CN102145134B - Detection methods of pharmaceutical composition for treatment of wind-heat cold of children - Google Patents
Detection methods of pharmaceutical composition for treatment of wind-heat cold of children Download PDFInfo
- Publication number
- CN102145134B CN102145134B CN2011100835144A CN201110083514A CN102145134B CN 102145134 B CN102145134 B CN 102145134B CN 2011100835144 A CN2011100835144 A CN 2011100835144A CN 201110083514 A CN201110083514 A CN 201110083514A CN 102145134 B CN102145134 B CN 102145134B
- Authority
- CN
- China
- Prior art keywords
- solution
- reference substance
- need testing
- pharmaceutical composition
- amount
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicinal Preparation (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention discloses a pharmaceutical composition for the treatment of wind-heat cold of children and preparation and detection methods of the pharmaceutical composition. The pharmaceutical composition of the invention consists of crude drugs: dyers woad leaf, radix isatidis, honeysuckle, forsythia, fructus gardeniae, moutan bark, baikal skullcap root, bamboo leaves, earthworm, paris rhizome, radix bupleuri and swallowwort root; the preparation method thereof comprises the steps of: distilling moutan bark, radix bupleuri and forsythia with water vapor, collecting distillate, adding water to decoct dregs and other nine crude drugs such as dyers woad leaf, merging decoctions filtering, concentrating filtrate, and adding ethanol for standing still; taking out supernatant and recovering ethanol, concentrating, adding water for uniformly stirring, standing still, filtering supernatant, concentrating the filtrate to reach the proper amount; additionally, preparing syrup from sucrose, merging the syrup with the above medicine liquid and distillate, adding the proper amount of flavoring agent and antiseptic, uniformly stirring, filtering, encapsulating and sterilizing to obtain the pharmaceutical composition. According to the invention, the content of chlorogenic acid is determined by high performance liquid chromatography. The pharmaceutical composition of the invention has good effect when being used for the treatment of the wind-heat cold of children.
Description
The present invention is for dividing an application, and the original bill application number is 200710064693.0, and the original bill applying date does
On March 23rd, 2007, the original bill denomination of invention is: a kind of pharmaceutical composition and preparation method and method of quality control of treating children's wind-heat cold.
Technical field
The present invention relates to a kind of pharmaceutical composition and preparation method and method of quality control, particularly a kind of pharmaceutical composition and preparation method and method of quality control of treating children's wind-heat cold.
Background technology
Flu, respiratory tract infection are one of the most common diseases of children's, all can take place throughout the year.The cold in children medication is prudent especially, has the cold drug of many adult's usefulness that child is had harm.Like medicines such as " capsule for cold ", " GANMAOTONG ", " antondins ", contain compositions such as paracetamol, phenacetin, aminopyrine, caffeine.These compositions can produce inhibiting effect to medulla hematopoietic system, influence the generation and the growth of children's's haemocyte, cause leukopenia and agranulocytosis, reduce children's's immunity, and the caused toxic that has liver damages.The medicine of treatment cold in children is also more at present, but the many spinoffs of Western medicine, should careful selection.
Chinese traditional treatment thinks that though cold in children also is divided into chill, wind-heat two big syndromes, clinical is many with the wind-heat syndrome person.Because the general interior heat of children's is contained, to hinder although belong to anemofrigid pathogen, also heat-transmission easily then more is prone to heat-transmission if dyspepsia stagnates, or heat closes for cold, causes other variations on the contrary, so clinical general employing Xin Wenxin cold usefulness also can chill wind-heat two be separated.Still do not move back like heat, also must help with antipyretic.Treatment by Chinese herbs cold in children has no side effect, but can't reach the produce effects characteristics rapid, evident in efficacy of Western medicine, so provide a kind of Chinese medicinal composition preparation that can rapidly, effectively treat children's wind-heat cold to be necessary.
Summary of the invention
The object of the invention is to provide a kind of pharmaceutical composition; Another purpose of the present invention is to provide a kind of pharmaceutical composition of treating children's wind-heat cold; The 3rd purpose of the present invention is to provide this preparation of drug combination method;
The 4th purpose of the present invention is to provide the method for quality control of this pharmaceutical composition.
The present invention seeks to realize through following technical scheme:
The bulk drug of pharmaceutical composition of the present invention consists of:
The bulk drug of pharmaceutical composition of the present invention consists of:
The bulk drug composition of pharmaceutical composition of the present invention is preferably:
The bulk drug composition of pharmaceutical composition of the present invention is preferably:
The bulk drug composition of pharmaceutical composition of the present invention is preferably:
Preparation of pharmaceutical compositions 4 methods of the present invention are:
Moutan bark, radix bupleuri, the capsule of weeping forsythia are added 6～12 times of water gagings, under the fluidized state, with steam distillation 3～6h; Collect distillate, nine flavor boilings such as the dregs of a decoction and all the other folium isatidis 2-3 time, each 1-2 hour; Collecting decoction filters, and filtrating is concentrated into an amount of; Add ethanol and make the alcohol amount of containing be 60-80%, leave standstill (24～48h).Get supernatant and reclaim ethanol, be concentrated into about 150-250 parts by volume, add water and stir, leave standstill (24～48h), get supernatant, filter, filtrating is concentrated into an amount of.Other gets sucrose 350-450 weight portion and processes syrup, merges in above-mentioned soup and distillate, and flavouring and antiseptic are an amount of adding, and adjustment total amount to 1000 parts by volume stirs, filter, and embedding, sterilization promptly gets.
Said parts by volume/weight portion is corresponding with g/ml.
Pharmaceutical composition method of quality control of the present invention comprises one or more in following discrimination method and/or the assay:
Differentiate:
(1) gets present composition oral liquid formulations 10ml, put evaporate to dryness in the water-bath, with acetone 1ml dissolving, as need testing solution; Other gets the Gardenoside reference substance, adds acetone and processes solution that every 1ml contains 0.5mg as reference substance solution; Get need testing solution 20 μ l, reference substance solution 8 μ l put respectively on same silica gel g thin-layer plate, with chloroform-methanol (2-4: 1-2) be developping agent, launch, take out, dry; Spray is with the 9-11% ethanol solution of sulfuric acid, and 100 ℃ to be heated to the spot colour developing clear; In the test sample chromatogram with reference substance chromatogram relevant position on show the spot of same color;
(2) get present composition oral liquid formulations 10ml, extract 2-4 time with water saturated normal butyl alcohol jolting, each 15ml merges normal butyl alcohol liquid; Extract 2-3 time each 20ml again with the ammonia solution jolting; Get n-butanol layer, evaporate to dryness, residue add methyl alcohol 1ml makes dissolving, as need testing solution; Get the forsythin reference substance, add methyl alcohol and process solution that every 1ml contains 1mg as reference substance solution; Draw each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, with chloroform-methanol (5-7: 1-2) be developping agent, launch, take out, dry; It is clear that spray is heated to spot colour developing with the 9-11% ethanol solution of sulfuric acid; In the test sample chromatogram with the corresponding position of reference substance chromatogram on show the spot of same color;
(3) get present composition oral liquid formulations 10ml, add watery hydrochloric acid and transfer pH to 2, extract 2-3 time with the ethyl acetate jolting, each 20ml merges ethyl acetate liquid, and evaporate to dryness, residue add methyl alcohol 2ml makes dissolving as need testing solution; Other gets the scutelloside reference substance and adds methyl alcohol and process the solution that every 1ml contains 2mg, as reference substance solution; Draw need testing solution 2 μ l, reference substance solution 5 μ l, put respectively on same silica gel thin-layer plate, (6-9: 3-5: upper solution 2-5) is a developping agent, launches, and takes out, and dries with butyl acetate-formic acid-water; Spray is with 1-3% ferric trichloride ethanolic solution, and it is clear to make it to develop the color; In the test sample chromatogram with reference substance chromatogram relevant position on show the spot of same color;
Assay:
According to high effective liquid chromatography for measuring, chromatographic condition and system suitability test use octadecylsilane chemically bonded silica to be filling agent; 0.02mol/ potassium dihydrogen phosphate: methyl alcohol (250-350: 25-40) be moving phase; The detection wavelength is 324nm;
It is an amount of that the preparation of reference substance solution, precision take by weighing the chlorogenic acid reference substance, adds moving phase and process the solution that every 1ml contains 0.02mg, as reference substance solution;
The present composition oral liquid formulations 5ml under the loading amount item is measured in the preparation of need testing solution, precision, puts in the 100ml measuring bottle, adds moving phase and is diluted to scale, filters with miillpore filter (0.45 μ m), gets subsequent filtrate as need testing solution;
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of determination method inject liquid chromatograph, measure, and promptly get;
Following experimental example and embodiment are used to further specify but are not limited to the present invention.
Experimental example 1 pharmacological testing
1) expelling wind to resolve the exterior effect:
Get 40 of the rats of body weight 150～200g, male and female half and half are divided into four groups at random; The numbering of weighing, first three groups is irritated stomach high and low concentration of drug composition oral liquid of the present invention and equal-volume physiological saline respectively, and the 4th group of contrast medicine group irritated the stomach children's particle high concentration group of inducing sweat; Irritate the stomach amount and be 10ml/100g, after administration 2 hours, neat ankle is instantaneous blocked two hind legs; Take off each 2-3 piece of biped sole of the foot portion meat lift skin and hypodermis immediately, fix, dehydration, embedding, cutting-out, HE dyeing by conventional method; The variation in the rat paw portion sweat gland epithelial cell is respectively organized in observation under the optical microscope, the incidence of mainly observing cavity, and the result sees the following form:
Relatively compare △ P＜0.01 with contrast medicine group in * P＜0.01 with the physiological saline group
The result shows: the induce sweat effect of particle comparison expelling wind to resolve the exterior of drug composition oral liquid of the present invention and control group children has significant difference.
2) detoxication:
Experiment was surveyed body temperature 3 in advance with rat, and experiment measured value on the same day is the rat basal body temperature, and the variation of screening body temperature is no more than 0.3 ℃ animal; Be divided into 5 groups at random; Every group 13: children's induce sweat particle positive controls (heavy dose), the large, medium and small dosage of drug composition oral liquid of the present invention, behind the gastric infusion, inject 1% carrageenan solution 0.1ml under the rat right hind leg sole immediately; Record causes before the inflammation and causes scorching back 1～6h rat foot volume, and calculating swelling rate.
Compare * P＜0.05 with positive controls
The result shows: drug composition oral liquid of the present invention and the comparison of positive control medicine can significantly suppress the volume of rat swelling sole, have the effect of antibacterial detoxifcation.
3) relieve sore throat effect:
Get 40 of body weight 20～22g mouse, male and female half and half are equally divided into 4 groups, and soup is smeared in the oral cavity, children's antipyretic oral liquid high and low dose group, positive controls (children's induce sweat particle), physiological saline control group.Every day 2 times, successive administration 3 days, 30 minutes pneumoretroperitoneums of administration in the 4th day injection 0.355% phenol red; Every 6ml put to death animal after 30 minutes, peeled off tracheae; With 5% soda mint 2ml flushing tracheae repeatedly; Washing fluid with ultraviolet in the 546nm place colorimetric, on phenol red typical curve, calculate the phenol red secretory volume of each treated animal, the result sees the following form:
The result shows: drug composition oral liquid of the present invention and the effect of positive control medicine comparison relieve sore throat have significant difference.
Experimental example 2 medicines are to the influence of rat expelling wind to resolve the exterior function
Compare according to the effect of the method for above-mentioned experimental example 1 each pharmaceutical composition of following different proportionings:
Drug group I:
Folium isatidis 190g Radix Isatidis 70g honeysuckle 130g
Capsule of weeping forsythia 70g cape jasmine 50g moutan bark 130g
Root of large-flowered skullcap 110g leaf of bamboo 90g earthworm 30g.
Paris polyphylla 75g radix bupleuri 110g radix cynanchi atrati 30g.
Drug group II:
Folium isatidis 220g Radix Isatidis 60g honeysuckle 150g
Capsule of weeping forsythia 60g cape jasmine 50g moutan bark 140g
Root of large-flowered skullcap 130g leaf of bamboo 100g earthworm 40g
Paris polyphylla 85g radix bupleuri 130g radix cynanchi atrati 40g.
Drug group III:
Indigo naturalis 23g Radix Isatidis 70g caulis lonicerae 170g
Cape jasmine 70g moutan bark 160g root of large-flowered skullcap 130g leaf of bamboo 100g earthworm 45g
Paris polyphylla 90g radix bupleuri 150g radix cynanchi atrati 25g.
Drug group IV:
Folium isatidis 150g Radix Isatidis 90g honeysuckle 90g
Capsule of weeping forsythia 90g cape jasmine 90g moutan bark 90g
Root of large-flowered skullcap 90g leaf of bamboo 60g earthworm 60g
Paris polyphylla 45g radix bupleuri 90g radix cynanchi atrati 60g
With drug group I, drug group II, drug group III respectively with the prepared oral liquid formulations of drug group IV, relatively the expelling wind to resolve the exterior function is investigated by above-mentioned pharmacodynamics test method, the result sees the following form.
Medicine is to the influence of rat expelling wind to resolve the exterior function
Compare * P＜0.05 with drug group IV of the present invention
Can find out that from last table drug group I of the present invention, II, III and drug group IV of the present invention relatively have significant difference to the influence of the cavity incidence in the rat paw portion sweat gland epithelial cell.The expelling wind to resolve the exterior effect that drug group I of the present invention, II, III are described is significantly higher than drug group IV of the present invention.
Experimental example 3 discrimination method screening experiments
(1) thin layer of cape jasmine is differentiated
1. the selection of chromogenic agent
Getting reference substance solution 8 μ l and put respectively on silica gel g thin-layer plate, is developping agent with chloroform-methanol (3: 1), launches, and takes out, and dries.Spray respectively with 4%, 6%, 8%, 10% ethanol solution of sulfuric acid, 100 ℃ are heated to the spot colour developing.Observe the effect of spot colour developing on the thin layer plate, the result sees the following form:
The optimization experiment result of chromogenic agent
Can find out chromogenic agent at 10% o'clock from last table, color developing effect is good on thin layer plate, is fit to testing requirements.
2. the selection of developping agent proportioning
Get drug oral liquid formulation 10ml of the present invention, put evaporate to dryness in the water-bath, dissolve as need testing solution with acetone 1ml.Other gets the Gardenoside reference substance and adds acetone and process solution that every 1ml contains 0.5mg as reference substance solution.Get need testing solution 20 μ l, reference substance solution 8 μ l put respectively on same silica gel g thin-layer plate, are developping agent with the chloroform-methanol, proportioning was respectively 2: 1,2: 2,3: 1,3: 2,4: 1, launched, and took out, and dried.Spray is with 10% ethanol solution of sulfuric acid, and 100 ℃ to be heated to the spot colour developing clear.Observe the effect that each spot of test sample launches on each thin layer plate, the result sees the following form:
Developping agent consumption proportion optimization experiment result
| The developping agent proportioning | 2∶1 | 2∶2 | 3∶1 | 3∶2 | 4∶1 |
| Launch effect | Difference | Very poor | Good | Very poor | Difference |
Can find out that from last table the developping agent proportioning is at 3: 1 o'clock, it is best that need testing solution launches effect, and appearance hangover, principal spot separate phenomenons such as bad.
3. the selection of need testing solution point sample amount
Get need testing solution 5 μ l, 10 μ l, 15 μ l, 20 μ l, 25 μ l, reference substance solution 8 μ l put respectively on same silica gel g thin-layer plate, are developping agent with chloroform-methanol (3: 1), launch, and take out, and dry.Spray is with 10% ethanol solution of sulfuric acid, and 100 ℃ to be heated to the spot colour developing clear.Observe the effect of test sample principal spot colour developing on the thin layer plate, the result sees the following form:
Sample solution point sample amount optimization experiment result
Can find out test sample point sample amount when the 20 μ l from last table, color developing effect is good on thin layer plate, is fit to testing requirements.
4. negative control test
Get the negative sample that lacks cape jasmine, prepare negative control solution, launch the back and corresponding spot on the reference substance solution correspondence position, do not occur, explain that selected identification experiment specificity is strong according to need testing solution preparation method in the above-mentioned discrimination method.
(2) thin layer of the capsule of weeping forsythia is differentiated
1. the preparation of need testing solution
1) investigation of normal butyl alcohol extraction time
Get drug oral liquid formulation 10ml of the present invention respectively; Extract 3 times, 4 times, 5 times with water saturated normal butyl alcohol jolting, each 15ml collects n-butanol extracting liquid the 3rd, 4 and 5 time; Evaporate to dryness; Residue adds methyl alcohol 1ml dissolving, relatively extracts the content of forsythin in the n-butanol extracting liquid of different number of times, and the result sees the following form:
Can find out from last table, detect content in the n-butanol extracting liquid of the 4th time and the 5th time, so selective extraction is extracted 3 times with normal butyl alcohol less than forsythin.
2) investigation of ammonia solution extraction time
Get drug oral liquid formulation 10ml of the present invention respectively, extract 3 times, extract 1 time, 2 times, 3 times with the ammonia solution jolting again, each 20ml with water-saturated n-butanol.Collect the ammonia solution evaporate to dryness the 1st time, 2 times, 3 times,
With the 1ml dissolve with methanol, measure forsythin content, the result sees the following form:
Can find out from last table, detect content in the ammonia solution extract of the 2nd time and the 3rd time, so select to extract 2 times with ammonia solution less than forsythin.
2. the selection of developping agent proportioning
Getting each 10 μ l of test sample and reference substance solution and put respectively on same silica gel g thin-layer plate, is developping agent with the chloroform-methanol, and proportioning was respectively 6: 2,5: 1,6: 1,7: 1,7: 2, launched, and took out, and dried.Spray is with aceticanhydride: sulfuric acid (20: 1) is developping agent, and 80 ℃ to be heated to the spot colour developing clear.Observe the effect that test sample launches on each thin layer plate, the result sees the following form:
Developping agent consumption proportion optimization experiment result
| The developping agent proportioning | 6∶2 | 5∶1 | 6∶1 | 7∶1 | 7∶2 |
| Launch effect | Very poor | Difference | Good | Difference | Very poor |
Can find out from last table, be developping agent with chloroform-methanol in 6: 1 ratio, and the expansion effect of test sample and reference substance solution is best, and clear spot principal spot do not occur and separates phenomenons such as unclear, hangover.
3. the selection of sample solution point sample amount
Get test sample 3 μ l, 5 μ l, 8 μ l, 10 μ l, 15 μ l, each 10 μ l puts respectively on same silica gel g thin-layer plate with reference substance solution, is developping agent with the chloroform-methanol; Proportioning is 6: 1, launches, and takes out; Dry, it is clear that spray is heated to spot colour developing with 10% ethanol solution of sulfuric acid.Observe the color developing effect of test sample on each thin layer plate, the result sees the following form:
Sample solution point sample amount optimization experiment result
Can find out test sample point sample amount when the 10 μ l from last table, color developing effect is good on thin layer plate, is fit to testing requirements.
4. negative control test
Get the negative sample that lacks the capsule of weeping forsythia, prepare negative control solution, launch the back and corresponding spot on the reference substance solution correspondence position, do not occur, explain that selected identification experiment specificity is strong according to need testing solution preparation method in the above-mentioned discrimination method.
(3) thin layer of the root of large-flowered skullcap is differentiated
1. the preparation of need testing solution
Get drug oral liquid formulation 10ml of the present invention respectively, add watery hydrochloric acid and transfer pH to 2, extract 2,3,4 times with the ethyl acetate jolting; Each 20ml collects n-butanol extracting liquid the 2nd, 3,4 time, evaporate to dryness; Residue respectively adds methyl alcohol 1ml makes dissolving, compares content of baicalin in each solution, and the result sees the following form:
Can find out from last table, extract in the n-butanol extracting liquid after 3 times and detect,, promptly can reach testing requirements so select normal butyl alcohol to extract 2 times less than content of baicalin.
2. the selection of chromogenic agent
Drawing reference substance solution 5 μ l, put respectively on same silica gel thin-layer plate, is developping agent with the upper solution of butyl acetate-formic acid-water (7: 4: 3), launches, and takes out, and dries.Spray the ferric trichloride ethanolic solution with 1%, 2%, 3% respectively, it is clear to make it to develop the color.Investigate the color developing effect of variable concentrations developer, the result sees the following form:
The optimization experiment result of chromogenic agent
Can find out chromogenic agent at 3% o'clock from last table, color developing effect is good on thin layer plate, is fit to testing requirements.
3. the selection of developping agent proportioning
Drawing need testing solution 2 μ l, reference substance solution 5 μ l, put respectively on silica gel thin-layer plate, is developping agent with the upper solution of butyl acetate-formic acid-water; Proportioning was respectively 6: 3: 3,7: 3: 2,7: 3: 3,7: 4: 3,8: 5: 3; Launch, take out, dry.Spray is with 2% ferric trichloride ethanolic solution, and it is clear to make it to develop the color.Observe the effect that test sample launches on each thin layer plate, the result sees the following form:
Developping agent consumption proportion optimization experiment result
| The developping agent proportioning | 6∶3∶3 | 7∶3∶2 | 7∶3∶3 | 7∶4∶3 | 8∶5∶3 |
| Launch effect | Very poor | Difference | Difference | Good | Very poor |
Can find out that from last table the developping agent proportioning is at 7: 4: 3 o'clock, it is best that need testing solution and sample solution launch effect, and phenomenons such as the principal spot separation is unclear, hangover do not appear in clear spot.
4. the selection of test sample point sample amount
Draw need testing solution 1 μ l, 2 μ l, 3 μ l, reference substance solution 5 μ l put respectively on silica gel thin-layer plate, are developping agent with the upper solution of butyl acetate-formic acid-water (7: 4: 3), launch, and take out, and dry.Spray is with 2% ferric trichloride ethanolic solution, and it is clear to make it to develop the color.Observe the color developing effect of test sample on each thin layer plate, the result sees the following form:
Sample solution point sample amount optimization experiment result
| The point sample amount | 1μl | 2μl | 3μl |
| Color developing effect | Spot colors is very shallow | The spot color developing effect is good | The spot color developing effect is good |
Can find out test sample point sample amount when the 2 μ l from last table, color developing effect is good on thin layer plate, and the Pass Test requirement is so select 2 μ l.
5. negative control test
Get the negative sample that lacks the root of large-flowered skullcap, prepare negative control solution, launch the back and corresponding spot on the reference substance solution correspondence position, do not occur, explain that selected identification experiment specificity is strong according to need testing solution preparation method in the above-mentioned discrimination method.
Experimental example 4 content assaying method screening experiments
Adopt the high-efficient liquid phase color popularize law to measure the chlorogenic acid contents in the medicine of the present invention, improving quality determining method of the present invention, the part test result as follows:
1, detects the selection of wavelength
With the maximum absorption wavelength of chlorogenic acid in the determined by ultraviolet spectrophotometry medicine of the present invention, through detecting, maximum absorption wavelength is 324nm.
2, proportion of mobile phase is preferred:
With the 0.02mol/ potassium dihydrogen phosphate: methyl alcohol is moving phase, and proportioning was respectively 250: 30,300: 30,300: 35,350: 40, carries out the assay that test sample dissolves night; Through comparing among the general figure of high-efficient liquid phase color; The separating effect at each peak is confirmed preferred moving phase, and the result is following:
Can find out that from last table proportion of mobile phase is selected 300: 35, chromatographic peak good separating effect, Pass Test requirement.
3, blank test
Ratio according to drug prescription taste of traditional Chinese medicine of the present invention; Press oral liquid formulations technology, preparation does not contain the negative sample of honeysuckle, according to need testing solution preparation method preparation and detection; Negative sample solution is that the identical retention time of chlorogenic acid reference substance place does not have chromatographic peak as a result, so negative noiseless.
4, the methodological study of content assaying method
To the detection method of content that medicine of the present invention adopted, carried out related side's science of law from aspects such as linear relationship, stability, precision, reappearance, the recovery and investigated, concrete outcome is following:
(1) linear relationship is investigated and to be got reference substance solution (0.0416mg/ml) and shake up; Accurate respectively 1,3,5,7, the 9 μ l of absorption inject high performance liquid chromatograph; Measure peak area, the result sees the following form, and the drawing standard curve; Show that chlorogenic acid is linear between 0.0416mg-0.3744mg, its regression equation is:
Area＝2908.023872*Amt-0.29035945(r＝0.99999)
(2) reference substance solution is got in stability test, respectively at preparing the back 0,2,4,6,12,24 hour, measures in accordance with the law, and the result shows that it is basicly stable in 24 hours, and the result sees the following form:
(3) the accurate need testing solution 10 μ l that draw this law invention medicine (oral liquid formulations) of precision test repeat sample introduction 5 times, try to achieve relative standard deviation＜2%, and the result sees the following form:
(4) the text method is pressed in the reappearance test, gets this law invention medicine oral liquid formulation samples and measures, and tries to achieve relative standard deviation＜2%, and the result sees the following form:
(5) the recovery test precision takes by weighing this law invention medicine oral liquid formulation samples 3ml of known content; Accurate respectively again chlorogenic acid reference substance solution (0.416mg/ml) 2ml that adds; Preparation method's operation by above-mentioned need testing solution; Measure its content, and calculate its recovery, measure the result and see the following form:
Can find out from above test findings; Effective ingredient chlorogenic acid in the pharmaceutical preparation of the present invention is carried out content detection control; Method is stable, science, can effectively guarantee drug quality and curative effect, and this also is the more significant reason of curative effect of medication of the present invention and like product.
Embodiment
Following embodiment all can realize the described effect of above-mentioned experimental example
Embodiment 1
Folium isatidis 150g Radix Isatidis 90g honeysuckle 90g capsule of weeping forsythia 90g cape jasmine 90g
Moutan bark 90g root of large-flowered skullcap 90g leaf of bamboo 60g earthworm 60g Paris polyphylla 45g
Radix bupleuri 90g radix cynanchi atrati 60g
More than 12 flavors, moutan bark, radix bupleuri, the capsule of weeping forsythia are used
Steam distillation, collect distillate, nine flavor boiling secondaries such as the dregs of a decoction and all the other folium isatidis, each 1 hour, collecting decoction filtered, and filtrating is concentrated into an amount of, adds ethanol and makes that to contain that alcohol measures be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into about 200ml, add water and stir, leave standstill, get supernatant, filter, filtrating is concentrated into an amount of.Other gets sucrose 400g and processes syrup, merges in above-mentioned soup and distillate, and flavouring and antiseptic are an amount of adding, and the adjustment total amount stirs to 1000ml, filter, and embedding, sterilization promptly gets.
These article 10ml is got in [discriminating] (1), puts evaporate to dryness in the water-bath, with acetone 1ml dissolving, as need testing solution.Other gets the Gardenoside reference substance, adds acetone and processes solution that every 1ml contains 0.5mg as reference substance solution.Get need testing solution 20 μ l, reference substance solution 8 μ l put respectively on same silica gel g thin-layer plate, are developping agent with chloroform-methanol (3: 1), launch, and take out, dry.Spray is with 10% ethanol solution of sulfuric acid, and 100 ℃ to be heated to the spot colour developing clear.In the test sample chromatogram with reference substance chromatogram relevant position on show the spot of same color.
(2) get these article 10ml, extract 3 times with water saturated normal butyl alcohol jolting, each 15ml merges normal butyl alcohol liquid.Extract 2 times each 20ml again with the ammonia solution jolting.Get n-butanol layer, evaporate to dryness, residue add methyl alcohol 1ml makes dissolving, as need testing solution.Get the forsythin reference substance, add methyl alcohol and process solution that every 1ml contains 1mg as reference substance solution.Drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with chloroform-methanol (6: 1), launches, and takes out, and dries.It is clear that spray is heated to spot colour developing with 10% ethanol solution of sulfuric acid.In the test sample chromatogram with the corresponding position of reference substance chromatogram on show the spot of same color.
(3) get these article 10ml, add watery hydrochloric acid and transfer pH to 2, extract 2 times with the ethyl acetate jolting, each 20ml merges ethyl acetate liquid, and evaporate to dryness, residue add methyl alcohol 2ml makes dissolving as need testing solution.Other gets the scutelloside reference substance and adds methyl alcohol and process the solution that every 1ml contains 2mg, as reference substance solution.Drawing need testing solution 2 μ l, reference substance solution 5 μ l, put respectively on same silica gel thin-layer plate, is developping agent with the upper solution of butyl acetate-formic acid-water (7: 4: 3), launches, and takes out, and dries.Spray is with 2% ferric trichloride ethanolic solution, and it is clear to make it to develop the color.In the test sample chromatogram with reference substance chromatogram relevant position on show the spot of same color.
Assay: measure according to high performance liquid chromatography (Chinese Pharmacopoeia version appendix in 2000 VID)
Chromatographic condition and system suitability test use octadecylsilane chemically bonded silica to be filling agent; 0.02mol/ potassium dihydrogen phosphate: methyl alcohol (300: 35) is moving phase; The detection wavelength is 324nm.
It is an amount of that the preparation precision of reference substance solution takes by weighing the chlorogenic acid reference substance, adds moving phase and process the solution that every 1ml contains 0.02mg, as reference substance solution.
The preparation precision of need testing solution is measured these article 5ml under the loading amount item, puts in the 100ml measuring bottle, adds moving phase and is diluted to scale, filters with miillpore filter (0.45 μ m), gets subsequent filtrate as need testing solution.
Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of determination method inject liquid chromatograph, measure, and promptly get.
Function cures mainly: expelling wind to resolve the exterior, detoxifcation relieve sore throat.Be used for children's wind-heat cold, fever and aversion to wind, headache hot eyes, abscess of throat.
Usage and dosage: oral, each 10ml below five years old, five years old to ten years old each 20ml～30ml, 3 times on the one.
Specification: every 10ml
Embodiment 2 suppositorys
Folium isatidis 190g Radix Isatidis 70g honeysuckle 130g
Capsule of weeping forsythia 70g cape jasmine 50g moutan bark 130g
Root of large-flowered skullcap 110g leaf of bamboo 90g earthworm 30g
Paris polyphylla 75g radix bupleuri 110g radix cynanchi atrati 30g
More than 12 flavors, moutan bark, radix bupleuri, the capsule of weeping forsythia use steam distillation, collect distillate, nine flavor boiling secondaries such as the dregs of a decoction and all the other folium isatidis, each 1 hour, collecting decoction filtered, filtrating is concentrated into an amount of, adds ethanol and makes that to contain pure measuring be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into about 200ml, add water and stir, leave standstill, get supernatant, filter, filtrating concentrates, vacuum drying.Getting an amount of semi-synthetic fatty acid (34 types or 36 types) is suppository base, mixes fusion in the rearmounted water-bath with distillate, adds above-mentioned vacuum drying medicine, mixing, and impouring scribbles in the bolt mould of release agent, and cooling is taken out, and promptly gets.
Embodiment 3 dispersing tablets
Folium isatidis 220g Radix Isatidis 60g honeysuckle 150g
Capsule of weeping forsythia 60g cape jasmine 50g moutan bark 140g
Root of large-flowered skullcap 130g leaf of bamboo 100g earthworm 40g
Paris polyphylla 85g radix bupleuri 130g radix cynanchi atrati 40g.
More than 12 flavors, moutan bark, radix bupleuri, the capsule of weeping forsythia use steam distillation, collect distillate, nine flavor boiling secondaries such as the dregs of a decoction and all the other folium isatidis, each 1 hour, collecting decoction filtered, filtrating is concentrated into an amount of, adds ethanol and makes that to contain pure measuring be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into about 200ml, add water and stir, leave standstill, get supernatant; Filter, filtrating concentrates, and vacuum drying is pulverized, and adds an amount of dextrin and sodium carboxymethyl starch (3%～7%); Granulate, drying, whole grain sifts out part particulate wherein, sprays into the distillate of collection; Mixing mixes with dried particle again, adds the moderate lubrication agent, and compressing tablet promptly gets.
Embodiment 4 dripping pills
Folium isatidis 230g Radix Isatidis 70g honeysuckle 170g
Capsule of weeping forsythia 75g cape jasmine 70g moutan bark 160g
Root of large-flowered skullcap 130g leaf of bamboo 100g earthworm 45g
Paris polyphylla 90g radix bupleuri 150g radix cynanchi atrati 25g.
More than 12 flavors, moutan bark, radix bupleuri, the capsule of weeping forsythia use steam distillation, collect distillate, nine flavor boiling secondaries such as the dregs of a decoction and all the other folium isatidis, each 1 hour, collecting decoction filtered, filtrating is concentrated into an amount of, adds ethanol and makes that to contain pure measuring be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into about 200ml, add water and stir, leave standstill, get supernatant, filter, filtrating concentrates, and vacuum drying is ground into fine powder.Distillate and an amount of polyglycol heating and melting add above-mentioned fine powder behind the mixing, mix, and 50～70 ℃ of insulations splash in the whiteruss of cooling (5～15 ℃), promptly get.
Embodiment 5 oral liquids
Folium isatidis 150g Radix Isatidis 100g honeysuckle 100g
Capsule of weeping forsythia 100g cape jasmine 90g moutan bark 150g
Root of large-flowered skullcap 110g leaf of bamboo 90g earthworm 30g.
Paris polyphylla 75g radix bupleuri 100g radix cynanchi atrati 80g.
More than 12 flavors, moutan bark, radix bupleuri, the capsule of weeping forsythia use steam distillation, collect distillate, nine flavor boiling secondaries such as the dregs of a decoction and all the other folium isatidis, each 1 hour, collecting decoction filtered, filtrating is concentrated into an amount of, adds ethanol and makes that to contain pure measuring be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into about 200ml, add water and stir, leave standstill, get supernatant, filter, filtrating is concentrated into an amount of.Other gets sucrose 400g and processes syrup, merges in above-mentioned soup and distillate, and flavouring and antiseptic are an amount of adding, and the adjustment total amount stirs to 1000ml, filter, and embedding, sterilization promptly gets.
Embodiment 6 effervescent tablets
Folium isatidis 120g Radix Isatidis 100g honeysuckle 120g
Capsule of weeping forsythia 90g cape jasmine 100g moutan bark 140g
Root of large-flowered skullcap 130g leaf of bamboo 100g earthworm 100g
Paris polyphylla 85g radix bupleuri 150g radix cynanchi atrati 40g.
More than 12 flavors, moutan bark, radix bupleuri, the capsule of weeping forsythia use steam distillation, collect distillate, nine flavor boiling secondaries such as the dregs of a decoction and all the other folium isatidis, each 1 hour, collecting decoction filtered, filtrating is concentrated into an amount of, adds ethanol and makes that to contain pure measuring be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into about 200ml, add water and stir, leave standstill, get supernatant, filter, filtrating concentrates, vacuum drying.After the polyglycol fusion, add soda mint. stir. cooling is pulverized, and crosses 80 mesh sieves.In addition citric acid, sweetener are crossed 80 mesh sieves, with medicinal powder, polyglycol wrappage fine powder mixing, granulate, drying is sifted out part particulate wherein, sprays into the distillate of collection, and mixing mixes with dried particle again, and compressed tablets promptly gets.
Embodiment 7 suppositorys
Folium isatidis 240g Radix Isatidis 100g honeysuckle 150g
Capsule of weeping forsythia 75g cape jasmine 70g moutan bark 160g
Root of large-flowered skullcap 130g leaf of bamboo 100g earthworm 45g
Paris polyphylla 90g radix bupleuri 160g radix cynanchi atrati 100g.
More than 12 flavors, moutan bark, radix bupleuri, the capsule of weeping forsythia use steam distillation, collect distillate, nine flavor boiling secondaries such as the dregs of a decoction and all the other folium isatidis, each 1 hour, collecting decoction filtered, filtrating is concentrated into an amount of, adds ethanol and makes that to contain pure measuring be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into about 200ml, add water and stir, leave standstill, get supernatant, filter, filtrating concentrates, vacuum drying.Getting an amount of semi-synthetic fatty acid (34 types or 36 types) is suppository base, mixes fusion in the rearmounted water-bath with distillate, adds above-mentioned vacuum drying medicine, mixing, and impouring scribbles fastening in the mould of release agent, and cooling is taken out, and promptly gets.
Embodiment 8 dripping pills
Folium isatidis 190g Radix Isatidis 70g honeysuckle 130g
Capsule of weeping forsythia 70g cape jasmine 50g moutan bark 130g
Root of large-flowered skullcap 110g leaf of bamboo 90g earthworm 30g.
Paris polyphylla 75g radix bupleuri 110g radix cynanchi atrati 30g.
More than 12 flavors, moutan bark, radix bupleuri, the capsule of weeping forsythia use steam distillation, collect distillate, nine flavor boiling secondaries such as the dregs of a decoction and all the other folium isatidis, each 1 hour, collecting decoction filtered, filtrating is concentrated into an amount of, adds ethanol and makes that to contain pure measuring be 70%, leaves standstill.Get supernatant and reclaim ethanol, be concentrated into about 200ml, add water and stir, leave standstill, get supernatant, filter, filtrating concentrates, and vacuum drying is ground into fine powder.Distillate and an amount of polyglycol heating and melting add above-mentioned fine powder behind the mixing, mix, and 50～70 ℃ of insulations splash in the whiteruss of cooling (5～15 ℃), promptly get.
Embodiment 9 oral liquids
Indigo naturalis 23g Radix Isatidis 70g caulis lonicerae 170g
Cape jasmine 70g moutan bark 160g root of large-flowered skullcap 130g leaf of bamboo 100g earthworm 45g
Paris polyphylla 90g radix bupleuri 150g radix cynanchi atrati 25g.
Process oral liquid by common process.
Claims (1)
1. detection method of treating the pharmaceutical composition of children's wind-heat cold is characterized in that this method is: choose following material medicine and process oral liquid:
Folium isatidis 150g Radix Isatidis 90g honeysuckle 90g capsule of weeping forsythia 90g cape jasmine 90g moutan bark 90g root of large-flowered skullcap 90g leaf of bamboo 60g earthworm 60g Paris polyphylla 45g radix bupleuri 90g radix cynanchi atrati 60g; Moutan bark, radix bupleuri, the capsule of weeping forsythia are used steam distillation, collect distillate, nine flavor boiling secondaries such as the dregs of a decoction and all the other folium isatidis, each 1 hour, collecting decoction filtered, and filtrating is concentrated into an amount of, adds ethanol and makes that to contain that alcohol measures be 70%, leaves standstill; Get supernatant and reclaim ethanol, be concentrated into about 200ml, add water and stir, leave standstill, get supernatant, filter, filtrating is concentrated into an amount of; Other gets sucrose 400g and processes syrup, merges in above-mentioned soup and distillate, and flavouring and antiseptic are an amount of adding, and the adjustment total amount stirs to 1000ml, filter, and embedding, sterilization promptly gets; Differentiate:
A, get these article 10ml, put evaporate to dryness in the water-bath, with acetone 1ml dissolving, as need testing solution; Other gets the Gardenoside reference substance, adds acetone and processes solution that every 1ml contains 0.5mg as reference substance solution; Get need testing solution 20 μ l, reference substance solution 8 μ l put respectively on same silica gel g thin-layer plate, are developping agent with 3: 1 chloroform-methanols, launch, and take out, dry; Spray is with 10% ethanol solution of sulfuric acid, and 100 ℃ to be heated to the spot colour developing clear; In the test sample chromatogram with reference substance chromatogram relevant position on show the spot of same color;
B, get these article 10ml, extract 3 times with water saturated normal butyl alcohol jolting, each 15ml merges normal butyl alcohol liquid; Extract 2 times each 20ml again with the ammonia solution jolting; Get n-butanol layer, evaporate to dryness, residue add methyl alcohol 1ml makes dissolving, as need testing solution; Get the forsythin reference substance, add methyl alcohol and process solution that every 1ml contains 1mg as reference substance solution; Drawing each 10 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, is developping agent with 6: 1 chloroform-methanols, launches, and takes out, and dries; It is clear that spray is heated to spot colour developing with 10% ethanol solution of sulfuric acid; In the test sample chromatogram with the corresponding position of reference substance chromatogram on show the spot of same color;
C, get these article 10ml, add watery hydrochloric acid and transfer pH to 2, extract 2 times with the ethyl acetate jolting, each 20ml merges ethyl acetate liquid, and evaporate to dryness, residue add methyl alcohol 2ml makes dissolving as need testing solution; Other gets the scutelloside reference substance and adds methyl alcohol and process the solution that every 1ml contains 2mg, as reference substance solution; Drawing need testing solution 2 μ l, reference substance solution 5 μ l, put respectively on same silica gel thin-layer plate, is developping agent with the upper solution of 7: 4: 3 butyl acetate-formic acid-water, launches, and takes out, and dries; Spray is with 2% ferric trichloride ethanolic solution, and it is clear to make it to develop the color; In the test sample chromatogram with reference substance chromatogram relevant position on show the spot of same color;
Assay:
According to high effective liquid chromatography for measuring, chromatographic condition and system suitability test use octadecylsilane chemically bonded silica to be filling agent; 300: 35 0.02mol/L potassium dihydrogen phosphate: methyl alcohol is moving phase; The detection wavelength is 324nm;
The preparation of reference substance solution: it is an amount of that precision takes by weighing the chlorogenic acid reference substance, adds moving phase and process the solution that every 1ml contains 0.02mg, as reference substance solution;
The preparation of need testing solution: precision is measured these article 5ml under the loading amount item, puts in the 100ml measuring bottle, adds moving phase and is diluted to scale, filters with 0.45 μ m miillpore filter, gets subsequent filtrate as need testing solution; Accurate respectively reference substance solution and each the 10 μ l of need testing solution of drawing of determination method inject liquid chromatograph, measure, and promptly get.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100835144A CN102145134B (en) | 2007-03-23 | 2007-03-23 | Detection methods of pharmaceutical composition for treatment of wind-heat cold of children |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011100835144A CN102145134B (en) | 2007-03-23 | 2007-03-23 | Detection methods of pharmaceutical composition for treatment of wind-heat cold of children |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007100646930A Division CN101269182B (en) | 2007-03-23 | 2007-03-23 | Pharmaceutical composition for treating children's wind-heat cold |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102145134A CN102145134A (en) | 2011-08-10 |
| CN102145134B true CN102145134B (en) | 2012-10-31 |
Family
ID=44419735
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011100835144A Active CN102145134B (en) | 2007-03-23 | 2007-03-23 | Detection methods of pharmaceutical composition for treatment of wind-heat cold of children |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102145134B (en) |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1785347A (en) * | 2005-11-21 | 2006-06-14 | 贵州益佰制药股份有限公司 | Quality control method of Chinese medicinal preparation for treating child hyperpyrexia |
| CN1785371A (en) * | 2005-11-10 | 2006-06-14 | 贵州益佰制药股份有限公司 | Chinese medicinal preparation for abating child fever and its preparation method |
-
2007
- 2007-03-23 CN CN2011100835144A patent/CN102145134B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1785371A (en) * | 2005-11-10 | 2006-06-14 | 贵州益佰制药股份有限公司 | Chinese medicinal preparation for abating child fever and its preparation method |
| CN1785347A (en) * | 2005-11-21 | 2006-06-14 | 贵州益佰制药股份有限公司 | Quality control method of Chinese medicinal preparation for treating child hyperpyrexia |
Non-Patent Citations (11)
| Title |
|---|
| "三步法"治疗小儿发热;肖挹等;《四川中医》;20021215;第20卷(第12期);10-11 * |
| HPLC法测定小儿退热口服液中绿原酸的含量;魏尊喜;《安徽医药》;20060528;第10卷(第05期);342 * |
| 卫生部.小儿退热口服液.《卫生部颁药品标准中药成方制剂第6册》.1992, * |
| 小儿退热口服液治疗小儿外感发热的临床观察;高之君等;《吉林医学》;20060925(第09期);1075 * |
| 小儿退热口服液的制备与质量标准;李祥永;《江苏临床医学杂志》;20021230;第6卷(第06期);649 * |
| 小儿退热口服液质量标准研究;黄莹等;《实用中西医结合临床》;20011231;第1卷(第01期);58 * |
| 李祥永.小儿退热口服液的制备与质量标准.《江苏临床医学杂志》.2002,第6卷(第06期),649. |
| 肖挹等."三步法"治疗小儿发热.《四川中医》.2002,第20卷(第12期),10-11. |
| 高之君等.小儿退热口服液治疗小儿外感发热的临床观察.《吉林医学》.2006,(第09期),1075. |
| 魏尊喜.HPLC法测定小儿退热口服液中绿原酸的含量.《安徽医药》.2006,第10卷(第05期),342. |
| 黄莹等.小儿退热口服液质量标准研究.《实用中西医结合临床》.2001,第1卷(第01期),58. |
Also Published As
| Publication number | Publication date |
|---|---|
| CN102145134A (en) | 2011-08-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1925864B (en) | Plant-based medicament for the treatment of hepatitis c | |
| CN102657823B (en) | Traditional Chinese medicine composition with anticancer effect and preparation method and detection method thereof | |
| CN102233119B (en) | Traditional Chinese medicine composition for treating fatty liver and preparation method thereof | |
| CN100533140C (en) | Checking method for depression relieving and tranquilizing preparation | |
| CN103071006B (en) | Preparation method and quality inspection method of traditional Chinese medicine for treating kidney failure | |
| CN102590433A (en) | Ganchang preparation quality detection method | |
| CN101269182B (en) | Pharmaceutical composition for treating children's wind-heat cold | |
| CN106620610A (en) | Preparation method of liquorice heart fire purging granule | |
| Li | Chinese herbal medicine | |
| CN102488837A (en) | Sugar-free granule for treating chronic fatigue syndrome and preparation method and detecting method thereof | |
| CN100443498C (en) | Use of anti-inflammatory medicine for scheelite total saponin and its saponin compound | |
| CN105434511B (en) | A kind of hymsleya amabilis medicine materical crude slice and its preparation method and application | |
| CN102266503B (en) | Sugar-free anemopyretic cold granules and preparation method thereof | |
| CN104116963A (en) | Radix fici simplicissimae compound preparation for resisting oxidation and delaying senescence and preparation method of radix fici simplicissimae compound preparation | |
| CN101912594A (en) | Traditional Chinese medicine preparation for treating gastrointestinal diseases | |
| CN101716270B (en) | Method for detecting quality of traditional Chinese herbal medicament compound preparation for invigorating blood and regulating menses | |
| CN100473987C (en) | Quality control method for Chinese medicine composition preparation for treating children's cold | |
| CN102008704B (en) | Detection method for composition having middle-warming stomach harmonizing function | |
| CN105535533A (en) | Traditional Chinese medicine composition for treatinggastritis | |
| CN102145134B (en) | Detection methods of pharmaceutical composition for treatment of wind-heat cold of children | |
| CN1954838B (en) | Medical composite of antineoplastic | |
| CN1331523C (en) | Compound stemona cough stopping medicine and its preparation method | |
| CN105456591A (en) | Manufacturing method of cedar seed preparation for heart nourishing | |
| CN101073611B (en) | Medicinal composition for preventing tumor | |
| CN102119978B (en) | Composition for relieving exterior syndrome and clearing away heat and toxic materials, and preparation method and detection method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |