CN101773563B - Medicine composition - Google Patents
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- CN101773563B CN101773563B CN2010101403853A CN201010140385A CN101773563B CN 101773563 B CN101773563 B CN 101773563B CN 2010101403853 A CN2010101403853 A CN 2010101403853A CN 201010140385 A CN201010140385 A CN 201010140385A CN 101773563 B CN101773563 B CN 101773563B
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Abstract
The invention provides a medicine composition, which is prepared from the following medicine effect raw materials: cholic acid, nacre, hyodesoxycholic acid, gardenia, cornu bubali, radix isatidis, baicalin and honeysuckle. The medicine composition comprises the following medicine effect ingredients in percentage by weight: 1.5 to 4.2 parts of cholic acid type ingredients, 3.5 to 5.5 parts of baicalin, 0.1 to 0.5 part of jasminoidin, 3.5 to 5.5 parts of amino acid, 0.05 to 0.08 part of nucleosides compounds and at most 0.1 part of chlorogenic acid. Experiments show that the medicine composition of the invention has the medicine effect similar to Qingkailing, but the anaphylactic reaction is obviously reduced, and the medicine use safety is improved.
Description
Technical field
The invention belongs to field of medicaments, be specifically related to a kind of pharmaceutical composition with heat-clearing and toxic substances removing, eleminating phlegm and freeing channels, consciousness and resuscitation restoring effect.
Background technology
QINKAILING ZHUSHEYE is derived from Qing Dynasty's Wu's a kind of jade and shows " cow-bezoar bolus for resurrection " in " Wenbing Tiaobian, Detailed Analysis of Epidemic Warm Diseases "; Be stated from that " one one of Chinese pharmacopoeia version in 2005 is made up of cholic acid, Concha Margaritifera (powder), Hyodeoxycholic Acid, Fructus Gardeniae, Cornu Bubali (powder), Radix Isatidis, baicalin and Flos Lonicerae.Cholic acid, Hyodeoxycholic Acid heat-clearing and toxic substances removing in the side, waking up the patient from unconsciousness by dissipating phlegm, cool liver endogenous wind stopping; The baicalin heat-clearing and toxic substances removing; Cornu Bubali, Flos Lonicerae, Fructus Gardeniae, Radix Isatidis phase 5, clearing away heat-fire, removing pathogenic heat from blood and toxic substance from the body; The Concha Margaritifera suppressing the hyperactive liver and subsiding YANG, tranquillizing and allaying excitement; All medicine phases 5 are played heat-clearing and toxic substances removing, the merit of eleminating phlegm and freeing channels, consciousness and resuscitation restoring altogether.The clinical calentura that is used for, coma, apoplectic hemiplegia, unconsciousness; Acute hepatitis, upper respiratory tract infection, pneumonia, cerebral thrombosis, cerebral hemorrhage are seen the treatment of above-mentioned patient.
2003, in effective control SARS Chinese patent medicine that control SARS tackling of key scientific and technical problems headquarter of country announce, QINKAILING ZHUSHEYE ranked first place, and was classified as integrative therapy SARS and antipyretic and antidotal type basis medication.In February, 2004, ministry of Health of China is listed QINKAILING ZHUSHEYE, oral liquid, soft capsule etc. in " human and bird fluenza diagnosis and treatment scheme (trying) " in again.A few days ago, State Administration of Traditional Chinese Medicine formulates and also recommends to use QINGKAILING medicine treatment hand-foot-mouth disease in " Chinese medicine prevention hand-foot-mouth disease clinical technology guide (version in 2009) " that issues.
But along with wide clinical application, its untoward reaction/incident also day by day causes people's extensive concern.Statistics shows that QINKAILING ZHUSHEYE untoward reaction/incident is mainly involved skin and the adnexa infringement damages with general, ranks first with anaphylaxis.Anaphylaxis after medication in 2-30 minute incidence rate the highest, general symptom shows as erythra, shiver with cold, hyperpyrexia, nervous, uncomfortable in chest, out of breath, dyspnea etc.Also effectively do not solve this anaphylactoid relevant report at present.
Summary of the invention
To above-mentioned deficiency, the present invention provides a kind of pharmaceutical composition, and its drug effect and QINGKAILING are suitable, but anaphylaxis is little, and safety is higher.
Pharmaceutical composition of the present invention; Process by following pharmacodynamic raw materials: cholic acid, Concha Margaritifera, Hyodeoxycholic Acid, Fructus Gardeniae, Cornu Bubali, Radix Isatidis, baicalin and Flos Lonicerae; This pharmaceutical composition comprises the active ingredient of following weight portion: bile acids 1.5-4.2 part, baicalin 3.5-5.5 part, jasminoidin 0.1-0.5 part, aminoacid 3.5-5.5 part, nucleoside compound 0.05-0.08 part, chlorogenic acid is no more than 0.1 part.Preferably, bile acids 2.0-3.5 part, baicalin 4.0-5.0 part, jasminoidin 0.1-0.3 part, aminoacid 4.0-5.0 part, nucleoside compound 0.05-0.08 part, chlorogenic acid is no more than 0.08 part.More preferably, bile acids 2.0-3.0 part, baicalin 4.5-5.0 part, jasminoidin 0.1-0.2 part, 4.5 parts in aminoacid, nucleoside compound 0.05-0.07 part, the chlorogenic acid proportion is no more than 0.05 part.
Wherein, the preferred proportion of cholic acid and Hyodeoxycholic Acid is 1 in the bile acid: 1.15-1.20 (weight); The preferred proportion of Cornu Bubali and Concha Margaritifera is 1: 1.5-2.5 (weight).
The present invention also provides a kind of method for preparing aforementioned pharmaceutical compositions; Comprise to extract jasminoidin in the Fructus Gardeniae; From Cornu Bubali and Concha Margaritifera, extract aminoacid, from Radix Isatidis, extract nucleoside compound, chlorogenic acid extracting from Flos Lonicerae; Then with these extracts in proportion with cholic acid, Hyodeoxycholic Acid and baicalin mix homogeneously, make pharmaceutical composition.
Above-mentioned jasminoidin, aminoacid, nucleoside compound, chlorogenic acid can prepare according to conventional method.
Particularly, nucleoside compound can prepare according to following method: Radix Isatidis decocte with water secondary, each 1 hour, collecting decoction; Filter, concentrate, add ethanol and make and contain the alcohol amount and reach 60%; Cold preservation filters filtrate recycling ethanol; Get the ucleosides crude extract, adopt repeatedly chromatography of macroporous adsorbent resin and ion exchange resin, get nucleoside compound.
Said aminoacid can prepare according to following method: Cornu Bubali powder with sulphuric acid difference hydrolysis 7～9 hours, filters merging filtrate with barium hydroxide solution, Concha Margaritifera powder; Regulate pH value to 3.5～4.0, filter, filtrating adds ethanol to be made and contains the alcohol amount and reach 60%; Cold preservation; Filter, filtrate recycling ethanol gets the aminoacid crude extract.Adopt crystallize method purification aminoacid.
Said jasminoidin can extract according to following method: Fructus Gardeniae decocte with water secondary, 1 hour for the first time, 0.5 hour for the second time, collecting decoction filtered, filtrating concentrates, and adds ethanol and makes and contain the alcohol amount and reach 60%, cold preservation filters, filtrate recycling ethanol, the Fructus Gardeniae crude extract.Get the Fructus Gardeniae crude extract, add water and suitably dilute, join and be equipped with on 1300 pretreated macroporous adsorption resin chromatography posts, absorption was 2 hours after last appearance finished.With 3 times of column volume water elutions, discard.10% ethanol elution of 4 times of column volumes of reuse discards, and with behind 3 times of column volume 20% ethanol elution stream part concentrating under reduced pressure, vacuum drying (60 ℃) gets the jasminoidin brown ceramic powder at last.
Said chlorogenic acid can extract according to following method: Flos Lonicerae decocte with water secondary, and each 0.5 hour, collecting decoction filtered; Filtrating concentrates, and adds ethanol and makes and contain the alcohol amount and reach 75%, filters, and filtrating is regulated pH value to 8.0; Ethanol is reclaimed in cold preservation, adds ethanol again and makes and contain the alcohol amount and reach 85%, cold preservation; Filter, filtrate recycling ethanol gets the chlorogenic acid bullion.Is in 1: 7 the chromatographic column with chlorogenic acid bullion and polyamide (80-100 order) by pack at 1: 5 post footpath and column length ratio of material ratio; Ethanol with 10% under the normal pressure is eluted to 14 times of column volumes with Peak Flow Rate; Collect the higher flow point of chlorogenic acid content, concentrate refining chlorogenic acid.
Pharmaceutical composition of the present invention can be injection, lyophilized injectable powder, tablet, capsule, granule, dispersible tablet, drop pill, effervescent tablet, soft capsule or the oral liquid that above-mentioned effective ingredient and suitable adjuvant are prepared into.Be preferably injection.
Experiment shows that pharmaceutical composition of the present invention has the drug effect suitable with QINGKAILING, but has significantly reduced anaphylaxis, has improved and has used high safety.
The specific embodiment
Following examples further specify content of the present invention, but should not be construed as limitation of the present invention.Under the situation that does not deviate from the present invention's spirit and essence, modification or replacement to the inventive method, step or condition are done all belong to scope of the present invention.
If do not specialize the conventional means that used technological means is well known to those skilled in the art among the embodiment.
The percentage sign that relates among the present invention " % " if do not specify, is meant mass percent; But the percentage ratio of solution except as otherwise herein provided, is meant and contains the some grams of solute among the solution 100ml; Percentage ratio between the liquid is meant the ratio of capacity in the time of 20 ℃.
Embodiment 1
1, extracts purification
1) gets Radix Isatidis 2000g decocte with water secondary, each 1 hour, add 8 times of water gagings (weight) for the first time; For the second time add 6 times of water gagings (weight), collecting decoction filters filtrating and is concentrated into 200ml; Add ethanol and make the alcohol amount of containing reach 60% ,-4 ℃ of cold preservations 8 hours, filter; Filtrate recycling ethanol gets the ucleosides crude extract.
Adopt the cationic resin column of dress post height about about 70-80ml to separate.Earlier crude extract is dissolved adjust pH to 1.5, carry out upper prop, collect effluent with the flow velocity of 8ml/min.Reuse deionized water eluting is collected effluent when pH value transfers to 2.5-3.0.Merge effluent, add ethanol precipitation, leave standstill filtration, oven dry gets nucleoside compound.
2) get Fructus Gardeniae 250g decocte with water secondary, add 8 times of water gagings (weight) for the first time and decocted 1 hour, add 6 times of water gagings (weight) for the second time and decocted 0.5 hour; Collecting decoction filters, and filtrating is concentrated into 25ml; Add ethanol and make the alcohol amount of containing reach 60% ,-4 ℃ of cold preservations 8 hours, filter; Filtrate recycling ethanol gets the Fructus Gardeniae crude extract.
Get the Fructus Gardeniae crude extract; Adding water to cumulative volume is 1000ml, joins 750g is housed (after resin soaked 2 hours with clear water, rinses well through pretreated; 3 times of volume 2mol/LHCl soaked 4 hours; The deionized water flushing is used 2mol/LNaOH instead and was soaked 4 hours to neutral, washes to neutral with deionized water.) 1300 macroporous adsorption resin chromatography posts on, the back absorption 2 hours that finishes of last appearance.Use the 3000ml water elution, discard.Reuse 4000ml 10% ethanol elution discards, and with behind the 3000ml 20% ethanol elution stream part concentrating under reduced pressure, vacuum drying (60 ℃) gets the jasminoidin brown ceramic powder at last.
3) extracting honeysuckle 50g decocte with water secondary, each 0.5 hour, add 8 times of water gagings (weight) for the first time, add 6 times of water gagings (weight), collecting decoction for the second time; Filter, filtrating is concentrated into 60ml, adds ethanol and makes and contain the alcohol amount and reach 75%, filters; Filtrating is regulated pH value to 8.0, and ethanol is reclaimed in-4 ℃ of cold preservation 8 hours, adds ethanol again and makes and contain the alcohol amount and reach 85%; Cold preservation-4 ℃ cold preservation 6 hours filters, and filtrate recycling ethanol gets the chlorogenic acid bullion.
Is in 1: 7 the chromatographic column with chlorogenic acid bullion and polyamide (80-100 order) by pack at 1: 5 post footpath and column length ratio of material ratio; Ethanol with 10% under the normal pressure is eluted to 14 times of column volumes with Peak Flow Rate; Collect the higher flow point of chlorogenic acid content, concentrate refining chlorogenic acid.
4) Cornu Bubali powder 250g with 7 times of amount 6mol/L sulphuric acid difference hydrolysis 8 hours, filters merging filtrate with 10 times of amount 4mol/L barium hydroxide solutions, Concha Margaritifera powder 500g; Regulate pH value to 3.5, filter, filtrating adds ethanol to be made and contains the alcohol amount and reach 60%;-4 ℃ of cold preservation 10 hours; Filter, filtrate recycling ethanol gets the aminoacid crude extract.
With crude extract dissolving, to regulate about pH value to 3 with ammonia, deposition is removed in centrifugalize, and solution decompression is concentrated, and puts into refrigerator overnight when having crystal to separate out, and separates out crystal, inclines to the supernatant and continue it is concentrated and separate out crystal, merges crystal twice.Use the water dissolution crystal, add small amount of activated, fully stir after-filtration, logical hydrogen chloride gas is put into refrigerator overnight after saturated in the filtrating, separates out the aminoacid crystal, and again that it is clean with absolute ethanol washing, 50 ℃ of oven dry promptly get in baking oven.
2, the preparation of injection with small volume
Preparation example 1
Get jasminoidin 0.2g, nucleoside compound 0.07g, aminoacid 4.5g after the purification, after the dissolving, be added in 75% alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 2g (1: 1.15); Mixing adds ethanol and makes and contain alcohol amount and reach 75%, regulates pH value to 7.0; Cold preservation filters filtrate recycling ethanol; Add water, cold preservation gets solution 1.Get the 4.5g baicalin and dissolve with water for injection, adjust pH to 7.5 adds the solution contain the 0.05g chlorogenic acid, and mixing merges with solution 1, mixing, and add the injection water to 1000ml, and again after charcoal treatment, cold preservation, embedding, sterilization promptly gets.
Preparation example 2
Get jasminoidin 0.1g, nucleoside compound 0.05g, aminoacid 5.5g (ratio of Cornu Bubali and Concha Margaritifera is 1: 2 in the raw material) after the purification, after the dissolving, be added in 75% alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 3.5g (1: 1.17); Mixing adds ethanol and makes and contain alcohol amount and reach 75%, regulates pH value to 7.0; Cold preservation filters filtrate recycling ethanol; Add water, cold preservation gets solution 1.Get the 5g baicalin and dissolve with water for injection, adjust pH to 7.5 adds the solution contain the 0.08g chlorogenic acid, and mixing merges with solution 1, mixing, and add the injection water to 1000ml, and again after charcoal treatment, cold preservation, embedding, sterilization promptly gets.
Preparation example 3
Get jasminoidin 0.5g, nucleoside compound 0.08g, aminoacid 3.5g (ratio of Cornu Bubali and Concha Margaritifera is 1: 2.5 in the raw material) after the purification, after the dissolving, be added in 75% alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 4g (1: 1.20); Mixing adds ethanol and makes and contain alcohol amount and reach 75%, regulates pH value to 7.0; Cold preservation filters filtrate recycling ethanol; Add water, cold preservation gets solution 1.Get the 4g baicalin and dissolve with water for injection, adjust pH to 7.5 adds the solution contain the 0.06g chlorogenic acid, and mixing merges with solution 1, mixing, and add the injection water to 1000ml, and again after charcoal treatment, cold preservation, embedding, sterilization promptly gets.
Preparation example 4
Get jasminoidin 0.3g, nucleoside compound 0.06g, aminoacid 5.0g (ratio of Cornu Bubali and Concha Margaritifera is 1: 1.5 in the raw material) after the purification, after the dissolving, be added in 75% alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 1.5g (1: 1.16); Mixing adds ethanol and makes and contain alcohol amount and reach 75%, regulates pH value to 7.0; Cold preservation filters filtrate recycling ethanol; Add water, cold preservation gets solution 1.Get the 3.5g baicalin and dissolve with water for injection, adjust pH to 7.5 adds the solution contain the 0.07g chlorogenic acid, and mixing merges with solution 1, mixing, and add the injection water to 1000ml, and again after charcoal treatment, cold preservation, embedding, sterilization promptly gets.
3, the preparation of lyophilized powder
Get jasminoidin 0.2g, nucleoside compound 0.07g, aminoacid 4.5g after the purification, after the dissolving, be added in 75% alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 2g (1: 1.15); Mixing adds ethanol and makes and contain alcohol amount and reach 75%, regulates pH value to 7.0; Cold preservation filters filtrate recycling ethanol; Add water, cold preservation gets solution 1.Get the 4.5g baicalin and dissolve with water for injection, adjust pH to 7.5 adds the solution contain the 0.05g chlorogenic acid, and mixing merges with solution 1, mixing, and add the injection water to 1000ml, and again after charcoal treatment, cold preservation, embedding, lyophilization promptly gets.
4, the preparation of high-capacity injection
Get jasminoidin 0.1g, nucleoside compound 0.05g, aminoacid 5.5g after the purification, after the dissolving, be added in 75% alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 3.5g (1: 1.16); Mixing adds ethanol and makes and contain alcohol amount and reach 75%, regulates pH value to 7.0; Cold preservation filters filtrate recycling ethanol; Add water, cold preservation gets solution 1.Get the 5g baicalin and dissolve with water for injection, adjust pH to 7.5 adds the solution that contains the 0.08g chlorogenic acid, and mixing merges with solution 1; Mixing adds sodium chloride solution or glucose solution or glucose saline, again after charcoal treatment, and cold preservation; Filter, embedding, sterilization promptly gets.
5, the preparation of granule
Get jasminoidin 0.5g, nucleoside compound 0.08g, aminoacid 3.5g after the purification; Chlorogenic acid 0.06g with the cane sugar powder mix homogeneously, adds the alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 4g (1: 1.20); Add the solution that contains baicalin 4g again; Behind the mix homogeneously, granulation, drying, granulate mix, pack, pack, and promptly get.
6, the preparation of tablet
Get jasminoidin 0.3g, nucleoside compound 0.06g, aminoacid 5.0g after the purification, chlorogenic acid 0.07g is behind adjuvant mix homogeneously such as cane sugar powder, dextrin, microcrystalline Cellulose; Add the alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 1.5g (1: 1.17), add the solution that contains baicalin 3.5g, mixing again; Cold drying is ground into fine powder, granulates; Tabletting, the bag film-coat promptly gets.
7, the preparation of effervescent tablet
Get jasminoidin 0.25g, nucleoside compound 0.05g, aminoacid 3.5g after the purification; Chlorogenic acid 0.05g with the dextrin mix homogeneously, adds the alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 3.0g (1: 1.18); Add the solution that contains baicalin 5.1g again; Mix homogeneously, cold drying, pulverize fine powder 1.Behind the polyethylene glycol 6000 heating and melting, add sodium bicarbonate, mixing, put condensation solid after, pulverize fine powder 2.Citric acid, cyclamate are crossed 80 mesh sieves and fine powder 1 and fine powder 2 mixings, use alcohol granulation, cold drying, tabletting promptly gets.
8, the preparation of capsule
Get jasminoidin 0.4g, nucleoside compound 0.07g, aminoacid 4.0g after the purification, chlorogenic acid 0.05g is behind the starch mix homogeneously; Add the alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 2.0g (1: 1.17), add the solution that contains baicalin 4.0g, mixing again; Cold drying; Be ground into fine powder, incapsulate, promptly get.
9, the preparation of oral liquid
Get jasminoidin 0.3g, nucleoside compound 0.06g, aminoacid 4.5g after the purification, chlorogenic acid 0.04g is dissolved in water.Join in the alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 3.0g (1: 1.16), it is an amount of to add ethanol, leaves standstill, and filters; Filtrate recycling ethanol, it is an amount of to add water, leaves standstill, and adds baicalin 3.8g; Regulate pH value and make dissolving, the adding correctives is an amount of and add water to 1000ml, regulates pH value to 7.2-7.5 with sodium hydroxide, stirs; Leave standstill, filter, promptly get.
10, preparation of soft capsule
Get jasminoidin 0.35g, nucleoside compound 0.07g, aminoacid 4.0g after the purification, chlorogenic acid 0.03g is dissolved in water.Join in the alcoholic solution that contains cholic acid, Hyodeoxycholic Acid 4.0g (1: 1.15); Be condensed into extractum, the miscella substrate that adding is processed with Semen Maydis oil, soybean phospholipid, Cera Flava is an amount of, fully mixes; After being ground to fully evenly with colloid mill; Add baicalin 4.3g again, be ground to evenly, process soft capsule.
Test Example 1 analgesic Test and Comparison Study
Sample: injection with small volume prepares routine 1 sample, commercially available QINKAILING ZHUSHEYE
Interior preparation of giving birth to pyrogen: collect rabbit heparinization whole blood; Dosage by 7 μ g/100ml adds escherichia coli endotoxin; Put vibration cultivation in 37 ℃ of-38 ℃ of water-baths, the centrifugal slurry of dehematizing after 1 hour adds the apyrogeneity normal saline with blood plasma equivalent; Continue vibration and cultivated 18 hours, the centrifuging and taking supernatant is put 4 ℃ of refrigerators and is preserved subsequent use.All operation is all carried out under aseptic condition, gives birth to pyrogen in the gained and all takes a sample and do heat-resistant experiment, can use after guaranteeing not have contaminated with endotoxins, tests rewarming in preposition 37 ℃ of water-baths.
Animal and body temperature are measured: male Japanese white big ear rabbit, and body weight 2.2kg-2.5kg, basic rectal temperature is between 38.7 ℃-39.5 ℃.Before the test animal is placed on the special rabbit frame, with digital thermometer probe insertion anal 10cm, simulated temperature measurement 2 days, carried out heat run on the 3rd day at 3 hours-4 hours every day.To pop one's head in during thermometric and insert anal 10cm and be fixed in root of the tail portion, treat that animal is stable after, whenever, get 3 meansigma methodss as the animal basal body temperature at a distance from 10 minutes thermometrics 1 time.
Divide into groups: 40 rabbit are divided into 4 groups at random, 10 every group.Negative control group: every injection gives normal saline; Positive controls: give birth to pyrogen in every injection gives; Test 1 group: every injection earlier gives the interior pyrogen of giving birth to, and injects after 0.5 hour to prepare routine 1 sample again; Test 2 groups: give birth to pyrogen in every injection gives earlier, inject again after 0.5 hour and give commercially available QINKAILING ZHUSHEYE.Dosage is 1ml/kg.
The result: preparing routine 1 sample and commercially available QINKAILING ZHUSHEYE all has refrigeration function.See table 1 for details.
Table 1 refrigeration function contrast table
Test Example 2 analgesic activity comparative studies
Sample: lyophilized powder prepares routine sample, commercially available QINGKAILING sample
Method: 40 mices are divided into 4 groups at random, 10 every group.Negative control group: every injection gives normal saline; Positive controls: every orally give ibuprofen; Test 1 group: every injection gives lyophilized powder and prepares routine sample; Test 2 groups: every injection gives commercially available QINGKAILING sample.Dosage sees table 2 for details.After the administration 1 hour, each organized lumbar injection 0.6% acetum 0.4ml, write down the number of times that 10 minutes endogenous cause of ill pain is turned round body, calculating mean value.
The result: with the normal saline group relatively, lyophilized powder prepares routine sample and commercially available QINGKAILING sample all can significantly be reduced and turn round the body number of times.See table 2 for details.
The influence of writhing response due to table 2 pair mice acetic acid stimulates
Test Example 3 antiinflammatory action comparative studies
Sample: injection with small volume prepares routine 1 sample, commercially available QINKAILING ZHUSHEYE
Method: select 30 of male mice in kunming for use, body weight 25-30g is divided into 3 groups at random, 10 every group.Be divided into model control group and 1 group of test, 2 groups of tests.Every group of mice is coated with xylene in the auris dextra exterior feature, and every 0.03ml causes auricle edema, and left ear compares.After the modeling 15 minutes, test 1 group of vein and prepare routine 1 sample, test 2 groups of veins and give commercially available sample; Dosage is 20ml/kg, puts to death mice after the administration in 45 minutes, with the card punch of diameter 8mm ears is downcut with the position homalographic; Precision is weighed, and calculates the poor of left and right auricle weight.
Result: prepare routine 1 sample and the equal xylol of commercially available sample and cause mice auricle swelling obvious inhibitory action is arranged.The result sees table 3.
Table 3 xylol causes the influence of mice auricle swelling
Test Example 4 hypersensitive test comparative studies
Sample: injection with small volume prepares routine 1 sample, commercially available QINKAILING ZHUSHEYE
Method: get 24 of body weight 250-300g Cavia porcelluss, be divided into four groups at random, 6 every group.Negative control group: lumbar injection 0.9% sodium chloride injection; Positive controls: lumbar injection 5% fresh albumen solution.Test 1 group: lumbar injection prepares routine 1 sample; Test 2 groups: the commercially available QINKAILING ZHUSHEYE of lumbar injection.Dosage only is 0.5ml/.The next day once, totally three times.After the first administration 14 days, 21 days, get 2 at random for every group, test 1 group and 2 groups respectively by auricular vein injection routine 1 sample of preparation and commercially available QINKAILING ZHUSHEYE; Negative control group is injected 0.9% sodium chloride injection, and positive controls is injected 5% fresh albumen solution.Dosage only is 1.0ml/.Observe immediately after the administration that animal has or not sneeze, scratches nose, dry cough or cough, tremble, the anaphylaxis of perpendicular hair, tic, dyspnea, gatism, shock and death, be 15 minutes observing time.Table 4 is seen in the anaphylaxis classification.
Table 4 anaphylaxis classification and decision method as a result
The result: the Cavia porcellus anaphylaxis progression of injecting the negative control group of 0.9% sodium chloride injection is 0, does not have irritated reaction; The positive controls Cavia porcellus of injecting 5% Ovum Gallus domesticus album sneeze occurs, scratches nose, retch or cough, twitch, tremble, anaphylaxiss such as dyspnea, gatism, shock, and all dead in 15min, anaphylaxis progression is level Four, experimental condition is set up.6 Cavia porcelluss that the test of routine 1 sample of injection preparation is 1 group all do not have irritated reaction, and anaphylaxis progression is 0.Injecting in 6 Cavia porcelluss of 2 groups of tests of commercially available QINKAILING ZHUSHEYE has 2 Cavia porcelluss nose, a perpendicular hair phenomenon to occur slightly grabbing, and anaphylaxis progression is 1.Show the safe of routine 1 sample of preparation in commercially available QINKAILING ZHUSHEYE.
Other preparation example with among the embodiment is carried out the above-mentioned test of pesticide effectiveness and hypersensitive test has also obtained similar effects.
Claims (10)
1. pharmaceutical composition; It is processed by following pharmacodynamic raw materials: cholic acid, Concha Margaritifera, Hyodeoxycholic Acid, Fructus Gardeniae, Cornu Bubali, Radix Isatidis, baicalin and Flos Lonicerae; This pharmaceutical composition comprises the active ingredient of following weight portion: bile acids 1.5-4.2 part, baicalin 3.5-5.5 part, jasminoidin 0.1-0.5 part, aminoacid 3.5-5.5 part, nucleoside compound 0.05-0.08 part, and chlorogenic acid is no more than 0.1 part;
Wherein said jasminoidin extracts according to following method: Fructus Gardeniae decocte with water secondary, 1 hour for the first time, 0.5 hour for the second time, collecting decoction filtered, filtrating concentrates, and adds ethanol and makes and contain the alcohol amount and reach 60%, cold preservation filters, filtrate recycling ethanol, the Fructus Gardeniae crude extract; Get the Fructus Gardeniae crude extract, add water and suitably dilute, join and be equipped with on 1300 pretreated macroporous adsorption resin chromatography posts, absorption was 2 hours after last appearance finished; With 3 times of column volume water elutions, discard; 10% ethanol elution of 4 times of column volumes of reuse discards, and with behind 3 times of column volume 20% ethanol elution stream part concentrating under reduced pressure, vacuum drying gets the jasminoidin brown ceramic powder at last;
Said chlorogenic acid extracts according to following method: Flos Lonicerae decocte with water secondary, and each 0.5 hour, collecting decoction filtered; Filtrating concentrates, and adds ethanol and makes and contain the alcohol amount and reach 75%, filters, and filtrating is regulated pH value to 8.0; Ethanol is reclaimed in cold preservation, adds ethanol again and makes and contain the alcohol amount and reach 85%, cold preservation; Filter, filtrate recycling ethanol gets the chlorogenic acid bullion; Is in 1: 7 the chromatographic column with chlorogenic acid bullion and polyamide by pack at 1: 5 post footpath and column length ratio of material ratio, and normal pressure is eluted to 14 times of column volumes with 10% ethanol with Peak Flow Rate down, collects the higher flow point of chlorogenic acid content, concentrate make with extra care chlorogenic acid;
Said aminoacid prepares according to following method: Cornu Bubali powder with sulphuric acid difference hydrolysis 7～9 hours, filters merging filtrate with barium hydroxide solution, Concha Margaritifera powder; Regulate pH value to 3.5～4.0, filter, filtrating adds ethanol to be made and contains the alcohol amount and reach 60%; Cold preservation filters filtrate recycling ethanol; Get the aminoacid crude extract, adopt crystallize method purification aminoacid then;
Said nucleoside compound prepares according to following method: Radix Isatidis decocte with water secondary, each 1 hour, collecting decoction; Filter, concentrate, add ethanol and make and contain the alcohol amount and reach 60%; Cold preservation filters filtrate recycling ethanol; Get the ucleosides crude extract, adopt macroporous adsorbent resin and resinbed to analyse respectively, get nucleoside compound.
2. pharmaceutical composition as claimed in claim 1; It is characterized in that comprising the active ingredient of following weight portion: bile acids 2.0-3.5 part, baicalin 4.0-5.0 part, jasminoidin 0.1-0.3 part, aminoacid 4.0-5.0 part, nucleoside compound 0.05-0.08 part, chlorogenic acid is no more than 0.08 part.
3. pharmaceutical composition as claimed in claim 1; It is characterized in that comprising the active ingredient of following weight portion: bile acids 2.0-3.0 part, baicalin 4.5-5.0 part, jasminoidin 0.1-0.2 part, 4.5 parts in aminoacid, nucleoside compound 0.05-0.07 part, the chlorogenic acid proportion is no more than 0.05 part.
4. pharmaceutical composition as claimed in claim 1 is characterized in that, the weight ratio of cholic acid and Hyodeoxycholic Acid is 1 in the said bile acid: 1.15-1.20; The weight ratio of said Cornu Bubali and Concha Margaritifera is 1: 1.5-2.5.
5. like each described pharmaceutical composition of claim 1～4, it is injection, lyophilized injectable powder, tablet, capsule, granule, dispersible tablet, drop pill, effervescent tablet, soft capsule or oral liquid that said effective ingredient and suitable adjuvant are prepared into.
6. method for preparing the arbitrary said pharmaceutical composition of claim 1～5; It comprises to extract jasminoidin in the Fructus Gardeniae; From Cornu Bubali and Concha Margaritifera, extract aminoacid, from Radix Isatidis, extract nucleoside compound, chlorogenic acid extracting from Flos Lonicerae; Then with these extracts in proportion with cholic acid, Hyodeoxycholic Acid and baicalin mix homogeneously, make pharmaceutical composition.
7. method as claimed in claim 6 is characterized in that, said nucleoside compound prepares according to following method: Radix Isatidis decocte with water secondary, each 1 hour; Collecting decoction filters, and concentrates, and adds ethanol and makes and contain the alcohol amount and reach 60%; Cold preservation filters filtrate recycling ethanol; Get the ucleosides crude extract, adopt macroporous adsorbent resin and resinbed to analyse respectively, get nucleoside compound.
8. method as claimed in claim 6 is characterized in that, said aminoacid prepares according to following method: Cornu Bubali powder, filters with sulphuric acid difference hydrolysis 7～9 hours with barium hydroxide solution, Concha Margaritifera powder; Merging filtrate is regulated pH value to 3.5～4.0, filters; Filtrating adds ethanol to be made and contains alcohol amount and reach 60%, and cold preservation filters; Filtrate recycling ethanol gets the aminoacid crude extract, adopts crystallize method purification aminoacid then.
9. method as claimed in claim 6 is characterized in that, said jasminoidin extracts according to following method: Fructus Gardeniae decocte with water secondary, 1 hour for the first time; 0.5 hour for the second time, collecting decoction filtered; Filtrating concentrates, and adds ethanol and makes and contain the alcohol amount and reach 60%, cold preservation; Filter, filtrate recycling ethanol gets the Fructus Gardeniae crude extract; Get the Fructus Gardeniae crude extract, add water and suitably dilute, join and be equipped with on 1300 pretreated macroporous adsorption resin chromatography posts, absorption was 2 hours after last appearance finished; With 3 times of column volume water elutions, discard; 10% ethanol elution of 4 times of column volumes of reuse discards, and with behind 3 times of column volume 20% ethanol elution stream part concentrating under reduced pressure, vacuum drying gets the jasminoidin brown ceramic powder at last.
10. method as claimed in claim 6 is characterized in that, said chlorogenic acid extracts according to following method: Flos Lonicerae decocte with water secondary, each 0.5 hour, collecting decoction; Filter, filtrating concentrates, and adds ethanol and makes and contain the alcohol amount and reach 75%, filters; Filtrating is regulated pH value to 8.0, and ethanol is reclaimed in cold preservation, adds ethanol again and makes and contain the alcohol amount and reach 85%; Cold preservation filters, and filtrate recycling ethanol gets the chlorogenic acid bullion; Is in 1: 7 the chromatographic column with chlorogenic acid bullion and polyamide by pack at 1: 5 post footpath and column length ratio of material ratio, and normal pressure is eluted to 14 times of column volumes with 10% ethanol with Peak Flow Rate down, collects the higher flow point of chlorogenic acid content, concentrate make with extra care chlorogenic acid.
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| CN104800234A (en) * | 2015-04-22 | 2015-07-29 | 张永胜 | Geniposide and baicalin medicinal composition |
| CN106668040B (en) * | 2015-11-06 | 2020-02-11 | 合肥华方医药科技有限公司 | Pharmaceutical composition for preventing and treating neonatal jaundice, preparation method and application |
| CN105878470B (en) * | 2016-06-19 | 2019-07-05 | 神威药业集团有限公司 | A kind of Qing kailing pharmaceutical composition |
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