml contains 1mg, in contrast product solution.According to the thin layer chromatography test, draw each 5～10ul of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with toluene-chloroform-acetone (5:4:1), launch, take out, dry.In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of identical redness.

[inspection] pH value is got two glasss of this product, puts in the band plug conical flask, and heating in water bath makes dissolving, under 70 ℃ of water bath heat preservations, measures according to pH value algoscopy (appendix VIIG of Chinese Pharmacopoeia version in 2005), and this product pH should be 5～7.

The limit test of microbe of this product should be up to specification according to microbial limit test (an appendix XIII of Chinese Pharmacopoeia version in 2005 C) inspection.Conventional method is adopted in count of bacteria; Mycete and yeast counting adopt conventional method; The control bacterium is checked and adopts conventional method.

The need testing solution preparation: get this product 10g, put in the conical flask, add the 45 ℃ of aseptic sodium chloride of pH7.0-peptone buffer solution 100ml, jolting makes dissolving in 45 ℃ of water-baths, is the test liquid of 1:10.

Media dilution method: get the test liquid 1ml of 1:10, put respectively by (0.2ml/ ware) in 5 plates

This product should meet under the gel item each relevant miscellaneous stipulations (one one of Chinese Pharmacopoeia version in 2005, appendix IC).

[assay] measured according to high performance liquid chromatography (one one of Chinese Pharmacopoeia version in 2005, appendix VI D).

Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; Methanol-0.1% phosphoric acid solution (85:15) is a mobile phase; Flow velocity 1.0ml/min; Detect wavelength 254nm; Column temperature is a room temperature.Number of theoretical plate calculates by the emodin peak should be not less than 2000.

Precision takes by weighing emodin respectively, the chrysophanol reference substance is an amount of in the preparation of reference substance solution, makes the solution that every 1ml contains 6 μ g, 10 μ g, promptly.

One glass of this product is got in the preparation of need testing solution, and accurate the title decides, chopping, put in the apparatus,Soxhlet's, added the methanol reflux 3 hours, put cold, be transferred in the 100ml measuring bottle, add methanol and be diluted to scale, shake up, precision is measured 25ml, puts in the flask, flings to solvent and adds 8% hydrochloric acid solution 10ml, supersound process 2 minutes adds chloroform 10ml again, reflux 1 hour, put coldly, put in the separatory funnel, with a small amount of chloroform washing container, incorporate in the separatory funnel, divide and get chloroform layer, acid solution reuse chloroform extraction 3 times, each 10ml, merge chloroform liquid, decompression and solvent recovery is to doing, and residue adds methanol makes dissolving, be transferred in the 10ml measuring bottle, add methanol to scale, shake up, filter, get subsequent filtrate, promptly.

Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

This product contains emodin (C for every glass ₁₅H ₁₀O ₅), chrysophanol (C ₁₅H ₁₀O ₄) total amount must not be less than 0.50mg.

[function with cure mainly] heat-clearing and toxic substances removing, relieving sore throat and pain.Be used for laryngopharynx swelling and pain due to the accumulated heat in the lung and stomach card, it is fidgety to generate heat, constipation.Infantile acute pharyngitis, acute tonsillitis see above patient.

[usage and consumption] is oral, children's below 3 years old, each oral 0.5 glass of children's below 3 years old, children's was each oral 1 glass in 3 years old～7 years old, 7 years old～12 years old each oral 1.5 glasss, 2 times on the one.

[specification] every glass of content 17g.

Shady and cool place is put in [storage] sealing.

Embodiment 3: the quality standard draft of clear pour point depression glue is drafted explanation

This product is by ten Six-element medical materials such as Bombyx mori L., the Radix Et Rhizoma Rhei gel through extracting, mix, making respectively.Now relevant issues in the clear pour point depression colloid amount draft standard are described as follows:

The gel gel is gel under this standard [character] item, behind the disengaging packing container, can keep original form substantially, and tissue is soft moderate, high resilience, and exquisiteness, even does not have obvious floccule.

This standard [discriminating] item down

(1) the thin layer discrimination test of Radix Paeoniae Rubra in the side of being is a reference substance with the peoniflorin, makes the negative sample that lacks Radix Paeoniae Rubra in the prescription ratio, presses the operation of need testing solution preparation method, makes negative controls.The test sample preparation method adopts methanol directly to extract, and disturbs very greatly, does not see the peoniflorin speckle, adopts the macroporous adsorbent resin processing then to reach Expected Results.And 30% extracting solution can be used as the test sample that Flos Lonicerae is differentiated simultaneously; 70% eluent can be used as the test sample that Radix Scrophulariae is differentiated.By text manipulation, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the bluish violet speckle of same color, though the negative control product also have a speckle, be yellow spotting, this discriminating identification that is positive.

(2) the thin layer discrimination test of Radix Scrophulariae in the side of being is a reference substance with the Radix Scrophulariae control medicinal material, makes the negative sample that lacks Radix Scrophulariae in the prescription ratio, presses the operation of need testing solution preparation method, makes negative controls.By text manipulation, the Radix Scrophulariae control medicinal material has two red principal spots, in the test sample chromatograph, with the corresponding position of first principal spot of Radix Scrophulariae control medicinal material chromatograph on show the punctation of same color, the identification that is positive of the no corresponding speckle of negative control product, this discriminating.

(3) the thin layer discrimination test of Flos Lonicerae in the side of being is a reference substance with the chlorogenic acid, makes the negative sample that lacks Flos Lonicerae in the prescription ratio, presses the operation of need testing solution preparation method, makes negative controls.By text manipulation, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the fluorescence speckle of same color, the no corresponding speckle of negative control product, this discriminating identification that is positive.See photo 3.

(4) the thin layer discrimination test of Indigo Naturalis in the side of being is a reference substance with the indirubin.Contain indirubin, indigo in the Indigo Naturalis, indigo in 80% ethanol extraction have, and indigo and indirubin relatively measures lowlyer, so and indigo instability is selection indirubin product in contrast.Make the negative sample that lacks Indigo Naturalis in the prescription ratio, press the operation of need testing solution preparation method, make negative controls.By text manipulation, in the test sample chromatograph, with the corresponding position of reference substance chromatograph on show the speckle of same color, the no corresponding speckle of negative control product.If Development of Thin-Layer Chromatography is undesirable, yellow spotting meeting determining interference, though through changing development system, effect is undesirable.After placing half an hour, the aubergine speckle of indirubin can be more clear.[inspection] 1, pH get two glasss of this product, put in the band plug conical flask, and heating in water bath makes dissolving, under 70 ℃ of water bath heat preservations, measures according to pH value algoscopy (appendix VIIG of Chinese Pharmacopoeia version in 2005), measures the pH of three batch samples, the results are shown in Table 1.

Table 1 PH measurement result

Lot number	060401	060402	060403
				pH	6.3	6.2	6.2

According to three batch sample pH measurement results, regulation this product this product pH should be 5～7.

2, content uniformity: according to (one one of Chinese Pharmacopoeia version in 2005, appendix IQ) regulation under the gel item, according to one one of Chinese Pharmacopoeia version in 2005, appendix XIIC minimum fill inspection technique is measured the loading amount of three batch samples.Every glass of labelled amount 17g of this product, average loading amount is no less than the sign loading amount, and each container loading amount is no less than 93% of sign loading amount.The results are shown in Table 2.

The inspection of table 2 content uniformity

Lot number	060401	060402	060403
				1	17.0567	16.8879	16.7867
2	17.3524	16.6787	17.1545
				3	17.2345	16.6545	16.2332
4	17.7867	16.5687	16.5845
				5	17.4512	17.5645	17.1243
6	17.0124	16.9786	16.4989
				7	17.3131	16.5634	17.0676
8	17.2367	16..4334	16.8524
				9	17.3465	17.2341	17.0945
10	17.4323	17.5678	17.3687
				Average loading amount	17.3223	16.9132	16.8765

The result shows that this product content uniformity meets the pertinent regulations of pharmacopeia appendix XIIC minimum fill inspection technique.3, limit test of microbe: this product limit test of microbe method validation test basis " Chinese Pharmacopoeia version in 2005 " limit test of microbe method is checked.

(1) lot number: 060401,060402,060403

(2) instrument: Roberval's balance; The IV mycete is cultivated; SKP-01 electro-heating standing-temperature cultivator DSHZ-300A; The constant temperature water bath agitator

(3) culture medium: nutrient broth medium, improvement Martin culture medium, nutrient agar, Rose Bengal Sodium culture medium, cholate lactose medium, 4-methyl umbelliferone heteroside culture medium (MUG), mannitol sodium chloride agar culture medium, pH7.0 sodium chloride peptone buffer agent, 0.9% sodium chloride solution, indole test solution.Cholate lactose fermentation culture medium, EMB agar.Four sulfacid sodium viride nitens culture medium, cholate sulfur breast agar culture medium.

(4) checking of antibacterial, mycete and yeast method of counting: checking strain: escherichia coli [CMCC (B) 44102]; Bacillus subtilis [CMCC (B) 63501]; Staphylococcus aureus [CMCC (B) 26003]; Candida albicans [CMCC (F) 98001]; Aspergillus niger [CMCC (F) 98003] (inspection institute in deriving from)

The preparation of bacterium liquid: staphylococcus aureus, escherichia coli and the bacillus subtilis meat soup liquid culture 2-3 oese of cultivating 18～24 hours of learning from else's experience 35 ℃ adds in the 9ml0.9% sodium chloride solution, and 10 times are diluted to 10 ^-4～10 ^-8Be about 50～100cfu/ml, it is standby to do the viable bacteria counting.

The Candida albicans liquid culture of learning from else's experience 25 ℃ and cultivating 18 ~ 24 hours, the 2-3 oese adds in the 9ml0.9% sodium chloride solution, and 10 times are diluted to 10 ^-4～10 ^-8Be about 50～100cfu/ml, it is standby to do the viable bacteria counting.

Learn from else's experience and cultivate the aspergillus niger slant culture in a week, add 0.9% sodium chloride solution 3ml, wash mycotic spore, get 0.1ml and add in the 9ml0.9% sodium chloride solution, 10 times are diluted to 10 ^-5～10 ^-8Be about 50～100cfu/ml, it is standby to do the viable bacteria counting.

Operational approach: test liquid preparation: get this product 10g, put in the conical flask, add the 45 ℃ of aseptic sodium chloride of pH7.0-peptone buffer agent 100ml, jolting makes moltenly in 45 ℃ of water-baths, is the test liquid of 1:10.

Determination of recovery rates: (1) bacterium liquid group: get bacterium liquid 1ml respectively, adopt conventional method to prepare plate and pour into corresponding culture medium respectively, after waiting to solidify, put set point of temperature and cultivated 24-72 hour, observed result and counting the results are shown in Table 1.

(2) test sample matched group: get test liquid 1ml, respectively by bacterium liquid group of methods, measure the bacterium number of test sample background, measurement result sees Table 1.

(3) test group: get test liquid 1ml, operate with method by the test sample matched group, each plate adds the corresponding test organisms 1ml of 50～100cfu simultaneously, pours into culture medium immediately, after waiting to solidify, puts set point of temperature and cultivates 24-72 hour, observed result and counting.The results are shown in Table 3.

Table 3 limit test of microbe method validation result

Strain	Escherichia coli	Bacillus subtilis	Staphylococcus aureus	Candida albicans	Aspergillus niger
						Algebraically	3	3	3	3	3
Dilution level 10 -n	6	6	7	5	5

Bacterium liquid group (CFU/ml)	88	69	90	89	87
						Test group (CFU/ml)	73	60	79	86	80
Test sample group (CFU/ml)	0	0	0	0	0
						The response rate (%)	83	87	88	97	92

As can be known from the above table, the response rate of antibacterial is all greater than 70%, and the response rate of fungus can adopt the conventional method counting also all greater than 70%.

(5) the control bacterium is checked: control the demonstration test of bacterium according to " Chinese Pharmacopoeia version in 2005 " microbial limit test demonstration test.

The preparation of bacterium liquid: the fresh cultured thing of inoculation escherichia coli, staphylococcus aureus is to the 10ml nutrient broth medium, cultivated 18～24 hours in 35～37 ℃, get this culture fluid 1ml and add 0.9% aseptic sodium chloride solution 9ml, adopt 10 times and increase progressively dilution method, make the bacterium number be about the bacteria suspension of 10～100cfu/ml.

Escherichia coli: the preparation of test liquid: with the preparation of test liquid under the above-mentioned operational approach item.

Verification method: test group: escherichia coli is got test liquid 10ml, add among the cholate lactose medium 100ml, as the test sample group, repeat 2 parts again, wherein 1 part adds escherichia coli 10-100 as test group, in addition the diluent of 1 part of adding and test liquid equivalent is as negative control group, cultivated 18～24 hours for 35～37 ℃, get above-mentioned culture fluid 0.2ml, adding contains in 4-methyl umbelliferone heteroside culture medium (MUG) test tube of 5ml, cultivated 5～24 hours in 35～37 ℃, observed result is after the observation, along several indole test solutions of tube wall adding of culture tube, observed result sees Table 2.

The negative bacterium matched group: other gets cholate lactose medium 100ml, operates with method by test group, adds staphylococcus aureus 10-100 as negative control bacterium group, and in 35～37 ℃ of cultivations 18～24 hours, below operation and the same method of test group the results are shown in Table 4.

Table 4 escherichia coli inspection [CMCC (B) 44102]

	Add the bacterium amount	BL	MUG	I	The high salt of mannitol	EMB	Gram's staining	Lac	IMViC	The result
											Test sample		Mix	—	—						—
Test group	88	Aerogenesis	+	+						+
											Negative control bacterium group	90	Mix	—	—	—					—
Negative control		Clearly								—

(6) conclusion:, determine that conventional method is adopted in the count of bacteria of the limit test of microbe of this product according to above-mentioned demonstration test result; Mycete and yeast counting adopt conventional method; The control bacterium is checked and adopts conventional method.4, heavy metal, arsenic salt are checked: three batches each one glass of this product is got in (1) heavy metal inspection, press one one of Chinese Pharmacopoeia version in 2005, appendix IX E " heavy metal inspection technique " second method detection this product content of beary metal down.

The result: this product content of beary metal is lower than 10/1000000ths, meets the pharmacopeia regulation, so exclude text.(2) each one glass of three batches of this product is got in the inspection of arsenic salt, press one one of Chinese Pharmacopoeia version in 2005, appendix IX F " arsenic salt inspection technique " first method (ancient Cai Shi method) detection arsenic salt content down.The result: the arsenic salt content is lower than 2/1000000ths, meets the pharmacopeia regulation, so exclude text.

The content assaying method of emodin, chrysophanol in the Radix Et Rhizoma Rhei in this standard [assay] following system side.Measure 5 kinds of compositions altogether, emodin, chrysophanol, chrysophanic acid, physcione, aloe-emodin under a Radix Et Rhizoma Rhei assay of Chinese Pharmacopoeia version in 20005 item.Emodin, chrysophanol are that two kinds of content are the highest, and the chromatographic isolation degree is good, and the normal composition of surveying of various preparation, so this product assay item selects emodin, chrysophanol to measure.With reference to method under a Radix Et Rhizoma Rhei assay of Chinese Pharmacopoeia version in 20005 item, emphasis is investigated the influence factor of the preparation of need testing solution.

1, instrument and reagent LC-10ATvp high performance liquid chromatograph; Chromatographic work station, Zhejiang University's intelligent information Graduate School of Engineering; Emodin, chrysophanol (for assay usefulness, crowd 0737-200511) Nat'l Pharmaceutical ﹠ Biological Products Control Institute; Agents useful for same is chromatographically pure or analytical pure.

2, maximum wavelength is chosen in the mensuration of in 200～400nm scope reference substance solution being carried out uv absorption, and the result shows that emodin, chrysophanol have absorption maximum at the 254nm place.So determine that detecting wavelength is 254nm, identical with pharmacopeia mensuration wavelength.The emodin chrysophanol assay ultra-violet absorption spectrum spectrogram source map 1 that sees reference.

3, the selection official method mobile phase of chromatographic condition is methanol-0.1% phosphoric acid solution (85:5), and this product test sample separating degree is fine, and analysis time is moderate, so mobile phase is defined as methanol-0.1% phosphoric acid solution (85:15).Source map 2 sees reference.

4, the investigation of need testing solution preparation method: a Radix Et Rhizoma Rhei assay of Chinese Pharmacopoeia version in 2005 test sample preparation method, adopt methanol eddy to extract hydrochloric acid hydrolysis, the preparation route of chloroform extraction hydrolyzed solution.Because this product is a compound preparation, and is complete for making methanol extraction, adopt Soxhlet reflux, extract, method, still select to measure free and bonded emodin, chrysophanol content, so continue to use the preparation route of hydrochloric acid hydrolysis, chloroform extraction.The dosage of high spot reviews hydrochloric acid and the quantity of solvent of chloroform extraction.

The same text of the preparation of reference substance solution.

Other flavor medical materials of removing Radix Et Rhizoma Rhei are got in the preparation of negative need testing solution, reach the operation of need testing solution preparation method down by the method for making item, make negative controls.Clear pour point depression glue test sample, reference substance, negative control product and methanol high performance liquid chromatography spectrogram.

5, linear relationship is investigated

Accurate respectively emodin, chrysophanol reference substance solution (the emodin 5.187 μ g/ml of injecting, chrysophanol 9.811 μ g/ml) 2.5,5.0,7.5,10.0,15.0,20 μ l, mensuration is abscissa with injection amount (μ g), the peak area integrated value is a vertical coordinate, draw emodin, chrysophanol standard curve, emodin, chrysophanol standard curve the results are shown in Table 5.

Table 5 emodin, chrysophanol standard curve result of the test

Annotate sample volume (μ l)	Emodin injection amount (* 10 -3μg)	The emodin integrated value	Chrysophanol injection amount (* 10 -3μg)	The chrysophanol integrated value
					2.5	14.5245	33387.199	24.5275	69667.203
5	29.0850	63952.000	49.0550	141971.203
					7.5	43.6275	96404.797	73.5825	217366.406
10	58.1700	128969.602	98.1100	284448.000
					15	87.2550	200729.594	147.165	433475.188
20	116.3400	265404.813	196.2200	571190.375

Emodin regression equation Y=-2378.998+2301756.551X, r=0.9997, emodin is good linear relationship between 0.015～0.116 μ g.

Chrysophanol regression equation Y=-870.638+2927568.042X, r=0.9999, chrysophanol is good linear relationship between 0.025 ~ 0.196 μ g.

6, solution stability testing result: get same need testing solution, measure once every 2 hours according to the text method, measure after 8 hours, measured once in 24 hours again, result of the test sees Table 6.

Table 6 stability test result

Minute (hour)	The emodin integrated value	The chrysophanol integrated value
			0	145430.406	339955.188
2	145904.000	343692.813
			4	144864.000	347360.000
6	147324.797	346416.000
			8	149588.406	351395.188
24	143072.000	328614.406
			Meansigma methods	146030.602	342905.599
RSD(％)	1.5	2.3

The result shows that sample is stable in 24 hours.

7, precision test: get same need testing solution, repeat to annotate sample 6 times, the results are shown in Table 7.

8, repeatability test: according to the text method, same lot number sample is carried out 6 times measure, the results are shown in Table 8.The result shows that this law repeatability is good

Table 7 Precision test result

The test sequence number	The emodin integrated value	The chrysophanol integrated value
			1	152668.797	356396.813
2	146844.797	333456.000
			3	152150.406	342995.188
4	152851.203	338630.406
			5	157379.203	347680.000
6	148982.406	347641.594

Meansigma methods	151812.802	344466.667
			RSD(％)	2.4	2.3

Table 8 reproducible test results

The test sequence number	Emodin content (mg/ cup)	Chrysophanol content (mg/ cup)
			1	0.270	0.520
2	0.266	0.538
			3	0.272	0.505
4	0.260	0.520
			5	0.263	0.532
6	0.274	0.500
			Meansigma methods	0.268	0.519
RSD(％)	2.0	2.8

9, accuracy test: adopt the application of sample absorption method.

Need testing solution preparation: get known content this product (emodin 0.228mg/ cup, chrysophanol 0.456mg/ cup) 1 glass, the accurate title, decide, accurate respectively emodin, chrysophanol reference substance methanol solution 1ml, the 0.9ml (every ml contains emodin 0.240mg, chrysophanol 0.450mg respectively) of adding, press the operation of need testing solution preparation method, make the accuracy test need testing solution, test sample sample introduction 5 μ l, reference substance sample introduction 10 μ l.Measure according to the text method, emodin, chrysophanol accuracy test the results are shown in Table 9,10.

Table 9 emodin accuracy test result

The test sequence number	Sampling amount (g)	Amount in the test sample (mg)	Reference substance addition (mg)	Measurement result (mg)	The response rate (%)	RSD (％)
							1	17.5928	0.236	0.240	0.476	100.0
2	17.4521	0.234	0.240	0.469	97.9
							3	17.6254	0.236	0.240	0.470	97.5	1.5
4	16.2513	0.218	0.216	0.425	95.8
							5	16.7529	0.225	0.216	0.433	96.3
6	16.6512	0.223	0.216	0.433	97.2

10, sample size is measured: press three batches of text method working samples, the results are shown in Table 11.

According to the measurement result of three batch samples, consider the fluctuation of different batches medical material content in the production, average 80% for limit, tentative every glass of total amount that contains emodin, chrysophanol of this product is no less than 0.50mg.

Table 10 chrysophanol accuracy test result

The test sequence number	Sampling amount (g)	Amount in the test sample (mg)	Reference substance addition (mg)	Measurement result (mg)	The response rate (%)	RSD (％)
							1	17.5928	0.472	0.450	0.921	99.9
2	17.4521	0.468	0.450	0.901	96.2
							3	17.6254	0.473	0.450	0.913	97.8	1.9
4	16.2513	0.436	0.405	0.834	98.3
							5	16.7529	0.449	0.405	0.837	95.8
6	16.6512	0.447	0.405	0.853	100.2

Emodin, chrysophanol assay result in table 11 sample

The sample lot number	Emodin content (mg/ cup)	Chrysophanol content (mg/ cup)	Emodin, chrysophanol total amount (mg/ cup)
				060401	0.23	0.46	0.69
060402	0.27	0.52	0.79
				060403	0.20	0.38	0.58
Average content	0.23	0.45	0.68

Embodiment 4: the process study data:

One, dosage form selection: falling the ball method for making clearly is after ten Six-element pulverizing medicinal materials such as Bombyx mori L. become fine powder, to add refined honey and water and make water-honeyed pill or big honeyed pills.Because falling ball clearly is children, the pill bitter in the mouth, and dose is bigger, the children taking difficulty.Gel is that gel is a kind of food of child's popular welcome, and we will fall ball clearly and change over pour point depression glue clearly, preparation high resilience, tasty and refreshing, and the child likes taking, and can effectively bring into play curative effect of medication.Close according to gel (acetaminophen gel (97) is defended the accurate word X-of medicine No. 62, and oral, Jiangsu is with safe pharmaceutcal corporation, Ltd) with the existing that of veriety at present and go on the market.

Two, Study on extraction:

(1) evaluation of medical material and pre-treatment: ten Six-element medical materials all should meet corresponding pertinent regulations under each medical material item of Chinese Pharmacopoeia version in 20005 in the prescription except that Semen Gleditsiae.Radix Et Rhizoma Rhei, Cortex Moutan powder respectively become coarse powder.

(2) extraction process design: gel is meant the semi-solid or thick back liquid preparation with gelation that medicinal substances extract and an amount of substrate are made, so this product Chinese crude drug need extract, uses after making extract.

Contain volatile oil in Fructus Forsythiae, Cortex Moutan, Herba Menthae, the Flos Lonicerae in the prescription, carry out the decocting extraction, collect volatile oil simultaneously so technological design is above-mentioned four flavors and Bombyx mori L., Semen Gleditsiae, Radix Paeoniae Rubra, Radix Ophiopogonis, Radix Isatidis, Radix Rehmanniae, Radix Glycyrrhizae, Rhizoma Imperatae.Radix Et Rhizoma Rhei, Indigo Naturalis, Radix Scrophulariae, Bulbus Fritillariae Cirrhosae adopt alcohol extraction technology according to the physicochemical property that it contains effective composition.

(3) extraction process technology Study on Conditions:

1. the investigation of the extraction process time of volatile oil:,, should carry out the extraction of volatile oil with reference to pertinent literature according to chemical constituent contained in Fructus Forsythiae, Cortex Moutan, Herba Menthae, the Chinese medicine honeysuckle.Method is as follows:

Get recipe quantity Fructus Forsythiae, Cortex Moutan, Herba Menthae, Chinese medicine honeysuckle, the Paeonia suffruticosa corium farinosum becomes coarse powder, add 8 times of amounts of medical material weight (g) (ml) water, connect volatile oil extractor, reflux condensing tube, put and slowly be heated to boiling in the electric jacket, read different time volatile oil extracted amount, oil mass stops heating when no longer increasing, the results are shown in Table 1.

Table 1 volatile oil extraction time investigation result

3 and 2 hours relatively, and the increase of volatilization oil mass is very slow, so determine that it is 3 hours that volatile oil extracts the receipts oil time.

Because above-mentioned four Chinese medicine material also adopts decocting to extract, so can eight distinguish the flavor of after water carries medical material and mix with other, decocting is collected volatile oil simultaneously.

2. extraction process by water is investigated

Physicochemical property and pertinent literature according to prescription Chinese crude drug effective ingredient, Bombyx mori L., Semen Gleditsiae, Radix Paeoniae Rubra, Radix Ophiopogonis, Radix Isatidis, Radix Rehmanniae, Radix Glycyrrhizae, Rhizoma Imperatae and Fructus Forsythiae, Cortex Moutan, Herba Menthae, Flos Lonicerae are adopted the decocting method, amount of water, decocting time and decocting number of times, the employing optimization of orthogonal test is selected, adopt four factors, three horizontal quadrature tables, the gauge outfit design sees Table 2.Extraction ratio with peoniflorin in the Radix Paeoniae Rubra serves as to investigate index, and paeoniflorin content adopts high performance liquid chromatography to measure, and experimental technique is as follows:

Get 1/8 recipe quantity, 12 flavor medical materials, amount of water, decocting time and decocting number of times are by the orthogonal table design operation, and the water-bath of 9 groups of experiment extracting solution is concentrated into dried, and drying under reduced pressure is weighed, calculated yield.Precision takes by weighing 1/250 amount respectively, adds 50% dissolve with ethanol, quantitatively is transferred in the 50ml measuring bottle, adds 50% ethanol dilution to scale, shakes up, as need testing solution.Precision takes by weighing the peoniflorin reference substance in addition, adds dissolve with methanol, makes the solution that every 1ml contains 0.05mg, in contrast product solution.

Accurate need testing solution, each the 10 μ l of reference substance solution of drawing of algoscopy, inject chromatograph of liquid, according to high performance liquid chromatography (one one of Chinese Pharmacopoeia version in 2005, appendix VID) test, be mobile phase with methanol-0.05mol/L potassium dihydrogen phosphate (15:85); The detection wavelength is 230nm, measures, and calculates.Orthogonal experiment plan is taken into account interpretation of result and be the results are shown in Table 3,4.

Calculate the percentage composition of peoniflorin in the extract by following formula.

A _Supply: test sample area integral value A _Right: reference substance area integral value

V: test sample constant volume (ml) v: test sample is annotated sample volume (μ l)

W: Radix Paeoniae crude drug amount (mg) V _Right: reference substance is annotated sample volume (μ l)

Table 2 decocting technology four factors three horizontal quadrature table gauge outfits

ANOVA showed significant A, B, C are the significantly factor, and intuitive analysis is the result show, though amount of water, extraction time to the extraction there was no significant difference of peoniflorin, extract to select for use more than 8 times, 6 times and add 10 times of water gagings and extract but add 10 times of water gaging peoniflorins; Extract 3 peoniflorin extracted amounts more than 2 times, 1 time, but consider and extract 2 times, most effective ingredient are proposed selective extraction 2 times, each 1.5 hours.

Table 3 analysis of variance table

F _{1-0.10(2，2)}＝9.16 F _{1-0.05(2，2)}＝19.16 F _{1-0.01(2，2)}＝99.17

Table 4 orthogonal experiment plan is taken into account interpretation of result (* 10 ^-2)

3. the selection of alcohol precipitation concentration: this product 12 flavor medical material decocting paste-forming rates are about 31.4%, and paste volume more directly feeds intake has solid content to separate out through trial-production, needs to adopt ethanol precipitation to make with extra care, and to guarantee that gel is transparent, no solid content is separated out.Getting three alcohol precipitation concentrations commonly used, serves as to investigate index with paste volume and content of paeoniflorin, and paeoniflorin content adopts high performance liquid chromatography to measure, and experimental technique is as follows:

Get 1/8 recipe quantity medical material, 10 times of water gagings are fried in shallow oil 3 times, and each 1 hour, filter, merging filtrate is concentrated into the clear paste of relative density 1.05～1.08 (50 ℃), puts to be divided into 4 parts after cold.A copy of it drying under reduced pressure (80 ℃ 0.05Mpa), are weighed.Other 3 parts add ethanol respectively, make to contain alcohol amount and be respectively 60%, 70%, 80%, leave standstill, and filter, and filtrate recycling ethanol is not to there being the alcohol flavor, and water-bath is concentrated into dried, drying under reduced pressure (80 ℃ 0.05Mpa), are weighed.Precipitation is weighed after the oven dry respectively.Precision weighing contains 60%, 70%, 80% 3 sample of alcohol amount respectively, adds 50% dissolve with ethanol, quantitatively is transferred in the 50ml measuring bottle, adds 50% ethanol dilution to scale, shakes up, and as need testing solution, carries out paeoniflorin content and measures.The results are shown in Table 5.The result shows, is that 70% precipitate with ethanol effect is best to contain the alcohol amount.

Table 5 precipitate with ethanol result of the test

Contain the alcohol amount	60％	70％	80％	Precipitate with ethanol not
					Precipitation heavy (g)	11.25	14.5	17.5
Filtrate evaporate to dryness solid heavy (g)	30.0	26.75	23.75
					Gross weight (g)	41.25	41，25	41.25	41.25
Paeoniflorin content (%)	0.60	0.90	0.82

4. alcohol extraction process is investigated

According to the physicochemical property of prescription Chinese crude drug effective ingredient, with reference to the extraction process of Qingjiangpian tablets, Radix Et Rhizoma Rhei, Indigo Naturalis, Radix Scrophulariae, Bulbus Fritillariae Cirrhosae adopt alcohol extraction.Concentration of alcohol, alcohol adding amount, extraction time and extraction time adopt optimization of orthogonal test to select.Adopt four factors, three horizontal quadrature tables, the gauge outfit design sees Table 6.Extraction ratio with emodin, chrysophanol in the Radix Et Rhizoma Rhei serves as to investigate index, and the content of emodin, chrysophanol adopts high performance liquid chromatography to measure, and experimental technique is as follows:

Get 1/10 recipe quantity four Chinese medicine material, concentration of alcohol, alcohol adding amount, extraction time and extraction time are got 9 groups of experiment extracting solution and are got the Radix Et Rhizoma Rhei 150mg amount that is equivalent to respectively by the orthogonal table design operation, be transferred in the 50ml measuring bottle, add methanol and be diluted to scale, shake up, as need testing solution.Precision takes by weighing emodin, chrysophanol reference substance in addition, adds dissolve with methanol, makes the mixed solution that every 1ml contains emodin 5 μ g, chrysophanol 10 μ g respectively, in contrast product solution.

The accurate need testing solution 10 μ l that draw of algoscopy, reference substance solution 10 μ l inject chromatograph of liquid, according to high performance liquid chromatography (one one of Chinese Pharmacopoeia version in 2005, appendix VI D) test, be mobile phase with methanol-0.1% phosphoric acid solution (85:15), the detection wavelength is 254nm, measures, and calculates.

Calculate the content of emodin, chrysophanol in the extracting solution by following formula.The emodin orthogonal experiment plan is taken into account interpretation of result and be the results are shown in Table 7,8, and the chrysophanol orthogonal experiment plan is taken into account interpretation of result and be the results are shown in Table 9,10.

A _Supply: test sample area integral value A _Right: reference substance area integral value

V: test sample constant volume (ml) v: test sample is annotated sample volume (μ l)

W: Radix Et Rhizoma Rhei crude drug amount (mg) V _Right: reference substance is annotated sample volume (μ l)

Table 6 alcohol extraction process four factors three horizontal quadrature table gauge outfits

Table 7 emodin orthogonal experiment plan is taken into account interpretation of result (* 10 ^-2)

Table 8 emodin analysis of variance table (* 10 ^-2)

F _{1-0.10(2，2)}＝9.16 F _{1-0.05(2，2)}＝19.16 F _{1-0.01(2，2)}＝99.17

Directly perceived or the variance analysis of emodin shows that all A is the remarkable factor from table, and C, D, B are not the significantly factor, and promptly concentration of alcohol have considerable influence to Radix Et Rhizoma Rhei.Optimum combination A ₃B ₂C ₃D ₂Or A ₂B ₂C ₃D ₂The variance analysis of chrysophanol shows that all A, B, C, D are not the significantly factor from table, but intuitive analysis is the result show, concentration of alcohol 60%, 80% chrysophanol extraction ratio is approaching, extract 3 times than extract 2 times, 1 time for good, 1.5 hours extraction times and 2 hours are approaching, all are higher than 1 hour.Excellent combination A ₂B ₂C ₃D ₂Or A ₃B ₂C ₃D ₂So select 8 times of amount 60% or 80% ethanol extractions 3 times, each 1.5 hours.It is higher than 80% ethanol to extract emodin 60% ethanol, the two is approaching to extract chrysophanol, take all factors into consideration other drug such as Indigo Naturalis, Radix Scrophulariae, Semen Gleditsiae (the extraction solvent of Qingjiangpian tablets two flavors is 80% ethanol), so determine 8 times of amount 80% ethanol extractions 3 times, each 1.5 hours.

Table 9 chrysophanol orthogonal experiment plan is taken into account interpretation of result (* 10 ^-2)

Table 10 analysis of variance table (* 10 ^-2)

F _{1-0.10(2，2)}＝9.16 F _{1-0.05(2，2)}＝19.16 F _{1-0.01(2，2)}＝99.17

The checking of 80% alcohol extraction number of times

Extract solvent, dosage and extraction time, optimize the result by orthogonal experiment and test, extracts three times, determine extraction time according to the extracted amount of three times paste volumes and emodin, chrysophanol.Emodin, chrysophanol content assaying method are with the investigation of alcohol extraction technology.

Test method: get 1/2 recipe quantity Radix Et Rhizoma Rhei, Indigo Naturalis, Radix Scrophulariae, Bulbus Fritillariae Cirrhosae, add 8 times of amount 80% ethanol, extract each 1.5 hours three times.Collect extracting solution respectively, filter, reclaim solvent, water bath method, drying under reduced pressure (0.05Mp, 80 ℃) is weighed.

The preparation of reference substance solution is with alcohol extraction technology.

The preparation of need testing solution precision respectively takes by weighing extract 20mg three times, puts in the round-bottomed flask.Add 8% hydrochloric acid solution 10ml, add chloroform 10ml again, reflux 1 hour.Put coldly, put in the separatory funnel, with a small amount of chloroform washing container, incorporate in the separatory funnel, divide and get chloroform layer, acid solution reuse chloroform extraction 3 times, each 10ml merges chloroform liquid, and decompression and solvent recovery is to doing, residue adds methanol makes dissolving, is transferred in the 10ml measuring bottle, adds methanol to scale, shake up, filter, get subsequent filtrate, promptly.

Accurate respectively reference substance solution 10ul and the need testing solution 20 μ l of drawing of algoscopy inject chromatograph of liquid, measure, promptly.

The investigation result of the test of table 11 80% alcohol extraction number of times

	Paste volume (g)	Paste-forming rate (%)	Emodin, chrysophanol total amount (%)	Emodin, chrysophanol (mg/ cup)
					For the first time	75.4	54.6	0.73	0.78
For the second time	40.0	28.9	0.19	0.20
					For the third time	22.9	16.5	0.04	0.04

Conclusion: extract for the first time, for the second time paste volume and account for three total amounts 83.5%, for the first time, the extraction total amount of emodin, chrysophanol accounts for three times and extracts 95.8% of total amount for the second time, extracting secondary proposes most effective ingredient, so determine that extraction time is a secondary, to save the solvent and the energy.

Three, preparations shaping Journal of Sex Research

Fructus Forsythiae, Flos Lonicerae, Cortex Moutan, Herba Menthae Haplocalycis volatile oil extraction process, extraction process by water, alcohol precipitation process and alcohol extraction process are selected through optimization of orthogonal test in the clear pour point depression glue, and stable process conditions is feasible, now carry out preparation prescription design and Study on Forming.

(1) preparation prescription design

This product is a gel, and gel means medicinal substances extract and suitable substrate semisolid that make, the tool gel characteristic or the thick liquid preparation of silk fabric.By the substrate difference, gel can be divided into aqueous gel and oil-base gel.

This product medicinal substances extract polarity is bigger, the suitable aqueous gel substrate of using.Aqueous gel substrate generally is made of water, glycerol, propylene glycol and cellulose derivative, Carmomer and alginate, tragcanth, gelatin, starch etc.

Carrageenan is the natural polysaccharide colloid that extracts from the red algae Sargassum, the chain polymer of being made up of salts such as the calcium of galactose and 3,6 inner ether galactose and sulfuric ester, sodium, potassium, magnesium on the structure.Belong to alginates.

Carrageenan can be brought into play the outstanding effect synergism with locust bean gum, Konjac glucomannan, xanthan gum etc., mixes to use obviously to change its gel characteristic, and the viscosity and the intensity of raising carrageenan make gel trend towards high resilience and excreting water phenomenon alleviates.

The safety of carrageenan is confirmed by FAO (Food and Agriculture Organization of the United Nation) and World Health Organization (WHO).Carrageenan is used widely in food industry and medical industry.

(2) determining of the kind of adjuvant: according to the kind of definite adjuvants such as the properties of colloid chemistry of K-carrageenan, dissolubility, gelling, thickening property, concertedness.

Dissolubility: can dissolve in cold water, dissolution velocity improves in hot water more than 70 ℃, and water is the substrate of gel.

Gelling: in the presence of potassium ion, can generate heat-convertible gel, can add potassium chloride and promote to generate heat-convertible gel.

Thickening property: form the colloidal sol of low-viscosity when concentration is low, near Newtonian fluid, concentration raises and forms high viscosity colloidal sol, then is non-Newtonian fluid.

Concertedness: produce synergism with locust bean gum, Konjac glucomannan, xanthan gum isocolloid, can improve the elasticity and the water-retaining property of gel, determine to add Konjac glucomannan to improve the elasticity and the water-retaining property of gel.

Healthy value: carrageenan has the fundamental characteristics of water soluble dietary fiber, and the carrageenan after the degradation in vivo can form the complex of solubility with fibrin.Can be become CO by big enterobacteria zymolysis ₂, H ₂, short-chain fatty acid such as biogas and formic acid, acetic acid, propanoic acid, become the energy source of probiotic bacteria

(3) orthogonal test of adjuvant and dosage examination: according to the adjuvant characteristics of gel, in conjunction with the pertinent literature of consulting, determining that carrageenan, Rhizoma amorphophalli powder, potassium chloride, water are main matrix, is the determiner of gel molding.Also comprise white sugar, sweeting agent, antiseptic, essence in all the other adjuvants.Adopt optimization of orthogonal test to select the dosage of above-mentioned main matrix.Adopt four factors, three horizontal quadrature tables, the gauge outfit design sees Table 12.A is carrageenan dosage (tumbler), and B is the Rhizoma amorphophalli powder dosage, and C is the potassium chloride dosage, and D is a gel weight.Amount of water deducts other adjuvant amounts for gel weight.Elasticity and mouthfeel, bleeding (water-retaining property) with gel are the examination index, and above-mentioned investigation index is carried out classification, composed and divide, and compose the branch standard and see Table 13, and the moulding process orthogonal experiment plan is taken into account interpretation of result and be the results are shown in Table 14,15,16,17.

Table 12 moulding process four factors three horizontal quadrature table gauge outfits

The elasticity of table 13 gel, mouthfeel, water-retaining property classification and tax divide standard

Compose and divide	Elasticity and mouthfeel	Water-retaining property
			1	Elasticity is hard or soft, and mouthfeel is satiny	Difference
2	Elasticity is harder or softer	Relatively poor
			3	Elasticity is moderate, and mouthfeel is moderate	Better
4	Elasticity is moderate, and mouthfeel is sliding than Cis	Good
			5	Elasticity is moderate, and mouthfeel is satiny	Fine

Table 15 elasticity and mouthfeel analysis of variance table

F _{1-0.10(2，2)}＝9.16 F _{1-0.05(2，2)}＝19.16 F _{1-0.01(2，2)}＝99.17

Table 14 orthogonal experiment plan is taken into account elasticity and mouthfeel interpretation of result

Table 16 orthogonal experiment plan is taken into account the water-retaining property interpretation of result

Table 17 water-retaining property analysis of variance table

F _{1-0.10(2，2)}＝9.16 F _{1-0.05(2，2)}＝19.16 F _{1-0.01(2，2)}＝99.17

Directly perceived or the variance analysis of elasticity, mouthfeel shows all that A, B are and is the remarkable factor from table, and D is the remarkable factor, and promptly the dosage of carrageenan, Rhizoma amorphophalli powder has considerable influence to elasticity, the mouthfeel of clear pour point depression glue, and amount of water takes second place.Optimum combination A ₁B ₂C ₃D ₃Or A ₁B ₃C ₃D ₃

Directly perceived and the variance analysis of water-retaining property shows that all A, B are the remarkable factor from table, and D is the not remarkable factor, and promptly the dosage of carrageenan, Rhizoma amorphophalli powder has considerable influence to the water-retaining property of clear pour point depression glue.Optimum combination A ₂B ₁C ₃D ₃Or A ₂B ₁C ₃D ₂

Comprehensive above two result of the tests, for reducing the consumption of carrageenan, the amount of the dosage employing level 2 of carrageenan, Rhizoma amorphophalli powder, the dosage of potassium chloride all adopt the amount of level 2, consider that the diameter of gel needs greater than 3.5cm, and every glass of weight is 17g behind the water so need determine to add.This product extract hardship so the dosage of sucrose adopts 1g, also need add a small amount of cyclamate and carry out flavoring, and when cyclamate was used with sucrose, its sugariness can reach more than 80 times; When using separately, its sugariness is that 10g is equivalent to sucrose 500g.The dosage of sorbic acid first antiseptic dosage 0.5g/kg, essence is according to operation instruction.

The ratio of adjuvant that adopts orthogonal test to determine carries out sample preparation, and the elasticity of sample, mouthfeel, water-retaining property are all very desirable.

Preparation prescription:

(3) preparations shaping technology

12 flavor water extract thick pastes such as Bombyx mori L. mix with alcohol extract thick paste, volatile oil extracting solution, citric acid, potassium chloride, white sugar, cyclamate, antiseptic, are dissolved in water; With carrageenan aqueous solution mixing, add volatile oil, essence, in 70 ℃ of water-baths, heat mixing, packing, sealing is behind the pasteurization, promptly.

Claims (4)

1, a kind of Chinese medicine composition for the treatment of painful swelling of throat and constipation is characterized in that making the raw materials of effective components medicine and consists of:

400 Radix Ophiopogonis 400 of silkworm excrement 400 Radix Et Rhizoma Rhei 400 Radix Scrophulariaes 400 Semen Gleditsiae 400 Radix Paeoniae Rubra

Fructus Forsythiae 400 Radix Isatidis 400 Radix Rehmanniae 400 Flos Loniceraes 400 Rhizoma Imperataes 400

Cortex Moutan 260 Indigo Naturaliss 200 Bulbus Fritillariae Cirrhosaes 200 Herba Menthaes 200 Radix Glycyrrhizaes 132;

Its preparation method is:

More than ten Six-elements, Radix Et Rhizoma Rhei powder is made coarse powder and is mixed with Indigo Naturalis, Radix Scrophulariae, Bulbus Fritillariae Cirrhosae, adds 8 times of amount 80% ethanol extractions twice, each 1.5 hours, merge alcohol extract, reclaim ethanol and be condensed into cream, relative density 1.30～11.35,60 ℃;

Cortex Moutan is made coarse powder, with silkworm excrement, Semen Gleditsiae, Radix Paeoniae Rubra, Radix Ophiopogonis, Fructus Forsythiae, Flos Lonicerae, Radix Isatidis, Radix Rehmanniae, Rhizoma Imperatae, Herba Menthae, Radix Glycyrrhizae mixes, adding 10 times of water gagings decocts twice, each 1.5 hours, collect volatile oil, the gradation of water extract filters, merging filtrate, be concentrated into relative density 1.05～11.08,60 ℃, put to room temperature, add ethanol and make that to contain alcohol amount be 70%, standing over night filters filtrate recycling ethanol, be concentrated into relative density 1.25～11.35,60 ℃, thick paste, make plain sheet or coated tablet or thin membrane coated tablet according to appendix rules of preparations of Chinese Pharmacopoeia version in 2000.

2, the Chinese medicine composition of treatment painful swelling of throat and constipation according to claim 1 is characterized in that described Chinese medicine composition is a pour point depression glue clearly, and it is prepared from by following processing step:

A, prescription:

Cortex Moutan, silkworm excrement, Semen Gleditsiae, Radix Paeoniae Rubra, Radix Ophiopogonis,

Fructus Forsythiae, Flos Lonicerae, Radix Isatidis, Radix Rehmanniae,

The water extract 0.703kg of Rhizoma Imperatae, Herba Menthae, Radix Glycyrrhizae

The ethanol extract 0.37kg of Radix Et Rhizoma Rhei, Indigo Naturalis, Radix Scrophulariae, Bulbus Fritillariae Cirrhosae

The extraction volatile oil 5.5ml of Fructus Forsythiae, Cortex Moutan, Herba Menthae, Flos Lonicerae

Carrageenan 0.3774kg

Rhizoma amorphophalli powder 0.3774kg

Potassium chloride 0.0943kg

Sucrose 3.774kg

Citric acid 0.0566kg

Cyclamate 0.1132kg

Antiseptic 0.0321kg

Water 58.3kg

B, preparation method: feed intake according to the described raw materials of effective components medicine composition that makes of claim 1:

Radix Et Rhizoma Rhei powder is made coarse powder and is mixed with Indigo Naturalis, Radix Scrophulariae, Bulbus Fritillariae Cirrhosae, adds 8 times of amount 80% ethanol extractions twice, and each 1.5 hours, merge alcohol extract, reclaim ethanol and be condensed into cream, relative density 1.30～11.35,60 ℃;

Cortex Moutan is made coarse powder, mix with silkworm excrement, Semen Gleditsiae, Radix Paeoniae Rubra, Radix Ophiopogonis, Fructus Forsythiae, Flos Lonicerae, Radix Isatidis, Radix Rehmanniae, Rhizoma Imperatae, Herba Menthae, Radix Glycyrrhizae, adding 10 times of water gagings decocts twice, each 1.5 hours, collect volatile oil, the gradation of water extract filters, merging filtrate, be concentrated into relative density 1.05 ~ 1.08,60 ℃; Put to room temperature, add ethanol and make that to contain alcohol amount be 70%, standing over night filters, and filtrate recycling ethanol is concentrated into relative density 1.25～11.35,, 60 ℃ thick paste;

Water is proposed thick paste, alcohol extraction thick paste, citric acid, potassium chloride, white sugar, cyclamate, antiseptic mixing, add the water stirring and dissolving; With carrageenan, Rhizoma amorphophalli powder aqueous solution mixing, heating for dissolving in 70 ℃ of water-baths, add volatile oil, essence, add water to 64.2Kg, mixing, packing, sealing is behind the pasteurization, promptly.

3, the clear pour point depression glue that makes of the preparation method of the Chinese medicine composition of treatment painful swelling of throat and constipation as claimed in claim 2 is characterized in that every glass contains emodin (C ₁₅H ₁₀O ₅), chrysophanol (C ₁₅H ₁₀O ₄) total amount must not be less than the quantitative target of 0.50mg.

4, the clear pour point depression glue that makes of the preparation method of the Chinese medicine composition of treatment painful swelling of throat and constipation as claimed in claim 2 is characterized in that being provided with in the quality standard diagnostic test project of emodin in Radix Paeoniae, Radix Scrophulariae, Flos Lonicerae, Indigo Naturalis and the Radix Et Rhizoma Rhei, chrysophanol assay:

(1) identification of test method of wherein set Radix Paeoniae is: get 1 glass of this product, be cut into small pieces, put in the round-bottomed flask, add 100ml methanol, water-bath backflow 30min filters, water bath method, residue add water 40ml makes dissolving, filters, by the AB-8 macroporous resin column, internal diameter 10～112mm, long 100mm, earlier with water 100ml eluting, discard water lotion, reuse 30% alcoholic solution 100ml eluting continues with 70% alcoholic solution 80ml eluting; 30% ethanol elution evaporate to dryness, residue add methanol 2ml makes dissolving, as need testing solution; Other gets the peoniflorin reference substance, adds methanol and makes dissolving, makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin layer chromatography, draw above-mentioned two kinds of solution, 5 μ l respectively, put respectively on same silica gel g thin-layer plate, with chloroform: ethyl acetate: methanol: formic acid=45:5:10:0.2 is developing solvent, launch, take out, dry, spray is with 10 ℅ ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing at 105 ℃; In the test sample chromatograph, with the corresponding position of peoniflorin reference substance chromatograph on, show the speckle of same color;

(2) identification of test method of wherein set Radix Scrophulariae is: get 70% ethanol elution of using of discriminating (1), water bath method, residue add methanol 2ml makes dissolving, as need testing solution; Other gets Radix Scrophulariae control medicinal material powder 2g, adds methanol 10ml, soaks 1 hour, and supersound process 15 minutes filters, and filtrate is product solution in contrast; Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw above-mentioned two kinds of solution, 3 μ l respectively, put respectively on same silica gel g thin-layer plate, with n-butyl alcohol: glacial acetic acid: water=7:1:2 is developing solvent, and lamellae launches with developing solvent presaturation 15 minutes, take out, dry, spray is with vanillin sulphuric acid test solution, and hot blast blows to clear spot; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of same color;

(3) identification of test method of wherein set Flos Lonicerae is: get the need testing solution of discriminating (1), be need testing solution; Other gets the chlorogenic acid reference substance, adds dissolve with methanol, makes the solution that every 1ml contains 1mg, in contrast product solution; Test according to an appendix VIB of Chinese Pharmacopoeia version in 2005 thin layer chromatography, draw above-mentioned two kinds of solution, 5 μ l respectively, put respectively on same silica gel g thin-layer plate, with butyl acetate: formic acid: water=7:2.5:2.5 is developing solvent, launches, take out, dry, put under the uviol lamp 365nm and inspect, in the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show the fluorescence speckle of same color;

(4) identification of test method of wherein set Indigo Naturalis is: get one glass of this product, shred, put in the round-bottomed flask, add chloroform 20ml, water-bath refluxed 10 minutes, filtered, and filtrate is as need testing solution; Other gets the indirubin reference substance, adds chloroform, makes the solution that every 1ml contains 1mg, in contrast product solution; According to thin layer chromatography test, draw each 5 ~ 10ul of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with toluene: chloroform: acetone=5:4:1 is developing solvent, launches, and takes out, and dries; In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, show the speckle of identical redness;

(5) emodin in the wherein set Radix Et Rhizoma Rhei, the method for chrysophanol assay are: according to one one of Chinese Pharmacopoeia version in 2005, and appendix VID high effective liquid chromatography for measuring,

Chromatographic condition and system suitability test octadecylsilane chemically bonded silica are filler; Methanol: 0.1% phosphoric acid solution=85:15 is a mobile phase; Flow velocity 1.0ml/min; Detect wavelength 254nm; Column temperature is a room temperature; Number of theoretical plate calculates by the emodin peak should be not less than 2000;

Precision takes by weighing emodin respectively, the chrysophanol reference substance is an amount of in the preparation of reference substance solution, makes the solution that every 1ml contains 6 μ g, 10 μ g, promptly;

One glass of this product is got in the preparation of need testing solution, and accurate the title decides, chopping, put in the apparatus,Soxhlet's, added the methanol reflux 3 hours, put cold, be transferred in the 100ml measuring bottle, add methanol and be diluted to scale, shake up, precision is measured 25ml, puts in the flask, flings to solvent and adds 8% hydrochloric acid solution 10ml, supersound process 2 minutes adds chloroform 10ml again, reflux 1 hour, put coldly, put in the separatory funnel, with a small amount of chloroform washing container, incorporate in the separatory funnel, divide and get chloroform layer, acid solution reuse chloroform extraction 3 times, each 10ml, merge chloroform liquid, decompression and solvent recovery is to doing, and residue adds methanol makes dissolving, be transferred in the 10ml measuring bottle, add methanol to scale, shake up, filter, get subsequent filtrate, promptly;

Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of algoscopy inject chromatograph of liquid, measure, promptly.