CN101152311A

CN101152311A - Traditional Chinese medicine composition, its preparing method and quality control method

Info

Publication number: CN101152311A
Application number: CNA2006101527794A
Authority: CN
Inventors: 曾雄辉
Original assignee: Individual
Current assignee: Individual
Priority date: 2006-09-29
Filing date: 2006-09-29
Publication date: 2008-04-02
Anticipated expiration: 2026-09-29
Also published as: CN101152311B

Abstract

The invention discloses a traditional Chinese medicine combination for remedying the inappetence, the nausea and vomitus, the abdominal flatulence and diarrhea and the dyspepsia and the preparation method and quality control method of the liquid capsule. Catechu uncaria, corktree bark, liquorice, tangerine peel and cassia bark are decocted by water, and filtrate is condensed as thick ointment; run oil is added into the thick ointment to be mixed uniformly for obtaining a traditional Chinese medicine combination; a pill preparation, a tablet preparation or a capsule preparation is prepared by adding the officinal auxiliary materials with the pharmic acceptable quantity into the traditional Chinese medicine combination. The traditional Chinese medicine combination which is prepared by the invention has the advantages of simple technology, good curative effect and being convenient for taking and can be used for remedying the symptoms of inappetence, the nausea and vomitus, the abdominal flatulence and diarrhea, the dyspepsia etc.

Description

A kind of Chinese medicine composition, its preparation method and method of quality control thereof

Technical field

The present invention relates to a kind of inappetence, nausea and vomiting, abdominal distention diarrhoea, dyspeptic Chinese medicine composition of being used for the treatment of, be specifically related to a kind of adult that unhygienic diet or being not acclimatized cause and Chinese medicine composition of infantile diarrhea of being used for the treatment of, the present invention also relates to the preparation method and the method for quality control of this Chinese medicine composition.

Background technology

The diarrhoea that unhygienic diet or being not acclimatized cause, stomachache are because people's body reacts a kind of imbalance of conditions such as new weather, physical features, water quality, food.Infantile diarrhea is one group to be increased by many cause of diseases, the multifactor times of defecation that causes and the character of defecating is changed into the usual diseases of childhood of characteristics.Can be divided into infectious and non-infectious two kinds.Onset can be delayed can be anxious, and light disease only has gastrointestinal symptom, inappetence, and idol has vomiting, times of defecation to increase and character changes; Heavy person's times of defecation will reach surplus one day ten time, even tens times, stool can be water sample, pasty state, mucus shape, and significantly dehydration and electrolyte disturbance and whole body poisoning symptom such as hyperpyrexia, agitation, lethargy etc. can appear simultaneously in the bloody purulent stool separated that has.The most onset of infantile diarrhea is very anxious, and frequent diarrhoea can make intravital moisture and nutrient lose rapidly, causes acute dehydration.Generally be to take that symptom does not take a turn for the better after the oral rehydration, lethargy, fever, frequent vomiting, water sample stool occur, even have pus and blood just, should remove hospital admission immediately, but continuous supplementary oral liquor body on the way.

The normal clinical commonly used drug of adult that unhygienic diet or being not acclimatized cause and infantile diarrhea is HUOXIANG ZHENGQI WAN/water and infection and digestant such as berberine, but HUOXIANG ZHENGQI WAN/water and berberine have the strong impulse abnormal smells from the patient, are difficult for the particularly child patient acceptance for the patient.

Summary of the invention

The Chinese medicine composition that the purpose of this invention is to provide a kind of effective treatment inappetence that can be easy to accept by the patient, nausea and vomiting, abdominal distention diarrhoea, indigestion symptom.

Another object of the present invention provides a kind of method for preparing above-mentioned Chinese medicine composition.

A further object of the present invention provides a kind of method of quality control of above-mentioned Chinese medicine composition.

For achieving the above object, the inventor designs through a large amount of experiment and performing creative labour on the basis of existing technology and is used for the treatment of inappetence, nausea and vomiting, abdominal distention diarrhoea, the thin compound of dyspeptic Chinese medicine, and described Chinese medicine composition is formed by the following components in part by weight processing and preparing:

Heat up in a steamer oily 20-60 Uncaria gambier Roxb. 30-200 Cortex Phellodendri 10-60

Radix Glycyrrhizae 8-35 Pericarpium Citri Reticulatae 15-50 Cortex cinnamomi japonici (Ramulus Cinnamomi) 30-70.

Preferably, described Chinese medicine composition is formed through processing and preparing by following parts by weight of Chinese traditional medicine raw material:

Heat up in a steamer oily 30-50 Uncaria gambier Roxb. 50-150 Cortex Phellodendri 15-30

Radix Glycyrrhizae 10-30 Pericarpium Citri Reticulatae 20-40 Cortex cinnamomi japonici (Ramulus Cinnamomi) 40-60.

Most preferably, described Chinese medicine composition is formed through processing and preparing by following parts by weight of Chinese traditional medicine raw material:

Heat up in a steamer oily 35-45 Uncaria gambier Roxb. 75-120 Cortex Phellodendri 30-40

Radix Glycyrrhizae 15-20 Pericarpium Citri Reticulatae 30-40 Cortex cinnamomi japonici (Ramulus Cinnamomi) 40-60.

Described Chinese medicine composition is prepared into pill, tablet or capsule with the pharmaceutic adjuvant of medically acceptable amount.

The described oil that heats up in a steamer is creosote, pine tar or bamboo tar.

A kind of method for preparing above-mentioned Chinese medicine composition comprises the steps:

Uncaria gambier Roxb., Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) pulverize separately are become fine powder, cross the 80-120 mesh sieve, mix homogeneously adds and heats up in a steamer oily mix homogeneously, gets Chinese medicine composition.

The method that another prepares above-mentioned Chinese medicine composition comprises the steps:

Uncaria gambier Roxb., Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) are decocted with water 2-3 time, and each 1-3 hour, collecting decoction filtered, and surveying relative density when filtrate is condensed into 60 ℃ is the thick paste of 1.10-1.30; Wherein amount of water be Uncaria gambier Roxb., Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) gross weight 6-10 doubly; To heat up in a steamer oil and join in the thick paste, stir, get Chinese medicine composition.

The method of the above-mentioned Chinese medicine composition of a preparation comprises the steps: again

1. getting Cortex Phellodendri is 60～90% alcohol heating reflux 2～3 times in percent by volume, each 1～3 hour, filter, and merging filtrate, filtrate recycling ethanol extremely do not have the alcohol flavor, filter, and get filtrate A; Or,

Cortex Phellodendri is processed into coarse powder, and doubly measuring saturated limewater with 8-12 is solvent, supersound extraction 2-3 time, 15-30min/ time, extracting solution is mixed with the solution of counting 30-35mg/ml with crude drug, filters, add the NaCl placement and spend the night, filter, oven dry is dissolved in water in precipitation, filters, and it is 1～2 that filtrate adds hydrochloric acid accent pH, treat that post precipitation filters, and gets filtrate A;

2. Uncaria gambier Roxb., Radix Glycyrrhizae, Pericarpium Citri Reticulatae and Cortex cinnamomi japonici (Ramulus Cinnamomi) are decocted with water 2～3 times, each 1～3 hour, collecting decoction filtered, and the survey relative density was 1.10～1.30 extractum B when filtrate was concentrated into 60 ℃; Wherein amount of water is Uncaria gambier Roxb., Radix Glycyrrhizae, Pericarpium Citri Reticulatae and Cortex cinnamomi japonici (Ramulus Cinnamomi) gross weight 6～10 times;

3. filtrate A is mixed with extractum B, relative density is 1.10～1.30 extractum when being concentrated into 60 ℃, and drying is made fine powder, adds to heat up in a steamer oil, stirs, and gets Chinese medicine composition.

The described oil that heats up in a steamer is with Fagaceae plant Fagus sinensis Oliv. Fagus sinensis Oliv., natural beech section natural plant Zelkova schneideriana Hand.-Mazz., maple, Xylosmae japonici, Quercus acutissima Carr., Pinaceae pinaceae Pinus pinus plant pinaster or Juniperus rigida Sieb.et Zucc., bamboo places distillating still to distill, getting dry distillation liquid distills under 180-360 ℃ of condition, the fraction that collection is heavier than water, handle as follows:

1. add the aqueous slkali that percentage by weight is 5-20%, stir crystallisation by cooling;

2. filter, discard filtrate, the washing of filtering residue clear water discards washings, adding weight percent concentration is the 20-35% sulfuric acid solution, stirs, and discards sulfate wastewater, clear water washing back is rectification under vacuum under the 0.08-0.09MPa condition in vacuum, collects 130-155 ℃ rectification branch, promptly; Described fraction: aqueous slkali: the weight part ratio of sulfuric acid solution is 1-3: 2-4: 2-3.5.

Add calcium acetate or magnesium acetate solution that percentage by weight is 10-30% after 1. described step stirs again; Described fraction: the weight part ratio of calcium acetate or magnesium acetate is 1-3: 4-7.

Described step aqueous slkali 1. is sodium hydroxide or potassium hydroxide solution.

The described method of heating up in a steamer oil of another preparation is with Fagaceae plant Fagus sinensis Oliv. Fagus sinensis Oliv., natural beech section natural plant Zelkova schneideriana Hand.-Mazz., maple, Xylosmae japonici, Quercus acutissima Carr., Pinaceae pinaceae Pinus pinus plant pinaster or Juniperus rigida Sieb.et Zucc., bamboo places distillating still to distill, getting dry distillation liquid distills under 180-360 ℃ of condition, the collection fraction heavier than water places rectifying still, in temperature is 130-155 ℃, withdrawing moisture and light fraction under the vacuum 0.08-0.09MPa condition, with the freezing 12-48 hour crystallization under subzero 20 to 0 ℃ of conditions of the fraction in the rectifying still, the crystal centrifugalize obtains heating up in a steamer oily crystal.

Add glycerol and carboxymethylcellulose calcium in the described Chinese medicine composition, mix homogeneously, water pill, cold drying is prepared into pill, film coating.

Described cold drying is 30-60 ℃ of drying.

Described pill is as the coating material coating with the mixture of using hydroxypropyl methylcellulose, hydroxypropyl cellulose, Polyethylene Glycol; Described excipient is water, ethanol, Mel or starch slurry; Described binding agent is a kind of or wherein several mixture in ethyl cellulose, hydroxypropyl emthylcellulose, the arabic gum.

Described film-coated rotating speed is 5-15rpm, is to carry out the coating operation under the 40-50 ℃ of condition in temperature.

A kind of or several mix homogeneously wherein in described Chinese medicine composition and disintegrating agent, filler, the wetting agent are granulated, and even with mix lubricant again, tabletting, film coating make tablet.

Described granulation back and carboxymethyl starch sodium, mix lubricant are even, and tabletting, film coating make tablet.

Described disintegrating agent is a kind of or wherein several mixture in carboxymethyl starch sodium, starch, methylcellulose, sodium bicarbonate, microcrystalline Cellulose, hydroxypropyl cellulose, crospolyvinylpyrrolidone, the cross-linking sodium carboxymethyl cellulose; Described filler is a kind of or wherein several mixture in dextrin, lactose, amylum pregelatinisatum, microcrystalline Cellulose or the mannitol; Described wetting agent is a kind of or wherein several mixture in distilled water, ethanol, starch slurry, ethyl cellulose, the hydroxypropyl emthylcellulose; Described lubricant is a kind of or wherein several mixture in magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, Polyethylene Glycol and the magnesium laurylsulfate.

The mixture of described tablet hydroxypropyl methylcellulose, hydroxypropyl cellulose, Polyethylene Glycol is as the coating material coating.

Described Chinese medicine composition and disintegrating agent mix homogeneously are granulated, and make capsule.

Described disintegrating agent is a kind of or wherein several mixture in carboxymethyl starch sodium, starch, methylcellulose, sodium bicarbonate, microcrystalline Cellulose, hydroxypropyl cellulose, crospolyvinylpyrrolidone, the cross-linking sodium carboxymethyl cellulose.

A kind of preparation is used for the treatment of the preparation method of inappetence, nausea and vomiting, abdominal distention diarrhoea, dyspeptic medicine pill, comprises the steps:

Leaf and the sprout of Uncaria gambier Roxb. Uncaria Gambir Roxb. decoct with water 2-3 time, and each 1-3 hour, merging filtrate filtered, and surveying relative density when filtrate is condensed into 60 ℃ is the thick paste of 1.10-1.30, and drying is ground into fine powder, gets the Uncaria gambier Roxb. dry extract;

Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) pulverize separately are become fine powder, cross the 80-120 mesh sieve, Cortex Phellodendri powder, Radix Glycyrrhizae powder, Pericarpium Citri Reticulatae powder and Uncaria gambier Roxb. dry extract mix homogeneously, add and heat up in a steamer oil and glycerol, add water pill, cold drying behind the mix homogeneously, use the Cortex cinnamomi japonici powder coating, promptly.

Described Chinese medicine composition is treated application in inappetence, nausea and vomiting, abdominal distention diarrhoea, dyspeptic medicine in preparation.

Chinese medicine composition of the present invention is that the inventor preferably comes out from numerous crude drug through a large amount of tests, and having stagnation is rushed down, and is used for adult and infantile diarrhea that eating and drinking without temperance or being not acclimatized cause, belongs to damp and hot, dyspepsia card person.Card is seen: inappetence, nausea and vomiting, abdominal distention diarrhoea, dyspepsia.Heating up in a steamer oily main component is guaiacol (Guaiacol), kreosol (Crosol) and other phenols, act on similar to phenol, but its toxicity and zest are all less, be colourless or pale yellow oily liquid, scurrying property cigarette is smelly, flavor burns strong, has pharmacological actions such as anticorrosion, sterilization, local anaesthesia, the clinical treatment that is used for antidiarrheal, whole intestinal and toothache.The Chinese medicine active component of preparation of the present invention has intensive penetrance smoke, for covering the bad smell of medicine, make the patient be easy to accept, the inventor has carried out a large amount of research to the dosage form of preparation and the selection of used adjuvant, moulding process to preparation has carried out performing creative labour simultaneously, determines that finally the preparation of selecting for use is a kind of preparation in pill, tablet, the capsule.

The dry concentrate of the leaf of Maguireothamnus speciosus gambier gambirplant leaf and branchlet (Uncariagambir) and sprout decocting liquid is used as medicine, property hardship, puckery, be slightly cold, nontoxic, go into lung meridian.Its main component is catechin (Cateehin) and Quercetin (Quereetin) etc.Have that removing dampness purges heat, promoting tissue regeneration and ulcer healing, the analgesic therapy hemostasis is promoted the production of body fluid and is reduced phlegm, effects such as astringing to arrest diarrhea.The clinical treatment that is used for diseases such as aphtha, incised wound, skin ulceration, hemorrhoid are swollen, watery diarrhea, endo-enteritis.The Uncaria gambier Roxb. dry extract plays convergence in preparation of the present invention, adjust the effect of enteral moisture.

Cortex Phellodendri (Cortex phellodendri) is the dry bark of Rutaceae Cortex Phellodendri (Phelloden-dron amurense Rupr.), and bitter in the mouth is cold in nature, returns kidney, urinary bladder channel.The main component of Cortex Phellodendri is the bitter rope (Li-monin) of berberine (Berberine) and Fructus Citri Limoniae, and contain a small amount of fibrauretin (Palmatine) and obacunone (Obakunone), staphylococcus aureus, bloody dysentery bacterium, gonococcus etc. there are potent antibacterial action, suppress the cellular antibody generation.Have effects such as antiinflammatory, blood pressure lowering.Clinical warm dysentery, yellow cellulitis, leukorrhagia, pyretic stranguria, beriberi, flaccidity base, the hectic fever due to YIN-deficiency consumptive fever of being used for; Night sweat, seminal emission, sore swollen toxin, the treatment of diseases such as eczema pruritus.Cortex Phellodendri plays antibiotic, spasmolytic effect in preparation of the present invention.

Pericarpium Citri Reticulatae has the be good for the stomach effect of sharp intestinal of fragrance, the inventor studies the plant amedica composition in the preparation of the present invention and the interaction of guaiacol, it is unexpected that the discovery Pericarpium Citri Reticulatae have significant effects to the pharmacokinetic parameter of guaiacol, and the mean dissolution time of guaiacol measured, experimental details is as follows:

Materials and methods: the 1. preparation of pill: with the powder mixes of Uncaria gambier Roxb. dry extract 4g, Cortex Phellodendri 6g, Radix Glycyrrhizae 3g, Pericarpium Citri Reticulatae 6g, add glycerol, water and creosote, in the porcelain alms bowl, knead 5min, make creosote ball (P4R) that is about 4.8mg and the pill (P4R-CUP2) that does not contain Pericarpium Citri Reticulatae, contain the pill (P4R-1/2CUP2) of half amount Pericarpium Citri Reticulatae.2. the mensuration of guaiacol stripping from pill: in (37 ± 0.5) ℃, 6 pills are put into dissolution medium, stir with 100r/min.Respectively at 5,10,20,40, behind the 60min, behind the sampling 1mL, supply volume with fresh medium again.Sample liquid is crossed microporous filter membrane, gets 500 μ L subsequent filtrates, adds mark liquid and 500 μ L ethyl acetate in the 20 μ L.Mixed liquor is stirred 3min, with the centrifugal 3min of 5000r/min, get ethyl acetate layer injection GC-MS system and analyze behind the mixing, observe the stripping of guaiacol from pill.3. pharmacokinetic: the Wistar ST in 10 ages in week is a rat feeding after 2 months, and the rat of choosing body weight 400～450g carries out pharmacokinetic.Fasting 18h is with pentobarbital sodium (30mg/kg) intraperitoneal injection of anesthesia, then in left side jugular vein intubate.P4R is bonded at the stomach probe tip, inserts administration in the stomach, distilled water 0.3mL reinjects.After the administration 0.5,10,20,30,60,90,120,180,240,300min, blood sampling 0.5mL is centrifugal from intubate, blood plasma-20 ℃ preservation.Oral castor oil causes the diarrheal rat model and also tests as stated above.4. the guaiacol concentration in the blood plasma: add buffer in the 150 μ L blood plasma, 37 ℃ of incubation 2h add 1N hydrochloric acid (60 μ L), fluorophenol (20 μ L) and ethyl acetate (1mL) again, stir 3min, with the centrifugal 3min of 5000r/min.The ethyl acetate soluble fraction is analyzed with GC-MS, and the standard curve that gets guaiacol concentration in the blood plasma is Y=0.0005X+0.0086 (r=0.999).

The result: 1. 5,10, during 20min, the dissolution rate of guaiacol from P4R-CUP2 is significantly higher than the dissolution rate of guaiacol from P4R, P4R-1/2CUP2.The MRT of P4R group guaiacol obviously prolongs than P4R-CUP2.Because AUC in two groups the blood _0～5hThere is not significant difference, so think that the effect of Pericarpium Citri Reticulatae prolongation MRT is the influence that is subjected to MDT.2. the diarrhoea of bringing out for Oleum Ricini, Pericarpium Citri Reticulatae also have the effect that prolongs MRT.After diarrhoea group rat was taken medicine, guaiacol concentration was similar to normal rat in the blood plasma, but the T of guaiacol _Max, AUC _0～5h, mean residence time (MRT) is lower than normal group, but C _MaxBe higher than normal group.3. normal rat is taken behind the P4R 5min that contains (286 ± 8) μ g guaiacol and can be detected guaiacol in the blood plasma, and behind 45～115min, guaiacol concentration peaking is lower than detectable limit in the blood plasma behind the 5h.Because prolonging MRT and MDT is the index that medicine has continuous action, therefore think that the lasting anti-diarrhea effect of pill is relevant with Pericarpium Citri Reticulatae.

Radix Glycyrrhizae in the preparation of the present invention has analgesia, detoxifcation, protection gastric mucosa, the effect of coordinating the actions of various ingredients in a prescription.

The inventor selects Cortex cinnamomi japonici (Ramulus Cinnamomi) and consumption thereof through a large amount of testing sieves, has synergism with other composition, makes curative effect improve greatly, and makes lasting medicine.

The inventor also by this preparation technology who becomes Chinese medicine composition, makes medicine more refining, and curative effect is further enhanced.

The inventor has carried out a series of research to the pharmaceutic adjuvant of the tablet of the present invention's preparation.Because the fine powder that crude drug is prepared into has certain hygroscopicity, the inventor adopts to granulate and improves the granule character, has effectively improved the hygroscopicity of tablet; In order to improve the disintegration time of tablet, improve bioavailability of medicament, the inventor is by carboxymethyl starch is received to finding to select for use through a large amount of tests, starch or the mixture of the two be as disintegrating agent.Unexpectedly, add in Chinese medicine composition earlier that the part carboxymethyl starch is received and the mixture of starch, the Extra Section carboxymethyl starch is received again, and disintegration time shortens greatly; For increasing mobility of particle, it is lubricant that the inventor selects Pulvis Talci, magnesium stearate, micropowder silica gel or its mixture for use.For shelf characteric and the taste thereof that improves tablet, tablet is carried out film coating, make the stability that it is specious, wetting resistance by force, also obviously increases the tablet lay up period, improved drug quality, ensure drug safety, and eliminated the poor taste of medical material itself.The inventor finally selects for use the mixture of adopting hydroxypropyl methylcellulose, hydroxypropyl cellulose, Polyethylene Glycol as coating material through a large amount of development tests.

The capsule preparations of the present invention preparation has good stability, long advantage of storage time, has overcome traditional capsule preparations and has been easy to oxidation, the defective of anti-storage not.And can cover the abnormal flavour of medicine, the problem that change is made us or made groups of people be difficult to take etc., and make that it is clean and tidy, attractive in appearance, swallow easily.Dosage is accurate relatively, and degree of accuracy is higher, can reach the metering of milligram/grain.The bioavailability of medicament height, comparatively speaking, capsule and tablet, pill are different, do not need to add binding agent and pressure during preparation, belong to dissolving or trickle powder again substantially and be scattered in the content, in case disintegrate just together discharges, imitate rapidly so be, it is good obviously also to absorb soon than pill, tablet.

The pharmacodynamics data shows that medicine of the present invention can significantly reduce the loose stool number of mice, has anti-diarrhea effect; Can promote the gastric emptying motion of mice; The intestinal propulsion of the hyperfunction model mice of intestinal motion due to inhibition normal mouse and the neostigmine, thereby the absorption of promotion nutrient substance; Promote the secretion of gastric juice and suppress pepsic activity, improve digestive function.Thereby for treatment inappetence, nausea and vomiting, abdominal distention, diarrhoea, dyspepsia etc. provide the pharmacodynamics foundation.

The pharmacodynamic study test

Having of the medicine of the present invention antidiarrheal function that stagnates is used for the treatment of adult that unhygienic diet or being not acclimatized cause and children's's inappetence, nausea and vomiting, abdominal distention, diarrhoea, dyspepsia etc.

This research is adopted Oleum Ricini induced mice diarrhoea and Folium Sennae induced mice diarrheal anti-diarrhea effect, small intestine movement of mice is advanced and to the influence of the hyperfunction model mice intestinal propulsion motion of intestinal due to the neostigmine, to the influence of mice gastric emptying motion and to the test method that influences of rat gastric acid, pepsinia, to verify the drug effect of medicine of the present invention.

1 experiment material

Animal: white mice, the Kunming kind, one-level is qualified, male and female half and half, body weight 18-21g; The SD rat, male and female half and half, body weight 180～200g, more than provide by The Fourth Military Medical University's Experimental Animal Center.

Medicine and reagent: the used preparation of test group is the preparation (creosote 40g, Uncaria gambier Roxb. 110g, Cortex Phellodendri 30g, Radix Glycyrrhizae 10g, Pericarpium Citri Reticulatae 40g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 40g) according to the embodiment of the invention eight preparations, it is the lab scale medicine, lot number 060319 is provided by Jiangxi Yaodu Renhe Pharmaceutical Co., Ltd.Control drug: belly pain is good for the stomach and puts in order intestinal ball, lot number 20051102, pharmaceutical factory, Thailand Lee Wanshan Mountain; Oleum Ricini, commercial, lot number 20060202, Nanchang white clouds medication chemistry factory; Folium Sennae, commercial, face the time spent to be mixed with 15% suspension; The methyl-sulfuric acid neostigmine, lot number: 2006201, letter friendship Pharmaceutical is produced; Metoclopramide, lot number: 20060301, Beijing doube bridge drugmaker; Motilium, lot number: 200601140, Xian-Janssen Pharmaceutical Ltd. produces; Phenol reagent: (Folin-Ciocalteu) compound method is seen " herbal pharmacology experimental methodology ", Li Yikui, Science and Technology of Shanghai publishing house, P242; Bovine hemoglobin, Shanghai uncle bio tech ltd difficult to understand, lot number: G200601; L-Tyrosine, Shanghai uncle bio tech ltd difficult to understand, lot number: 20018402; 0.1% thimerosal, 5% trichloroacetic acid, 0.5mol/l sodium carbonate, 0.3mol/l hydrochloric acid, 0.04mol/l hydrochloric acid.

Instrument: the multi-functional analyzer of BECKMAN series type; PHS-3C type acidometer, Shanghai thunder magnetic instrument plant; Sartrius electronic balance (precision 1/1000).

2 experimental techniques and result

2.1 to Oleum Ricini induced mice diarrheal anti-diarrhea effect

Choose 50 of white mice, be divided into 5 groups at random by body weight, positive drug matched group filling stomach is good for the stomach to belly pain and puts in order the obtain solution 0.4mL/20g of intestinal ball institute, be 1mg/kg, the high, medium and low dosage group of tablet is irritated the dosing 0.4mL/20g of lab scale medicine institute that stomach is given variable concentrations, i.e. 1.8g/kg, 0.9g/kg, 0.45g/kg respectively; Blank group group is irritated the normal saline 0.4mL/20g of stomach equal volume.Successive administration 3 days is irritated stomach and is given Semen Ricini fluid 0.4mL/20g behind the last administration 1h; Then with the mice sub-cage rearing, 1 in every cage, cage heelpiece adularescent filter paper is surveyed the incubation period of its appearance, and every h changes paper 1 time, observes 6h continuously, the loose stool number on the recorder chart.Experimental result sees Table 1.

Table 1 pair Oleum Ricini induced mice diarrheal anti-diarrhea effect

Annotate: compare with the blank group ^*P＜0.01, ^*P＜0.05 (down together).

Table 1 is the result show, the low and high dose group of tablet can make the loose stool of mice obviously reduce, parallel with positive control (P＜0.01).

2.2 to Folium Sennae induced mice diarrheal anti-diarrhea effect

Choose 50 of white mice, be divided into 5 groups at random by body weight, positive drug matched group filling stomach is good for the stomach to belly pain and puts in order the obtain solution 0.4mL/20g of intestinal ball institute, be 1mg/kg, the high, medium and low dosage group of tablet is irritated the dosing 0.4mL/20g of lab scale medicine institute that stomach is given variable concentrations, i.e. 1.8g/kg, 0.9g/kg, 0.45g/kg respectively; Blank group group is irritated the normal saline 0.4mL/20g of stomach equal volume.Successive administration 3 days is irritated stomach and is given Folium Sennae suspension 0.4mL/20g behind the last administration 1h; With the mice sub-cage rearing, 1 in every cage, cage heelpiece adularescent filter paper are surveyed it, are surveyed the incubation period of its appearance, per hour change paper 1 time, observe 6h continuously, the loose stool number on the recorder chart then.Experimental result sees Table 2.

Table 2 pair Folium Sennae induced mice diarrheal anti-diarrhea effect

Table 2 result as seen, after blank group was given Folium Sennae, the loose stool of mice increased, and has showed symptom of diarrhea, the low dose group of tablet can make the loose stool of mice reduce, and middle and high dosage group can make the loose stool of mice obviously reduce (P＜0.01).

2.3 influence to normal mouse intestinal ahead running

Choose 50 of white mice, be divided into 5 groups at random by body weight, positive drug matched group filling stomach is good for the stomach to belly pain and puts in order the obtain solution 0.4mL/20g of intestinal ball institute, be 1mg/kg, the high, medium and low dosage group of tablet is irritated the dosing 0.4mL/20g of lab scale medicine institute that stomach is given variable concentrations, i.e. 1.8g/kg, 0.9g/kg, 0.45g/kg respectively; Blank group group is irritated the normal saline 0.4mL/20g of stomach equal volume.Successive administration 3 days is irritated stomach and is given active carbon 0.4mL/ only behind the last administration 1h; Putting to death animal after 20 minutes, is starting point with the pylorus, measures the distance that active carbon is pushed into and the total length of small intestinal.Calculate the propelling rate of active carbon then:

Result such as table 3.

The influence of table 3 pair normal mouse intestinal ahead running

Table 3 is the result show, the dosage group can suppress the propelling moving (P≤0.05) of the small intestinal of normal mouse in the tablet, and the visible trend that suppresses intestinal motility of other each group, but not statistically significant.

2.4 neostigmine is caused the influence of the hyperfunction model intestinal propulsion motion of mice intestinal

Choose 50 of white mice, be divided into 5 groups at random by body weight, positive drug matched group filling stomach is good for the stomach to belly pain and puts in order the obtain solution 0.4mL/20g of intestinal ball institute, be 1mg/kg, the high, medium and low dosage group of tablet is irritated the dosing 0.4mL/20g of lab scale medicine institute that stomach is given variable concentrations, i.e. 1.8g/kg, 0.9g/kg, 0.45g/kg respectively; Blank group group is irritated the normal saline 0.4mL/20g of stomach equal volume.Successive administration 5d, last administration 40min lumbar injection neostigmine 0.1mg/kg causes the hyperfunction model of small intestinal, irritating stomach behind the 15min gives active carbon 0.4mL/ only, putting to death animal behind the 20min, is starting point with the pylorus, measures the distance that active carbon is pushed into and the total length of small intestinal.Calculate the propelling rate of active carbon then:

Result such as table 4.

Table 4 pair neostigmine causes the inhibitory action of the hyperfunction model intestinal propulsion motion of mice intestinal

Table 4 is the result show, the ahead running (P＜0.01) of the small intestinal of the hyperfunction model that low and high dose group can obviously suppress.Middle dosage group has the trend that suppresses motion, but not statistically significant.

2.5 influence to the motion of normal mouse gastric emptying

Choose 50 of white mice, be divided into 5 groups at random by body weight, positive drug matched group filling stomach is good for the stomach to belly pain and puts in order the obtain solution 0.4mL/20g of intestinal ball institute, be 1mg/kg, the high, medium and low dosage group of tablet is irritated the dosing 0.4mL/20g of lab scale medicine institute that stomach is given variable concentrations, i.e. 1.8g/kg, 0.9g/kg, 0.45g/kg respectively; Blank group group is irritated the normal saline 0.4mL/20g of stomach equal volume.Successive administration 5d, last administration 1h irritate stomach and give gelatinized corn starch 0.8mL/ only, put to death animal behind the 20min, and ligation cardia and pylorus are got stomach then.The full weight of stomach with clean after the net weight difference for being residual quantity, and then calculate residual rate.Experimental result sees Table 5.

The facilitation of table 5 pair normal mouse gastric emptying motion

Table 5 is the result show, the middle dosage of tablet can promote the gastric emptying motion of mice, compares (P＜0.05) with matched group.

2.6 to the pepsic influence of rat gastric acid

Choose 50 of white mice, be divided into 5 groups at random by body weight, positive drug matched group filling stomach is good for the stomach to belly pain and puts in order the obtain solution 0.4mL/20g of intestinal ball institute, be 1mg/kg, the high, medium and low dosage group of tablet is irritated the dosing 0.4mL/20g of lab scale medicine institute that stomach is given variable concentrations, i.e. 1.8g/kg, 0.9g/kg, 0.45g/kg respectively; Blank group group is irritated the normal saline 0.4mL/20g of stomach equal volume.

Successive administration 10d, fasting 48 hours is freely drunk water.The etherization animal is used in the back, cuts off the hair of abdominal part, and routine disinfection skin is opened the otch of about 2.5cm in xiphoid-process lower edge hunter's line, and the careful stomach of mentioning in pylorus and the suture ligation of duodenum joint portion, is avoided blood vessel.The syringe duodenal administration is used in the back, sends back to after the stitching in the cage, and water is prohibited in the postoperative fasting, and 5 hours femoral vein are got blood and put to death animal, take out stomach, collect gastric juice in graduated centrifuge tube, with the centrifugal 15min of 3000r/min, draws supernatant and surveys gastric acid, pepsin respectively.The gastric acid amount is calculated by the NaoH of the 0.01mmol/L that consumes; Pepsin is pressed " herbal pharmacology experimental methodology ", Li Yikui, Science and Technology of Shanghai publishing house, and P242 stipulates pepsic assay method.Experimental result sees Table 6.

The influence of table 6 pair rat gastric acid pepsin activity

Table 6 is the result show, the middle and high dosage group of tablet can improve pepsic activity, has statistical significance, compares (P＜0.01) with matched group.

3 discuss

Experimentation by pharmacodynamics shows that medicine of the present invention can significantly reduce the loose stool number of mice, has anti-diarrhea effect; Can promote the gastric emptying motion of mice; The intestinal propulsion of the hyperfunction model mice of intestinal motion due to inhibition normal mouse and the neostigmine, thereby the absorption of promotion nutrient substance; Promote the secretion of gastric juice and suppress pepsic activity, improve digestive function.Thereby for treatment inappetence, nausea and vomiting, abdominal distention, diarrhoea, dyspepsia etc. provide the pharmacodynamics foundation.

The specific embodiment:

Embodiment one

Chinese medicine active component: creosote 50g, Uncaria gambier Roxb. 120g, Cortex Phellodendri 10g, Radix Glycyrrhizae 35g, Pericarpium Citri Reticulatae 30g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 45g;

Preparation method:

The preparation of creosote:

Place distillating still to distill Fagaceae plant Fagus sinensis Oliv., get dry distillation liquid and under 180 ℃ of conditions, distill, collect the fraction heavier, handle as follows than water:

1. add percentage by weight and be 15% sodium hydroxide solution, stir crystallisation by cooling;

2. filter, discard filtrate, the washing of filtering residue clear water discards washings, adding weight percent concentration is 35% sulfuric acid solution, stirs, and discards sulfate wastewater, clear water washing back is rectification under vacuum under the 0.08-0.09MPa condition in vacuum, collects 130-155 ℃ rectification branch, promptly gets wooden pomegranate oil;

Described fraction: sodium hydroxide solution: the weight part ratio of sulfuric acid solution is 1: 2: 3;

The preparation of preparation:

Uncaria gambier Roxb., Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) pulverize separately are become fine powder, cross 80 mesh sieves, mix homogeneously adds 50g creosote mix homogeneously, get Chinese medicine composition, the glycerol and the carboxymethylcellulose calcium that add pharmaceutically acceptable amount, mix homogeneously, water pill, dry under 30 ℃ of conditions, being prepared into pill, is 10rpm at rotating speed, is to carry out the film coating operation under 45 ℃ of conditions in temperature.

Coating material wherein is a hydroxypropyl methylcellulose: hydroxypropyl cellulose: Polyethylene Glycol is by weight than being to mix at 40: 40: 20; Be that 85% ethanol progressively adds in the mixer of belt stirrer with the coating material percent by volume, stir, promptly get the coating suspension.

Embodiment two

Chinese medicine active component: creosote 20g, Uncaria gambier Roxb. 150g, Cortex Phellodendri 35g, Radix Glycyrrhizae 14g, Pericarpium Citri Reticulatae 20g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 60g;

Preparation method:

The preparation of creosote:

Place distillating still to distill natural Zelkova schneideriana Hand.-Mazz., get dry distillation liquid and under 200 ℃ of conditions, distill, collect the fraction heavier, handle as follows than water:

1. add percentage by weight and be 5% sodium hydroxide solution, stir, add percentage by weight and be 15% calcium acetate solution, crystallisation by cooling;

2. filter, discard filtrate, the washing of filtering residue clear water discards washings, adding weight percent concentration is 25% sulfuric acid solution, stirs, and discards sulfate wastewater, clear water washing back is rectification under vacuum under the 0.08-0.09MPa condition in vacuum, collects 130-155 ℃ rectification branch, promptly gets wooden pomegranate oil;

Described fraction: sodium hydroxide solution: calcium acetate solution: the weight part ratio of sulfuric acid solution is 2: 3: 5: 2.5;

The preparation of preparation:

Uncaria gambier Roxb., Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) are decocted with water 3 times, and 2 hours for the first time, 1 hour for the second time, 3 hours for the third time, collecting decoction filtered, and the survey relative density was 1.15 thick paste when filtrate was condensed into 60 ℃; Wherein amount of water is respectively Uncaria gambier Roxb., Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) gross weight 10,8,6 times; The 20g creosote is joined in the thick paste, stir, get Chinese medicine composition, the glycerol and the carboxymethylcellulose calcium that add pharmaceutically acceptable amount, mix homogeneously, water pill, dry under 45 ℃ of conditions, being prepared into pill, is 15rpm at rotating speed, is to carry out the film coating operation under 40 ℃ of conditions in temperature.

Coating material wherein is a hydroxypropyl methylcellulose: hydroxypropyl cellulose: Polyethylene Glycol is by weight than being to mix at 30: 50: 20; Be that 80% ethanol progressively adds in the mixer of belt stirrer with the coating material percent by volume, stir, promptly get the coating suspension.

Embodiment three

Chinese medicine active component: creosote 35g, Uncaria gambier Roxb. 30g, Cortex Phellodendri 60g, Radix Glycyrrhizae 8g, Pericarpium Citri Reticulatae 31g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 30g;

Preparation method:

The preparation of creosote:

Place distillating still to distill maple, get dry distillation liquid and under 360 ℃ of conditions, distill, collect the fraction heavier, handle as follows than water:

1. add percentage by weight and be 20% sodium hydroxide solution, stir, add percentage by weight and be 30% magnesium acetate solution, crystallisation by cooling;

2. filter, discard filtrate, the washing of filtering residue clear water discards washings, adding weight percent concentration is 20% sulfuric acid solution, stirs, and discards sulfate wastewater, clear water washing back is rectification under vacuum under the 0.08-0.09MPa condition in vacuum, collects 130-155 ℃ rectification branch, promptly gets wooden pomegranate oil;

Described fraction: sodium hydroxide solution: magnesium acetate solution: the weight part ratio of sulfuric acid solution is 3: 4: 7: 3.5;

The preparation of preparation:

1. getting Cortex Phellodendri is 90% alcohol heating reflux 2 times in percent by volume, 2 hours for the first time, and 1.5 hours for the second time, filter, merging filtrate, filtrate recycling ethanol extremely do not have the alcohol flavor, filter, and get filtrate A;

2. Uncaria gambier Roxb., Radix Glycyrrhizae, Pericarpium Citri Reticulatae and Cortex cinnamomi japonici (Ramulus Cinnamomi) are decocted with water 3 times, 2 hours for the first time, 3 hours for the second time, 1 hour for the third time, collecting decoction filtered, and the survey relative density was 1.10 extractum B when filtrate was concentrated into 60 ℃; Wherein amount of water is respectively Uncaria gambier Roxb., Radix Glycyrrhizae, Pericarpium Citri Reticulatae and Cortex cinnamomi japonici (Ramulus Cinnamomi) gross weight 10,8,6 times;

3. filtrate A is mixed with extractum B, relative density is 1.30 extractum when being concentrated into 60 ℃, and drying is made fine powder, adds the 35g creosote, stirs, and gets Chinese medicine composition.

The glycerol and the carboxymethylcellulose calcium that add pharmaceutically acceptable amount in the described Chinese medicine composition, mix homogeneously, water pill, dry under 60 ℃ of conditions, be prepared into pill, be 5rpm at rotating speed, be to carry out the film coating operation under 50 ℃ of conditions in temperature.

Coating material wherein is a hydroxypropyl methylcellulose: hydroxypropyl cellulose: Polyethylene Glycol is by weight than being to mix at 20: 60: 20; Be that 70% ethanol progressively adds in the mixer of belt stirrer with the coating material percent by volume, stir, promptly get the coating suspension.

Embodiment four

Chinese medicine active component: creosote 41g, Uncaria gambier Roxb. 75g, Cortex Phellodendri 25g, Radix Glycyrrhizae 25g, Pericarpium Citri Reticulatae 15g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 55g;

Preparation method:

The preparation of creosote:

Place distillating still to distill Xylosmae japonici, get dry distillation liquid and under 300 ℃ of conditions, distill, collect the fraction heavier, handle as follows than water:

1. add percentage by weight and be 10% potassium hydroxide solution, stir, add percentage by weight and be 10% magnesium acetate solution, crystallisation by cooling;

2. filter, discard filtrate, the washing of filtering residue clear water discards washings, adding weight percent concentration is 30% sulfuric acid solution, stirs, and discards sulfate wastewater, clear water washing back is rectification under vacuum under the 0.08-0.09MPa condition in vacuum, collects 130-155 ℃ rectification branch, promptly gets wooden pomegranate oil;

Described fraction: potassium hydroxide solution: magnesium acetate solution: the weight part ratio of sulfuric acid solution is 2.5: 3: 4: 2;

The preparation of preparation:

1. Cortex Phellodendri being processed into coarse powder, is solvent with 10 times of amount saturated limewaters, supersound extraction 2 times, 20min for the first time, 10min is mixed with extracting solution the solution of counting 33mg/ml with crude drug for the second time, filter, add the NaCl placement and spend the night, filter oven dry, in precipitation, be dissolved in water, filter, it is 1～2 that filtrate adds hydrochloric acid accent pH, treats that post precipitation filters, and gets filtrate A;

2. Uncaria gambier Roxb., Radix Glycyrrhizae, Pericarpium Citri Reticulatae and Cortex cinnamomi japonici (Ramulus Cinnamomi) are decocted with water 2 times, 3 hours for the first time, 1 hour for the second time, collecting decoction filtered, and the survey relative density was 1.30 extractum B when filtrate was concentrated into 60 ℃; Wherein amount of water is respectively Uncaria gambier Roxb., Radix Glycyrrhizae, Pericarpium Citri Reticulatae and Cortex cinnamomi japonici (Ramulus Cinnamomi) gross weight 6,8 times;

3. filtrate A is mixed with extractum B, relative density is 1.25 extractum when being concentrated into 60 ℃, and drying is made fine powder, adds the 41g creosote, stirs, and gets Chinese medicine composition.

The glycerol and the carboxymethylcellulose calcium that add pharmaceutically acceptable amount in the described Chinese medicine composition, mix homogeneously, water pill, dry under 50 ℃ of conditions, be prepared into pill, be 12rpm at rotating speed, be to carry out the film coating operation under 48 ℃ of conditions in temperature.

Coating material wherein is with embodiment three.

Embodiment five

Chinese medicine active component: pine tar 60g, Uncaria gambier Roxb. 200g, Cortex Phellodendri 50g, Radix Glycyrrhizae 16g, Pericarpium Citri Reticulatae 29g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 70g;

Preparation method:

The preparation of pine tar:

Place distillating still to distill pinaster, get dry distillation liquid and under 280 ℃ of conditions, distill, collect the fraction heavier, handle as follows than water:

1. add percentage by weight and be 12% potassium hydroxide solution, stir, add percentage by weight and be 20% magnesium acetate solution, crystallisation by cooling;

2. filter, discard filtrate, the washing of filtering residue clear water discards washings, adding weight percent concentration is 28% sulfuric acid solution, stirs, and discards sulfate wastewater, clear water washing back is rectification under vacuum under the 0.08-0.09MPa condition in vacuum, collects 130-155 ℃ rectification branch, promptly gets unguentum picis pini;

Described fraction: potassium hydroxide solution: magnesium acetate solution: the weight part ratio of sulfuric acid solution is 1.5: 2.5: 6: 3;

The preparation of preparation:

Uncaria gambier Roxb., Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) pulverize separately are become fine powder, cross the 80-120 mesh sieve, mix homogeneously, add 60g pine tar mix homogeneously, make Chinese medicine composition, with disintegrating agent carboxymethyl base Starch Sodium, filler mannitol, the wetting agent ethyl cellulose mix homogeneously of pharmaceutically acceptable amount, granulate, with lubricant micropowder silica gel mix homogeneously, tabletting, film coating make tablet again.

Wherein film-coated technology is with embodiment one;

Coating material wherein is a hydroxypropyl methylcellulose: hydroxypropyl cellulose: Polyethylene Glycol is by weight than being to mix at 15: 60: 25; Be that 75% ethanol progressively adds in the mixer of belt stirrer with the coating material percent by volume, stir, promptly get the coating suspension

Embodiment six

Chinese medicine active component: bamboo tar 30g, Uncaria gambier Roxb. 140g, Cortex Phellodendri 40g, Radix Glycyrrhizae 30g, Pericarpium Citri Reticulatae 25g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 35g;

Preparation method:

The preparation of bamboo tar:

Place distillating still to distill in bamboo, getting dry distillation liquid distills under 180 ℃ of conditions, the collection fraction heavier than water places rectifying still, in temperature is 130-155 ℃, withdrawing moisture and light fraction under the vacuum 0.08-0.09MPa condition, with the crystallization in freezing 12 hours under subzero 20 conditions of the fraction in the rectifying still, the crystal centrifugalize obtains the bamboo tar crystal, place normal temperature condition, standby;

The preparation of preparation:

Uncaria gambier Roxb., Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) are decocted with water 2 times, and 1.5 hours for the first time, 2 hours for the second time, collecting decoction filtered, and the survey relative density was 1.20 thick paste when filtrate was condensed into 60 ℃; Wherein amount of water is respectively Uncaria gambier Roxb., Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) gross weight 8,6 times; The 30g bamboo tar is joined in the thick paste, stir, get Chinese medicine composition, with the disintegrating agent methylcellulose of pharmaceutically acceptable amount and starch, filler lactose and dextrin, wetting agent ethanol mix homogeneously, granulate, with carboxymethyl starch sodium, magnesium stearate lubricant, hydroxylation vegetable oil mix homogeneously, tabletting, film coating make tablet again.

The preparation of coating material wherein and coating suspension is with embodiment 1, and film-coated technology is with embodiment three.

Embodiment seven

Chinese medicine active component: creosote 55g, Uncaria gambier Roxb. 50g, Cortex Phellodendri 65g, Radix Glycyrrhizae 20g, Pericarpium Citri Reticulatae 35g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 60g;

Preparation method:

The preparation of creosote:

Place distillating still to distill Quercus acutissima Carr., getting dry distillation liquid distills under 360 ℃ of conditions, the collection fraction heavier than water places rectifying still, in temperature is 130-155 ℃, withdrawing moisture and light fraction under the vacuum 0.08-0.09MPa condition, with the crystallization in freezing 48 hours under 0 ℃ of condition of the fraction in the rectifying still, the crystal centrifugalize obtains the creosote crystal, place normal temperature condition, standby;

The preparation of preparation:

1. getting Cortex Phellodendri is 75% alcohol heating reflux 3 times in percent by volume, 3 hours for the first time, and 2 hours for the second time, 1 hour for the third time, filter, merging filtrate, filtrate recycling ethanol extremely do not have the alcohol flavor, filter, and get filtrate A;

2. Uncaria gambier Roxb., Radix Glycyrrhizae, Pericarpium Citri Reticulatae and Cortex cinnamomi japonici (Ramulus Cinnamomi) are decocted with water 2 times, 2 hours for the first time, 1.5 hours for the second time, collecting decoction filtered, and the survey relative density was 1.20 extractum B when filtrate was concentrated into 60 ℃; Wherein amount of water is Uncaria gambier Roxb., Radix Glycyrrhizae, Pericarpium Citri Reticulatae and Cortex cinnamomi japonici (Ramulus Cinnamomi) gross weight 6～10 times;

3. filtrate A is mixed with extractum B, relative density is 1.10 extractum when being concentrated into 60 ℃, and drying is made fine powder, add the 55g creosote, stir, Chinese medicine composition, with the disintegrating agent sodium bicarbonate of pharmaceutically acceptable amount and hydroxypropyl cellulose, filler amylum pregelatinisatum, wetting agent hydroxypropyl emthylcellulose mix homogeneously, granulate, with carboxymethyl starch sodium, lubricant Pulvis Talci, magnesium laurylsulfate mix homogeneously, tabletting, film coating make tablet again.

The preparation of coating material wherein and coating suspension is with embodiment 2, and film-coated technology is with embodiment one.

Embodiment eight

Chinese medicine active component: creosote 40g, Uncaria gambier Roxb. 110g, Cortex Phellodendri 30g, Radix Glycyrrhizae 10g, Pericarpium Citri Reticulatae 40g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 40g;

Preparation method:

The preparation of creosote:

Place distillating still to distill natural Zelkova schneideriana Hand.-Mazz., getting dry distillation liquid distills under 220 ℃ of conditions, the collection fraction heavier than water places rectifying still, in temperature is 130-155 ℃, withdrawing moisture and light fraction under the vacuum 0.08-0.09MPa condition, with the crystallization in freezing 20 hours under subzero 10 ℃ of conditions of the fraction in the rectifying still, the crystal centrifugalize obtains the creosote crystal, place normal temperature condition, standby;

The preparation of preparation:

The preparation method of Chinese medicine composition is with embodiment seven, wherein

1. step for Cortex Phellodendri being processed into coarse powder, is solvent with 8 times of amount saturated limewaters, supersound extraction 3 times, 30 minutes for the first time, 20 minutes for the second time, 15 minutes for the third time, extracting solution is mixed with the solution of counting 35mg/ml with crude drug, filters, add the NaCl placement and spend the night, filter, oven dry is dissolved in water in precipitation, filters, and it is 1～2 that filtrate adds hydrochloric acid accent pH, treat that post precipitation filters, and gets filtrate A;

With the disintegrating agent microcrystalline Cellulose of Chinese medicine composition and pharmaceutically acceptable amount and crospolyvinylpyrrolidone, filler lactose, wetting agent distilled water mix homogeneously, granulate, again with carboxymethyl starch sodium, lubricant Pulvis Talci, Polyethylene Glycol mix homogeneously, tabletting, film coating make tablet.

The preparation of coating material wherein and coating suspension is with embodiment three, and film-coated technology is with embodiment one.

Embodiment nine

Chinese medicine active component: creosote 45g, Uncaria gambier Roxb. 90g, Cortex Phellodendri 29g, Radix Glycyrrhizae 15g, Pericarpium Citri Reticulatae 50g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 65g;

Preparation method:

The preparation method of wood pomegranate oil is with embodiment three;

Uncaria gambier Roxb., Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) pulverize separately are become fine powder, cross the 80-120 mesh sieve, mix homogeneously, add 45g creosote mix homogeneously, get Chinese medicine composition, with disintegrating agent methylcellulose, the sodium bicarbonate mix homogeneously of pharmaceutically acceptable amount, granulate, make capsule

Embodiment ten

Chinese medicine active component: creosote 39g, Uncaria gambier Roxb. 180g, Cortex Phellodendri 45g, Radix Glycyrrhizae 12g, Pericarpium Citri Reticulatae 45g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 70g;

Preparation method:

The preparation method of wood pomegranate oil is with embodiment four;

The preparation method of Chinese medicine composition is with embodiment six;

The disintegrating agent microcrystalline Cellulose of described Chinese medicine composition and pharmaceutically acceptable amount, carboxymethyl starch sodium, crospolyvinylpyrrolidone mix homogeneously are granulated, and make capsule.

Embodiment 11

Chinese medicine active component: pine tar 25g, Uncaria gambier Roxb. 130g, Cortex Phellodendri 20g, Radix Glycyrrhizae 32g, Pericarpium Citri Reticulatae 43g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 50g;

Preparation method:

Wherein the preparation method of pine tar is with embodiment five;

The preparation method of Chinese medicine composition is with embodiment eight;

Wherein 1. step for Cortex Phellodendri being processed into coarse powder, is solvent with 12 times of amount saturated limewaters, supersound extraction 3 times, 30 minutes for the first time, 20 minutes for the second time, 15 minutes for the third time, extracting solution is mixed with the solution of counting 30mg/ml with crude drug, filters, add the NaCl placement and spend the night, filter, oven dry is dissolved in water in precipitation, filters, and it is 1～2 that filtrate adds hydrochloric acid accent pH, treat that post precipitation filters, and gets filtrate A;

The disintegrating agent starch of described Chinese medicine composition and pharmaceutically acceptable amount, hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose mix homogeneously are granulated, and make capsule.

Embodiment 12

Chinese medicine active component: creosote 39g, Uncaria gambier Roxb. 100g, Cortex Phellodendri 31g, Radix Glycyrrhizae 16g, Pericarpium Citri Reticulatae 29g, Cortex cinnamomi japonici (Ramulus Cinnamomi) 50g;

The preparation method of wood pomegranate oil is with embodiment two;

Leaf and the sprout of Uncaria gambier Roxb. Uncaria Gambir Roxb. decoct with water 2 times, and 1.5 hours for the first time, 2 hours for the second time, merging filtrate filters, and the survey relative density was 1.15 thick paste when filtrate was condensed into 60 ℃, drying is ground into fine powder, gets the Uncaria gambier Roxb. dry extract;

Cortex Phellodendri, Radix Glycyrrhizae, Pericarpium Citri Reticulatae, Cortex cinnamomi japonici (Ramulus Cinnamomi) pulverize separately are become fine powder, cross 100 mesh sieves, Cortex Phellodendri powder, Radix Glycyrrhizae powder, Pericarpium Citri Reticulatae powder and Uncaria gambier Roxb. dry extract mix homogeneously, add creosote and glycerol, add water pill behind the mix homogeneously, cold drying, make 900, use the Cortex cinnamomi japonici powder coating, promptly.

The method of quality control of described medicine pill, its qualitative identification method comprise following one or more:

A. according to gas chromatography determination

System suitability test is immobile phase with PEG-20M, and coating concentration is 5%, 160 ℃ of column temperatures, 210 ℃ of injector temperatures, detector temperature ℃; Theoretical pedal number calculates by the guaiacol peak should be not less than 3000;

The about 40mg of guaiacol reference substance is got in the reference substance solution preparation, and accurate the title decides, and adds dissolve with methanol and is diluted to the solution that every ml contains 8mg, in contrast product solution;

27 of pills are got in the need testing solution preparation, and accurate the title decides weight and obtain 1 average weight, puts in the tool plug conical flask, with glass rod crushing, the washing 5 times that adds diethyl ether, each 5ml, merging filtrate and washing liquid, volatilize ether naturally after residue add dissolve with methanol and be diluted to 50ml, as need testing solution;

Algoscopy is drawn reference substance solution and each 2 μ l of test sample respectively, and inject gas chromatograph is measured, and calculates, promptly;

Contain more wood wound phenol (C in per 9 of this product ₇H ₈O ₂) should be 80-120mg;

B. according to high effective liquid chromatography for measuring

Strong to close silica gel be filler ODS post 250X4.6mm to system suitability test with octadecylsilane; Acetonitrile-3% acetic acid-methanol-triethylamine (50: 50: 20: 0.4) be mobile phase, detect wavelength 254nm; Theoretical pedal number calculates by berberine hydrochloride should be not less than 2000;

It is an amount of that the berberine hydrochloride reference substance is got in the reference substance solution preparation, and accurate the title decides, and adds 3% acetate methanol-water (3: 1) and makes the solution that every ml contains 0.2mg, in contrast product solution;

Down remaining residue behind the ether extraction of [assay] (1) is got in need testing solution preparation, add 3% acetate methanol-water (3: 1) 50ml, reflux is 15 minutes in water-bath, filter while hot, residue is with 3% acetate methanol-water (3: 1) heated scrub 3 times, each 5ml, merging filtrate and washing liquid, place the 100ml measuring bottle, put coldly, be diluted to scale with 3% acetate methanol-water (3: 1); Precision is measured 5ml, puts in the 20ml measuring bottle, and the accurate inner mark solution 2ml that adds is diluted to scale with 3% acetate methanol-water (3: 1), again as need testing solution;

Algoscopy is drawn each 10 μ l of reference substance solution and need testing solution respectively, injects chromatograph of liquid, measures, and calculates, promptly;

Hydrochloric berberine (C in per 9 of this product ₂₀H ₁₈ClNO ₄2H ₂O) should be 80-120mg.

Claims

1. one kind is used for the treatment of inappetence, nausea and vomiting, abdominal distention diarrhoea, dyspeptic Chinese medicine composition, and described Chinese medicine composition is formed by the following components in part by weight processing and preparing:

2. according to the described Chinese medicine composition of claim 1, it is characterized in that described Chinese medicine composition is formed through processing and preparing by following parts by weight of Chinese traditional medicine raw material:

3. according to the described Chinese medicine composition of claim 2, it is characterized in that described Chinese medicine composition is formed through processing and preparing by following parts by weight of Chinese traditional medicine raw material:

4. according to claim 1,2 or 3 described Chinese medicine compositions, be prepared into pill, tablet or capsule with the pharmaceutic adjuvant of medically acceptable amount.

5. according to the described Chinese medicine composition of claim 4, it is characterized in that the described oil that heats up in a steamer is creosote, pine tar or bamboo tar.

6. one kind prepares the method that is used for the treatment of inappetence, nausea and vomiting, abdominal distention diarrhoea, dyspeptic Chinese medicine composition, comprises the steps:

7. one kind prepares the method that is used for the treatment of inappetence, nausea and vomiting, abdominal distention diarrhoea, dyspeptic Chinese medicine composition, comprises the steps:

8. one kind prepares the method that is used for the treatment of inappetence, nausea and vomiting, abdominal distention diarrhoea, dyspeptic Chinese medicine composition, comprises the steps:

9. according to claim 6,7 or 8 described methods, it is characterized in that the described oil that heats up in a steamer is with Fagaceae plant Fagus sinensis Oliv. Fagus sinensis Oliv., natural beech section natural plant Zelkova schneideriana Hand.-Mazz., maple, Xylosmae japonici, Quercus acutissima Carr., Pinaceae pinaceae Pinus pinus plant pinaster or Juniperus rigida Sieb.et Zucc., bamboo places distillating still to distill, get dry distillation liquid and under 180-360 ℃ of condition, distill, collect the fraction heavier, handle as follows than water:

2. filter, discard filtrate, the washing of filtering residue clear water discards washings, adding weight percent concentration is the 20-35% sulfuric acid solution, stirs, and discards sulfate wastewater, clear water washing back is rectification under vacuum under the 0.08-0.09MPa condition in vacuum, collects 130-155 ℃ rectification branch, promptly;

Described fraction: aqueous slkali: the weight part ratio of sulfuric acid solution is 1-3: 2-4: 2-3.5.

10. in accordance with the method for claim 9, it is characterized in that adding again after 1. described step stirs calcium acetate or the magnesium acetate solution that percentage by weight is 10-30%; Described fraction: the weight part ratio of calcium acetate or magnesium acetate is 1-3: 4-7.

11. in accordance with the method for claim 9, it is characterized in that described step aqueous slkali 1. is sodium hydroxide or potassium hydroxide solution.

12. according to claim 6,7 or 8 described methods, it is characterized in that the described oil that heats up in a steamer is with Fagaceae plant Fagus sinensis Oliv. Fagus sinensis Oliv., natural beech section natural plant Zelkova schneideriana Hand.-Mazz., maple, Xylosmae japonici, Quercus acutissima Carr., Pinaceae pinaceae Pinus pinus plant pinaster or Juniperus rigida Sieb.et Zucc., bamboo places distillating still to distill, getting dry distillation liquid distills under 180-360 ℃ of condition, the collection fraction heavier than water places rectifying still, in temperature is 130-155 ℃, withdrawing moisture and light fraction under the vacuum 0.08-0.09MPa condition, with the freezing 12-48 hour crystallization under subzero 20 to 0 ℃ of conditions of the fraction in the rectifying still, the crystal centrifugalize obtains heating up in a steamer oily crystal.

13. according to claim 6,7 or 8 described methods, it is characterized in that adding in the described Chinese medicine composition glycerol and carboxymethylcellulose calcium, mix homogeneously, water pill, cold drying is prepared into pill, film coating.

14. in accordance with the method for claim 13, it is characterized in that described cold drying is 30-60 ℃ of drying.

15. in accordance with the method for claim 13, it is characterized in that described pill is as the coating material coating with the mixture of using hydroxypropyl methylcellulose, hydroxypropyl cellulose, Polyethylene Glycol; Described excipient is water, ethanol, Mel or starch slurry; Described binding agent is a kind of or wherein several mixture in ethyl cellulose, hydroxypropyl emthylcellulose, the arabic gum.

16. in accordance with the method for claim 13, it is characterized in that described film-coated rotating speed is 5-15rpm, is to carry out the coating operation under the 40-50 ℃ of condition in temperature.

17. according to claim 6,7 or 8 described methods, it is characterized in that a kind of or several mix homogeneously wherein in described Chinese medicine composition and disintegrating agent, filler, the wetting agent, granulate, even with mix lubricant again, tabletting, film coating make tablet.

18. in accordance with the method for claim 17, it is characterized in that granulating back and carboxymethyl starch sodium, mix lubricant are even, and tabletting, film coating make tablet.

19. in accordance with the method for claim 17, it is characterized in that described disintegrating agent is a kind of or wherein several mixture in carboxymethyl starch sodium, starch, methylcellulose, sodium bicarbonate, microcrystalline Cellulose, hydroxypropyl cellulose, crospolyvinylpyrrolidone, the cross-linking sodium carboxymethyl cellulose; Described filler is a kind of or wherein several mixture in dextrin, lactose, amylum pregelatinisatum, microcrystalline Cellulose or the mannitol; Described wetting agent is a kind of or wherein several mixture in distilled water, ethanol, starch slurry, ethyl cellulose, the hydroxypropyl emthylcellulose; Described lubricant is a kind of or wherein several mixture in magnesium stearate, micropowder silica gel, Pulvis Talci, hydrogenated vegetable oil, Polyethylene Glycol and the magnesium laurylsulfate.

20. the mixture that it is characterized in that in accordance with the method for claim 17, described tablet hydroxypropyl methylcellulose, hydroxypropyl cellulose, Polyethylene Glycol is as the coating material coating.

21. in accordance with the method for claim 17, it is characterized in that described film-coated rotating speed is 5-15rpm, is to carry out the coating operation under the 40-50 ℃ of condition in temperature.

22., it is characterized in that described Chinese medicine composition and disintegrating agent mix homogeneously according to claim 6,7 or 8 described methods, granulate, make capsule.

23. in accordance with the method for claim 22, it is characterized in that described disintegrating agent is a kind of or wherein several mixture in carboxymethyl starch sodium, starch, methylcellulose, sodium bicarbonate, microcrystalline Cellulose, hydroxypropyl cellulose, crospolyvinylpyrrolidone, the cross-linking sodium carboxymethyl cellulose.

24. one kind prepares the preparation method that is used for the treatment of inappetence, nausea and vomiting, abdominal distention diarrhoea, dyspeptic medicine pill, it is characterized in that comprising the steps:

25. the method for quality control of the described medicine pill of claim 24, its qualitative identification method comprise following one or more:

A. according to gas chromatography determination

Pill is got in the need testing solution preparation, and accurate the title decides weight and obtain 1 average weight, puts in the tool plug conical flask, with glass rod crushing, the washing 5 times that adds diethyl ether, each 5ml, merging filtrate and washing liquid, volatilize ether naturally after residue add dissolve with methanol and be diluted to 50ml, as need testing solution;

B. according to high effective liquid chromatography for measuring

Strong to close silica gel be filler ODS post 250 * 4.6mm to system suitability test with octadecylsilane; Acetonitrile-3% acetic acid-methanol-triethylamine (50: 50: 20: 0.4) be mobile phase, detect wavelength 254nm; Theoretical pedal number calculates by berberine hydrochloride should be not less than 2000;

Down remaining residue behind the ether extraction of assay (1) is got in need testing solution preparation, add 3% acetate methanol-water (3: 1) 50ml, reflux is 15 minutes in water-bath, filter while hot, residue is with 3% acetate methanol-water (3: 1) heated scrub 3 times, each 5ml, merging filtrate and washing liquid, place the 100ml measuring bottle, put coldly, be diluted to scale with 3% acetate methanol-water (3: 1); Precision is measured 5ml, puts in the 20ml measuring bottle, and the accurate inner mark solution 2ml that adds is diluted to scale with 3% acetate methanol-water (3: 1), again as need testing solution;

26. claim 1,2 or 3 described Chinese medicine compositions are treated application in inappetence, nausea and vomiting, abdominal distention diarrhoea, dyspeptic medicine in preparation.