CN101912564A - Traditional Chinese medicine for treating chronic gastritis - Google Patents

Abstract

The invention discloses a traditional Chinese medicine for treating chronic gastritis. The traditional Chinese medicine aims to treat the chronic gastritis by adopting Chinese medicinal theory of warming middle jiao and dissipating cold and rectifying qi and relieving pain. Active ingredients of the traditional Chinese medicine consist of the following raw materials in part by weight: cassia twigs, megnolia hypoleuca, agastache, eupatorium, tangerine peel, pinellia tuberifera, putchuck, amomum fruit, pollen typnae, trogopterus dung and liquorice. The traditional Chinese medicine is suitable for treating: (1) chronic superficial gastritis, chronic atrophic gastritis, stomach and duodenal bulb ulcer; (2) nausea, emesis, hiccough and the like caused by disorder of gastrointestinal nerve function; and (3) spleen-stomach deficiency cold and the like diagnosed by doctors of traditional Chinese medicine.

Description

A kind of Chinese medicine for the treatment of chronic gastritis

Technical field

The invention belongs to the field of Chinese medicines.

Background technology

Gastric abscess is called for short stomachache, is commonly encountered diseases, one of frequently-occurring disease, the occurrence cause of stomachache is more, every and direct stimulation, and feelings will is not smooth, intemperance of taking food, fatigue are caught cold etc. substantial connection, wherein lose in retrenching with diet especially, the impairing the spleen and stomach yang-energy, cold amass in, venation is lost in replenishing vital QI with drugs of warm nature, the power deficiency of sun fortune, and the Deficiency and coldness of spleen and stomach person of having a pain is taken place, much more comparatively to see.The edge taste are arranged in Jiao, post fortuneization, lifting, and as if plain body weakness, the taste yang-energy is on the decline, and is cold from Nei Sheng or intemperance of taking food, has a liking for food raw food, causes dysfunction of the spleen in transportation and transformation, wet gathering due to cold the Sheng.

Summary of the invention

The objective of the invention is to adopt theory of Chinese medical science, warming spleen and stomach for dispelling cold, the Chinese medicine of the treatment chronic gastritis of regulating QI to relieve pain.

The present invention makes the raw materials of effective components weight portion and consists of:

Ramulus Cinnamomi 5-15, Cortex Magnoliae Officinalis 5-15, Herba Pogostemonis 5-10, Herba Eupatorii 5-10, Pericarpium Citri Reticulatae 5-10, Rhizoma Pinelliae 5-10, Radix Aucklandiae 5-10,

Fructus Amomi 5-10, Pollen Typhae 5-10, WULINGZI 5-10, Radix Glycyrrhizae 3-5.

The present invention makes raw materials of effective components optimum weight part and consists of:

Ramulus Cinnamomi 15, Cortex Magnoliae Officinalis 10, Herba Pogostemonis 10, Herba Eupatorii 10, Pericarpium Citri Reticulatae 10, the Rhizoma Pinelliae 10, the Radix Aucklandiae 10,

Fructus Amomi 10, Pollen Typhae 10, WULINGZI 10, Radix Glycyrrhizae 5.

Indication of the present invention:

(1) chronic superficial gastritis, chronic atrophic gastritis, stomach and duodenal bulbar ulcer.

(2) feeling sick due to the gastrointestinal nerve dysfunction, vomiting, singultus etc.

(3) traditional Chinese medical science distinguishes that disease belongs to the Deficiency and coldness of spleen and stomach pattern of syndrome.

The specific embodiment

The present invention makes the raw materials of effective components weight portion and consists of:

Ramulus Cinnamomi 5-15, Cortex Magnoliae Officinalis 5-15, Herba Pogostemonis 5-10, Herba Eupatorii 5-10, Pericarpium Citri Reticulatae 5-10, Rhizoma Pinelliae 5-10, Radix Aucklandiae 5-10,

Fructus Amomi 5-10, Pollen Typhae 5-10, WULINGZI 5-10, Radix Glycyrrhizae 3-5.

The present invention makes raw materials of effective components optimum weight part and consists of:

Ramulus Cinnamomi 15, Cortex Magnoliae Officinalis 10, Herba Pogostemonis 10, Herba Eupatorii 10, Pericarpium Citri Reticulatae 10, the Rhizoma Pinelliae 10, the Radix Aucklandiae 10,

Fructus Amomi 10, Pollen Typhae 10, WULINGZI 10, Radix Glycyrrhizae 5.

Compound method is: with above 11 flavor Chinese medicines, add the water of 10 times of amounts, soaked 20 minutes, the back decocted 1 hour, filtered to be concentrated into 1000ml(relative density 1.02-1.06,20 ℃ of surveys) add benzoic acid and receive mixing filtration packing promptly, every bag is 100ml.

Embodiment 1:

The present invention makes the raw materials of effective components weight portion and consists of:

Ramulus Cinnamomi 5, Cortex Magnoliae Officinalis 5, Herba Pogostemonis 5, Herba Eupatorii 5, Pericarpium Citri Reticulatae 5, the Rhizoma Pinelliae 5, the Radix Aucklandiae 5,

Fructus Amomi 5, Pollen Typhae 5, WULINGZI 5, Radix Glycyrrhizae 3.

Compound method is with above 11 flavor Chinese medicines, adds the water of 10 times of amounts, soaks 20 minutes, and the back decocted 1 hour, filtered to be concentrated into 1000ml(relative density 1.02-1.06,20 ℃ of surveys) add benzoic acid and receive mixing filtration packing promptly, every bag is 100ml.

Embodiment 2:

The present invention makes the raw materials of effective components weight portion and consists of:

Ramulus Cinnamomi 10, Cortex Magnoliae Officinalis 10, Herba Pogostemonis 7.5, Herba Eupatorii 7.5, Pericarpium Citri Reticulatae 7.5, the Rhizoma Pinelliae 7.5, the Radix Aucklandiae 7.5,

Fructus Amomi 7.5, Pollen Typhae 7.5, WULINGZI 7.5, Radix Glycyrrhizae 4.

Compound method is with embodiment 1.

Embodiment 3:

The present invention makes the raw materials of effective components weight portion and consists of:

Ramulus Cinnamomi 15, Cortex Magnoliae Officinalis 10, Herba Pogostemonis 10, Herba Eupatorii 10, Pericarpium Citri Reticulatae 10, the Rhizoma Pinelliae 10, the Radix Aucklandiae 10,

Fructus Amomi 10, Pollen Typhae 10, WULINGZI 10, Radix Glycyrrhizae 5.

Compound method is with embodiment 1.

The side separates:

The present invention controls according to debating disease executing, and follows Chinese medical theory, the saying of " taste Central Region, Wen Yunwei is expensive ", and corresponding Deficiency and coldness of spleen and stomach disease pattern of syndrome, its rule of treatment is legislation with the warming spleen and stomach for dispelling cold regulating QI to relieve pain.

Monarch drug Ramulus Cinnamomi warming the spleen warming the stomach in the side, regulating QI and blood, " herbal argument record " says " Ramulus Cinnamomi institute is excellent, and at warming the meridian and promoting blood circulation, interior exterior symptoms is suitable, must not recognize Ramulus Cinnamomi and be the antiperspirant medicine also ".Zhang Zhongjing " Medical Treasures of the Golden Chamber " Xiao Jianzhong Tang is principal agent with the strong fortune of tonify deficiency cold expelling middle-jiao yang, function of the spleen and stomach promptly, ministerial drug Cortex Magnoliae Officinalis circulation of qi promoting removing dampness, and warming middle-JIAO to relieve pain " Mingyi Bielu " is said " Cortex Magnoliae Officinalis is controlled with contrary the reaching of cold in the stomach and vomitted in the heart incessantly ".Fructus Amomi circulation of qi promoting removing dampness warming the spleen preventing or arresting vomiting, " Bencao Jingshu " said: " for the key medicine of opening taste and the certified products of middle gas ".Radix agastaches, Herba Eupatorii removing dampness for regulating stomach, the stomach function regulating of being amusing, " Bencao Jingshu " said: " appetizing removes and dislikes, and the lung heat clearing expectorant is loose strongly fragrant panacea also ".Rhizoma Pinelliae regulating the stomach and sending down the abnormal ascending QI, dissolving lump and resolving mass, " Datong District's materia medica " said: " for normalizing the stomach by guiding QI downward will product ".Five concentrate the auxiliary monarch drug of the efficacy of a drug, give full play to the drug effect of warming the spleen warming the stomach damp eliminating dissipating fluid-retention, and strong fortune Central Region important department and ascending the clear and descending the turbid are just accord with the meaning (seeing "guide to clinical practice with medical record") in " the normal function of the spleen tending to ascent, stomach should fall then and ".Assistant Pollen Typhae removing stasis to stop bleeding, row stagnation pain, Compendium of Material Medica is said: " removing heat from blood and promoting blood circulation ends all pains of trusted subordinate ".The Oletum Trogopterori blood circulation promoting and blood stasis dispelling, hemostasis and pain-relieving, Compendium of Material Medica is said: " all trusted subordinates of men and women, side of body rib, few all pains of abdomen ".Pollen Typhae must be joined the i.e. SHIXIAO SAN of " prescription of peaceful benevolent dispensary " of Oletum Trogopterori, is the name side of treatment precordial pain due to metrorrhagia, and these fragrant promoting the circulation of QI to relieve pain are changed the stomach function regulating that stagnates, and " Japan hanako materia medica " said: " controlling all stagnation of QIs of trusted subordinate, antidiarrheal, antiabortive, strengthening the spleen to promote digestion ".Pericarpium Citri Reticulatae circulation of qi promoting spleen invigorating, drying dampness to eliminate phlegm, Compendium of Material Medica is said: " treatment vomit the sound of vomiting regurgitation noisy, the time vomiting watery fluid, accumulation of phlegm in the hypochondrium ".The minister adjuvant drug is the root base of a fruit of negative and positive of qi and blood together with monarch drug spleen invigorating stomach strengthening to help taste altogether.(seeing " secret record of the orchid chamber yang invigorating dehumidifying soup ") makes with the invigorating middle warmer of Radix Glycyrrhizae QI invigorating, and to be in harmonious proportion the property of medicine, all medicines share, and play warming spleen and stomach for dispelling cold altogether, the effect of regulating QI to relieve pain.

Pharmacological experiment research:

One, animal model is set up

Materials and methods

(1) animal

40 of kunming mices, body weight 20 native 2g, male and female half and half, age in 6-8 week.Wistar is 120 of white mouse too, body weight 80-110g, male and female half and half, 8-10 age in week.Large and small Mus is bought the back back in 1 week of animal indoor feeding, to conform all available from animal housing of Jilin University.The quantitative Formula Diets of experimental session freely absorbs tap water.

(2) medication preparation

The prescription prescription: Ramulus Cinnamomi 15, Cortex Magnoliae Officinalis 10, Herba Pogostemonis 10, Herba Eupatorii 10, Pericarpium Citri Reticulatae 10, the Rhizoma Pinelliae 10, the Radix Aucklandiae 10, Fructus Amomi 10, Pollen Typhae 10, WULINGZI 10, Radix Glycyrrhizae 5 are provided by Chinese medicine pharmacy of No.1 Hospital of Jilin Univ..

(3) animal model is set up

1, experiment material

Fresh pig bile, bacillus calmette-guerin vaccine 75mg/ props up (the Changchun institute of Biological Products provides), infull freund adjuvant (FA) (Jilin Province's endemic diseases institute Pathological Staff Room provides), glass homogenizer, high speed centrifuge (U.S. Suo Fu company), electric power blender (Hangzhou motor for instrument factory), automatic clinical chemistry analyzer (HIT's 7070 types), full-automatic blood cell analyser (Japanese K-3500 type), trace electronic balance (Chinese Shanghai 120-1), histotome.

2, homogenate preparation

(1) get the disconnected neck of rat of the same race, cut open the belly and get stomach, cut off along lesser curvature side, expose gastric mucosa, normal saline cleans gastric mucosa surface, peel off mucosa with dental forceps after, put in the glass homogenizer, add a little normal saline and stir homogenate repeatedly.

(2) the freezing 24h of tissue homogenate with the centrifugal 30min of 3000r/min, gets supernatant with 20000r/min high speed centrifugation 20min after the thawing.

(3) it is standby that the preservation of albumin content (being about 1g/ml) supernatant (including soluble antigen) refrigerator is gone up in the biuret method survey, adds during use (FA) fully.

3, complete FA and adjuvant antigen preparation

Adding the 3mg bacillus calmette-guerin vaccine with the full FA of 1ml is that ratio is mixed with complete FA, and the antigen supernatant is made into adjuvant antigen with complete FA by 1:1.

4, modeling method

(1) active immunity: every rat toes of modeling the 1st all model group subcutaneous injection adjuvant antigen 0.3ml, duplicate injection 1 time (not adding adjuvant) after 1 month.

(2) cold and cool Fel Sus domestica is irritated stomach: with standby in the Fel Sus domestica centrifugal postposition-20 ℃ refrigerator, thaws to frozen water half and half with tap water before irritating stomach, give rat oral gavage (the filling stomach was stopped eating in preceding 4 hours, freely drank water) every day 1 time by 12.5ml/kg, continuous 90 days.

(3) hot water gastric lavage: (irritated stomach 5 hours at interval) on the same day what irritate stomach with Fel Sus domestica, press 12.5ml/kg filling stomach, every day 1 time, continuous 90 days with 50 ℃ of hot water with bile.

Observe rat general state, dietary amount and stool character every day during the modeling.The modeling time is 90 days.

Two, pharmacodynamic study

(1) hypoxia endurance test

1, this experiment of experiment purpose is observed its anti-stress ability by the influence of the present invention to the mice resisting oxygen lack.

2. experiment material

(1) medicine and reagent

The prescription prescription: Ramulus Cinnamomi 15, Cortex Magnoliae Officinalis 10, Herba Pogostemonis 10, Herba Eupatorii 10, Pericarpium Citri Reticulatae 10, the Rhizoma Pinelliae 10, the Radix Aucklandiae 10, Fructus Amomi 10, Pollen Typhae 10, WULINGZI 10, Radix Glycyrrhizae 5 are provided by Chinese medicine pharmacy of No.1 Hospital of Jilin Univ..Clinical recommended dose concentration is that to contain crude drug be 162.5 g to every 100ml solution, according to herbal medicine efficacy concentration relativity, at the basis of clinical dosage difference simmer down to 867.2%, 433.6%, 216.8%, as heavy dose group, middle dosage group, small dose group, 4 ℃ of preservations are heated to during use about 15 ℃.

Vitacoenzyme: pulverize, sieve, be mixed with 1.5% suspension with distilled water, 4 ℃ of preservations.

Propranolol: pulverize, sieve, be mixed with 1.5% suspension with distilled water, 4 ℃ of preservations.

(2) animal and material

Mice, 42, body weight 18-20g, sex is identical, 150ml wide mouthed bottle, stopwatch, balance, vaseline, sodica calx.

3, method

(1) grouping is divided into 6 groups at random with mice, 7 every group, is respectively blank group, the large, medium and small dosage group of the present invention, vitacoenzyme group, Propranolol group.

(2) the continuous gastric infusion of administration is 7 days, 1 time/day, 12.5ml/kg, blank group gives 0.9% normal saline, behind the last administration lh, 7 mices of every group are put into the airtight wide mouthed bottle of volume identical (150ml) respectively, equivalent sodica calx (25g) is housed in the bottle to absorb water and carbon dioxide.Bottle cap is coated with vaseline, puts into behind the mice bottle is airtight, observes the mouse breathing dwell time with stopwatch.

(3) result adopts the SPSS statistical software, carries out variance analysis, sees Table 1

Annotate: * P＜0.05

Results suggest: middle low dose has tangible oxygen lack resistant function (P＜0.05), compares no significant difference (P＞0.05) with the vitacoenzyme group, and three groups of oxygen lack resistant functions are starkly lower than Propranolol group (P＜0.05), the no obvious oxygen lack resistant function of heavy dose of group.

Two) analgesic experiment

1, experiment purpose: the prescription of the present invention of variable concentrations and positive drug cause the mitigation comparison of mouse writhing to glacial acetic acid.

2, experiment material

(1) medicine and reagent: Ramulus Cinnamomi 15, Cortex Magnoliae Officinalis 10, Herba Pogostemonis 10, Herba Eupatorii 10, Pericarpium Citri Reticulatae 10, the Rhizoma Pinelliae 10, the Radix Aucklandiae 10, Fructus Amomi 10, Pollen Typhae 10, WULINGZI 10, Radix Glycyrrhizae 5 are provided by Chinese medicine pharmacy of No.1 Hospital of Jilin Univ., clinical recommended dose concentration is that to contain crude drug be 162.5g to every 100ml solution, according to herbal medicine efficacy concentration relativity, at the basis of clinical dosage difference simmer down to 867.2%, 433.6%, 216.8%, as people's dosage group, middle dosage group, small dose group, 4 ℃ of preservations are heated to during use about 15 ℃.

Vitacoenzyme: pulverize, sieve, be mixed with 1.5% with distilled water and mix breath liquid, 4 ℃ of preservations.

99% glacial acetic acid: adding distil water is mixed with 0.7% glacial acetic acid.

(2) instrument.

(3) animal: kunming mice, 35, body weight 18-22g, sex is identical.

3, method: mice is divided into 5 groups at random by body weight: the heavy dose of group of blank group (0.9%Nacl 12.5ml/kg) the present invention (108.4g/kg), middle dosage group (54.2g/kg), small dose group (27.1g/kg), vitacoenzyme group (0.50g/kg).The continuous gastric infusion of animal 7 days, 1h after the last administration, lumbar injection 0.7% glacial acetic acid 0.lml/ are only.Observe and write down every and after injection, turn round the number of times that body takes place in the 30min.The mice typical case turns round body and shows as abdominal part and shrink and to cave in, the body distortion, and hind leg stretches and wriggling.

4, result: adopt SAS software to carry out variance analysis, the results are shown in Table 2

The influence of the table 2 pair mouse writhing reaction (n=7 of X ± s)

Group	Metering (g/kg)	Turn round the body number of times
			Blank group	0.1	82±2.89
The vitacoenzyme group	0.50	63±7.81*
			Heavy dose of group	108.4	73±3.26
Middle dosage group	54.2	56±6.54*
			Small dose group	27.1	53±4.51*

Annotate: * P＜0.05

Results suggest: middle small dose group and vitacoenzyme group can obviously reduce the twisting number of times, have than significant analgesia role (P＜0.05) no significant difference between middle small dose group and the vitacoenzyme group (P＞0.05), the no obvious analgesic activity of heavy dose of group.

(3) antiinflammatory experiment

1, experiment purpose: this experiment is observed its antiinflammatory action by observing the influence that on Carrageenan of the present invention causes the swelling of rat paw toe.

2, experiment material

(1) medicine and reagent:

The prescription prescription: Ramulus Cinnamomi 15, Cortex Magnoliae Officinalis 10, Herba Pogostemonis 10, Herba Eupatorii 10, Pericarpium Citri Reticulatae 10, the Rhizoma Pinelliae 10, the Radix Aucklandiae 10, Fructus Amomi 10, Pollen Typhae 10, WULINGZI 10, Radix Glycyrrhizae 5 are provided by Chinese medicine pharmacy of No.1 Hospital of Jilin Univ., clinical recommended dose concentration is that to contain crude drug be 162.5g to every 100ml solution, according to herbal medicine efficacy concentration relativity, at the basis of clinical dosage difference simmer down to 867.2%, 433.6%, 216.8%, as heavy dose group, middle dosage group, small dose group, 4 ℃ of preservations are heated to during use about 15 ℃.

Vitacoenzyme: pulverize, sieve, be mixed with 1.5% suspension with distilled water, 4 ℃ of preservations.

Aspirin: be configured to 1.0% suspension with 0.5% methylcellulose, be used for oral.

(2) instrument: capillary three-way device

Animal: the Wister rat, totally 54, about body weight 180-220g, male.

3, method

(1) grouping: reference literature, will be divided into 6 groups in the rat junctor at random, 9 every group, be respectively blank group, vitacoenzyme group, large, medium and small dosage group, aspirin group.

(2) administration: gastric infusion is 7 days continuously, 1 time/day, 12.5ml/kg, only cause inflammation in the right back sufficient sole of the foot toe subcutaneous injection 1.0% carrageenin solution 0.lml/ of animal behind the last administration lh, and before the Yu Zhiyan and cause scorching back 1,2,4,5, hour with capillary tube measurement by magnification foot sole of the foot toe volume.Observe the variation of administration each Mus ankle joint volume of front and back (being the swelling degree), so that volume is the basis before scorching, different time swelling rate (causing the volume gain percentage ratio in scorching back) is respectively organized in calculating, adopts the SPSS statistical software to carry out the branch difference analysis, the results are shown in Table 3

Annotate; Compare * P＜0.05, * * P＜0.01 with the blank group

Results suggest: in, small dose group has tangible anti-toes swelling effect (P＜0.05), and compare no significant difference (P＞0.05) with the vitacoenzyme group, three's antiinflammatory action is starkly lower than aspirin (P＜0.05), the no obvious anti-inflammatory and anti effect (P＞0.05) of heavy dose of group.Illustrate that this compound Chinese medicinal preparation has tangible antiinflammatory action when middle low dose, this effect is similar to the demonstration effect of vitacoenzyme, and heavy dose of Chinese medicine antiinflammatory action is not obvious.

The drug toxicology experimentation

1, acute toxicity testing method

Because of being subjected to the influence of drug level of the present invention and volume, single administration can't be measured its LD50, so according to the dose of the tolerant Cmax of animal, maximum volume, successive administration was 2 times in 24 hours, measured its maximum dosage-feeding.Choose 40 of healthy Kunming mouses, body weight 18-22g, male and female half and half are divided 4 groups, each 5 of every group of male and female.Under normal raising situation, observed for 1 week before the experiment, not seeing has dietary behavior, movable unusual; Irritate the preceding fasting of stomach, can't help water 12h, irritate stomach 2 times in 24 hours, the concentrated solution 40ml/kg(concentration that each filling stomach gives Cmax of the present invention is 2321%), always advance dose 1857g/kg(and be the crude drug amount that contains), be about 343 times that recommend clinical dosage (body weight for humans press 60kg and calculated), raise routinely then, diet, feces, activity, general state, fur glossiness and death condition in 7 days after the observation administration.Dead animal should in time perform an autopsy on sb, and the discovery diseased organ is done histopathologic examination.Mice is weighed after 7 days, puts to death, whether dissect perusal important organ (heart, liver, spleen, lung, kidney) has pathological change, and pathological changes is arranged, and does histopathologic examination.

2, long term toxicity test method

1) grouping of animal: animal is weighed, and 80 rats are divided into four groups at random.1st, 2,3 groups are the high, medium and low dosage group of the present invention, medication is respectively 271g/kg, 216.8g/kg, 162.6g/kg, be equivalent to recommend 50 times, 40 times, 30 times of clinical consumption, low dose group is higher than the high dose group (108.4g/kg is equivalent to 20 times of the clinical consumption of people) under the drug efficacy study, long malicious high dose group concentration is 2168%, is lower than Cmax 2321%.The 4th group is matched group, gives distilled water 12.5ml/kg.

2) medication: all by 12.5ml/kg volume gastric infusion, weigh weekly 1 time every day 1 time, and adjust dosage, altogether 12 weeks of administration.

3) experimental technique: be administered to for 12 weeks, after the last administration in 24 hours, randomly draw 16 rats for every group, after the pentobarbital sodium general anesthesia (50mg/kg), abdominal aortic blood 6ml, do hematology and the inspection of serum biochemistry index, each internal organs of perusal are dissected by system, and main organs (heart, liver, spleen, lung, kidney, stomach) is carried out tissue pathology checking's (only sending high dose group and matched group).All the other animals stop administration, continue to observe for 2 weeks, if pathological examination is found to have ANOMALOUS VARIATIONS that remaining animal is lived and cutd open inspection extremely, primary part observation toxic reaction organ is with the degree of reversibility of understanding toxic reaction and the slowness toxicity that may occur.

4) observation index: (1) overview project: observation activity, the mental status, two just, diet and body weight change etc.(2) hematological indices: erythrocyte (RBC), hemoglobin (HB), total white blood cells (WBC) and classification thereof, platelet (PLT).(3) serum biochemistry index: aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine (CR), total protein (TB), albumin (ALB), T-CHOL (TCHO), serum alkaline phosphatase (ALP).(4) become celestial and histological examination: system becomes celestial, and gets the heart, liver, spleen, lung, kidney, the stomach of every group of rat.Organ coefficient: the heart, liver, spleen, lung, kidney, thymus, uterus (ovary), testis (epididymis).

3, statistics is disposed

Enumeration data is handled with the SAS software kit, and data represent that with ± S measurement data adopts the t check.

4, the result of acute toxicity test

Observe diet in the mice 7 days, feces, activity, the mental status, by hair glossiness and death condition.The result shows, in mice 7 days after irritating stomach, diet, activity and general state are good, and be glossy by hair, the colour of skin is no abnormal, nose, eye, the no abnormal secretions in oral cavity, and urine is normal, and stool is black pasty state (consideration may be the Chinese medicine color), survival is good, and ergasia is normal, none death.Therefore think that maximum of the present invention tolerates MTD＞1857g/kg, is equivalent to 343 times of clinical consumption.

5, long term toxicity test result

1) ordinary circumstance: in 12 weeks of administration, activity, diet, the mental status of each administration group and animal are no abnormal, and be glossy by hair, and each administration group rat stool is sepia, and character is no abnormal.

2) to the influence of rat body weight: in 90 days of administration, rat body weight is respectively organized in administration to be increased, and matched group is with no significant difference relatively between the sex, P〉0.05, rat does not have death in the experiment, the results are shown in Table 2-1, table 2-2.

Table 2-1 is to influence (n=10, the X ± s unit: g) of each group female rats body weight

Dosage group small dose group in the heavy dose of group of time matched group
	Stable phase 89.50 ± 8.87 87.80 ± 8.26 87.90 ± 8.97 87.10 ± 7.09
First week 101.00 ± 8.22 101.10 ± 6.61 104.20 ± 9.83 103.30 ± 8.17
	Second week 116.30 ± 7.83 116.70 ± 6.93 119.10 ± 11.15 120.20 ± 9.85
The 3rd week 134.70 ± 7.97 135.40 ± 5.97 138.20 ± 11.55 138.90 ± 9.27
	Around the 155.70 ± 8.81 156.00 ± 7.73 157.70 ± 11.17 158.60 ± 9.23
The 5th week 176.60 ± 9.73 176.30 ± 8.92 179.30 ± 12.95 178.70 ± 8.91
	The 6th week 190.60 ± 10.32 188.50 ± 8.81 192.60 ± 13.53 192.00 ± 9.04
The 7th week 203.40 ± 11.79 201.50 ± 9.99 205.00 ± 15.20 205.00 ± 9.48
	The 8th week 218.00 ± 11.92 216.00 ± 9.33 221.60 ± 14.62 220.30 ± 10.97
The 9th week 233.00 ± 12.04 232.70 ± 8.91 235.40 ± 15.54 237.70 ± 12.44
	The tenth week 249.00 ± 12.16 250.30 ± 9.73 249.60 ± 14.59 251.90 ± 14.21
The 11 week 262.60 ± 10.59 265.50 ± 9.90 262.90 ± 13.93 266.20 ± 13.81
	The 12 week 274.40 ± 10.99 278.50 ± 8.50 275.20 ± 13.51 278.70 ± 13.53

Table 2-2 is to influence (n=10, the X ± s unit: g) of each group male rat body weight

Dosage group small dose group in the heavy dose of group of time matched group
	Stable phase 92.30 ± 7.94 90.30 ± 7.15 88.00 ± 6.86 86.00 ± 5.35
First week 112.90 ± 7.84 110.70 ± 7.51 107.60 ± 6.28 107.10 ± 5.59
	Second week 131.50 ± 7.41 129.80 ± 8.27 128.00 ± 6.78 127.10 ± 7.08
The 3rd week 151.20 ± 8.68 149.40 ± 8.19 149.90 ± 7.43 147.90 ± 9.29
	Around the 171.70 ± 8.63 169.60 ± 8.64 169.90 ± 8.60 168.30 ± 9.64
The 5th week 191.60 ± 10.29 189.30 ± 9.74 190.20 ± 8.34 188.90 ± 9.37
	The 6th week 207.80 ± 10.25 205.80 ± 9.86 206.60 ± 10.05 204.90 ± 10.25

The 7th week 227.50 ± 11.07 228.90 ± 10.50 229.90 ± 14.88 225.90 ± 9.28
	The 8th week 242.40 ± 10.86 243.40 ± 12.07 243.40 ± 13.86 239.90 ± 9.87
The 9th week 260.50 ± 8.73 257.80 ± 12.36 258.00 ± 14.53 254.10 ± 10.20
	The tenth week 276.20 ± 10.56 274.20 ± 11.49 273.60 ± 13.72 270.30 ± 10.04
The 11 week 288.30 ± 10.34 284.50 ± 11.27 286.30 ± 13.20 281.80 ± 9.20
	The 12 week 301.70 ± 11.08 298.60 ± 11.84 300.20 ± 12.15 295.50 ± 9.98

3) monitor the food ration (preceding 8 weeks) of each treated animal, the feed situation of administration group and matched group is basic identical, sees table 3-1 for details.

Table 3-1 is to influence (n=20, the X ± S unit: g) of each group rat diet amount

Time	Matched group	Heavy dose of group	Middle dosage group	Small dose group
					Stable phase	16.31±1.58	15.83±1.26	15.79±0.98	15.67±1.56
First week	18.41±1.63	18.67±0.69	19.01±0.96	18.56±1.21
					Second week	21.14±0.60	21.19±0.42	21.20±0.84	21.77±0.68
The 3rd week	19.63±1.17	13.79±1.66	20.26±1.09	19.29±1.01
					Around	19.50±1.90	18.16±1.06	20.13±2.23	20.29±2.08
The 5th week	20.70±1.15	18.67±2.35	21.01±1.48	21.01±1.69
					The 6th week	21.23±1.31	18.94±0.81	18.25±3.09	21.33±1.63
The 7th week	21.70±1.31	17.56±1.14	17.87±1.08	21.49±1.07
					The 8th week	21.90±1.60	17.60±1.06	18.45±2.33	20.51±3.01

4) after administration finishes, randomly draw 16 of rats for every group, abdominal aortic blood carries out routine blood test and detects.The result shows: every physical signs such as the high, medium and low dosage group of the present invention rat WBC and classification thereof, RBC, PLT, HB all in range of normal value, and with the relatively equal no significant difference (P＞0.05) of matched group.The result sees table 4-1 for details.

Table 4-1 is to the influence of rat serum routine (n=16, X ± s)

5) assay of the serum biochemistry index relevant with liver function, administration finishes back serum biochemistry result and shows: AST, ALT, ALP, TP, ALB, T-BIL, CHOL, administration group and matched group more all do not have significant difference (P＞0.05), point out long-term prescription of the present invention harmless to the liver function of animal, for details see attached table 5.

The biochemical influence of table 5 pair rat blood serum (n=16, X ± s)

Group

AST

ALT

ALP

TP

ALB

T-BIL

CHOL

?

（u/L）

（u/L）

（u/L）

（g/L）

（g/L）

（umol/L）

（mmol/L）

The saline group

233.18±45.13

77.51±18.79

248.58±49.47

70.01±4.23

33.49±2.12

7.30±0.81

1.97±0.23

Heavy dose of group

190.14±38.86

68.80±12.05

256.65±32.58

70.66±7.02

33.18±2.28

7.80±0.36

1.80±0.17

Middle dosage group

190.53±33.53

65.16±6.96

228.98±42.60

71.09±6.78

33.33±2.45

7.79±0.57

1.80±0.24

Small dose group

229.04±45.64

62.16±6.82

230.33±48.67

73.86±5.62

32.98±2.09

7.67±0.41

1.72±0.30

6) the present invention is to the influence of kidney of rats function, and each administration group creatinine (CR), blood urea nitrogen (BUN) all compare with matched group in normal range, there was no significant difference (P＞0.05), and the result sees table 6 for details.

The influence of table 6 pair rat kidney function (n=16, X ± s).

7) organ coefficient: the organ coefficient of the heart of each administration group rat, liver, spleen, lung, kidney, thymus, uterus (ovary), testis (epididymis) and matched group be no significant difference (P＞0.05) relatively, and the result is 7-1,7-2 for details see attached table.

Table 7-1 is to influence (n=8, the X ± s unit: g/kg) of female rats main organs coefficient

Group

Heart

Liver

Lungs

Spleen

Kidney

Thymus

Uterus (ovary)

The blank group

0.45±0.03

4.71±0.50

0.78±0.04

0.47±0.04

0.38±0.02

0.26±0.05

0.35±0.05

Small dose group

0.46±0.04

4.82±0.40

0.80±0.02

0.47±0.03

0.37±0.01

0.25±0.06

0.23±0.05

Middle dosage group

0.44±0.04

4.49±0.41

0.80±0.03

0.49±0.04

0.39±0.02

0.27±0.05

0.36±0.04

Heavy dose of group

0.43±0.03

5.09±0.24

0.79±0.03

0.50±0.04

0.38±0.02

0.22±0.04

0.35±0.05

Table 7-2 is to influence (n=8, the X ± s unit: g/kg) of male rat main organs coefficient

Group

Heart

Liver

Lungs

Spleen

Kidney

Thymus

Testis (epididymis)

The blank group

0.47±0.04

4.54±0.33

0.80±0.03

0.49±0.03

0.39±0.02

0.25±0.04

0.95±0.04

Small dose group

0.46±0.03

4.95±0.30

0.82±0.03

0.50±0.04

0.38±0.02

0.25±0.05

0.92±0.03

Middle dosage group

0.45±0.05

4.48±0.17

0.82±0.04

0.49±0.04

0.38±0.02

0.28±0.05

0.92±0.03

Heavy dose of group

0.43±0.02

4.87±0.23

0.79±0.02

0.48±0.03

0.37±0.01

0.26±0.05

0.93±0.03

8) main organs pathologic finding, gross necropsy is not seen obvious pathological change, after neutral formalin solution is fixing, gets a block organization respectively in each internal organs same area, does paraffin section according to a conventional method, after HE dyeing, carries out light microscopy checking.The result of histopathologic examination, the high, medium and low three kinds of various dose of the present invention are to each internal organs of rat and organize and all do not have overt toxicity infringement.Each treated animal heart cardiac muscle fiber morphosis is normal, red the dying of heart cell slurry, and nuclear keeps to the side, and cardiac muscle cross striation, longitudinal grin are clear, the myocardial cell intercalated disc mays be seen indistinctly; The lobules of liver clear in structure, the liver plate is level and smooth, the hepatic cords queueing discipline, the hepatocyte endochylema is red to be dyed, examines between two parties, the portal area clear in structure, interlobular arteries, interlobular veins, interlobular bile duct is high-visible; Lung bronchioles clear in structure at different levels, false multiple layer cilia morphology is normal, and alveolar duct is clear, and firsts and seconds alveole epithelium form is normal; Kidney skin, medullary epithelium are clear, and the glomerular capillary form is normal, and renal tubules at different levels and manifold structure are clear.But the individual samples lung tissue has slight interstitial pneumonia in every group, individual samples degree of taking a favourable turn spleen congestion and hemosiderosis, but the above-mentioned change of each administration group is all consistent with matched group, do not have dose-dependence between the administration group, blood-letting in time was not relevant after these changes may and be put to death animal with the gastric infusion mode.

The present invention confirms it is Chinese medicine preparation safely and effectively through the malicious experimental result of acute toxicity and chronic length.

Five, clinical and experimental study

Chronic gastritis is meant the chronic gastric mucosa inflammatory lesion that the different causes of disease cause, main clinical manifestation is symptoms such as epigastric discomfort, pain and dyspepsia, atypical hyperplasia or epithelial metaplasia appearred in visible gastric mucosa when wherein the atrophic gastritis state of an illness was serious, were considered to a kind of precancerous lesion.

(1) tcm diagnosis(with reference to the clinical research guideline of new Chinese medicine treatment syndrome of deficient cold of spleen and stomach)

1, gastral cavilty portion distension, have a dull ache, like warm pain relieved by pressing, the time belch feel sick.

2, the just pool of fatigue and weakness, lack of appetite.

3, pale and tender tongue, white and thin fur, indentations at the margin of the tongue, deep-thready pulse or slow.

4, the traditional Chinese medical science is debated disease: the Deficiency and coldness of spleen and stomach pattern of syndrome.

(2) Western medicine diagnose (with reference to internal medicine " the national medical specialty teaching material third edition ").

1, symptom: the chronic gastritis clinical manifestation is that glutted discomfort of epigastrium or pain are obvious after the meal especially, feels sick with belch simultaneously, and the delay of the courses of disease such as inappetence can show effect repeatedly.

2, objective determination: electronic gastroscope and mucosa tissue pathologic finding are the reliable basis of diagnosis primary disease.

1) electronic gastroscope finding: the chronic gastritis mucosa is congestion and edema more, sometimes be dispersed in smooth erosion; pathological changes often is diffusivity also can be limitation; as atrophic gastritis; its mucosa is pale or canescence; also can be red and white, the wrinkle wall attenuates or is smooth, and also visible mucosa attenuation or mucomembranous surface are graininess or brief summary nodular projection.

2) mucosa pathologic finding: the shallow inflammatory cell infiltration is shown in the superficial gastritis biopsy, and body of gland does not generally have change.The atrophic gastritis biopsy sees that body of gland reduces, or disappears or atypical hyperplasia, intestinal epithelial metaplasia are arranged.

3) the dried bacterium of pylorus spiral shell (HP) is checked: 60%-90% chronic gastritis patient HP(+).

(3) test case standard

1, clarifies a diagnosis and be that chronic gastritis, tcm diagnosis are that the syndrome of deficient cold of spleen and stomach person all can include the test case in.

2, get rid of case standard (comprising inadaptation or rejecting standard).

1) influential curative effect of medication is observed and various complications and the hobby estimated.

2) age is at under-18s or over-65s, and gestation or women breast-feeding their children are to research drug allergy person.

3) be associated with serious primary disease such as cardiovascular, liver, kidney and hemopoietic system, psychotic.

4) do not meet the standard of including in, not medication in accordance with regulations can't be judged that curative effect or data are not congruent to affect the treatment or safety judgement person.

(4) clinical research

1, physical data: according to including the performance of case standard clinical in, glutted discomfort of stomach wrist or dull pain with belch feel sick, stomachache with cool feeling, happiness temperature like, deep-thready pulse or slow, pale and tender tongue, white and thin fur, indentations at the margin of the tongue, differential diagnosis in tcm is the Deficiency and coldness of spleen and stomach pattern of syndrome, and Western medicine diagnose is the observational study case for chronic gastritis person.Case is taken from year January in January, 1999-2002, out-patient's totally 120 examples in the period of 3, male's 75 examples, women's 45 examples, the age reckling is 25 years old, the maximum is 60 years old, wherein 35-60 between year sickness rate higher, account for 78%.The course of disease accounts for more than 60% person more than 5 years, and elder is for 15 years.120 routine patient's random packet, treatment group (the present invention) 90 examples, matched group (Marzulene) 30 examples are with subjective symptoms, pulse condition, picture of the tongue, electronic gastroscope, HP check and necessary pathological examination, as the criterion of curative effect.

2, inspection method

1) inspection method: normal and HbsAg (-) person all uses the Olympas-R2 type electronic fiber gastroscopy that Japan produces to the example of all genus observations through liver function, electrocardiographic examination, main form of observing gastric mucosa, color and luster secretion situation and NIP, edema, rotten to the corn hemorrhage, ulcer, swollen thing are arranged, exist if any suspicious hypertrophy intestinalization or swollen thing and all to get gastric mucosa and carry out pathological examination, every routine chronic gastritis must be HP and check simultaneously.Its result is alive thrifty through electronic gastroscopy and pathology, with chronic gastritis 120 routine random packet, in treatment group (the present invention) 90 examples, superficial gastritis 56 examples, limit office property atrophic gastritis 25 examples, atrophic gastritis 9 examples, pathologic finding have intestinal epithelial metaplasia and (or) atypical hyperplasia person's 10 examples, HP ⁽⁺⁾Person's 54 examples (90%).In matched group (Marzulene) 30 examples, superficial gastritis 18 examples, limit office property atrophic gastritis 7 examples, atrophic gastritis 5 examples.Pathologic finding have intestinal epithelial metaplasia and (or) atypical hyperplasia person's 8 examples, HP ⁽⁺⁾Person's 29 examples (96%)

2) Therapeutic Method: be packed Chinese medicine preparation, every bag is 100ml, and a twice-daily is sooner or later respectively obeyed one bag, and all the heating back is oral is good.The matched group Marzulene is the effective Western medicine by the treatment chronic gastritis of Japanese Kotobuki Seiyaku Co., Ltd. production, three times on the one, and each bag, oral.Above-mentioned two kinds of Drug therapys are 30 days the course of treatment.Carry out symptom around the course of treatment, picture of the tongue, pulse condition, the electronic fiber gastroscope, pathology and HP check contrast, other Chinese medicines and the Western medicine of the treatment chronic gastritis of stopping using during the medication.

3, therapeutic outcome

A, curative effect judging standard (with reference to the curative effect judging standard that in November, 1984, CAIM (Chinese Association Of Integrative Medicine) digestive system disease Professional Committee formulated)

1) recent clinical cure: just clinical cardinal symptom such as stomachache with cool feeling, belch, stomach alkane distension, fatigue and weakness, the lack of appetite pool, deep-thready pulse or late, diseases such as pale and tender tongue, white and thin fur, indentations at the margin of the tongue all disappear; gastroscopy; the activeness inflammation disappears; chronic inflammatory disease takes a turn for the better, and pathologic finding confirms that the atrophy of gastroscope finding body of gland recovers normal or disappearance.

2) produce effects: clinical cardinal symptom is most of to disappear, and gastroscope check mucosa acute inflammation disappears substantially, and chronic inflammatory disease takes a turn for the better, and pathologic finding confirms the atrophy of gastroscope finding body of gland, and intestinalization or atypical hyperplasia alleviate.

3) effective: clinical cardinal symptom obviously alleviates, and gastroscope check mucosa infection scope is dwindled more than 1/2, and inflammation alleviates to some extent, and pathologic finding confirms that gastroscope finding acute inflammation alleviates, the body of gland atrophy, and intestinalization or atypical hyperplasia alleviate.

4) invalid: as not reach the case of effective standard and deterioration person is arranged.

B, clinical effectiveness:

1) the clinical symptoms improvement sees Table 8

See that from table 8 the present invention treats chronic gastritis gastral cavilty distension cold type of pain and the indigestion and loss of appetite effect of lack of appetite is comparatively outstanding.

2) objective indicator is improved

A, treatment back electronic gastroscope, pathology, HP improvement see Table 9

From table 9, the present invention is more higher than Marzulene group to the HP negative conversion rate

The improvement that b, pathology of gastric mucosa change

B1, finding of naked eye: the normal rats gastric mucosa presents pink, glossy, the more mucus that is covered, Xiao is sliding for mucosa wrinkle wall surface, move towards regular, coat of the stomach elasticity is good, model group coat of the stomach elastic force weakens, the mucous layer attenuation, and color is pale, wrinkle wall chap or move towards disorderly, the mucomembranous surface that has has xanthochromia mucus to be covered.Gastric antrum portion visible one is to several canescence tuberositys, and the part gastric mucosa of rat still has rotten to the corn kitchen range or ulcer.Model recovery group pathological changes is not only recovered, and the trend of increasing the weight of is arranged on the contrary.The present invention has therapeutical effect preferably, and the mucosa of pathological changes is substantially near normal group.

B2, light microscopic finding: normal rats gastric epithelial cell marshalling, N/D or come off, body of gland shape great debate rule, the size basically identical, glandular epithelium is monolayer alignment more, accidental a little inflammatory cell infiltration of lamina propria, muscular layer of mucosa smooth muscle circular array, the end is seen hypertrophy and is goed deep into phenomenon to mucous layer.Model group gastric mucosa body of gland reduces, volume-diminished, in the form of sheets or the distribution of many kitchen ranges property, the part body of gland is cystic dilatation, the a large amount of lymphocytic infiltrations of lamina propria, part have lymph follicle to form the telangiectasis blood stasis, muscular layer of mucosa thickens, and connective tissue and proliferation of smooth muscle also stretch between the mucous layer body of gland.Model recovers level and shows as atrophy kitchen range scope and strengthen, and smoothly to the mucosa heighten degree that stretches, the atypical hyperplasia degree increases the weight of muscular layer of mucosa.Heavy dose of group mucosa infection recovers to some extent, and the lamina propria cell infiltration obviously reduces, and the atrophy kitchen range disappears or reduces, and glandular epithelium atypical hyperplasia degree alleviates or disappears.Small dose group then mucosa infection is obviously improved, and lamina propria and tela submucosa inflammatory cell obviously reduce.As seen the present invention has therapeutical effect to the change of chronic gastritis rat mucosa inflammatory.

3) therapeutic outcome: see Table 10.

As seen from Table 10, treatment group (the present invention) obvious effective rate in the recent period is 52%, and total effective rate 97%, matched group (Marzulene) obvious effective rate in the recent period are 46%, total effective rate 96%.Two groups of curative effects compare there was no significant difference (P＞0.05).Reached desired therapeutic effect.

Conclusion:The present invention is effective Chinese medicinal formulae of treatment chronic gastritis.

Medicine is checked:

1, the relative density of this product is 1.02-1.06

2, the pH value of this product should be 4.50-5.50

Claims (2)

1. Chinese medicine for the treatment of chronic gastritis is characterized in that: make the raw materials of effective components weight portion and consist of:

Ramulus Cinnamomi 5-15, Cortex Magnoliae Officinalis 5-15, Herba Pogostemonis 5-10, Herba Eupatorii 5-10, Pericarpium Citri Reticulatae 5-10, Rhizoma Pinelliae 5-10, Radix Aucklandiae 5-10,

Fructus Amomi 5-10, Pollen Typhae 5-10, WULINGZI 5-10, Radix Glycyrrhizae 3-5.

2. Chinese medicine for the treatment of chronic gastritis is characterized in that: make raw materials of effective components optimum weight part and consist of:

Ramulus Cinnamomi 15, Cortex Magnoliae Officinalis 10, Herba Pogostemonis 10, Herba Eupatorii 10, Pericarpium Citri Reticulatae 10, the Rhizoma Pinelliae 10, the Radix Aucklandiae 10,

Fructus Amomi 10, Pollen Typhae 10, WULINGZI 10, Radix Glycyrrhizae 5.