CN100406030C - Chinese medicinal preparation for treating ulcerative stomatitis and method for preparing same - Google Patents

Abstract

The present invention provides a traditional Chinese medicinal preparation for treating aphthous ulcer and a preparation method thereof. The traditional Chinese medicinal preparation of the present invention is made from 50 to 200g of inula cappa, 10 to 40g of licorice, 1 to 4g of pearl, 0.5 to 2g of borneol and a proper quantity of supplementary material. Compared with the prior art, the prescription of the present invention, which is used as an empirical prescription and applied for many years, has a solid clinic basis and reasonable extraction process, prepared dripping pills overcome the defects of easy moisture absorption, inconvenient storage, large daily dose, poor mouth feelings, difficult quality control, bad stability, etc. of a finished product. Compared with congener varieties, the present invention has the characteristics of refined prescription, special efficacy, clear ingredients, safe and effective clinical application, stable and controllable quality, etc. In addition, the preparation is locally taken in the mode of oral taking, medicine directly acting on an ulcer position is absorbed by mucous membranes, and fast therapeutical effect is achieved.

Description

Chinese medicine preparation of treatment oral ulcer and preparation method thereof

Technical field:

The present invention relates to a kind of Chinese medicine preparation for the treatment of oral ulcer and preparation method thereof, belong to the technical field of herbal pharmaceutical.

Background technology:

Recurrent oral ulceration comprises recurrent aphtha, mikulicz's ulcer and herpesvirus type ulcer, it is a kind of disease of sickness rate height in the diseases of oral mucosa, comparison stubbornness, mainly show as oral mucosa and occur isolated, circular or oval shallow-layer aphtha repeatedly, but single-shot or multiple at any position of oral mucosa, part have the violent sample pain of burning.Cold and hot stimulation such as sour-sweet makes all that the pain increased, and is agonizing, influences language, diet, and the course of disease is touching, sends out the author Ke Da several years repeatedly, even many decades, treats rather thornyly, has a strong impact on patient body health and work and study.This disease is the highest disease of diseases of oral mucosa sickness rate, sickness rate in general crowd is not less than 10%, in specific crowd, prevalence can reach 60%, and the women is a little more than the male, but sees so that between twenty and fifty, oral cavity is anterior more, morbidity just is many at 10～20 years old, the no seasonal difference of falling ill, the course of disease has self limiting, but spontaneous recovery in general about 10 days.

For recurrent oral ulceration, in clinical treatment, because of oral cavity state of an illness complexity, symptom different, the easy mistaken diagnosis treatment of patient, the waste that has also brought spiritual misery and financial resources, material resources simultaneously.The common method majority is an anti symptom treatment clinically at present, promptly adopts means such as antiinflammatory, pain relieving and promotion ulcer healing, methods such as control disease multiselect hormone, antibiotic therapy and immunosuppressant, cellulose dissolution.Hormones and antibiotics treatment oral ulcer have had very long history, still are widely used now.Hormone medicine commonly used has kenalog in Orabase, dexamethasone acetate oral cavity sticking tablet, generally is used for the long-term patient who does not more reach recurrence.Antibiotics can be eliminated local inflammation in clinical treatment, the control secondary infection is mainly used in the oral ulcer treatment of acute stage, and the effect of necessarily antibiotic, antiinflammatory and prevention secondary infection is arranged.Some contain hormone and antibiotic compound formulation is more extensive in clinical practice, as hospital preparation oral ulcer ointment, KOUQIANG KUIYANG MO and compound recipe chlortetracycline medicine film etc.But the common side effect of hormone medicine can appear in long-term topical application steroid hormone, as edema, hypertension, bring out and increase the weight of to infect etc.The antibiotics topical application is easy to produce drug resistance, and long-term topical application also can cause dysbacteriosis and fungal infection.As seen, at present unsatisfactory for the therapeutic effect of oral ulcer routine, side effect is bigger, and the relapse rate height often makes patient lose the confidence of treatment.In the weary art of western medical treatment, the traditional Chinese medical science is with its exclusive determination of treatment based on pathogenesis obtained through differentiation of symptoms and signs thought, for the oral ulcer treatment provides sturdy theoretical basis and abundant clinical application data." back to nature ", " green remedy " are accepted by more people with its distinctive curative effect and safety.And the traditional medicine of this disease is many based on external powder and various dosage form for oral administration (ball, loose, soup, gargarism etc.), spray, ointment and some medicine membrane of exploitation in recent years in addition, and novel form remains phoenix feathers and unicorn horns, and the market share is also very limited.According to the feedback of consumer, the medicine major part of these dosage forms exist the mouthfeel discomfort in varying degrees, stimulate wound surface, can not be slow in the pathological changes stop of local long period, onset, use shortcoming such as inconvenience.Therefore,, should under the guidance of theory of Chinese medical science, give full play to and use the advantage of novel form, new technique, new material, develop determined curative effect, steady quality new product of Chinese medicine reliable, easy to use for the research of the medicine of oral ulcer.Traditional Chinese medicine theory is fully combined with the modern pharmaceutical technology, is an inevitable direction of such drug development

Summary of the invention:

The objective of the invention is to: a kind of Chinese medicine preparation for the treatment of oral ulcer and preparation method thereof is provided, the present invention is used for the treatment of recurrent oral ulceration, has solid clinical practice basis, can obviously alleviate patient's pain, accelerate wound healing, do not find obvious toxic-side effects, for the oral ulcer patient provides a kind of effective, safe, inexpensive Chinese patent medicine.

The present invention constitutes like this: it is the oral formulations made from Herba Inulae cappae 50～200g, Radix Glycyrrhizae 10～40g, Margarita 1～4g, Borneolum Syntheticum 0.5～2g and appropriate amount of auxiliary materials.

Say that exactly it is made with Herba Inulae cappae 100g, Radix Glycyrrhizae 20g, Margarita 2g, Borneolum Syntheticum 1g and appropriate amount of auxiliary materials.

Described Chinese medicine preparation is a drop pill.

The preparation method of the Chinese medicine preparation of treatment oral ulcer is: add 8-12 times of water gaging after Herba Inulae cappae and Radix Glycyrrhizae merge and decoct 2-4 time, each 1 hour, filter, merging filtrate is evaporated to 50 ℃ of relative densities 1.08, adds ethanol and makes that to contain the alcohol amount be 60%, left standstill 12 hours, sucking filtration, decompression recycling ethanol adds the suitable quantity of water dilution; Last D ₁₀₁Macroporous adsorptive resins discards and penetrates liquid, with washing on a small quantity, continues and uses the 60-80% ethanol elution, collects eluent, reclaims ethanol, concentrates, and microwave vacuum drying is pulverized, and gets Herba Inulae cappae, Radix Glycyrrhizae extract; Margarita powder is broken into fine powder, crosses 120～200 mesh sieves; The Borneolum Syntheticum porphyrize; Margarita, Borneolum Syntheticum fine powder and said extracted thing mixing add suitable adjuvant and make oral formulations.

The preparation method of drop pill: add 10 times of water gagings after Herba Inulae cappae and Radix Glycyrrhizae merge and decoct 3 times, each 1 hour, filter merging filtrate, be evaporated to 50 ℃ of relative densities 1.08, add ethanol and make that to contain the alcohol amount be 60%, left standstill 12 hours, sucking filtration, decompression recycling ethanol adds the suitable quantity of water dilution; Last D ₁₀₁Macroporous adsorptive resins discards and penetrates liquid, with washing on a small quantity, continues and uses 70% ethanol elution, collects eluent, reclaims ethanol, concentrates, and microwave vacuum drying is pulverized, and gets Herba Inulae cappae, Radix Glycyrrhizae extract; Margarita powder is broken into fine powder, crosses 120～200 mesh sieves; The Borneolum Syntheticum porphyrize; Margarita, Borneolum Syntheticum fine powder and said extracted thing mixing add an amount of polyethylene glycol 6000, put heating in water bath and make fusion, and stirring and evenly mixing moves in the drop pill machine liquid reservoir, and insulation splashes in the coolant, promptly.

Side of the present invention separates: oral ulcer belongs to Chinese medicine " aphtha ", " aphtha " scope, and its pathogenesis mainly is the abnormal ascending-descending of QI of heart taste, and negative and positive are become estranged, deficient QI of the spleen and stomach, thus making on the burning hot inflammation, pyretic toxicity smoulders and causes aphtha of the mouth and tongue.Control suitable pathogenic fire purging, removing heat from blood, detoxifcation.We are at the excess syndrome of pathogenic heat, and to have diffusing wind heat clearing away, the ethnic groups common drug Herba Inulae cappae of removing toxic substances and promoting subsidence of swelling is monarch; The Margarita that is aided with sweet in the mouth cold in nature, heat-clearing and toxic substances removing, expelling pus and promoting granulation; The hot hardship of loosing of Borneolum Syntheticum is rushed down, and the clearing away heat and cooling blood pain relieving is assistant; The Radix Glycyrrhizae sour and sweet drugs can transforme into YIN, relieving spasm to stop pain is for making.All medicines share, and the merit of detoxifcation analgesic therapy, removing the necrotic tissue and promoting granulation is arranged, and also can receive the effect of reducing swelling and alleviating pain.

Function of the present invention cures mainly: have the detoxifcation analgesic therapy, the removing the necrotic tissue and promoting granulation function; Be used for recurrent aphtha, the card see on the oral mucosa (lip, cheek, maxillary, lingual surface etc.) occur differing in size, ulcer in irregular shape, congested on every side rubescent edema, local scorching hot pain, dysphoria with smothery sensation is thirsty, dry stool, yellowish urine, red tongue with yellow fur, wiry and frequent pulse.

Compared with prior art, write out a prescription prescription science, rationally of the present invention, product has solid clinical basis; Preferred extraction process route rationally, the drop pill of preparation has overcome the easy moisture absorption of finished product, storage inconvenience, day dose is big, and mouthfeel is poor, and quality is wayward, shortcomings such as poor stability; With with veriety relatively, characteristics such as the side's of having energy is specially, medicinal ingredient is clear substantially, clinical practice is safe and effective, stable and controllable for quality have been guaranteed effectiveness, safety and the quality stability of preparation.And this preparation is local buccal administration, and medicine directly acts on ulcer spot, and through mucous membrane absorbs and plays therapeutical effect fast.

Compare with veriety with existing national standard, this product has following characteristics:

1. this product prescription has solid clinical basis as using for many years through proved recipe.Research by key technologies such as Natural Medicine Chemistry composition, standard substance, preparation technology, effectiveness and safety evaluatio, quality standard, study on the stability, use Modern New Technology, new technology extraction separation, refining pure chemical medicine effective ingredient, the preparation drop pill.Overcome the easy moisture absorption of finished product, storage inconvenience, day dose is big, and mouthfeel is poor, and quality is wayward, shortcomings such as poor stability.With with veriety relatively, characteristics such as the side's of having energy is specially, medicinal ingredient is clear substantially, clinical practice is safe and effective, stable and controllable for quality.

2. prescription is formed from traditional Chinese medical science clinical practice, draw traditional Chinese medical science tradition and medication experience among the people, select the medicine prescription according to recurrent oral ulceration clinical characters and adaptation syndrome, at the excess syndrome of pathogenic heat, to have diffusing wind heat clearing away, the Guizhou minority nationality common drug Herba Inulae cappae of removing toxic substances and promoting subsidence of swelling is monarch; The Margarita that is aided with sweet in the mouth cold in nature, heat-clearing and toxic substances removing, expelling pus and promoting granulation; The hot hardship of loosing of Borneolum Syntheticum is rushed down, and the clearing away heat and cooling blood pain relieving is assistant; The Radix Glycyrrhizae sour and sweet drugs can transforme into YIN, relieving spasm to stop pain is for making.All medicines share, and the merit of detoxifcation analgesic therapy, removing the necrotic tissue and promoting granulation is arranged, and also can receive the effect of reducing swelling and alleviating pain.Meet traditional Chinese medical science prescription theory.

3. identical with indication similar medicine is compared, this preparation prolongs silk floss, pain clinical characters unbearably at the recurrent oral ulceration state of an illness, reuse the product of heat-clearing and toxic substances removing, the Margarita that is aided with merit with expelling pus and promoting granulation, and Chinese medicine such as Radix Glycyrrhizae of relieving spasm to stop pain, Borneolum Syntheticum, and be local buccal administration, medicine directly acts on ulcer spot, and through mucous membrane absorbs and plays therapeutical effect fast.

In preparation technology provided by the invention, physicochemical property according to effective ingredient and impurity, utilize new techniques such as macroporous adsorbent resin, new technology is carried out the extraction separation purification, the active effective ingredient of enrichment, and be index with the dynamic change of pharmacodynamics and index components, preferred extraction process route rationally under bioequivalent prerequisite, preparation quality is stable, the drop pill of feasible process, effectively improve the Chinese medical concrete moisture absorption, dose is big, shortcomings such as poor stability, guarantee the effectiveness of preparation, safety and stable and controllable for quality, the quality and the development level of raising Chinese medicine preparation.

Prescription provided by the invention is a folk remedy, for verifying the reasonability of its pharmacological action and prescription, is evaluation index with the pharmacodynamics test, and we have carried out the side of tearing open and prescription proportion research to prescription, has determined the prescription and the best prescription proportioning of this product.

With with veriety relatively, this product has prescription medicine and simplifies the chief that power is special, action pathway is direct.Have characteristics such as medicinal ingredient and pharmacological action are clear substantially, clinical practice is safe and effective, quality controllability is better, effect is rapid.

Have excellent curative in order to ensure preparation of the present invention, the applicant has carried out following experimental study:

One, dosage form selection

Oral ulcer is a common oral disease, and medicine mostly is powder, gargarism, membrane and ointment etc. at present.The mucoadhesive of powder is bad, easily by saliva dilution, break up and be with from ulcer surface, do not reach due drug effect, use inconvenience, patient's poor compliance; Gargarism also exists action time short, the shortcoming of medication inconvenience; The preparation of membrane is comparatively complicated, and it is very not convenient to use, and oral ulcer ointment is adjuvant with vaseline, lanoline mainly, owing to mostly be oil-soluble substrate greatly, is difficult for sticking to oral mucosa surface, poor effect.And most of compound Chinese medicinal preparation of existing treatment oral ulcer to have a body many in a large number, the defective of medication inconvenience, and the coarse powder pharmacy is difficult to absorb, complicated component, dosage form do not match, lack shortcomings such as quick-acting.

In recent years, along with the continuous development of form of Chinese drug, the application of drop pill in form of Chinese drug is also more and more noticeable, becomes a kind of rising Chinese medicine novel form.Traditional Chinese Medicine Dropping Pill is after Chinese medicine extracts through processing, make suspension or emulsion with the solid matrix heating and melting, splash in the not miscible condensing agent, because the interfacial tension effect shrinks drop and be condensed into solid dispersion, the dissolubility of medicine, release property are good again.The present invention adopts modern preparation technique, dynamic change with pharmacodynamics test and chemical constituent is an index, extraction separation, purification refine to Herba Inulae cappae, Radix Glycyrrhizae are studied, Herba Inulae cappae, Radix Glycyrrhizae are through the macroporous adsorption resin technology separation and purification, total solid matters obviously reduces, the pharmacologically active that has kept former side, effective ingredient obtains abundant enrichment, overcome the easy moisture absorption of Chinese medicine finished product, storage inconvenience, day dose is big, mouthfeel is poor, quality is wayward, and shortcomings such as poor stability provide the possibility of molding for preparing the little drop pill of drug loading.The present invention is used for the treatment of oral disease, sick in the oral cavity, according to the traditional Chinese medical science theory of " attacking heresy nearby ", making buccal drop pills takes, the absorption of local mucous membrane to medicine can improve in the medicine sick institute that goes directly, and plays therapeutical effect fast, alleviate rapidly or eliminate the patients clinical symptom, promote the quickly-healing of ulcer surface.All obtain satisfied result through pharmacodynamics test and clinical principium checking.

Traditional Chinese Medicine Dropping Pill has following characteristics: 1. aspect production, process equipment is simple, and is convenient for production, and cost is low, is easy to control of quality, and helps sanitation and hygiene and labor protection etc.; 2. bioavailability height; 3. be applicable to Chinese medicine emergency case preparation, reach efficient, quick-acting purposes; 4. be applicable to local applications such as ear, nose, oral cavity, have quick-acting effects; 5. be applicable to slow releasing preparation, have prolongation of effect effect etc.This novel form of Traditional Chinese Medicine Dropping Pill has the potential extensive market space, and the research and development impetus in recent years is swift and violent.Therefore, the present invention is by the research of key technologies such as Natural Medicine Chemistry composition, standard substance, preparation technology, effectiveness and safety evaluatio, quality standard, study on the stability, use Modern New Technology, new technology extraction separation, refining pure chemical medicine effective ingredient, and be index with the dynamic change of pharmacodynamics and chemical constituent, preferred extraction process route rationally is prepared into drop pill under bioequivalent prerequisite.

Two, the prescription and the side of tearing open research

We come from folk remedy, application prescription proportioning among the people is not quite similar, for further inquiring into the reasonability of its prescription and proportioning, on the basis of use among the people, according to we's clinical application, the pharmacodynamics test that heals with stomatocace is an evaluation index, write out a prescription with quadrature t value method experimental design and to form and proportion research, screen this side's best proportioning and form and proportional quantity,, inquire into the primary and secondary and the mutual relation of prescription taste of Chinese medicine simultaneously by the reciprocal action and the variance analysis of orthogonal experiment.

Main pharmaceutical analysis in 1 prescription

1.1 experiment material

Be subjected to the reagent thing according to the operating position to our Herba Inulae cappae, Radix Glycyrrhizae, Margarita and Borneolum Syntheticum four Chinese medicine material among the people, we adopt, and every flavor medical material designs not medication, two levels of medication among quadrature t value method the other side, and totally 8 proportioning groups are tested.

Sample A1～A8: take by weighing Herba Inulae cappae and/or licorice medicinal materials in the prescription ratio, add 10 times of water gagings and decoct 3 times, each 1 hour, filter, concentrate, 50 ℃ of microwave vacuum dryings are pulverized, and get Herba Inulae cappae, Radix Glycyrrhizae extract; Margarita powder is broken into fine powder, sieve (150 order), Borneolum Syntheticum porphyrize; With said extracted thing and Margarita, Borneolum Syntheticum fine powder mixing.

With the ultrasonic mixing of 0.5% carboxymethylcellulose sodium solution, be mixed with the suspension of 1.2g crude drug/ml before the drug dilution method test, standby.

1.2 experimental animal

Cleaning level SD rat, 180～220g, male and female dual-purpose.The quality certification number: SCXK (Guizhou Province) 2002-0001.Provide by the Guiyang Medical College Experimental Animal Center.

The raising condition: the male and female sub-cage rearing is in clean animal feeding cabinet, and 5 in every cage is by special messenger's feeding and management.Receptacle illumination abundance, heating ventilation and air-conditioning equipment is good, 18～25 ℃ of room temperatures, relative humidity 50～70%, laboratory and clean animal feeding cabinet be sterilization regularly routinely all.Animal is used for test after this environment is raised a week.

1.3 other materials

Glacial acetic acid Wuhan City Central-South chemical reagent factory produces, lot number 980605.

Chloral hydrate Shanghai fine chemistry industry Science and Technology Ltd., lot number 20040809.

1.4 date processing

(X ± S) expression adopts Excel 2000 to take statistics and learns processing data with mean standard deviation.

According to literature method [Qi Chen chief editor, herbal pharmacology research methodology [M], People's Health Publisher, the 1993:55 Sun Wei people, Sun Ruiyuan. the quadrature t value method of Chinese medicinal formulae research. Pharmacology and Clinics of Chinese Materia Medica .1992,8 (1): 41], to L8 (2 ⁷) 8 groups of test datas carry out the analysis of quadrature t value in the orthogonal table, determine medicine primary and secondary and mutual relation.

1.5 test method

1.5.1 glacial acetic acid is caused the influence of rat stomatocace healing

The SD rat is got in the animal model preparation, body weight 180～220g, after 10% chloral hydrate (0.4ml/100g) anesthesia 10% glacial acetic acid solution, 50 Cheng are injected under the cheek mucosa of rat oral cavity, form ulcer (surperficial canescence, circle or oval ulcer after 24 hours, diameter is between 4.5～5.5mm), promptly make the film success.

80 of the rats of making the film success are got in grouping and administration, and male and female half and half are divided 8 groups at random, 10 every group.(the dosage 0.6g/kg/d of 1.2g crude drug/ml) takes the direct administering mode of ulcer surface to the trial drug group, and ulcer surface drips medicine, 1 droplet/time; Test group without medicine gives normal saline.Below respectively organize rat in modeling beginning in the 2nd day, morning and afternoon every day, each administration was 1 time, observed and recorded ulcer surface size (in the ulcer diameter) and ulcer healing situation before administration every day (do not have macroscopic ulcer and be considered as healing), administration in continuous 5 days, the observation back was put to death and is respectively organized rat in the 6th day.

Every animal of observation index is pressed different time ulcer diameter (mm) after regression treatment, calculates 50% healing time, carries out statistical analysis as index.Result of the test sees Table 1.

Table 1 pair glacial acetic acid causes the influence (X ± S) of rat stomatocace healing time

Group	n	Dosage (g/kg/d)	Ulcer 50% healing time (h)
				A1	10	_	168.4±44.5
A2	10	0.015	139.0±32.9
				A3	10	0.102	134.7±42.5
A4	10	0.107	139.2±42.4
				A5	10	0.493	131.9±33.0
A6	10	0.498	127.6±40.7*
				A7	10	0.585	123.0±27.5*
A8	10	0.600	89.2±33.9*

Compare with model group: * P＜0.05, * * P＜0.01, down together.

Table 2 prescription proportioning factor level table

Table 3L8 (2 ⁷) quadrature t value method experiment table and result (n=10)

M ₁, M ₂, be the drug effect sum of these row 1,2 levels, D is differential, Se is the actual experiment error, fe experimental error degree of freedom, P are represented the significance level of these flavour of a drug to drug effect influence, * * represents that P＜0.01* represents 0.01＜P＜0.05, down with.

Result of the test shows that we are Herba Inulae cappae and Radix Glycyrrhizae to the apparent author's (principal agent) of drug effect influence.Not showing author's (may be auxiliary flavour of a drug) be Margarita and Borneolum Syntheticum, but may have reciprocal action (can tentatively find out effect trend from the A8 group) between itself and the principal agent, can not arbitrarily cast out, still need further decide, interactive analysis that accessory drugs is distinguished the flavor of.

2. the interactive analysis (quadrature t value method) of auxiliary flavour of a drug in the prescription

2.1 experiment material, date processing, test method are the same.

Be subjected to the reagent thing according to afore-mentioned test, main Herba Inulae cappae, Radix Glycyrrhizae are used as basis side in the general side, add Margarita and/or Borneolum Syntheticum (being that Margarita, Borneolum Syntheticum are provided with not medication, two levels of medication), and totally 4 proportioning groups are tested.

Sample B1～B4: take by weighing Herba Inulae cappae and licorice medicinal materials in the prescription ratio, add 10 times of water gagings and decoct 3 times, each 1 hour, filter, concentrate, 50 ℃ of microwave vacuum dryings are pulverized, and get Herba Inulae cappae, Radix Glycyrrhizae extract, as basic formula extraction; Margarita powder is broken into fine powder, sieve (150 order), Borneolum Syntheticum porphyrize; With said extracted thing and Margarita, Borneolum Syntheticum fine powder mixing.

With the ultrasonic mixing of 0.5% carboxymethylcellulose sodium solution, be mixed with the suspension of 1.2g crude drug/ml before the drug dilution method test, standby.

2.2 result of the test and analysis

Table 4 pair glacial acetic acid causes the influence (X ± S) of rat stomatocace healing time

Compare with model group: * P＜0.05, * * P＜0.01, down together.

Table 5 prescription proportioning factor level table

Table 6L8 (2 ⁷) quadrature t value method experiment table and result (n=10)

M ₁, M ₂Be the drug effect sum of these row 1,2 levels, D is differential, and Se is the actual experiment error, and fe experimental error degree of freedom, P are represented the significance level of these flavour of a drug to the drug effect influence, and * * represents that P＜0.01* represents 0.01＜P＜0.05, down together.

Result of the test shows that our adjuvant Margarita is remarkable to principal agent drug effect raising effect, and when merging the Borneolum Syntheticum medication, drug effect significantly improves, and Margarita has significance with Borneolum Syntheticum reciprocal action row, and it is more reasonable to illustrate that basis side and Margarita, Borneolum Syntheticum share.Interactive analysis is as follows:

Interactive analysis	Without Margarita (∑ x)	With Margarita (∑ x)
			Without Borneolum Syntheticum (∑ x)	1235	1235
With Borneolum Syntheticum (∑ x)	1284	856

With not medication test group as radix (1235), Margarita drug effect=(1235-1235), Borneolum Syntheticum drug effect=(1284-1235), Margarita+Borneolum Syntheticum drug effect=(1235-856).Because (1235-856)＞(1235-1235)+(1284-1235),, illustrate that four medicines share and have synergy so there are reciprocal action in Margarita and Borneolum Syntheticum.

3. prescription taste of Chinese medicine dosage ratio function analysis

3.1 experiment material, date processing, test method are the same.

Be subjected to the reagent thing according to aforementioned pharmacodynamics test, we should be made of jointly Herba Inulae cappae, Radix Glycyrrhizae, Margarita and Borneolum Syntheticum.We are medication proved recipe among the people, and each flavour of a drug proportioning is not quite similar in the prescription, and the medical material of therefore respectively distinguishing the flavor of in the general side designs high, normal, basic three dosage, takes Orthogonal Method, with pharmacodynamics index to prescription proportioning research experiment.

Sample C1～C9: press L9 (3 ⁴) orthogonal table prescription ratio takes by weighing Herba Inulae cappae and licorice medicinal materials, add 10 times of water gagings and decoct 3 times, each 1 hour, filter, concentrate, 50 ℃ of microwave vacuum dryings are pulverized, Herba Inulae cappae, Radix Glycyrrhizae extract; Margarita powder is broken into fine powder, sieve (150 order), Borneolum Syntheticum porphyrize; With the said extracted thing in proportion with Margarita, Borneolum Syntheticum fine powder mixing.

With the ultrasonic mixing of 0.5% carboxymethylcellulose sodium solution, be mixed with the suspension of 1.2g crude drug/ml before the drug dilution method test, standby.

3.2 result of the test and analysis

Table 7 pair glacial acetic acid causes the influence of rat stomatocace healing time

Group	n	Dosage (g/kg/d)	Ulcer 50% healing time (h)
				C1	10	0.6	110.9±33.2
C2	10	0.6	113.9±37.4
				C3	10	0.6	118.8±49.7
C4	10	0.6	90.7±25.2
				C5	10	0.6	86.4±38.7
C6	10	0.6	89.3±29.9
				C7	10	0.6	100.6±34.2
C8	10	0.6	93.3±30.5
				C9	10	0.6	96.6±26.4

Compare with model group: * P＜0.05, * * P＜0.01, down together.

Table 8 prescription proportioning factor level table

Table 9L9 (3 ⁴) orthogonal design table and result (n=10)

M ₁, M ₂, M ₃Be the drug effect sum of these row 1,2,3 levels, S is same column M ₁, M ₂, M ₃Standard deviation, R is differential, Se is the actual experiment error, fe experimental error degree of freedom, P are represented the significance level of these flavour of a drug to drug effect influence, * * represents P＜0.01, * represents 0.01＜P＜0.05.

Result of the test shows that each administration group all can be resisted by Cavia porcellus stomatocace due to the staphylococcus epidermidis, and the effect of obvious quickening ulcer surface healing is arranged.Visual result analysis from table 9, the order of each flavour of a drug factor affecting ulcer healing effect is Herba Inulae cappae＞Margarita＞Radix Glycyrrhizae＞Borneolum Syntheticum, wherein Herba Inulae cappae is bigger to the drug effect influence; The orthogonal experiment The results of analysis of variance shows that the DM of Herba Inulae cappae has statistical significance (P＜0.05) to the influence of drug effect, and other three flavour of a drug influences are not remarkable.Determine that our best proportioning is A ₂B ₂C ₁D ₁, promptly Herba Inulae cappae, Radix Glycyrrhizae, Margarita and Borneolum Syntheticum ratio are 100: 20: 2: 1.

Three, pharmacodynamics test

(1) removing the necrotic tissue and promoting granulation effect

1. the rat glacial acetic acid is caused the influence of oral ulcer

1.1 experimental technique is got the SD rat, male, body weight 180～220g injects 10% glacial acetic acid solution 0.05ml under the rat oral mucosa after 10% chloral hydrate (0.4ml/100g) anesthesia, form ulcer (surperficial canescence, circle or oval ulcer) after 24 hours, promptly make the film success.Get 50 of the rats of making the film success, divide 5 groups at random: model group (normal saline), positive controls (0.1g/kg), high dose group (0.52g/kg), middle dosage group (0.26g/kg), low dose group (0.13g/kg).Below respectively organize rat in making film beginning in the 2nd day, in the ulcer topical, every day 1 time (0.25ml/kg); Positive drug takes ulcer surface directly to apply administration, continuous 5 days.Observe ulcer area size (in the ulcer diameter) and ulcer healing situation (do not have macroscopic ulcer and be considered as healing) before administration every day, rat is respectively organized in execution in the 6th day, gets buccal mucosa, does the pathology histological examination.

1.2 the experimental result result of the test shows, each dosage of drop pill of the present invention all can shorten rat stomatocace 50% healing time due to the glacial acetic acid in various degree, wherein high dose group and model group relatively have significant difference (P＜0.01), point out drop pill of the present invention rat stomatocace due to the glacial acetic acid to be had the effect of accelerating healing.Result of the test sees Table 10.

Table 10 pair glacial acetic acid causes the influence (X ± S) of rat stomatocace healing time

Group	n	Dosage (g/kg)	Ulcer 50% healing time (h)
				Model group	10	_	187.3±54.1
The positive drug group	10	0.05	90.3±10.1**
				High dose group	10	0.52	78.9±14.6**
Middle dosage group	10	0.26	146.3±29.7
				Low dose group	10	0.13	162.8±21.7

Compare with model group: * P＜0.05, * * P＜0.01.

2. the Pyrogentisinic Acid causes the influence of rat oral ulcer

2.1 experimental technique is got the SD rat, male, body weight 180～220g, 10% chloral hydrate (0.4ml/100g) anesthesia is back with a long dropper of 6cm, bottom diameter 3mm, built-in cotton pellet, make cotton pellet bottom and glass tubing end opening flat, then in pipe, drip 90% phenol solution to just soaking into cotton pellet, the dropper lower end that is equipped with phenol is contacted 30 seconds with rats with left buccal mucosa place, both seen that there is the white infringement of the about 3mm of diameter in this zone, the visible rat lip of naked eyes next day limit humidity, sialorrhea, buccal mucosa place redness is promptly made the film success.Get 50 of the rats of making the film success, divide 5 groups at random: model group (normal saline), positive controls (0.1g/kg), high dose group (0.52g/kg), middle dosage group (0.26g/kg), low dose group (0.13g/kg).Below respectively organize rat and make film beginning in the 2nd day, in the ulcer topical, every day 1 time (0.25ml/kg); Positive drug takes ulcer surface directly to apply administration, successive administration 5 days.Observe ulcer area size (in the ulcer diameter) and ulcer healing situation (do not have macroscopic ulcer and be considered as healing) before administration every day, rat is respectively organized in execution in the 6th day, gets buccal mucosa, does the pathology histological examination.

2.2 the experimental result result of the test shows, each dosage of drop pill of the present invention all can shorten rat stomatocace 50% healing time due to the phenol in various degree, wherein high dose and middle dosage group and model group relatively have significant difference (P＜0.01, P＜0.05), the rat stomatocace has the effect of accelerating healing due to the prompting drop pill Pyrogentisinic Acid of the present invention.Result of the test sees Table 11.

Table 11 Pyrogentisinic Acid causes the influence (X ± S) of rat stomatocace healing time

Group	n	Dosage (g/kg)	Ulcer 50% healing time (h)
				The membranous type group	10	_	246.3±60.0
The positive drug group	10	0.04	65.2±7.6**
				High dose group	10	0.52	61.1±6.9**
Middle dosage group	10	0.26	167.0±70.5*
				Low dose group	10	0.13	205.4±60.1

Compare with model group: * P＜0.05, * * P＜0.01.

3. the rat Candida albicans is caused the influence of oral ulcer

3.1 experimental technique is got rat, ip10% chloral hydrate (0.4ml/100g) anesthesia, and under the Candida albicans bacterium liquid 0.07ml injection rat oral mucosa with 1,500,000,000 cfu/mL, the pustule that forms behind 48h diabrosis voluntarily forms ulcer.Get 50 of the rats of making the film success, divide 5 groups at random: model group (normal saline), positive controls (0.1g/kg), high dose group (0.52g/kg), middle dosage group (0.26g/kg), low dose group (0.13g/kg).Below respectively organize rat and make film the 2nd day beginning, ulcer topical every day 1 time, continuous 5 days.Observe ulcer area size (in the ulcer diameter) and ulcer healing situation (do not have macroscopic ulcer and be considered as healing) before administration every day, rat is respectively organized in execution in the 6th day, gets buccal mucosa, does the pathology histological examination.

3.2 the experimental result result of the test shows that drop pill high dose group of the present invention can obviously promote Candida albicans to cause the healing of oral ulcer (P＜0.01), points out drop pill of the present invention rat stomatocace due to the Candida albicans to be had the effect of accelerating healing.Result of the test sees Table 12.

Table 12 pair Candida albicans causes the influence (X ± S) of rat stomatocace healing time

Group	n	Dosage (g/kg)	Ulcer 50% healing time (h)
				Model group	10	_	138.0±33.9
The positive drug group	10	0.04	75.7±8.6**
				High dose group	10	0.52	85.7±14.9**
Middle dosage group	10	0.26	113.2±18.8
				Low dose group	10	0.13	121.8±29.8

Compare with model group: * P＜0.05, * * P＜0.01.

4. the rat staphylococcus epidermidis is caused the influence of oral ulcer

4.1 experimental technique is got rat, ip10% chloral hydrate (0.4ml/100g) anesthesia is injected in the staphylococcus epidermidis bacterium liquid 0.07ml of 1,500,000,000 cfu/ml under the rat oral mucosa, forms abscess and diabrosis voluntarily behind the 48h, forms ulcer.Get 50 of the rats of making the film success, divide 5 groups at random: model group (normal saline), positive controls (0.1g/kg), high dose group (0.52g/kg), middle dosage group (0.26g/kg), low dose group (0.13g/kg).Below respectively organize rat in making film the 2nd day beginning, ulcer topical every day 1 time, continuous 5 days.Observe ulcer area size (in the ulcer diameter) and ulcer healing situation (do not have macroscopic ulcer and be considered as healing) before administration every day, rat is respectively organized in execution in the 6th day, gets buccal mucosa, does the pathology histological examination.

4.2 the experimental result result of the test shows, each dosage of drop pill of the present invention all can shorten rat stomatocace 50% healing time due to the phenol in various degree, wherein high dose group can promote obviously that staphylococcus epidermidis causes the healing of oral ulcer, with model group significant difference (P＜0.01) is arranged relatively.Result of the test sees Table 13.

Table 13 pair staphylococcus aureus causes the influence (X ± S) of rat stomatocace healing time

Group	n	Dosage (g/kg)	Ulcer 50% healing time (h)
				Model group	10	_	123.4±21.8
The positive drug group	10	0.04	70.5±8.3**
				High dose group	10	0.52	65.9±5.7**
Middle dosage group	10	0.26	111.5±27.5
				Low dose group	10	0.13	115.3±13.9

Compare with model group: * P＜0.05, * * P＜0.01.

(2) antiinflammatory action

1. the inhibitory action that increases of Dichlorodiphenyl Acetate induced mice abdominal cavity capillary permeability

1.1 experimental technique is got 50 of KM mices, male and female half and half, body weight 18～22g is divided into normal control group (normal saline), hydrocortisone group (0.05g/kg), high dose group (6.0g/kg), middle dosage group (3.0g/kg), low dose group (1.5g/kg), 10 every group at random.Gastric infusion, successive administration 3 days, each organizes 1h after the last administration, the blue normal saline solution 0.1ml/10g of tail vein injection 0.5%Evens, lumbar injection 0.6% acetic acid 0.2ml/ is only immediately.After 30 minutes mice is put to death, cut off stomach wall, divide with the 6ml normal saline and wash the abdominal cavity for several times, collect the merging flushing liquor, add normal saline to 10ml.The centrifugal 15min of 3000rpm gets supernatant, measures the absorbance of supernatant in the 590nm place, organizes a t check.

Increase 1.2 experimental result drop pill height of the present invention, middle dosage group can obviously be resisted acetic acid induced mice abdominal cavity capillary permeability,, the results are shown in Table 14 with normal control group comparing difference remarkable (P＜0.05, P＜0.01).

The inhibitory action that table 14 Dichlorodiphenyl Acetate induced mice abdominal cavity capillary permeability increases (X ± S)

Group	Dosage g/kg	n	Absorbance	Suppression ratio (%)
					Matched group	_	10	0.426±0.185	_
Hydrocortisone	0.05	10	0.115±0.028	73.00
					High dose group	6.0	10	0.225±0.093 **	47.18
Middle dosage group	3.0	10	0.294±0.060 *	30.98
					Low dose group	1.5	10	0.340±0.153	20.19

Compare * P＜0.05 * * P＜0.01 with model group.

2. xylol causes the inhibitory action of mice auricle swelling

2.1 test method is got 50 of KM mices, male and female half and half, body weight 18～22g, grouping is the same with administration, 1h after the last administration is applied to the mouse right ear auricle with 0.1ml dimethylbenzene and causes inflammation, and left ear is a matched group, put to death mice after causing scorching back 15 minutes, cut two ears along the auricle baseline, lay left and right sides auricle with the card punch of diameter 8mm, weigh in same position,, calculate swelling and suppress percentage rate as the swelling degree with the difference of left and right sides auricle weight.

2.2 result of the test drop pill height of the present invention, middle dosage group xylol causes mice auricle swelling that the obvious suppression effect is arranged, and with normal control group comparing difference significantly (P＜0.01), the results are shown in Table 15.

Table 15 xylol causes the inhibitory action (X ± S) of mice auricle swelling

Group	Dosage g/kg	n	Swelling degree (mg)	Suppression ratio (%)
					Matched group	_	10	23.7±9.19	_
Hydrocortisone	0.05	10	5.2±1.14**	78.06
					High dose group	6.0	10	12.7±3.68**	46.41
Middle dosage group	3.0	10	14.8±5.77**	37.55
					Low dose group	1.5	10	17.3±5.31	27.00

Compare * P＜0.05 * * P＜0.01 with model group.

(3) analgesic activity

The analgesic activity of 1 pair of mice (hot plate method)

1.1 experimental technique is got female mice, carries out the responsive screening of pain, measures each mice pain threshold, chooses 50 of the female mice of pain threshold between 5～30s (licking the time of metapedes after being subjected to thermostimulation), body weight 18～22g surveys the preceding pain threshold of mice administration.Experiment mice is divided into 5 groups at random, is respectively normal control group (isometric(al) normal saline), positive controls (0.15g/kg), high dose group (6.0g/kg), middle dosage group (3.0g/kg), low dose group (1.5g/kg), 10 every group.Gastric infusion, successive administration 3 days.15min, 30min, 60min measure each Mus pain threshold (the 60s mice is still reactionless, takes out mice and calculates with 60s) respectively after the last medication.

1.2 experimental result: high after the administration, middle dosage group all can obviously prolong the mice pain threshold, with normal control group comparing difference remarkable (P＜0.05, P＜0.01), shows that drop pill of the present invention has obvious analgesic activity to the thermostimulation mice.The results are shown in Table 16.

The analgesic activity (hot plate method) of table 16 pair mice (n=10)

Compare * P＜0.05 * * P＜0.01 with model group.

2. to the analgesic activity (writhing method) of mice

2.1 experimental technique is got 50 of mices, male and female half and half, body weight 18～22g.Experiment mice is divided into 5 groups at random, is respectively normal control group (isometric(al) normal saline), positive controls (0.15g/kg), high dose group (6.0g/kg), middle dosage group (3.0g/kg), low dose group (1.5g/kg), 10 every group.Gastric infusion, successive administration 3 days.30min after the last administration, each Mus only causes pain by lumbar injection 0.6% acetic acid 0.2ml/, observes the number of times that writhing response (abdominal part indent, trunk and back leg extension, buttocks are raised) appears in each Mus in the 20min, calculates and suppresses percentage rate.

2.2 high dose can obviously reduce acetic acid induced mice reaction times after the experimental result administration, with normal control group comparing difference remarkable (P＜0.01), shows that the writhing response of drop pill high dose Dichlorodiphenyl Acetate induced mice of the present invention has significant analgesia role.The results are shown in Table 17.

The analgesic activity of table 17 pair mice (writhing method, X ± S)

Group	Dosage g/kg	n	Turn round body number (10min)	Suppression ratio (%)
					Matched group	_	10	28.6±5.62	_
Aspirin	0.15	10	12.9±3.60**	54.90
					High dose group	6.0	10	20.1±5.63**	29.72
Middle dosage group	3.0	10	25.4±9.95	11.19
					Low dose group	1.5	10	28.2±10.32	1.2

(4) antibacterial action

1. liquid diluting method

1.1 the preparation of pastille culture medium: get reagent test liquid (0.7374g/ml) 10ml to the first ware respectively, add 40ml and melted and be incubated Carnis Bovis seu Bubali cream soup culture medium in 56 ℃, mixing is made the pastille agar culture medium; Draw above-mentioned Carnis Bovis seu Bubali cream soup agar 25ml again in second ware, add 25ml Carnis Bovis seu Bubali cream soup agar culture medium, mixing; As these times dilution, making final concentration is the pastille culture medium of 147mg/ml, 73.5mg/ml, 36.75mg/ml, 18.38mg/ml, 9.19mg/ml, 4.60mg/ml (1/5,1/10,1/20,1/40,1/80,1/160).The bacterial strain contrast and the negative control culture medium that do not contain medicine with the method preparation.

1.2 the inoculation of bacterial strain and cultivation: get small test tube and add above-mentioned each concentration pharmaceutical liquid culture medium 1ml respectively, add 10 again ^-3The fresh bacterium liquid 0.1ml of dilution; Be equipped with reagent contrast (not adding bacterium liquid) and bacterial strain contrast (adding the fluid medium that does not contain medicine) with legal system.Escherichia coli, staphylococcus epidermidis, Klebsiella Pneumoniae, Bacillus proteus, Pseudomonas aeruginosa, Shigella flexneri, Candida albicans are put 37 ℃ of incubators and were cultivated 24 hours; Streptococcus pneumoniae, beta hemolytic streptococcus are put CO ₂Cultivated 24 hours for 37 ℃ in the incubator.Observe the bacterial growth situation, not show muddiness, the reagent concentration of integral asepsis growth is the minimum inhibitory concentration (MIC) of medicine to this bacterial strain.Select the cultivation parent tube of asepsis growth in the MIC test, get a ring with inoculating loop and be inoculated in respectively on the corresponding culture medium that does not contain reagent.Escherichia coli, staphylococcus epidermidis, Klebsiella Pneumoniae, Bacillus proteus, Pseudomonas aeruginosa, Shigella flexneri, Candida albicans are put common incubator and are cultivated observed result after 24 hours for interior 37 ℃, and streptococcus pneumoniae, beta hemolytic streptococcus are put CO ₂Cultivate after 24 hours for 37 ℃ in the incubator, observe the bacterial growth situation, the reagent concentration of integral asepsis growth is the minimum bactericidal concentration (MBC) of medicine to this bacterial strain, the results are shown in Table 18,19.

The bacteriostatic test result of table 18 pair reference culture

The bacteriostatic test result of table 19 pair clinical strains

1.3 result of the test drop pill of the present invention all has in various degree inhibitory action to escherichia coli, staphylococcus epidermidis, Klebsiella Pneumoniae, Bacillus proteus, Pseudomonas aeruginosa, Shigella flexneri, Candida albicans, streptococcus pneumoniae, beta hemolytic streptococcus type strain and clinical isolates strain.Wherein better to the bacteriostasis of reference culture staphylococcus epidermidis, Klebsiella Pneumoniae, Bacillus proteus, Pseudomonas aeruginosa, streptococcus pneumoniae, beta hemolytic streptococcus, Candida albicans, MIC is less than or equal to 36.8mg/ml, and MBC is less than or equal to 73.5mg/ml; Bacteriostasis to clinical isolates staphylococcus epidermidis, Klebsiella Pneumoniae, streptococcus pneumoniae is better, and MIC is more than or equal to 36.8mg/ml, and MBC is less than or equal to 73.5mg/ml.The bacterial strain controlled trial has bacteria growing, reagent controlled trial asepsis growth.

2. antibacterial tests in the body-to the protective effect of bacterial infection induced mice death

2.1 medicine is to the determination of acute toxicity of mice

Preparation of the present invention is given the mouse stomach administration with maximum administration concentration and maximum administration volume, observes continuously 14 days, measures the LD of this preparation ₅₀Or maximum dosage-feeding.Result of the test shows that toxic reaction does not appear in animal, none animal dead, and the maximum dosage-feeding that records mice is 147.6g crude drug/kg, points out this preparation toxicity lower.

2.2 antibacterial causes the mensuration of mice minimum lethal dose (MLD)

With staphylococcus epidermidis, Klebsiella Pneumoniae, Bacillus proteus type strain and clinical strain, be inoculated in the liquid nutrient media respectively, put 37 ℃ of incubators and cultivated 24 hours; Streptococcus pneumoniae, beta hemolytic streptococcus type strain and clinical strain are inoculated in the liquid blood meida, put CO ₂Cultivated 24 hours for 37 ℃ in the incubator.With the normal saline dilution is 10 ^-3, 10 ^-4, 10 ^-5, 10 ^-6, 10 ^-7The bacterium liquid of concentration is with the bacterium liquid difference lumbar injection infecting mouse of variable concentrations, every Mus 0.5ml, 8 every group; Observe the death condition of animal in 5 days, measure the MLD that test strain causes mice 100% death, result of the test sees Table 20.

Table 20 experiment is extremely measured (MLD) with bacterial strain entirely to the minimum of mice

2.3 test method is got 144 of mices, male and female half and half, body weight 18～22g, 6 various dose Margarita drop pill of the present invention groups that are divided into normal control group (isometric(al) normal saline), positive drug control group, antibacterial matched group at random and prepare by proportional diluted, every group 16, carry out antibacterial tests in the body.Gastric infusion, successive administration 3 days, 30min after the last administration except that the normal control group, in the MLD 0.5ml of lumbar injection different strains infecting mouse, continued administration 3 days again.Observed and recorded infects the death toll of respectively organizing mice in one week of back, presses the Biliss method and calculates median effective dose ED50 and 95% fiducial limit, the results are shown in Table 21,22,23,24 and 25.

Table 21 Margarita drop pill of the present invention is to epidermis staphy lococcus infection mice ED ₅₀Influence (n=16)

Compare with the antibacterial matched group: * P＜0.05, * * P＜0.01.

Table 22 Margarita drop pill of the present invention is to beta hemolytic streptococcus infecting mouse ED ₅₀Influence (n=16)

Table 23 Margarita drop pill of the present invention is to streptococcus pneumoniae infection mice ED ₅₀Influence (n=16)

Table 24 Margarita drop pill of the present invention is to Bacillus proteus infecting mouse ED ₅₀Influence (n=16)

Table 25 Margarita drop pill of the present invention is to Klebsiella Pneumoniae infecting mouse ED ₅₀Influence (n=16)

2.4 test results test result shows; drop pill of the present invention is to the deadly protective effect that all has in various degree of staphylococcus epidermidis, beta hemolytic streptococcus, streptococcus pneumoniae, Bacillus proteus, Klebsiella Pneumoniae type strain and clinical strain infecting mouse, and high dose group survival rate and antibacterial matched group relatively have significant difference (P＜0.05, P＜0.01).ED to the reference culture infecting mouse ₅₀Be respectively 3825.8mg/kg, 5011.6mg/kg, 4382.1mg/kg, 4619.8mg/kg, 3525.0mg/kg; ED to the clinical strains infecting mouse ₅₀Be respectively 4330.9mg/kg, 4898.9mg/kg, 5501.2mg/kg, 5832.6mg/kg, 5168.5mg/kg.

Above experimental result shows: preparation of the present invention has tangible removing the necrotic tissue and promoting granulation, antiinflammatory, analgesia, antibacterial action.

The specific embodiment:

Embodiments of the invention 1: Herba Inulae cappae 100g, Radix Glycyrrhizae 20g, Margarita 2g, Borneolum Syntheticum 1g

Herba Inulae cappae, Radix Glycyrrhizae add 10 times of water gagings and decoct 3 times, and each 1 hour, filter, merging filtrate is evaporated to 50 ℃ of relative densities 1.08, adds ethanol and makes that to contain the alcohol amount be 60%, left standstill 12 hours, sucking filtration, decompression recycling ethanol adds the suitable quantity of water dilution; Last D ₁₀₁Macroporous adsorptive resins discards and penetrates liquid, with washing on a small quantity, continues and uses 70% ethanol elution, collects eluent, reclaims ethanol, concentrates, and microwave vacuum drying is pulverized, and gets Herba Inulae cappae, Radix Glycyrrhizae extract; Margarita powder is broken into fine powder, crosses 120～200 mesh sieves; The Borneolum Syntheticum porphyrize; Margarita, Borneolum Syntheticum fine powder and said extracted thing mixing add an amount of polyethylene glycol 6000, put heating in water bath and make fusion, and stirring and evenly mixing moves in the drop pill machine liquid reservoir, and insulation splashes in the coolant, promptly gets drop pill.Usage and dosage: buccal, one time 2 ball, 4 times on the one.

Embodiments of the invention 2: Herba Inulae cappae 50g, Radix Glycyrrhizae 10g, Margarita 1g, Borneolum Syntheticum 0.5g

Herba Inulae cappae, Radix Glycyrrhizae add 8 times of water gagings and decoct 2 times, and each 1 hour, filter, merging filtrate is evaporated to 50 ℃ of relative densities 1.08, adds ethanol and makes that to contain the alcohol amount be 60%, left standstill 12 hours, sucking filtration, decompression recycling ethanol adds the suitable quantity of water dilution; Last D ₁₀₁Macroporous adsorptive resins discards and penetrates liquid, with washing on a small quantity, continues and uses 60% ethanol elution, collects eluent, reclaims ethanol, concentrates, and microwave vacuum drying is pulverized, and gets Herba Inulae cappae, Radix Glycyrrhizae extract; Margarita powder is broken into fine powder, crosses 120～200 mesh sieves; The Borneolum Syntheticum porphyrize; Margarita, Borneolum Syntheticum fine powder and said extracted thing mixing add an amount of polyethylene glycol 6000, put heating in water bath and make fusion, and stirring and evenly mixing moves in the drop pill machine liquid reservoir, and insulation splashes in the coolant, promptly gets drop pill.

Embodiments of the invention 3: Herba Inulae cappae 200g, Radix Glycyrrhizae 40g, Margarita 4g, Borneolum Syntheticum 2g

Herba Inulae cappae, Radix Glycyrrhizae add 12 times of water gagings and decoct 4 times, and each 1 hour, filter, merging filtrate is evaporated to 50 ℃ of relative densities 1.08, adds ethanol and makes that to contain the alcohol amount be 60%, left standstill 12 hours, sucking filtration, decompression recycling ethanol adds the suitable quantity of water dilution; Last D ₁₀₁Macroporous adsorptive resins discards and penetrates liquid, with washing on a small quantity, continues and uses 80% ethanol elution, collects eluent, reclaims ethanol, concentrates, and microwave vacuum drying is pulverized, and gets Herba Inulae cappae, Radix Glycyrrhizae extract; Margarita powder is broken into fine powder, crosses 120～200 mesh sieves; The Borneolum Syntheticum porphyrize; Margarita, Borneolum Syntheticum fine powder and said extracted thing mixing add an amount of polyethylene glycol 6000, put heating in water bath and make fusion, and stirring and evenly mixing moves in the drop pill machine liquid reservoir, and insulation splashes in the coolant, promptly gets drop pill.

Embodiments of the invention 4: Herba Inulae cappae 100g, Radix Glycyrrhizae 30g, Margarita 3g, Borneolum Syntheticum 1g and suitable adjuvant: will Herba Inulae cappae and Radix Glycyrrhizae add 10 times of water gagings after merging and decoct 3 times, each 1 hour, filter, merging filtrate is evaporated to 50 ℃ of relative densities 1.08, adds ethanol and makes that to contain the alcohol amount be 60%, left standstill 12 hours, sucking filtration, decompression recycling ethanol adds the suitable quantity of water dilution; Last D ₁₀₁Macroporous adsorptive resins discards and penetrates liquid, with washing on a small quantity, continues and uses 70% ethanol elution, collects eluent, reclaims ethanol, concentrates, and microwave vacuum drying is pulverized, and gets Herba Inulae cappae, Radix Glycyrrhizae extract; Margarita powder is broken into fine powder, crosses 120～200 mesh sieves; The Borneolum Syntheticum porphyrize; Margarita, Borneolum Syntheticum fine powder and said extracted thing mixing add conventional adjuvant, make the oral formulations that needs according to common process.

Claims (5)

1. Chinese medicine preparation for the treatment of oral ulcer is characterized in that: it is with Herba Inulae cappae 50～200g, Radix Glycyrrhizae 10～40g, Margarita 1～4g, Borneolum Syntheticum 0.5～2g and the suitable oral formulations made of adjuvant.

2. according to the Chinese medicine preparation of the described treatment oral ulcer of claim 1, it is characterized in that: it is made with Herba Inulae cappae 100g, Radix Glycyrrhizae 20g, Margarita 2g, Borneolum Syntheticum 1g and appropriate amount of auxiliary materials.

3. according to the Chinese medicine preparation of claim 1 or 2 described treatment oral ulcer, it is characterized in that: described preparation is a drop pill.

4. as the preparation method of the Chinese medicine preparation of treatment oral ulcer as described in each among the claim 1-3, it is characterized in that: add 8-12 times of water gaging after Herba Inulae cappae and Radix Glycyrrhizae merge and decoct 2-4 time, each 1 hour, filter merging filtrate, be evaporated to 50 ℃ of relative densities 1.08, add ethanol and make that to contain the alcohol amount be 60%, left standstill sucking filtration 12 hours, decompression recycling ethanol adds the suitable quantity of water dilution; Last D101 macroporous adsorptive resins discards and penetrates liquid, with washing on a small quantity, continues and uses the 60-80% ethanol elution, collects eluent, reclaims ethanol, concentrates, and microwave vacuum drying is pulverized, and gets Herba Inulae cappae, Radix Glycyrrhizae extract; Margarita powder is broken into fine powder, crosses 120～200 mesh sieves; The Borneolum Syntheticum porphyrize; Margarita, Borneolum Syntheticum fine powder and said extracted thing mixing add suitable adjuvant and make oral formulations.

5. according to the preparation method of the Chinese medicine preparation of the described treatment oral ulcer of claim 4, it is characterized in that: add 10 times of water gagings after Herba Inulae cappae and Radix Glycyrrhizae merge and decoct 3 times, each 1 hour, filter merging filtrate, be evaporated to 50 ℃ of relative densities 1.08, add ethanol and make that to contain the alcohol amount be 60%, left standstill sucking filtration 12 hours, decompression recycling ethanol adds the suitable quantity of water dilution; Last D101 macroporous adsorptive resins discards and penetrates liquid, with washing on a small quantity, continues and uses 70% ethanol elution, collects eluent, reclaims ethanol, concentrates, and microwave vacuum drying is pulverized, and gets Herba Inulae cappae, Radix Glycyrrhizae extract; Margarita powder is broken into fine powder, crosses 120～200 mesh sieves; The Borneolum Syntheticum porphyrize; Margarita, Borneolum Syntheticum fine powder and said extracted thing mixing add an amount of polyethylene glycol 6000, put heating in water bath and make fusion, and stirring and evenly mixing moves in the drop pill machine liquid reservoir, and insulation splashes in the coolant, promptly.