CN100394949C - Compound vitex negundo capsule, preparation method and uses thereof - Google Patents

Abstract

The present invention discloses a compound finger citron capsule prepared from 30 wt% of finger citron, 30 wt% of mahonia, 20 wt% of holly root and 20 wt% of screwtree. The present invention has the preparation method that the four medicines are used according to the weight proportion, are heated and backflow extracted with 50 to 80% of ethanol with the weight 6 to 8 times the total weight of each component for 1 to 4 times, and each time takes 1.0 to 2.0 hours. The components are filtered, filtrate is mixed and decompressed to be recovered to be without ethanol taste, thick extract is prepared by concentrating, the relative specific weight is from 1.28 to 1.30 (at 60 DGE C), the extract is placed in a vacuum drying oven and is decompressed and dried for 48 to 96 hours at 60 to 80 DEG C, and the extract is taken out of the vacuum drying oven and pulverized and is filtered with a sieve of 60 to 80 meshes. Medicinal powder and auxiliary materials are mixed evenly and than are filtered with the sieve of 60 to 80 meshes, soft materials are prepared from 70 to 90% of ethanol, granules are prepared with a sieve of 20 to 30 meshes and are dried at 60 to 80 DEG C, the granules are sized with the sieve of 20 to 30 meshes, 0 to 1.0% of magnesium stearate is added into the mixture to be mixed evenly, a capsule is filled, and the compound finger citron capsule is obtained.

Description

The preparation method of compound vitex negundo capsule

Technical field

The present invention relates to a kind of capsule that contains Folium vilicis Negundo and its production and use, specifically, the present invention relates to a kind of compound vitex negundo capsule and preparation method thereof and the purposes in acute gastroenteritis, dysentery, anemopyretic cold.

Background technology

The data that arrives according to the retrieval, the indication that contains the Folium vilicis Negundo Chinese patent medicine mainly concentrates on flu, and product has Cui Lian detoxifcation sheet, fast Su Da, guangdong herbal tea, the life luxuriant period of the day from 11 a.m. to 1 p.m of tea etc.

Cui Lian detoxifcation sheet phonetic name: Cuilian Jiedu Pian, [prescription] CUIYUNCAO 1140g Herba Andrographis 380g Radix Helicteris 570g Flos Ilicis Asprellae 570g Folium vilicis Negundo 285g Herba Menthae 190g is mainly used in heat-clearing and toxic substances removing, the diffusing wind heat of table.Be used for hyperpyrexia, headache, symptoms such as laryngopharynx swelling and pain and cough.[usage and consumption] is oral, one time 4,3～4 times on the one.What wherein play a major role is CUIYUNCAO, Herba Andrographis, and Folium vilicis Negundo just exists as ancillary drug simply, and its indication mainly is the external respiration disease, uses trouble to need repeatedly take in a large number.Also there are similar problem in fast Su Da, guangdong herbal tea, the life luxuriant period of the day from 11 a.m. to 1 p.m of tea etc.

Existing FUFANG WUZHIGAN PIAN (the accurate word Z24402162 of traditional Chinese medicines) is developed to form on the basis of Guangdong folk remedy, possesses more clinical basis.This side is made up of the Chinese medicine of heat-clearing and toxic substances removing such as Folium vilicis Negundo, Mahonia fortunei (Lindl.) Fedde, and Folium vilicis Negundo acrid in the mouth, hardship in the side and cool in nature are principal agent in the side, and the Mahonia fortunei (Lindl.) Fedde of compatibility bitter cold is a minister.Two medicines match, and Folium vilicis Negundo relatively induces sweat heat radiation and removing dampness stagnates, and Mahonia fortunei (Lindl.) Fedde is partial to heat clearing and damp drying to control dysentery, refinforces each other, loose outward pathogenic factor in the exterior and interior heat clearing away poison, and effect brings out the best in each other.Be equipped with kind removing summer-heat poison again, the cough-relieving that expels the heat-evil, the Flos Ilicis Asprellae that sore-throat relieving promotes the production of body fluid, Radix Helicteris, four flavors share, and reach clearing away heat and expelling pathogen in the exterior, removing heat from the lung and relieving sorethroat, the merit of dampness removing and diarrhea-relieving is used for acute gastroenteritis, dysentery, anemopyretic cold.

FUFANG WUZHIGAN PIAN

Fufang?Wuzhigan?Pian

[title] FUFANG WUZHIGAN PIAN

[prescription] Folium vilicis Negundo 900g Mahonia fortunei (Lindl.) Fedde 900g Flos Ilicis Asprellae 600g Radix Helicteris 600g makes 1000

[method for making] above four flavors decoct with water secondary, collecting decoction, filter, filtrate is concentrated in right amount, and the ethanol of adding 85% makes that to contain amount of alcohol be 47%, leave standstill, filter, filtrate is condensed into thick paste, drying is ground into fine powder, adds right amount of auxiliary materials, mixing is made granule, is pressed into 1000, sugar coating, promptly.

[character] this product is a coated tablet, removes to show brown or pale brown color behind the sugar-coat; Bitter in the mouth.

5 of this product are got in [discriminating] (1), remove sugar-coat, and porphyrize adds 1mol/L sulfuric acid solution 5ml and makes dissolving, filter, and get filtrate 2ml, put in the evaporating dish, heat in water-bath, and aubergine appears earlier in the ware edge, after overstrike gradually, become black at last.

(2) get 10 of this product, remove sugar-coat, porphyrize adds water 10ml and makes dissolving, filters, and filtrate adds isopyknic 3% sodium carbonate liquor, and heating in water bath 5 minutes takes out, and puts coldly, adds 1～2 of the paranitroanilinum test solution of new preparation, promptly shows red.

(3) get 10 of this product, remove sugar-coat, porphyrize adds ethanol 20ml, and warm macerating 15 minutes filters, and filtrate is put evaporate to dryness in the water-bath, and residue adds ethanol 5ml makes dissolving, as need testing solution.Other gets the berberine hydrochloride reference substance, adds ethanol and makes the solution that every ml contains 0.5mg, in contrast product solution.According to thin layer chromatography (appendix VIB) test, draw each 15 μ l of above-mentioned two kinds of solution, put respectively on same silica gel g thin-layer plate, be developing solvent with n-butyl alcohol-glacial acetic acid-water (7: 1: 2), launch, take out, airing is put under the ultra-violet lamp and is inspected under (254nm).In the test sample chromatograph, with the corresponding position of reference substance chromatograph on, the fluorescence speckle of existing same color.

[inspection] should meet every regulation relevant under the tablet item (appendix ID)

[function with cure mainly] is used for toxic indigestion, and be anxious, chronic gastroenteritis, dysentery, anemopyretic cold.

[usage and consumption] is oral, one time 4～6,3 times on the one.

[storage] sealing.

Analyze with modern technologies, find that the Folium vilicis Negundo (Folium Viticis Negundo, Folium Viticis Negundo) in the compound vitex negundo capsule prescription is rich in compositions such as volatile oil, flavonoid, diterpenoids, have antibacterial, effect such as eliminate the phlegm, relieving asthma.Multiple alkaloids such as the main component berberine hydrochloride of Mahonia fortunei (Lindl.) Fedde, palmatine, jateorhizine have effects such as antibiotic, antiinflammatory, analgesia.Flos Ilicis Asprellae and Radix Helicteris also are rich in low-polarity component.But, effective ingredient is to extract with decoction alcohol precipitation method in the former FUFANG WUZHIGAN PIAN, be unfavorable for the stripping of low-polarity component, so this coated tablet, not only technology is complicated, dose is big (one time 4～6,3 times on the one), and no assay item in its quality standard, product quality (quality standard of face FUFANG WUZHIGAN PIAN as follows) can't be controlled comprehensively.

Summary of the invention

At the problems referred to above, the inventor finds, adopts alcohol reflux, can improve the utilization rate and the content of effective of medical material, thereby reduces dose.And capsule has, and dosage is accurate, technology simple, disintegration rate is fast than tablet, release is rapid, the bioavailability height, aesthetic in appearance and be easy to carry about with one, advantages such as taking convenience are so the inventor develops out a kind of compound vitex negundo capsule on the basis of the FUFANG WUZHIGAN PIAN of Livzon Group Limin Pharmaceutical Factory.That is, an object of the present invention is to provide a kind of compound vitex negundo capsule.

Another object of the present invention provides the preparation method of this medicine.

The invention still further relates to the purposes of medicine of the present invention aspect acute gastroenteritis, dysentery, anemopyretic cold.

Medicine of the present invention is made by following component: Folium vilicis Negundo 20-40%, Mahonia fortunei (Lindl.) Fedde 20-40%, Flos Ilicis Asprellae 10-30%, Radix Helicteris 10-30%.

Preferred proportioning is: Folium vilicis Negundo 30%, Mahonia fortunei (Lindl.) Fedde 30%, Flos Ilicis Asprellae 20%, Radix Helicteris 20%.

The preparation method that above-mentioned each component is made medicine of the present invention is:

(1) get Folium vilicis Negundo, Mahonia fortunei (Lindl.) Fedde, Flos Ilicis Asprellae, Radix Helicteris, more than 6-10 times of 50-80% ethanol of each component gross weight, heating and refluxing extraction 1-4 time, each 1.0-2.0 hour.

(2) filter, merging filtrate, reclaim under reduced pressure is to there being the ethanol flavor, and is condensed into thick extractum, proportion is 1.28～1.30 (60 ℃ of surveys) relatively, places vacuum drying oven, 50-80 ℃ drying under reduced pressure 48-96 hour, take out, pulverize, cross the 60-80 mesh sieve;

(3) with medicated powder and adjuvant mix homogeneously, cross the 60-80 mesh sieve, with 70-90% ethanol system soft material, the 20-30 mesh sieve is granulated, 50-80 ℃ of oven dry, 20-30 mesh sieve granulate, the magnesium stearate mix homogeneously of adding 0-1.0%, filled capsules, promptly.

Preferred manufacturing procedure is:

(1) gets Folium vilicis Negundo 30%, Mahonia fortunei (Lindl.) Fedde 30%, Flos Ilicis Asprellae 20%, Radix Helicteris 20%,, add 10 times of amounts for the first time with 60% alcohol reflux 3 times, reflux, extract, 1.5 hours adds 8 times of amounts for the second time, during reflux, extract, 1, add 6 times of amounts for the third time, reflux, extract, 1 hour;

(2) filter, merging filtrate, reclaim under reduced pressure is to there being the ethanol flavor, and is condensed into thick extractum, and proportion is 1.28～1.30 (60 ℃ of surveys) relatively, places vacuum drying oven, and 70 ℃ of drying under reduced pressure 72 hours take out, and pulverize, and cross 80 mesh sieves;

(3) with medicated powder and microcrystalline Cellulose mix homogeneously, cross 60 mesh sieves, with 90% ethanol system soft material, 20 mesh sieves are granulated, 70 ℃ of oven dry, 20 mesh sieve granulate, the magnesium stearate mix homogeneously of adding 0.5%, filled capsules, promptly.

Adopt orthogonal test method that the optimised process of alcohol reflux is studied, and compare from aspect such as Caulis Mahoniae total alkaloid content, thin layer chromatography discriminating and former water decoction-alcohol sedimentation technology, total alkaloid contents is apparently higher than former technology as a result; The medicine index components that new technology is extracted reaches the purpose that reduces the medical material consumption, reduces dose obviously more than former technology.Every of this product contains Mahonia fortunei (Lindl.) Fedde with berberine hydrochloride (C ₂₀H ₁₇NO ₄HCL) meter must not be less than 1.26mg.

The quality standard of this medicine is except that by " capsule item of Chinese pharmacopoeia version in 2000 is down the projects such as moisture, disintegrate, content uniformity of requirements regulation, the thin layer chromatography discriminating of formulating Mahonia fortunei (Lindl.) Fedde (berberine hydrochloride, palmatine hydrochloride, Jatrorrhizine chloride).Formulated the content measuring standard of berberine hydrochloride in the Mahonia fortunei (Lindl.) Fedde simultaneously.Result of the test shows: berberine hydrochloride has good linear relationship in 2.52～12.6 μ g/ml scopes, r=0.9998, average recovery rate are 97.15%, and RSD% is 0.97%.Strong, simple and feasible, the favorable reproducibility of this method specificity can be used as the method for controlling this product quality.

Middle test agent to three batches of this medicines has carried out the preliminarily stabilised test, and by clinical research quality standard and " the requirement check of an appendix XIIIC of Chinese pharmacopoeia version in 2000 microbial limit test, the result shows: compound vitex negundo capsule is (temperature 15-30 ℃ of room temperature, relative humidity 40-95%) (40 ± 1 ℃ of temperature and under the acceleration environment, relative humidity 75 ± 1%) projects all change steady quality less than significant.

Compound vitex negundo capsule and FUFANG WUZHIGAN PIAN have been carried out following contrast test in pharmacodynamic study: the influence of (1) Dichlorodiphenyl Acetate induced mice capillary permeability; (2) xylol causes the influence of mouse ear inflammatory reaction; (3) PARA FORMALDEHYDE PRILLS(91,95) causes the influence of rat ankle joint inflammation; (4) Dichlorodiphenyl Acetate causes the influence (writhing method) of pain; (5) thermostimulation is caused influence (hot plate method) bitterly; (6) refrigeration function (to the influence of yeast pyrogenicity); (7) to the influence of mouse small intestine carbon powder propelling rate; (8) to the influence of isolated rabbit intestinal smooth muscle; (9) anti-diarrhea effect (Radix Et Rhizoma Rhei being caused the influence of letting out); (10) bacteriostatic test: representational to 13 kinds of external staphylococcus aureus, Salmonella enteritidis etc., mainly be the bacteriostasis that causes the pathogen and the conditioned pathogen of digestive tract infection.The result shows: improve extraction process, after reducing dose (by former one time 4～6,3 times on the one, reduce to one time 2,3 times on the one) the effect of compound vitex negundo capsule azovan blue seepage discharge when reducing acetic acid and cause the mouse peritoneal capillary permeability and increase stronger than FUFANG WUZHIGAN PIAN, P＜0.05; Other antiinflammatory, ease pain, bring down a fever, antidiarrheal, bacteriostatic effect is suitable with FUFANG WUZHIGAN PIAN, there was no significant difference.

Specific as follows:

1. medicine

Compound vitex negundo capsule---National Traditional Chinese Medicine Modernization Engineering Research Center provides, lot number: 030409, and specification: 3.0g crude drug/grain.Clinical consumption per day is: 2/time, and 3 times/day.Establish high, medium and low three dosage groups during experiment, press the body surface area conversion and be 4,2,1 dose,equivalents of clinical consumption per day.

FUFANG WUZHIGAN PIAN---Livzon Group Limin Pharmaceutical Factory provides, lot number: 020904.Specification: 3.0g crude drug/sheet.Clinical consumption per day is: 4～6 slices/time, and 3 times/day.Dosage group in establishing during experiment is pressed the body surface area conversion and is 2 dose,equivalents of clinical consumption per day.

Indometacin---Linfen, Shanxi Province biochemical-pharmaceutical factory is produced, lot number: 990808405.Specification: 25mg/ sheet.To press body surface area conversion be 2 dose,equivalents of clinical consumption per day to consumption during experiment.

Atropine-China Drug Co. GuangZhou, Guangdong Province city company packing, lot number: 920202

Dimethylbenzene---the Chinese People's Liberation Army's the 9066 plant produced, lot number: 932082

Azovan blue---Shanghai chemical reagent purchasing and supply station is sold lot number: 82-11-02.

2. strain

Staphylococcus aureus (26112), Jia Xingrongxuexinglianqiujun (32209), beta hemolytic streptococcus (32210), Bing Xinglianqiujun (32206), streptococcus pneumoniae (31001), salmonella typhi (50071), first type are paid salmonella typhi (50001), B-mode pair of salmonella typhi, Salmonella enteritidis (50041), shigella flexneri (51571), colon bacillus (44155), Pseudomonas aeruginosa (10211) and Candida albicans (98001), totally ten three kinds.Except that Candida albicans from the drug inspection office, Guangzhou, above strain provides by Beijing Nat'l Pharmaceutical ﹠ Biological Products Control Institute.

3. animal:

NIH hour mice, SD rat---provide by medicine zoopery center, Guangdong Province,

The quality certification number: 26-2003A001,26-2003A003

4. instrument

722 grating spectrophotometers----Shanghai the 3rd analytical tool factory

ANGPING JA1023 electronic balance------Shanghai balance equipment factory

The intelligent bio signal collection of BL-420----Chengdu, Sichuan Tai Meng science and technology

5. experimental technique and result:

5.1 antiinflammatory action

5.1.1 influence to capillary permeability

Selecting body weight for use is 72 of 18～22gNIH mices, male and female half and half, be divided into 6 groups at random, press 20ml/Kg body weight volume gastric infusion, matched group gavages the distilled water of equivalent, once a day, continuous 4 days, behind the last medicine 1 hour, by the experiment of capillary permeability laboratory method, to the quantitative 1.0% azovan blue normal saline of each group mouse mainline, the quantitative acetic acid of lumbar injection is put to death mice behind the 15min simultaneously, opens the abdominal cavity, use the normal saline flushing abdominal cavity, with the content of 722 spectrophotometric determination mouse peritoneal eluate azovan blue.Experimental result is done the t check.

The result shows: the seepage discharge of azovan blue when compound vitex negundo capsule high, middle dosage all can significantly reduce acetic acid and causes the mouse peritoneal capillary permeability and increase, compare with matched group, P＜0.05～0.01, show that compound vitex negundo capsule can reduce the permeability of blood capillary, has certain antiinflammatory action.Its effect is stronger than FUFANG WUZHIGAN PIAN, P＜0.05; Experimental result sees Table 1.

Table 1 pair capillary permeability influence n:12 x ± SD

Annotate: * refers to compare with matched group, * P＜0.05, and * * P＜0.01,

# refers to compare with FUFANG WUZHIGAN PIAN, #P＜0.05, and ##P＜0.01, down together.

5.1.2 xylol causes the influence of mouse ear inflammatory reaction

Selecting body weight for use is 78 of 18～22gNIH mices, male and female half and half, grouping is identical with medication and 1.1, behind the last medicine 1 hour, drip the caused by dimethylbenzene xylene inflammation of equivalent by the mice ear method to each group mice left side ear, took off cervical vertebra and put to death mice in 15 minutes, along auricle baseline clip two ears, and lay auricle with card punch in same position, and use scales/electronic balance weighing, be inflammation swelling degree with two ear weight differences.Experimental result is done the t check.

Experimental result shows: the compound vitex negundo capsule of high dose can significantly alleviate the swelling degree of mice caused by dimethylbenzene xylene ear inflammatory reaction, compares P＜0.05 with matched group, shows that compound vitex negundo capsule has certain antiinflammatory action.Its effect does not relatively have significant difference, P＞0.05 with FUFANG WUZHIGAN PIAN; Experimental result sees Table 2.

What table 2 xylol caused the mouse ear inflammatory reaction influences n:13 x ± SD

5.1.3 PARA FORMALDEHYDE PRILLS(91,95) causes the influence of rat ankle joint inflammation

Selecting body weight for use is 60 of 150～180gSD rats, male and female half and half, press rat paw edema method, with the diameter of one thousandth kind of calliper rat ankle joint, the formaldehyde at rat ankle subcutaneous injection 0.1ml causes inflammation simultaneously, causes the swelling degree of using one thousandth kind of calliper rat ankle joint after scorching 6 hours, be divided into 6 groups then at random, press the volume gastric infusion of 20ml/kg, once a day, for three days on end.Matched group gavages the distilled water of equivalent; The diameter of 1 hour reuse one thousandth kind of calliper rat ankle joint is an index with difference before and after the administration after each administration, and experimental result is made t and detected.

Experimental result shows: compound vitex negundo capsule high, middle dosage can significantly suppress formaldehyde and cause rat ankle joint inflammation swelling degree, compare P＜0.05～0.01 with matched group, show that compound vitex negundo capsule has certain antiinflammation, its effect does not relatively have significant difference with FUFANG WUZHIGAN PIAN, P＞0.05, experimental result sees Table 3.

What table 3 PARA FORMALDEHYDE PRILLS(91,95) caused the ankle swelling in rat degree influences n:10 x ± SD

5.2 analgesic activity

5.2.1 Dichlorodiphenyl Acetate causes the influence (writhing method) of pain

Selecting body weight for use is 60 of 1g～22gNIH mice, male and female half and half, grouping is identical with medication and 1.1, behind the last medicine 1 hour, by chemical stimulation method (mouse writhing method), inject 0.6% acetic acid to each group mouse peritoneal and cause pain, and the observed and recorded mouse writhing reacts time of occurrence and writhing response number of times in 10 minutes immediately.Experimental result is done the t check.

Experimental result shows: the number of times of mouse writhing reaction when the compound vitex negundo capsule of high dose can reduce acetic acid and causes pain, with matched group relatively, P＜0.05 shows that compound vitex negundo capsule has certain analgesic activity.Its effect does not relatively have significant difference, P＞0.05 with FUFANG WUZHIGAN PIAN; Experimental result sees Table 4.

What table 4 pair chemical stimulation caused pain influences n:10 x ± SD

5.2.2 influence (hot plate method) to the thermic pain

Select 60 of the female mices of qualified (occurring licking metapedes in the 30s) by hot plate method, be 6 groups at random, medication is identical with 1.1, measured each Mus pain threshold by hot plate method again every 30 minutes behind the last medicine, totally 5 times, (if still analgesia reaction of mice 60s, then stop test, pain threshold is pressed 60s and is calculated).Experimental result is made t and is detected.

Experimental result shows: the pain threshold of mice in the time of all can significantly improving the thermic pain in 30,60,90,120 minutes behind the compound vitex negundo capsule medicine of high, middle dosage, compare with matched group, P＜0.05～0.01, show that compound vitex negundo capsule has certain analgesic activity, its effect does not relatively have significant difference with FUFANG WUZHIGAN PIAN, P＞0.05, experimental result sees Table 5.

What table 5 pair thermostimulation caused pain influences n:10 x ± SD

Annotate: ↓ expression reduces; ↑ expression improves

5.3 antipyretic effect (to the influence of yeast pyrogenicity)

Select 160～180gSD male rat for use, by heating pathology modelling ^[1]Measure rat normal body temperature (anus temperature) with clinical thermometer, give rat skin lower injection 15% yeast 1ml/100g body weight pyrogenicity then, after 6 hours, measure rat temperature with same procedure, select 60 of the heating rat of fervescence more than 1.0 ℃ for use, be divided into 6 groups at random, press 20ml/kg body weight gastric infusion, totally 2 times, 2 times delivery time is 1.5 hours, the blank group gavages the distilled water of equivalent, respectively at 1,1.5,2,2.5,3 hour measurement rat temperature behind the medicine, be experimental index with difference before and after the administration, experimental result is made t and is detected.

Experimental result shows: all can significantly reduce the body temperature that yeast causes rat fever in 1,1.5,2,2.5 hour behind the compound vitex negundo capsule medicine of high, middle dosage, the body temperature that 1.5,2.0,2.5 hour also can reduce heating rat of the compound vitex negundo capsule of low dosage behind medicine, compare P＜0.05～0.01 with the blank group, show that compound vitex negundo capsule has certain refrigeration function, this effect is close with the dose,equivalent tablet, both compare P＞0.05, and experimental result sees Table 6.

Table 6 compound vitex negundo capsule influences n=10 x ± SD to yeast pyrogenicity rat model body temperature

Continuous table 6 compound vitex negundo capsule influences n=10 x ± SD to yeast pyrogenicity rat model body temperature

Annotate: * represents to compare P＜0.05 with the blank group, and * * represents to compare P＜0.01 with the blank group: ↑ expression raises, ↓ expression reduction

5.4 influence to gastrointestinal peristalsis

5.4.1 influence to mouse small intestine charcoal end propelling rate

Selecting body weight for use is 72 of 18～22gNIH mices, ♀ ♂ half and half, be divided into 6 groups at random, medication is identical with 1.1, press small intestinal charcoal end propulsion trial method behind the last medicine to each group mice fasting 24 hours, the medicinal liquid 20ml/kg that contains 5% carbon powder then to mouse gavaging put to death mice in 15 minutes behind the medicine, pressed small intestinal carbon powder propulsion trial method and calculated mouse small intestine carbon powder propelling rate.Experimental result is made t and is detected.

Experimental result shows: the compound vitex negundo capsule of high dose can significantly suppress mouse small intestine carbon powder propelling rate, compares P＜0.05 with matched group, shows that compound vitex negundo capsule has the effect that suppresses the mice gastrointestinal peristalsis.Its effect does not relatively have significant difference with FUFANG WUZHIGAN PIAN, P＞0.05, and experimental result sees Table 7.

Table 5 pair mouse small intestine charcoal end propelling rate influence n:12 x ± SD

5.4.2 influence to the isolated rabbit intestinal smooth muscle

Press isolated guinea pig ileum laboratory method experiment, get rabbit ileum 3～4cm segment and put into and fill the 30ml tyrode's solution

In the container of (37 ℃ ± 0.5 ℃ of constant temperature), logical oxygen, intestinal tube one end lies on the suspension hook; The other end lies on the transducer hook.Be connected in intelligent bio signal collection of BL-420 and processing system, observe shrinkage amplitude and frequency with record isolated rabbit intestinal smooth muscle.With difference before and after the administration is experimental index, and experimental result is done the t check.

Experimental result shows: compound vitex negundo capsule high, middle dosage can significantly suppress normally to reach the contractility of the isolated rabbit intestinal smooth muscle of spasticity, compare P＜0.05～0.01 with matched group, show that compound vitex negundo capsule has the effect of lax isolated rabbit intestinal smooth muscle, its effect does not relatively have significant difference with FUFANG WUZHIGAN PIAN, P＞0.05, experimental result see Table 6,7.

The influence of table 8 pair isolated rabbit enterokinesia frequency

Annotate: () data instance number, sheet one FUFANG WUZHIGAN PIAN, capsule one compound vitex negundo capsule, down together.

The influence of table 9 pair isolated rabbit intestinal contractility

5.5. anti-diarrhea effect (Radix Et Rhizoma Rhei being caused the influence of letting out)

Select 91 of 18～22gNIH mices for use, ♀ ♂ half and half is divided into 7 groups at random, presses 20ml/kg body weight gastric infusion, and once a day, continuous 4 days, the blank group gavaged the distilled water of equivalent, behind the medicine the 3rd day, presses charcoal end efflux time ^[2]And feces color dot algoscopy ^[3], the mice fasting be can't help water 24 hours, except that normal group, pressed Radix Et Rhizoma Rhei diarrhea inducing method for all the other 6 groups ^[4]Give mouse gavaging 100% Radix Et Rhizoma Rheidecocted solution (including 0.5% carbon powder) 0.5ml/ only, behind the medicine in the time and 3 hours of record mice row melena defecation count, 3 hours defecations not, the time of row's melena calculated by 3 hours, just counted and calculated by 1, experimental result is made t and is detected.

Experimental result shows: the defecation frequency the when compound vitex negundo capsule of high, medium and low three dosage all can reduce Radix Et Rhizoma Rhei and causes diarrhea of mouse and prolong defecation time, compare P＜0.05～0.01 with the blank group, show that compound vitex negundo capsule has certain anti-diarrhea effect, this effect is close with the dose,equivalent tablet, both compare P＞0.05, and experimental result sees Table 10.

Table 10 compound vitex negundo capsule influences n:13 x ± SD to what Radix Et Rhizoma Rhei caused diarrhea of mouse

Annotate: * refers to compare with matched group, * P＜0.05, and * * P＜0.01,

# refers to compare with model control group, #P＜0.05, and ##P＜0.01, down together.

5.6 bacteriostasis

Liquid tube method can be quantitatively, sensitivity is higher.

Compound vitex negundo capsule and tablet (all are that 1.0g crude drug/ml) be mixed with every ml with nutrient broth respectively contains crude drug amount 0.40g, 0.20g, 0.10g, 0.05g, 0.025g ... 0.0031g totally eight drug level, every pipe total amount 1ml, steam sterilization.Streptococcic test still needed add 1% glucose in the sterilization medicinal liquid, streptococcus pneumoniae is then added 10% deactivation rabbit anteserum, oidiomycetic test will be used husky Bao Shi culture fluid preparating liquid to white.

The contrast of contrast strain is not for containing the culture medium of medicine, and the medicine contrast is not for adding the medicinal liquid of test organisms.

The test organisms liquid that each concentration pipe of every row's medicinal liquid and strain control tube add 1: 2000 respectively (8 hours cultures) 0.1ml cultivates 18 hours observed results for 37 ℃.24 hours cultures are then used in oidiomycetic test to white, and medicinal liquid adds behind the bacterium liquid 28 ℃ and cultivates 48 hours observed results.With the turbidity is that each pipe of index naked-eye observation has asepsis growth.

Judge that minimal inhibitory concentration (MIC) MIC is meant the minimum drug level that complete inhibition test growth is contained.

Experimental result shows: compound vitex negundo capsule all has in various degree antibacterial action to the examination strain, and between 0.20g/ml～0.40g/ml, the antibacterial efficacy of capsule and tablet is similar to the MIC of each bacterium.See Table 11

The bacteriostasis of table 11 compound vitex negundo capsule

Annotate: it is normal that strain contrasts each bacteria growing.Medicine contrast asepsis growth.

6, conclusion: above experimental result shows that compound vitex negundo capsule has following pharmacological action,

1. antiinflammatory action is arranged:

Azovan blue seepage discharge in the time of significantly reducing acetic acid and cause the mouse peritoneal capillary permeability and increase, P＜0.05～0.01;

Can alleviate the swelling degree of mice caused by dimethylbenzene xylene ear inflammatory reaction, P＜0.05;

Can alleviate the swelling degree that formaldehyde causes the rat ankle joint inflammation, P＜0.01;

2. analgesic activity is arranged

Acetic acid be can prolong and when pain mouse writhing reaction times, P＜0.01 caused;

The pain threshold of mice in the time of improving the thermic pain, P＜0.01;

3. antipyretic effect

Can significantly reduce the body temperature that yeast causes rat fever, P＜0.05～0.01;

4. the effect that suppresses gastrointestinal peristalsis is arranged

Can suppress mouse small intestine carbon powder propelling rate, P＜0.01;

The contractility that can suppress the isolated rabbit intestinal smooth muscle, P＜0.01;

5. anti-diarrhea effect

Defecation frequency in the time of reducing Radix Et Rhizoma Rhei and cause diarrhea of mouse and prolong defecation time, P＜0.05～0.01.

6. bacteriostasis

Representational to 13 kinds of external staphylococcus aureus, Salmonella enteritidis etc., mainly be to cause that the pathogen of digestive tract infection and conditioned pathogen all have antibacterial action in various degree, to the MIC of each bacterium between 0.20g/ml～0.40g/ml.

So, the clinical consumption per day of compound vitex negundo capsule lacks than FUFANG WUZHIGAN PIAN, and its part pharmacological action is stronger than FUFANG WUZHIGAN PIAN, when causing the mouse peritoneal capillary permeability and increase as reducing acetic acid the effect of azovan blue seepage discharge stronger than FUFANG WUZHIGAN PIAN, P＜0.05; Other effects relatively do not have significant difference, P＞0.05 with FUFANG WUZHIGAN PIAN.

The specific embodiment

Embodiment 1

Medicine of the present invention is made by following component: Folium vilicis Negundo 30%, Mahonia fortunei (Lindl.) Fedde 30%, Flos Ilicis Asprellae 20%, Radix Helicteris 20%.

Its weight can take by weighing like this: Folium vilicis Negundo 900g, Mahonia fortunei (Lindl.) Fedde 900g, Flos Ilicis Asprellae 600g, Radix Helicteris 600g.

The preparation method that above-mentioned each component is made medicine of the present invention is:

(1) gets Folium vilicis Negundo, Mahonia fortunei (Lindl.) Fedde, Flos Ilicis Asprellae, Radix Helicteris,, add 10 times of amounts of each component gross weight for the first time more than with 60% alcohol reflux 3 times, reflux, extract, 1.5 hours adds 8 times of amounts for the second time, during reflux, extract, 1, add 6 times of amounts for the third time, reflux, extract, 1 hour.

(2) filter, merging filtrate, reclaim under reduced pressure is to there being the ethanol flavor, and is condensed into thick extractum, and proportion is 1.28 (60 ℃ of surveys) relatively, places vacuum drying oven, and 70 ℃ of drying under reduced pressure 72 hours take out, and pulverize, and cross 80 mesh sieves;

(3) with medicated powder and microcrystalline Cellulose 180g mix homogeneously, cross 60 mesh sieves, with 90% ethanol system soft material, 20 mesh sieves are granulated, 70 ℃ of oven dry, 20 mesh sieve granulate, the magnesium stearate mix homogeneously of adding 0.5%, filled capsules, promptly.

Embodiment 2

The preparation method that above-mentioned each component is made medicine of the present invention is:

(1) get Folium vilicis Negundo 900g, Mahonia fortunei (Lindl.) Fedde 900g, Flos Ilicis Asprellae 600g, Radix Helicteris 600g, more than 8 times of 80% ethanol of each component gross weight, heating and refluxing extraction 4 times, each 1.0 hours.

(2) filter, merging filtrate, reclaim under reduced pressure is to there being the ethanol flavor, and is condensed into thick extractum, and proportion is 1.30 (60 ℃ of surveys) relatively, places vacuum drying oven, and 80 ℃ of drying under reduced pressure 48 hours take out, and pulverize, and cross 60 mesh sieves;

(3) with medicated powder and microcrystalline Cellulose 170g mix homogeneously, cross 80 mesh sieves, with 70% ethanol system soft material, 30 mesh sieves are granulated, 50 ℃ of oven dry, 30 mesh sieve granulate, the magnesium stearate mix homogeneously of adding 1.0%, filled capsules, promptly.

Embodiment 3

Its weight can take by weighing like this: Folium vilicis Negundo 900g, Mahonia fortunei (Lindl.) Fedde 900g, Flos Ilicis Asprellae 600g, Radix Helicteris 600g, and the preparation method that above-mentioned each component is made medicine of the present invention is:

(1) get Folium vilicis Negundo, Mahonia fortunei (Lindl.) Fedde, Flos Ilicis Asprellae, Radix Helicteris, more than 7 times of 50% ethanol of each component gross weight, heating and refluxing extraction 2 times, each 2.0 hours.

(2) filter, merging filtrate, reclaim under reduced pressure is to there being the ethanol flavor, and is condensed into thick extractum, and proportion is 1.29 (60 ℃ of surveys) relatively, places vacuum drying oven, and 50 ℃ of drying under reduced pressure 96 hours take out, and pulverize, and cross 70 mesh sieves;

(3) with medicated powder and adjuvant mix homogeneously, cross 70 mesh sieves, with 80% ethanol system soft material, 208 mesh sieves are granulated, 80 ℃ of oven dry, 20 mesh sieve granulate, the magnesium stearate mix homogeneously of adding 0.1%, filled capsules, promptly.

Claims (2)

1. the preparation method of a compound vitex negundo capsule, wherein (1) gets Folium vilicis Negundo 30%, Mahonia fortunei (Lindl.) Fedde 30%, Flos Ilicis Asprellae 20%, Radix Helicteris 20%, with 6-10 times of 50-80% ethanol of each component gross weight, heating and refluxing extraction 1-4 time, each 1.0-2.0 hour;

(2) filter, merging filtrate, reclaim under reduced pressure is to there being the ethanol flavor, and is condensed into thick extractum, compares to focus on 60 ℃ and be measured as 1.28～1.30, places vacuum drying oven, 60-80 ℃ drying under reduced pressure 48-96 hour, take out, pulverize, cross the 60-80 mesh sieve;

(3) with medicated powder and adjuvant mix homogeneously, cross the 60-80 mesh sieve, with 70-90% ethanol system soft material, the 20-30 mesh sieve is granulated, 60-80 ℃ of oven dry, 20-30 mesh sieve granulate, the magnesium stearate mix homogeneously of adding 0-1.0%, filled capsules, promptly.

2. preparation method according to claim 1, wherein (1) gets Folium vilicis Negundo 30%, Mahonia fortunei (Lindl.) Fedde 30%, Flos Ilicis Asprellae 20%, Radix Helicteris 20%, with 60% alcohol reflux 3 times, add for the first time 10 times of amounts, reflux, extract, 1.5 hours adds 8 times of amounts for the second time, during reflux, extract, 1, add 6 times of amounts for the third time, reflux, extract, 1 hour;

(2) filter, merging filtrate, reclaim under reduced pressure is to there being the ethanol flavor, and is condensed into thick extractum, compares to focus on 60 ℃ and be measured as 1.28～1.30, places vacuum drying oven, and 70 ℃ of drying under reduced pressure 72 hours take out, and pulverize, and cross 80 mesh sieves;

(3) with medicated powder and microcrystalline Cellulose mix homogeneously, cross 60 mesh sieves, with 90% ethanol system soft material, 20 mesh sieves are granulated, 70 ℃ of oven dry, 20 mesh sieve granulate, the magnesium stearate mix homogeneously of adding 0.5%, filled capsules, promptly.