CN101890079B - Medical preparation for preventing and treating rhinitis and preparation method thereof - Google Patents

Medical preparation for preventing and treating rhinitis and preparation method thereof Download PDF

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CN101890079B
CN101890079B CN201010159712.XA CN201010159712A CN101890079B CN 101890079 B CN101890079 B CN 101890079B CN 201010159712 A CN201010159712 A CN 201010159712A CN 101890079 B CN101890079 B CN 101890079B
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preparation
rhinitis
caulis
herba
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CN101890079A (en
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周强
皮海燕
罗阳洋
刘燕
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GUIYANG CHUNKE PHARMACY GROUP TECHNICAL RESEARCH Co Ltd
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GUIYANG CHUNKE PHARMACY GROUP TECHNICAL RESEARCH Co Ltd
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Abstract

The invention provides a medical preparation for preventing and treating rhinitis and a preparation method thereof. The medical preparation is prepared into an oral preparation or external preparation by using open-herding, Centipeda minima, serissa serissoide, polygonum perfoliatum and angelica root as bulk drugs, or is matched with the part or the whole of medicinal materials of campanumaea pilosula and wild Chrysanthemum to use. Compared with the prior art, the medical preparation has the efficacy of clearing away heat and toxic material, and benefiting lung and promoting the restoration consciousness, has favorable treatment effect on the symptoms including stuffy nose, nasosinusitis rhinorrhoea and the like, and chronic rhinitis, chronic sinusitis and allergic rhinitis, and has the advantages of safe use, no toxicity, no side effect and no drug resistance, thereby being a new traditional Chinese medicine with security, effectiveness and controlled quality and being worthy of clinical popularization.

Description

Prevent and treat pharmaceutical preparation of rhinitis and preparation method thereof
Technical field
The present invention relates to a kind of pharmaceutical preparation that prevents and treats rhinitis and preparation method thereof, belong to technical field of Chinese medicines.
Background technology
Chronic rhinitis is that the mankind are common, a kind of disease occurred frequently, be referred to as clinically can not be cured pertinacious disease, in medical prophylaxis treatment, do not paid attention in the past, in addition there is no corresponding Therapeutic Method and medicine, while making it to treat clinically, still continue to use over general anti-inflammatory treatment, can not obtain good curative effect, the general absolutely not inflammation of rhinitis, but a kind of " non-specific sense of organization rhinitis ", with conventional anti-inflammatory treatment, can not obtain good effect, in addition the disease of chronic rhinitis again with people's spirit, emotion has much relations, so antiinflammatory simply, antibacterial, only meeting delay treatment, health is caused damage.According to national otorhinolaryngology expert statistics, chronic rhinitis sick sickness rate in the whole nation is up to 87.3%, and regardless of the South and the North, general northern area patient symptom is attached most importance to, and chronic rhinitis cannot be prevented again, just as cannot preventing viral flu, people's nasopharynx part is again the nasopharynx larynx place that body weight for humans is wanted, breathe the only way which must be passed, can play prevention kill bacteria, virus etc., the full nasopharynx part lymphoid tissue of leaning on plays immunologic function, the upper respiratory tract infection such as viral influenza repeatedly, can aggravate the hypertrophy of pharyngeal lymph follicle and the hypertrophy of compensatory, there is a series of chronic rhinitis symptoms and general malaise, nose mucosa occurs that pathologic changes, the even loss of function of nasopharynx lymphoid tissue Immune Dysfunction, pathogenic bacteria is driven straight in and enter in body, cause the infection inflammation of nasopharynx part to involve other system, can concurrent chronic trachea and bronchitis, nephritis, heart disease etc., long-term rheuminess thing is swallowed in stomach, can cause dyspepsia, esophagitis, gastritis, intestinal inflammation, the general reactions such as toxin absorbs can cause dizziness, headache, tired, energy goes down, become thin, low grade fever.So cause the attention of height.Up to the present, chronic rhinitis there is no the method for radical cure, and existing part Chinese patent medicine for oral administration and medicine for external use are for clinical, but curative effect is all not remarkable.In order to develop the Chinese medicine of energy safety, effective anti-treatment rhinitis, applicant has carried out a large amount of explorations and research.
Summary of the invention
Technical problem to be solved by this invention be to provide a kind of can safety, effectively prevent and treat pharmaceutical preparation of rhinitis and preparation method thereof, medicine effect of the present invention is fast, have no side effect, and is a kind of safe, effective, quality controllable new Chinese medicine of preventing and treating rhinitis.
In order to solve the problems of the technologies described above, the present invention adopts following technical scheme: prevent and treat the pharmaceutical preparation of rhinitis.Mainly to be made by the crude drug of following weight ratio example: Caulis et folium pavettae hongkongensis 10%～40%, Herba Centipedae 10%～15%, Serissa foetida 20%～30%, Herba Polygoni cymosi 20%～30%, the Radix Angelicae Dahuricae 10%～15%.
In the above-mentioned pharmaceutical preparation that prevents and treats rhinitis, the consumption of each crude drug is preferably: Caulis et folium pavettae hongkongensis 20%, Herba Centipedae 13.3%, Serissa foetida 26.7%, Herba Polygoni cymosi 26.7%, the Radix Angelicae Dahuricae 13.3%.
The preparation method of the aforementioned pharmaceutical preparation that prevents and treats rhinitis is: get Caulis et folium pavettae hongkongensis, Herba Centipedae, Serissa foetida, Herba Polygoni cymosi, Radix Angelicae Dahuricae gomi herbs, 5～12 times of decoctings that add the total amount of writing out a prescription boil 1～4 time, each decoction 1～4 hour, filter, filtrate is concentrated into the extractum that 60 DEG C of relative densities are 1.20～1.40, and then preparation process is made different pharmaceutical preparation routinely.
In the above-mentioned pharmaceutical preparation that prevents and treats rhinitis, in order to reach better therapeutic effect, can also add crude drug Radix Codonopsis, Flos Chrysanthemi Indici, the part by weight of each crude drug is: Caulis et folium pavettae hongkongensis 5%～30%, Herba Centipedae 8%～11%, Radix Codonopsis 12%～18%, Serissa foetida 17%～22%, Herba Polygoni cymosi 17%～22%, Flos Chrysanthemi Indici 8%～11%, the Radix Angelicae Dahuricae 8%～11%.
In the above-mentioned pharmaceutical preparation that prevents and treats rhinitis, the consumption of each component is preferably: Caulis et folium pavettae hongkongensis 15%, Herba Centipedae 10%, Radix Codonopsis 15%, Serissa foetida 20%, Herba Polygoni cymosi 20%, Flos Chrysanthemi Indici 10%, the Radix Angelicae Dahuricae 10%.
The preparation method of the above-mentioned pharmaceutical preparation that prevents and treats rhinitis is: get Caulis et folium pavettae hongkongensis, Herba Centipedae, Radix Codonopsis, Serissa foetida, Herba Polygoni cymosi, Flos Chrysanthemi Indici, Radix Angelicae Dahuricae seven flavor medicine material, 5～12 times of decoctings that add the total amount of writing out a prescription boil 1～4 time, each decoction 1～4 hour, filter, filtrate is concentrated into the extractum that 60 DEG C of relative densities are 1.20～1.40, and then preparation process is made different pharmaceutical preparation routinely.
Medicine of the present invention can be prepared into oral formulations or external preparation.Wherein oral formulations comprises decoction, granule, oral liquid, syrup, soft extract, pill, tablet, hard capsule, soft capsule and drop pill etc.
We are according to theory of Chinese medical science, utilize oral medicine to control rhinitis, in line with " wind-heat rhinitis dispeling the wind, removing dampness, heat clearing away, have one's ideas straightened out; Wind-cold rhinitis inducing sweat, cold relieving, removing dampness, have one's ideas straightened out." basic principle, focus on adjusting the relation between part and entirety, treatment nasal obstruction is obstructed, nasal sinusitis watery nasal discharge etc. and chronic rhinitis, chronic paranasal rhinitis, allergic rhinitis is shown in above-mentioned disease, determined curative effect, effect is obviously.
Prescription medicine characteristic of the present invention: Caulis et folium pavettae hongkongensis (having another name called Herba Hydrocotyles): property is flat, acrid in the mouth.Clearing away heat and promoting diuresis, preventing phlegm from forming and stopping coughing.For acute icterohepatitis, acute nephritis, pertussis.Herba Centipedae: pungent, temperature.Return lung, Liver Channel.Clearing the nasal passage, cough-relieving, for headche due to wind-cold, cough with copious phlegm, has a stuffy nose obstructed, nasal sinusitis watery nasal discharge.Radix Codonopsis: property is flat, sweet in the mouth, micro-acid.Return spleen, lung meridian.Invigorating the spleen and replenishing QI, spleen invigorating lung benefiting.For deficiency of the spleen and lung, the cardiopalmus of breathing hard, anorexia and loose stool, dyspnea due to deficiency cough, interior-heat is quenched one's thirst.Serissa foetida: light, micro-pungent, cool.Dispelling wind to relieve the exterior syndrome, clearing away heat-damp and promoting diuresis, relaxing muscles and tendons and activating QI and blood in the collateral.With what flu, cough, toothache, acute tonsillitis, pharyngolaryngitis, acute hepatitis, chronic hepatitis, enteritis, dysentery, infantile malnutrition, hypertension complicated headache, migraine, rheumatic arthralgia.Herba Polygoni cymosi: property is cold, sour in the mouth.Enter hot warp.Heat-clearing and toxic substances removing, inducing diuresis to remove edema; Control cough, upper respiratory tract infection.Flos Chrysanthemi Indici: be slightly cold; Pungent, bitter; Return lung, Liver Channel.Heat-clearing and toxic substances removing; Dispelling wind suppressing the hyperactive liver.Anemopyretic cold; Laryngopharynx swelling and pain; Hypertension.The Radix Angelicae Dahuricae: pungent, temperature.Attach to the lung and stomach meridians.Dispel the wind, dampness, detumescence, pain relieving.Control headache, supraorbital bone pain, toothache, nasal sinusitis.
Side of the present invention separates: the traditional Chinese medical science thinks, rhinitis is divided into two classes: a class is wind-heat rhinitis (as sinusitis), and a class is wind-cold rhinitis (as allergic rhinitis).No matter any rhinitis is all because suffering exopathogen: wind (length of all kinds of diseases and ailments), summer-heat (hot in nature hold under the arm wet), wet (checking mechanism of qi), dry (impairment of body fluid criminal lung), cold (impairment of YANG stagnates), heat (the scorching raw wind of property) by fur (especially vest) or because of diet as drink (how wet heat-dissipating is), eat the food intrusion pulmonary such as pungent (heat-dissipating is got angry), (raw cold impairment of YANG) cool in nature.Nose is the key of lung, and the function of lung is normal, and nasal mucus is moistened nose key and do not outflowed; It is impaired that lung is subject to the invasion and attack of exopathogen, will reflect by nose.If lung cold, rhinorrhea with clear discharge; Lung-heat, tears Huang is turbid; The dryness of the lung, dryness in the nasal cavity; Lung is wet, nasal obstruction; And then also may cause other pathological changes of nasal cavity.When wind heat occupies when leading, rhinitis shows as dryness in the nasal cavity, nasal obstruction, the turbid tears of stream, even epistaxis, raw nasal abscess, nasal conchae hypertrophy etc.; When wind and cold occupies when leading, rhinitis shows as nasal obstruction, snivel, sneeze etc.Primary disease starts from ailment said due to cold or exposure more and attacks outward, lung meridian accumulation of heat, or close with spleen wetting phase, wind heat damp is stopped up in nasal meatus, steams the body fluid that burns, and turbid tears are dirty, form nasal sinusitis.Therefore dispeling the wind, heat clearing away, dampness removing, removing toxic substances, sensible as main, be aided with the ruling by law such as QI invigorating lung qi dispersing.
We cure mainly wind heat stop up have a stuffy nose due to lung obstructed, nasal sinusitis watery nasal discharge etc. and chronic rhinitis, chronic paranasal rhinitis, allergic rhinitis is shown in above-mentioned disease, controls with heat-clearing and toxic substances removing, lung benefiting is sensible.In side, reduce phlegm as main taking Caulis et folium pavettae hongkongensis heat-clearing and toxic substances removing, dampness removing; With Herba Centipedae clearing the nasal passage; With Serissa foetida dispelling wind to relieve the exterior syndrome, clearing away heat-damp and promoting diuresis; With Herba Polygoni cymosi, Flos Chrysanthemi Indici heat-clearing and toxic substances removing, dispelling wind; With Radix Codonopsis invigorating the spleen and replenishing QI, spleen invigorating lung benefiting; With the Radix Angelicae Dahuricae: dispel the wind, dampness, pain relieving; All medicines share, and receive altogether heat-clearing and toxic substances removing, the merit that lung benefiting is sensible.
Function of the present invention cures mainly: medicine of the present invention has heat-clearing and toxic substances removing, and lung benefiting is sensible.Be used for having a stuffy nose obstructed, nasal sinusitis watery nasal discharge etc. and chronic rhinitis, chronic sinusitis, allergic rhinitis is shown in above-mentioned disease, uses safety, has no side effect, not producing drug resistance, is a kind of safe, effective, quality controllable new Chinese medicine of preventing and treating rhinitis, and clinic is promoted the use of.
In order to verify that medicine of the present invention has good therapeutic effect, applicant has carried out series of experimental research, specific as follows:
one, formula clinical application research
1, physical data: this group case, through department of otorhinolaryngology inspection, has the diseases such as nasal membrane hyperemia, concha nasalis swelling (plumpness) and sticky purulent secretion, meets acute and chronic rhinitis or acute and chronic nasal sinusitis diagnosis person.Meet Chinese medical discrimination simultaneously and belong to nasal sinusitis.
Observed patient is divided into two groups at random: treatment group 120 examples, matched group 100 examples.Two groups of cases, at aspects such as sex, age, the course of disease, ill-distribution and Syndrome Differentiation of Traditional Chinese Medicines, are learned by statistics and are processed equal no significant difference.
Table 1 liang group sex, mean age, the comparison of average course of disease situation
Table 2 liang group case doctor trained in Western medicine ill-distribution situation comparison
2, case selection standard
(1) diagnostic criteria
1. Western medicine diagnose standard: have the scorching history of repeated attack of acute nose (hole); Long-term nasal obstruction, the sticky pus of stream or pus tears, headache and dizziness, absent minded, hyposmia or disappearance; Nasal cavity checks: nasal mucosa swelling or plumpness, and middle nasal concha enlargement or Polypoid changes, have sticky pus tears in the corresponding nasal meatus of sick hole; X-ray checks: hole chamber is fuzzy, muddy, increase in density, pachymucosa or have liquid level; Puncture or catheters irrigation have pus overflow.
2. Standards of Chinese Medical Syndrome Differentiation: wind heat is stopped up lung card: the thick Huang of nasal mucus, turbinate mucosa is red red, and neck distending pain is had a stuffy nose obstructed, olfactory disorder, thirsty, the cough expectorant Huang that generates heat, red tongue is red, yellow fur, full and large pulse and counting.
3, Therapeutic Method
(1) observation index: main clinic symptoms and sign: nasal obstruction, flows turbid tears, olfactory disorder, headache (swollen), heating, nasal mucosa swelling, picture of the tongue, pulse condition etc.Untoward reaction after taking medicine (gastrointestinal reaction or dermoreaction).
(2) efficacy assessment standard: be divided into the standards such as effective, effective and invalid according to " guideline of clinical investigations of new Chinese medicine treatment nasal sinusitis ".1. effective: to treat and alleviate completely with interior cardinal symptom and sign for 4 weeks; 2. effective: to treat and take a favorable turn with interior cardinal symptom and sign for 4 weeks; 3. invalid: to treat 4 weeks, do not reach effective standard.
4, case inclusive criteria and rejecting Standard Selection case in method of administration foundation " new Chinese medicine treatment acute and chronic nasal sinusitis guideline of clinical investigations ", include in and observe first inactive other treatment drug for treating rhinitis of case, is divided at random treatment group and matched group.(1) treatment group: adopt the present invention fill a prescription Caulis et folium pavettae hongkongensis 15g, Herba Centipedae 10g, Radix Codonopsis 15g, Serissa foetida 20g, Herba Polygoni cymosi 20g, Flos Chrysanthemi Indici 10g, Radix Angelicae Dahuricae 10g, decoct water for oral administration, 1 day 1 dose, point take for 3 times.30 doses of continuous uses were 1 course for the treatment of, can be used in conjunction if desired for 2～3 courses for the treatment of.(2) matched group: sinusitis capsule group; Ingredients: Fructus Xanthii, Flos Magnoliae, Flos Lonicerae, Flos Chrysanthemi Indici, Radix Rubiae.Specification: every dress 0.5g; Usage: oral, one time 2～3,3 times on the one; Surrounding was 1 course for the treatment of.
5, therapeutic outcome:
(1) two group of Clinical efficacy comparison
Table 3 Clinical efficacy comparison
(2) two groups of main clinic symptoms and the comparative analysis of sign curative effect
The curative effect comparison of table 4 cardinal symptom
The comparison of (3) two groups of different disease curative effects:
The table 5 liang different disease curative effect of group comparison
(4) untoward reaction: two groups of patients are showed no untoward reaction and toxic and side effects at period in a medicine.Illustrate that formula of the present invention is safe and effective to treatment rhinitis, sinusitis.
6, conclusion
1, formula of the present invention is 95.8% to treatment chronic rhinitis, sinusitis total effective rate, and obvious effective rate is 46.6%.Matched group is respectively 88.0% and 32.0%, and curative effect is better than sinusitis capsule.
2, to improving, nasal sinusitis main clinic symptoms nasal obstruction is obstructed, the curative effect of turbid nasal discharge, headache feeling of fullness in the head, hyposmia, reddening and swelling of mucosa etc. is good for formula of the present invention, and curative effect is better than sinusitis capsule.
3, formula of the present invention is respectively different disease curative effects: allergic rhinitis 88.5%, chronic rhinitis 98.1%, sinusitis 97.6%; Matched group proportion by subtraction is 72.2%, 90.9%, 92.1%, and curative effect is better than sinusitis capsule.
4, period in a medicine, has no untoward reaction and toxic and side effects.Illustrate that formula of the present invention is safe and effective to treatment rhinitis, sinusitis.
two, Pharmacodynamic test and prescription compatibility of medicines research
1, experiment material
1.1 laboratory animals: Kunming mouse, clean level, body weight 18-22g, is provided by Chongqing Chinese medicine research institute Experimental Animal Center, the quality certification number: SCXK(Chongqing) 20020014.
1.2 medicines and reagent: be subject to reagent: No. 2, No. 1, preparation rhinitis of the present invention and rhinitis, for the section's Pharmaceutical research and development of Kweiyang spring, company limited provides, specification: each 2 bags × 100g, clinical usage and consumption: 3 times on the one, 0.8g/ time (being equivalent to primary crude drug 8g), facing the used time, to be made into suspension with distilled water for subsequent use.Dimethylbenzene is Chongqing chemical reagent factory product, lot number: 20060104.
1.3 experiment equipments: BS110S precise electronic balance (Beijing Sai Duolisi joint-stock company), SHA-C temperature controlled water bath oscillator (all over the country industrial corporation in Shenzhen), timer (Kweiyang Heng Yin biotech firm).
2, method and result
2.1 In vitro Bactericidal Experiments
2.1.1 method adopts In vitro Bactericidal Experiments, mensuration is subject to reagent to staphylococcus aureus, the lowest concentration of antimicrobial (minimal inhibitory concentration, MIC) of bacillus pyocyaneus, escherichia coli, beta hemolytic streptococcus, streptococcus pneumoniae, Bacillus proteus.(1) select different culture media according to different strain.(2) preparation of the present invention is diluted to the culture medium of making different pharmaceutical concentration.(3) quantitatively the different test organisms of inoculation is cultivated respectively, can suppress the MIC of this bacteria growing in Observe and measure pipe.
2.1.2 result extracorporeal bacteria inhibitor test shows, preparation rhinitis of the present invention has significant bacteriostasis at low concentration (0.2g/ml-0.6g/ml) to Bacillus proteus and staphylococcus aureus No. 2 at low concentration (0.1g/ml-0.2g/ml) and formula No. 1, but formula is better than filling a prescription for No. 2 No. 1.
The bacteriostasis of table 6 preparation of the present invention
The impact of 2.2 xylol induced mice ear swellings
2.2.1 method is got 80 of mices, and body weight is 20～22g, is divided at random 8 groups, 10 every group, is respectively blank group, No. 1, preparation rhinitis of the present invention and No. 2 (low dosage, middle dosage, high dose) groups of rhinitis, positive drug group.Gavage gives normal saline, variable concentrations is subject to reagent preparation of the present invention (0.4g/kg, 0.8g/kg, 1.6g/kg) and positive drug (aspirin: 0.2g/kg), administration volume 10ml/kg, successive administration 5d, once a day, after last administration 1h, two sides before and after animal auris dextra is only coated with to dimethylbenzene 0.02ml/, left ear is left intact.After 4h, disconnected animal vertebra is put to death, cut ears, lay round auricle respectively with 9mm diameter card punch at same position, precise electronic balance is weighed, and it is swelling degree that every Mus auris dextra weight deducts left ear weight, and presses formula and calculate inhibitory rate of intumesce.Result of the test represents with meansigma methods standard deviation, result employing t inspection, p<0.05 shows to have significance.
2.2.2 result table 7 result shows, with matched group comparison, No. 1, pharmaceutical formulation of the present invention and No. 2 high dose group xylol of formula cause mice ear all obvious inhibitory action, and swelling obviously reduces, and suppression ratio is respectively 49.0%, 61.0%( p<0.05); No. 1, pharmaceutical formulation of the present invention and No. 2 low dosages of formula, middle dosage group xylol causes mice ear all certain inhibitory action trend, but with relatively obviously significant difference of nothing of matched group, between different formulations, its formula is approximately better than for No. 2 filling a prescription No. 1, but without obvious significant difference.
Table 7 preparation xylol of the present invention causes the impact of mice ear
The impact of 2.3 analgesic experiments-on mouse writhing reaction
2.3.1 method is got 80 of mices, and body weight is 20～22g, is divided at random 8 groups, 10 every group, is respectively blank group, No. 1, preparation rhinitis of the present invention and No. 2 (low dosage, middle dosage, high dose) groups of rhinitis, positive drug group.Gavage gives normal saline, variable concentrations is subject to reagent preparation of the present invention (0.4g/kg, 0.8g/kg, 1.6g/kg) and positive drug (morphine: 0.01g/kg), administration volume 10ml/kg, after administration, 1 hour each treated animal is pressed 0.1ml/10g body weight lumbar injection 0.9% glacial acetic acid.After injection, observe immediately the writhing number of times of each animal in 15 minutes.
2.2.2 result table 8 result shows, with matched group comparison, No. 1, pharmaceutical formulation of the present invention and formula 2 high dose group Dichlorodiphenyl Acetates cause writhing number of times obvious inhibitory action, and suppression ratio is respectively 55.8%, 67.4%( p<0.05); Between different formulations, its formula is approximately better than for No. 2 filling a prescription No. 1.
The impact of table 8 preparation of the present invention on mouse writhing reaction
3, conclusion
3.1 preparations of the present invention are in vitro in antibacterial experiment, to upper respiratory tract infection common pathogen: staphylococcus aureus, bacillus pyocyaneus, escherichia coli, beta hemolytic streptococcus, lung streptococcus, Bacillus proteus have antibacterial action, point out preparation of the present invention to produce preventive and therapeutic effect to upper respiratory tract infection due to above-mentioned pathogenic bacterium.
3.2 preparation 1.6g/kg xylol induced mice auricle edemas of the present invention produce obvious inhibitory action, point out this medicine to have the acute inflammation of inhibition transudation.
3.3 No. 2, pharmaceutical formulations of the present invention (Caulis et folium pavettae hongkongensis 15%, Herba Centipedae 10%, Radix Codonopsis 15%, Serissa foetida 20%, Herba Polygoni cymosi 20%, Flos Chrysanthemi Indici 10%, the Radix Angelicae Dahuricae 10%) be approximately better than filling a prescription in different tests No. 1 (Caulis et folium pavettae hongkongensis 20%, Herba Centipedae 13.3%, Serissa foetida 26.7%, Herba Polygoni cymosi 26.7%, the Radix Angelicae Dahuricae 13.3%).Point out pharmaceutical formulation of the present invention No. 2 nephritis to be had to better preventive and therapeutic effect.
two, preparation process thereof research
1, preparation technology
1.1 prescriptioncaulis et folium pavettae hongkongensis 300g, Herba Centipedae 200g, Radix Codonopsis 300g, Serissa foetida 400g, Herba Polygoni cymosi 400g, Flos Chrysanthemi Indici 200g, Radix Angelicae Dahuricae 200g.
1.2 preparation technologyabove seven flavor medicine material amount, decocts with water twice, adds water 10 times at every turn, decocts 3 hours at every turn, filters merging filtrate, being evaporated to relative density is 1.25～1.35(60 DEG C) extractum, add right amount of auxiliary materials, mix, granulate, dry, mix, tabletting, coating, makes 1000, to obtain final product.
1.3 technological process
2, Study on Preparation
2.1 process routes are determinedthis product prescription is made up of Caulis et folium pavettae hongkongensis 15g, Herba Centipedae 10g, Radix Codonopsis 15g, Radix Serissae 20g, Herba Lespedezae Cuneatae 20g, Flos Chrysanthemi Indici 10g, Radix Angelicae Dahuricae 10g seven flavor medicine, takes to decoct soup.The determining of process route should on the basis of respecting original prescription clinical usage, take into full account prescription in the character of each medical material.In this project prescription, the character of each medical material is as follows:
1. Caulis et folium pavettae hongkongensis nature and flavor: lightly seasoned micro-hardship, property is flat.Function cures mainly: clearing away heat to improve acuity of vision, move back nebula, detumescence.Control corneal leukoma, conjunctival congestion and swelling pain.Chemical composition: containing campesterol, stigmasterol, cupreol, cyclolaudenol, the nor-cyclolaudenol of 31-.
2. Herba Centipedae meridian distribution of property and flavor: pungent, temperature.Effect: dispel the wind, cold expelling, victory is wet, removing nebula, stuffy nose relieving plug.Cure mainly: flu, asthma of cold-type, sore throat, pertussis, nasal sinusitis, the flat meat of nose.Effective ingredient: containing multiple Triterpenoid, taraxerol, taraxasterol, arnidiol and another kind of three unknown terpinums, still contain stigmasterol, sitosterol, flavonoid, volatile oil, organic acid etc. in herb.
3. Radix Codonopsis meridian distribution of property and flavor: property is flat, sweet in the mouth, micro-acid.Return spleen, lung meridian.Function cures mainly: invigorating the spleen and replenishing QI, spleen invigorating lung benefiting.For deficiency of the spleen and lung, the cardiopalmus of breathing hard, anorexia and loose stool, dyspnea due to deficiency cough, interior-heat is quenched one's thirst.Effective ingredient: Radix Codonopsis is containing triterpenoid compound freidelin, alnulin acetas, bessisterol and glycoside, △ 7-stigmastenol and glycoside thereof, spinach sterone.Another containing atractyloide III, atractyloide II, syringic aldehyde, and nicotinic acid, 4 kinds of heteropolysaccharide and monosaccharide etc.In addition, still, containing a small amount of volatile oil, identify 32 kinds of compositions in oil, wherein 11 of acid ingredients, account for 50% of volatile oil total amount, and taking Palmic acid as main; Another containing Alkaloid, vitamin B2 and a large amount of inulin.
4. Serissa foetida nature and flavor: toil; Cool; Nontoxic.Gui Jing: liver, spleen channel.Function cures mainly: dispel the wind; Dampness removing; Heat clearing away; Removing toxic substances.Main flu; Icterohepatitis; Oedema due to nephritis; Cough; Laryngalgia; Keratitis; Acute toothache.Chemical analysis: Radix Serissae herb is containing glycoside and tannin.Radix Serissae contains phenoloid, organic acid, sterol and triterpene.Herb is containing ursolic acid and cupreol.
5. Herba Polygoni cymosi meridian distribution of property and flavor: property is cold, sour in the mouth.Enter hot warp.Effect: heat-clearing and toxic substances removing, inducing diuresis to remove edema.Chemical analysis: herb is containing indigo glycoside, flavonoid glycoside, anthracene glycoside, cardiotonic glycoside, phenols.Cure mainly: cough, Serpentis string pellet, venom.
6. Flos Chrysanthemi Indici meridian distribution of property and flavor: be slightly cold, bitter in the mouth, pungent.Return lung, Liver Channel.Function cures mainly: heat-clearing and toxic substances removing; Dispelling wind suppressing the hyperactive liver; Carbuncle; Erysipelas; Eczema; Dermatitis; Anemopyretic cold; Laryngopharynx swelling and pain, treatment respiratory inflammation etc.Chemical composition: containing volatile oil, containing alantol, chrysanthanone, australene, Camphora, Borneolum Syntheticum, lauro lene etc., still contain yejuhua lactone, artoglasin A, acaciin, linarin, chrysanthemum glycoside, luteolin in oil.
7. Radix Angelicae Dahuricae meridian distribution of property and flavor: warm in nature, acrid in the mouth.Enter lung, spleen, stomach warp.Function cures mainly: wind-damp dispelling, the evacuation of pus of invigorating blood circulation, granulation promoting pain relieving.For headache, toothache, nasal sinusitis, ulcer sores, skin pruritus.
In sum, in conjunction with the character feature of each medical material in prescription, this preparation determines to adopt water extraction, and the existing report the test of being tested is as follows.
2.2 decocting process researchs
(1) factor level is establishedthe factor that impact decocts mainly contains the following aspects: amount of water, decocting time, decoction number of times etc.Therefore we have carried out the orthogonal investigation of 3 factor 3 levels to these three principal elements, with preferred optimal processing parameter.The factor level table of orthogonal test is in table 9:
Table 9 decocts orthogonal test factor level table
(2) index is selectedin we, multi-flavor medicine contains flavone compound, modern study shows, chromocor compound is to cardiac-cerebral ischemia damage, hepatic injury, ARR protective effect and analgesia thereof, and therefore free radical resisting and antitumor etc. act on, using its extracted amount as orthogonal test evaluation index; Prescription Chinese crude drug also contains the fat-soluble active ingredients such as alkaloid, and in order fully to reflect extraction effect, we measure the content of 60% ethanol soluble extraction in extract, and also make orthogonal test evaluation index with it; In addition, dry cream yield is also the conventional index of evaluating extraction effect, and it directly affects the regulation that day takes dosage and single oral dose, therefore also using it as one of orthogonal test evaluation index.It is preferred that this test intended adopts comprehensive scoring method to carry out process conditions, due to dry cream yield and effect amount not proportional, specify that its balance is divided into 30 points; 60% ethanol soluble extraction balance is divided into 30 points; Effective ingredient in the total flavones side of being, can directly reflect extraction effect, is 40 points therefore specify that the balance of this index divides.
(3) sample preparationget 1 recipe quantity medical material, amount to 100g, carry out water extraction by the each orthogonal test condition of table 9, medicinal liquid, with after 300 order filter-cloth filterings, concentrates and is settled to 100ml.For subsequent use.
(4) dry cream yield is measuredprecision is got the medicinal liquid 25ml of each orthogonal test after concentrated, put respectively in the evaporating dish that has been dried to constant weight, water bath method, residue in 105 DEG C dry 3 hours, take out, put in exsiccator and place 30 minutes, weigh, calculate dry cream yield.
(5) 60% ethanol soluble extractions are measuredprecision is got the medicinal liquid 50ml after each orthogonal test concentrates, and adds respectively ethanol and makes to reach 60% containing alcohol amount, leaves standstill cold preservation 24 hours, filters, filtrate water bath method, residue is dried 3 hours, taking-up in 105 DEG C, be placed in exsiccator and place 30 minutes, weigh, calculate extractum yield.
(6) Determination of Total Flavonoids
total flavonesthe preparation of reference substance solution: precision takes 120 DEG C of control substance of Rutin that are dried to constant weight appropriate, puts in 25ml measuring bottle, adds methanol appropriate, puts slight fever in water-bath and makes to dissolve, and lets cool, and adds methanol to scale, shakes up; Precision measures 10ml, puts in 100ml measuring bottle, adds water to scale, shakes up, and makes the solution containing rutin 0.20192 mg in every lml, obtains reference substance solution;
Standard curve preparation: precision measures reference substance solution 1ml, 2ml, 3ml, 4ml, 5ml, 6ml, put respectively in 25ml measuring bottle, respectively add water to 6.0ml, add 5% sodium nitrite solution 1ml, shake up, place 6 minutes, add 10% aluminum nitrate solution 1ml, place 6 minutes, hydro-oxidation sodium test solution 10ml, then add water to scale, shake up, place 15 minutes, taking corresponding reagent as blank; According to ultraviolet visible spectrophotometry, measure absorbance at 510nm wavelength place, taking absorbance as vertical coordinate, concentration is abscissa, drawing standard curve;
The preparation of need testing solution: get this product under content uniformity item, mix, get 0.2g, accurately weighed, put in tool plug conical flask, precision adds 70% ethanol 25ml, weigh, ultrasonic 10min, places room temperature, supply less loss weight with 70% ethanol, filter, accurate absorption in subsequent filtrate 1ml to 25ml volumetric flask, adds water to 5ml, method under sighting target directrix curve preparation, from " adding water to 6.0ml ", make need testing solution with method operation, measure absorbance in accordance with the law, read the weight containing anhydrous rutin in need testing solution from standard curve, calculate, to obtain final product.Orthogonal experiments and interpretation of result are in table 10, table 11.
Table 10 decocts orthogonal experiments table
Note: dry cream yield scoring=(dry cream yield/maximum dry cream yield) × 30
60% ethanol soluble extraction scoring=(extractum yield/maximum extractum yield) × 30
Total flavones extracted amount scoring=(puerarin extracted amount/maximum puerarin extracted amount) × 40
Comprehensive grading=dry cream yield scoring+60% ethanol soluble extraction scoring+puerarin taken amount scoring
Table 11 decocts analysis of variance table
Note: F 0.05(2,2)=19.00; F 0.01(2,2)=99.00
From table 10,11 analysis results, each factor effect primary and secondary is A > B > C; A, B, C factor all have significant difference, A in A factor 3> A 2> A 1so, select A 3; B in B factor 3> B 1> B 2so, select B 3; C in C factor 2> C 3> C 1so, select C 2.Therefore optimised process is A 3b 3c 2.Add 10 times of water gagings, decoct 3 hours at every turn, decoct twice.
2.3 best decocting process checkingsbecause preferred optimised process is not included in 9 tests of orthogonal array, therefore it is verified.Get orthogonal test with a collection of medical material, by A 3b 3c 2test, verify altogether 3 batches, the result is in table 12:
Table 12 decocts optimised process the result
The result shows, this technique extractum yield, 60% ethanol soluble extraction content and total flavones extracted amount are all more stable, can be used as the optimised process of extraction.
2.4 concentration technologies are investigatedthe method for concentration that workshop is conventional has normal pressure to concentrate and concentrating under reduced pressure.Concentrating under reduced pressure have consuming time less, feature that thickening temperature is low, therefore heat-sensitive ingredients is destroyed littlely, along with improving constantly of pharmaceutical equipment manufacturing technology, present Chinese medicine workshop is more, and to adopt concentrating under reduced pressure be main.For with produce actual combining closely, the concentrated mode of this product adopts concentrating under reduced pressure method.
Get 2 times of recipe quantity medical materials, extract decoction liquor concentrating under reduced pressure (0.06～-0.08 Mpa by best decocting process, 80 DEG C), to thick extractum, record now extractum relative density and be about 1.25(60 DEG C), extractum got appropriate, the same method is measured wherein general flavone content, and result of the test is in table 13.
Determination of total flavonoids result in table 13 concentrated extract
Result of the test shows: adopt pressure reducing mode to concentrate this product extracting solution, in prescription, general flavone content is stable, and illustration method is feasible.
2.5 drying processwe adopt respectively normal pressure and two kinds of modes of drying under reduced pressure to investigate drying process: the thick extractum during concentration technology is investigated mixes, be divided into 3 parts, be dried by table 14 conditional respectively, taking the content of puerarin in gained extract powder, color and luster, drying time as investigating object, with this, drying mode is carried out preferably, the results are shown in Table 14.
The different drying mode investigation tables of table 14
Upper watch test result shows, drying mode and drying condition have no significant effect general flavone content, but constant pressure and dry extractum color and luster is dark, required time is long, by contrast, adopt reduce pressure 70 DEG C be that Drying Technology Parameter is more suitable.
2.6. preparation prescription research
(1) character of extract powderthis product extract powder is the pitchy powder being prepared into after drying under reduced pressure, in order to grasp the character of extract powder, is convenient to preparation research, and we have measured moisture absorption percentage rate and the mobility of extract powder.
(2) moisture absorption percentage rate is measuredget proper amount of dry extractum, pulverize, cross 80 mesh sieves, put P2O5 exsiccator inner drying 48 hours, the glass exsiccator that simultaneously bottom is filled to NaCl supersaturated solution is put into the calorstat 24 hours of 25 DEG C, and its internal relative humidity (RH) is 75%.In the weighing botle of dry constant weight, add appropriate extract powder, the about 2mm of thickness, precise weighing is placed in above-mentioned glass exsiccator, opens weighing bottle cap; Timing weighs, and is calculated as follows moisture absorption percentage rate:
Table 15 extract powder moisture absorption percentage rate measurement result table
(3) measure angle of reposeadopt fixed funnel method to measure extract powder (80 order) angle of repose: 3 funnels are connected and be fixed on height suitable on the graph paper of horizontal positioned (3cm), carefully extract powder is poured in uppermost funnel along hopper walls, until the extract powder apex partis petrosae termination forming on graph paper contacts bottom bell mouth, measure conical base diameter, be calculated as follows out a angle of repose:
Table 16 extract powder measurement result angle of repose
Extract powder moisture absorption percentage rate and angle of repose measurement result show, extract powder moisture resistance is poor, mobility is bad, is unsuitable for direct granulation, should add appropriate amount of auxiliary materials adjustment.
2.7 adjuvant screenings
2.7.1 supplementary product kind screeningthe kind of adjuvant directly determines hygroscopicity and the mobility of granule.The adjuvant that is commonly used to improve granule hygroscopicity and mobility has lactose, starch and dextrin etc.Get respectively above-mentioned 3 kinds of adjuvants by table 17 and add in extract powder, mix, with 75% ethanol soft material processed, cross 10 order granulations, 65 DEG C of dry 15min, cross after 10 mesh sieve granulate, drier in 65 DEG C.Press preceding method and measure moisture absorption percentage rate and the angle of repose of granule.The results are shown in Table 17,18.
Table 17 different auxiliary material and extract powder compatibility table
Table 18 different auxiliary material makes the index checking of granule
Table 19 different auxiliary material proportioning makes the moisture absorption percentage rate of granule
As seen from table, after different auxiliary material is mixed in varing proportions with dried cream powder, 3 groups of sample hydroscopicity orders are 1 > 3 > 2.The wherein hydroscopicity minimum (60h) of No. 2 prescriptions (alone starch), good fluidity; No. 3 micro-tides of prescription (alone dextrin) granule.Consider No. 2 prescriptions of lower selection.
2.7.2 supplementary product consumption screeningthe consumption of adjuvant should meet under the prerequisite that preparation requires, and reduce consumption is principle as far as possible.Get respectively starch by table 20 and add in extract powder, after granulating by preceding method, measure moisture absorption percentage rate and the angle of repose of granule.The results are shown in Table 20,21.
Table 20 supplementary product consumption compatibility table
The moisture absorption percentage rate of table 21 different auxiliary material consumption granule
The angle of repose of the different starch consumption of table 22 granule
Above-mentioned result of the test shows, add adjuvant amount more, anti-wettability power and the mobility of granule are better, and wherein every 20g extractum adds adjuvant 10g and adds 12g effect suitable, in order to save production cost, we select every 20g extract powder to add adjuvant 10g is supplementary product consumption parameter.
2.8 preparations shaping technical studies
(1) granulation concentration of alcohol is selectedget extract powder 20g, add starch 10g, mix, use respectively 60%, 80%, 95% alcohol granulation, investigate the quality of granulating and being difficult to degree and making granule, the results are shown in Table 23.
Table 23 different concentration ethanol granulation information slip
Experimental result shows, makes granular mass the best with 80% ethanol, and therefore, selecting 80% ethanol is this product granulation solvent.
(2) tablettingsticking not when improving the mobility of granule and tabletting, in granule, need to add a certain amount of lubricant, and magnesium stearate is the most frequently used, research data shows, when tabletting, add 0.3%～1.0% magnesium stearate to have good lubricant effect, taking mobility of particle, the hard-hearted degree of sheet, sheet cardiolysis time and tabletting situation as index, the concrete consumption of magnesium stearate is carried out preferably, the results are shown in Table 24.
Table 24 magnesium stearate consumption is investigated result table
As seen from the experiment, add 0.5% magnesium stearate can meet tablet forming technique requirement in granule, therefore selecting 0.5% magnesium stearate is lubricant addition.From front test, in this prescription, be total to 100g medical material water extraction, receiving cream rate is 10%, every side receives cream 10g; In pelletization, every prescription adds starch 5g; Full side makes granule and amounts to 15g.Therefore, add magnesium stearate amount to be: 0.075g.
(3) coatingget the sheet heart, film coating, last polishing, dry, it is satisfactory for result that result makes Film coated tablets, and color and luster is even, and without be full of cracks and dew limit, disintegrate is rapid.In table 25.
Table 25 coating is investigated result table
2.9 preparation prescriptions and the amount of making are determinedthe laws and regulations requirement of declaring by new drug, new drug prescription must, by 1000 preparation unit's statements, be about 10% according to 3 batches of dry cream yields of pilot scale and calculate, and this product preparation prescription calculates that process is as follows:
(1) each taste dose in preparation prescriptionoriginal prescription ratio is :caulis et folium pavettae hongkongensis 15%, Herba Centipedae 10%, Radix Codonopsis 15%, Radix Serissae 20%, Herba Lespedezae Cuneatae 20%, Flos Chrysanthemi Indici 10%, the Radix Angelicae Dahuricae 10%, calculating each medical material amount in this product preparation prescription in this ratio is: Caulis et folium pavettae hongkongensis 300g, Herba Centipedae 200g, Radix Codonopsis 300g, Serissa foetida 400g, Herba Polygoni cymosi 400g, Flos Chrysanthemi Indici 200g, Radix Angelicae Dahuricae 200g, preparation prescription is 2000g containing crude drug total amount.
(2) every contains crude drug total amountevery containing crude drug total amount=crude drug total amount ÷ preparation unit.That is: every contains crude drug total amount=2000g ÷ 1000=2.0g
(3) in preparation process, add adjuvant amount
1. every prescription dry extract receipts amountpreparation prescription is 2000g containing crude drug total amount, if be about 10% calculating according to dry cream yield, every prescription dry extract receipts amount is: every prescription dry extract receipts amount=prescription is containing crude drug total amount × dry cream yield.That is: every prescription dry extract receipts amount=2000g × 10%=200g
2. starch Determination of quantityfrom front test, in this product preparation process, dry extract is 20: 10 with adding the ratio of starch, calculates thus starch consumption and is: dry cream receipts amount × 10 ÷ 20 of every prescription starch consumption=every prescription.That is: starch consumption=200g × 10 ÷ 20=100g
3. magnesium stearate Determination of quantityfrom front test, in this product preparation process, magnesium stearate consumption is: every prescription magnesium stearate consumption=(the dry cream receipts of every prescription amount+every prescription starch consumption) × 0.5%.That is: magnesium stearate consumption=(200+100) × 0.5%=1.5g
Every prescription amount of making is dry extract receipts amount, 0.5% magnesium stearate and starch consumption sum, by 1., 2., 3.known, this product makes content 301.5g.Consider that medical material collecting season is different with the place of production, and the impact of production technology, dry extract receipts amount can slightly fluctuate, and we are described as starch consumption: add starch appropriate, making the amount of making is 300g.
2.10 finished product loading amounts are determinedfinished product loading amount =the amount of the making ÷ amount of making.That is: finished product sheet weight =1000=0.3g/ of 300g ÷ sheet.
2.11 pilot scale researchget 20 times of recipe quantity medical materials, by work out to such an extent that process route carries out middle trial production, production technology index is carried out to comprehensive assessment, medical material and finished product are carried out to performance rating, the results are shown in Table 26.
Table 26 pilot plant test result
Pilot plant test result of study shows, the every technical parameter of product of the present invention is stable, and feasible process be described, is applicable to producing in batches.
four, pharmacodynamics test research
1, summary
1.1 objects: antiinflammatory, antiallergic, analgesia and the bacteriostasis of research preparation of the present invention.
1.2 methods: adopt the swollen model of rat granuloma, dimethylbenzene induced mice auricle edema and acetic acid to bring out the hyperfunction model of capillary permeability and observe its antiinflammatory action; Set up models of passive skin irritability of rats model, observe its anti-allergic effects; By hot plate method in mice and writhing method experiment, observe its analgesic activity; Adopt antibacterial flat band method, observe its bacteriostasis.
1.3 results: the acute inflammatory reactions such as preparation of the present invention is swollen to chronic inflammatory disease rat granuloma, dimethylbenzene induced mice auricle edema and acetic acid induced mice capillary permeability increase have significant antiinflammatory action; To models of passive skin irritability of rats, reaction has significant inhibitory action; Hot plate method and writhing method analgesic experiment have all shown significant analgesic activity; Extracorporeal bacteria inhibitor test shows, preparation of the present invention is to staphylococcus aureus, and bacillus pyocyaneus, escherichia coli, beta hemolytic streptococcus, streptococcus pneumoniae, Bacillus proteus all have certain bacteriostasis.
1.4 conclusions: preparation of the present invention has antiinflammatory, analgesia, antiallergic and certain bacteriostasis.Effects such as this is preparation heat-clearing and toxic substances removing of the present invention, and lung benefiting is sensible and to be applied to treatment nasal obstruction obstructed, nasal sinusitis watery nasal discharge etc. and chronic rhinitis, chronic sinusitis, allergic rhinitis is shown in that above-mentioned disease provides pharmacological experiment foundation.
2, experiment material
2.1 laboratory animals: Kunming mouse, clean level, body weight 18-22g, rat, body weight 180-220g, is provided by Chongqing Chinese medicine research institute Experimental Animal Center.
2.2 experimental strains: staphylococcus aureus (CMCC26003), bacillus pyocyaneus (CMCC38002), escherichia coli (CMCC44185), beta hemolytic streptococcus (CMCC23220), streptococcus pneumoniae (CMCC54610), Bacillus proteus (CMCC6380).
2.3 medicines and reagent: be subject to reagent: preparation of the present invention (nose Shu Kang) semi-finished product, for the section's Pharmaceutical research and development of Kweiyang spring, company limited provides, specification: 5kg/ bag (totally 2 bags); Character: powdery, clinical usage and consumption: 3 times on the one, 1.2g/ time, facing the used time, to be made into suspension with distilled water for subsequent use; Positive control drug: aspirin tablet, Guilin Pharmaceutical Co., Ltd., the accurate word H45020572 of traditional Chinese medicines, specification: 0.3g.Usage: oral.A 0.3g～0.6g, 3 times on the one, if desired can every 4 hours once.Rotundine sulfate injection, Guizhou light positive Pharmaceutical Co, the accurate word H52020803 of traditional Chinese medicines, specification: 2ml:60mg.Ampicillin Sodium For Injection, HARBIN PHARMACEUTICAL GROUP CO., LTD. General Pharm. Factory, the accurate word H20023720 of traditional Chinese medicines.Specification: 2g.Positive control Chinese medicine: sinusitis capsule, Fuzhou Jinxiang Chinese Medicine Pharmaceutical Co., Ltd., the accurate word Z20025081 of traditional Chinese medicines, every of specification dress 0.5g, usage: oral, one time 2～3,3 times on the one.Dimethylbenzene, acetic acid are Chongqing chemical reagent factory product.
2.4 experiment equipments: BS110S precise electronic balance (Beijing Sai Duolisi joint-stock company), SHA-C temperature controlled water bath oscillator (all over the country industrial corporation in Shenzhen), timer (Kweiyang Heng Yin biotech firm).Visible ultraviolet spectrophotometer (Beijing Pu Xi General Corporation), biochemical cultivation case etc.
3, test method and result
3.1 antiinflammatory experiments
3.1.1 on the swollen impact experiment of rat granuloma
(1) method: get 60 of SD rats, 180～220g, male and female half and half, divide equally at random 6 groups, every group 10, blank group (normal saline group), preparation nose Shu Kang high dose of the present invention (1.44g/kg), middle dosage (0.72g/kg), low dose group (0.36g/kg), positive controls aspirin (0.2g/kg), sinusitis capsule group ((1.8g/kg).When experiment, rat is sucked to etherization, at the left and right of every rat axillary region iodine tincture disinfection, after the de-iodine of 75% cotton ball soaked in alcohol, each long osculum of 1cm that cuts, with ophthalmic tweezers, the autoclaving cotton balls of 30mg (each cotton balls adds ampicillin 10mg/mL, 50 DEG C of oven dry) is subcutaneous from incision implantation, skin suture subsequently.Started administration the same day from operation, 1 times/day, 7d, opens former otch on the 8th day continuously, and cotton balls is taken out together with connective tissue around, rejects fatty tissue, and 70 DEG C of oven dry, weigh quality.By claim weight deduct the former weight of cotton balls, be granuloma weight.
(2) experimental result: shown in table 27, with the comparison of blank group, the high, medium and low dosage of preparation nose Shu Kang of the present invention all can reduce rat granuloma quality (P < 0.01), show good antiphlogistic effects, wherein the antiphlogistic effects of preparation nose Shu Kang high dose of the present invention approaches positive control aspirin, and sinusitis capsule also has same function.
Table 27 preparation of the present invention is on the swollen impact of rat granuloma
3.1.2 the impact of xylol induced mice auricle edema experiment
(1) method: get 60 of NIH mices, divide equally at random 6 groups, every group 10, blank group (normal saline group), preparation nose Shu Kang high dose of the present invention (2.4g/kg), middle dosage (1.2g/kg), low dose group (0.6g/kg), positive controls aspirin (0.3g/kg), sinusitis capsule group ((3.0g/kg).Each experimental mice gastric infusion every day 1 time, blank group is to isometric(al) normal saline, continuous 3 times, 1h after last administration, respectively organizes mouse right ear and is only coated with dimethylbenzene 0.05mL/, left ear compares, after 15min, put to death mice, cut two ears along auricle baseline, lay the same position of ears disk with the card punch of diameter 7mm, precision weighing quality, is calculated as follows auris dextra swelling rate respectively.
(2) result: result is shown in table 28, the high, medium and low dosage of preparation nose Shu Kang of the present invention and positive control drug all can significantly suppress dimethylbenzene induced mice auricle edema rate, relatively there is statistical significance (P < 0.01) with blank group, prompting nose Shu Kang has good antiphlogistic effects, wherein the effect of preparation nose Shu Kang high dose inhibition swelling of the present invention approaches aspirin, and sinusitis capsule also has same function.
The impact of table 28 preparation xylol of the present invention induced mice auricle edema
3.1.3 the impact experiment on mice capillary permeability
(1) method: get 60 of NIH mices, divide equally at random 6 groups, every group 10, blank group (normal saline group), preparation nose Shu Kang high dose of the present invention (2.4g/kg), middle dosage (1.2g/kg), low dose group (0.6g/kg), positive controls aspirin (0.3g/kg), sinusitis capsule group (3.0g/kg).Each experimental mice gastric infusion every day 1 time, blank group gavage isometric(al) normal saline, 3d continuously, after last administration 1h, give respectively mouse tail vein injection 0.5% azovan blue normal saline solution 10mL/kg, lumbar injection 0.6% acetic acid (is got glacial acetic acid 0.30mL immediately, being dissolved in normal saline 50 mL) 0.20 mL/ is only, after 20 min, put to death, cut off skin of abdomen muscle, divide and wash abdominal cavity for several times with 6mL normal saline, sucking-off cleaning mixture, add normal saline to 10 mL, centrifugal 15 min, get supernatant spectrophotometer and measure its trap Uv value in wavelength 590nm place.
(3) result: result is shown in table 29, with the comparison of blank group, the high, medium and low dosage of preparation nose Shu Kang of the present invention can significantly reduce acetic acid induced mice abdominal cavity capillary permeability rising (P<0.01), point out the good antiphlogistic effects of preparation nose Shu Kang of the present invention, sinusitis capsule also has same function.
The impact of table 29 on mouse peritoneal capillary permeability
3.2 antiallergic experiments
3.2.1 the preparation of ovaserum: get 4 of SD rats, with 5% Ovum Gallus domesticus album normal saline solution 0.10 mL, intramuscular injection back leg both sides, lumbar injection pertussis vaccine 0.2mL/ only, after 14d, takes a blood sample simultaneously, and separation of serum is for subsequent use.
3.2.2 passive sensitization of skin: get 60 of SD rats, male and female half and half, are divided into 6 groups at random, 10 every group.In the cropping of dorsal line both sides, every side 2 points, interval 1.5～2cm.Get above-mentioned antiserum, 5(1) and 1 become 1 with normal saline dilution:: 10(2), intradermal injection is in the each point of cropping successively, gastric infusion or normal saline simultaneously, 1 times/day, 3d continuously, 1h after last administration (pressing table 30 dosage), after sensitization, 48h carries out antigen attack, tail vein injects 5% Ovum Gallus domesticus album and 0.5% azovan blue normal saline solution 10mL/kg, after 30min, put to death animal, upset skin of back, measures blue reaction spot diameter.
3.2.3 result: result is shown in table 30, with the comparison of blank group, to models of passive skin irritability of rats, reaction all has significant inhibitory action (P < 0.01) to the high, medium and low dosage of preparation nose Shu Kang of the present invention, points out preparation nose Shu Kang of the present invention to have good antiallergic effect.
Table 30 is on the anaphylactoid impact of rat skin
3.3 analgesic experiment
3.3.1 writhing experiment
(1) method: get 60 of mices, be divided at random 6 groups, every group 10, blank group (normal saline group), preparation nose Shu Kang high dose of the present invention (2.4g/kg), middle dosage (1.2g/kg), low dose group (0.6g/kg), positive controls aspirin (0.3g/kg), sinusitis capsule group (3.0g/kg).Each experimental mice gastric infusion every day 1 time, blank group gavage isometric(al) normal saline, continuous 3 times, 1h after last administration, each Mus lumbar injection 0.6% acetic acid 0.2mL/ only, observes the writhing number of times that in 15min, each Mus occurs, and calculates the analgesia percentage rate of each medicine.
(2) result is shown in table 31, the mouse writhing reaction that the high, medium and low dosage group of preparation nose Shu Kang of the present invention Dichlorodiphenyl Acetate causes all has significant inhibitory action, relatively there is statistical significance (P < 0.01) with blank group, show that nose preparation of the present invention has certain analgesic activity.
Table 31 Dichlorodiphenyl Acetate stimulates the impact that causes mouse writhing reaction
3.3.2 hot-plate
(1) method: the temperature of regulating thermostatic water-bath is in (55 ± 0.5) DEG C, by hot plate preheating 10 min.Get 18～22g female mice, each 1 is placed on hot plate, mice on being placed on hot plate to occurring licking the pain threshold of metapedes required time (s) as this Mus.Allly lick the metapedes time and be less than 5s or be greater than 30s or leaper, give it up.50 qualified mices are divided into 6 groups at random, be normal saline group, preparation nose Shu Kang high dose of the present invention (2.4g/kg), middle dosage (1.2g/kg), low dose group (0.6g/kg), positive controls aspirin (0.3g/kg), sinusitis capsule group (3.0g/kg).Repeat to survey its normal pain threshold, the meansigma methods of getting the two subnormal threshold of pains as this Mus administration before pain threshold.Each experimental mice gastric infusion every day 1 time, the normal saline of matched group gavage equivalent, 3d continuously, after last administration, 120min measures mice pain threshold, as still reactionless in 60s, and mice is taken out, in order to avoid scald, its pain threshold is pressed 60s and is calculated.
(2) result is shown in table 32, the high, medium and low dosage of preparation nose Shu Kang of the present invention all can significantly suppress hot plate stimulates the mice pain reaction of induction, show as pain threshold and raise, relatively have statistical significance (P < 0.01) with blank group.
Table 32 stimulates the impact that causes mice pain reaction on hot plate
3.4 bacteriostatic experiment
3.4.1 the preparation of bacterium liquid: first 7 kinds of lyophilizing bacterial strains are seeded to respectively in serum broth, cultivate 18 h for 37 DEG C, picking one encircles in microbionation to 5 mL serum broth respectively from each bacterium liquid, and 37 DEG C, centrifugal 10 min of 18h, 2 000 r/min, abandon supernatant; With physiological saline solution washing, recentrifuge; Each pipe precipitation is diluted with physiological saline solution.Adopt turbidimetry to make 6 kinds of bacteria suspension concentration be 1 × 105CFU/mL, for subsequent use.
2.4.2 diluted sample: press medicine dish dilution method, take medicine 2g, join respectively 18 mL containing in the agar culture medium of the thawing of 10% serum (approximately 55 DEG C), shake up; On this basis with same culture medium two-fold dilution make 120,60,30,15,7.5, the agar plate of 3.25mg/mL6 kind different pharmaceutical concentration.
3.4.3 microbionation: at 7 aseptic Oxford cups of the each placement of the pastille agar plate surface preparing, then add respectively 6 kinds of different bacteria suspensions, each cup adds 10 μ L; Set up the positive, feminine gender and blank group, wherein negative control: not dosing, adds bacterium simultaneously; Positive control: add 80 μ g/mL ampicillins, add bacterium; Blank: dosing, does not add bacterium.
3.4.4 result: the MIC and the MBC that measure each strain, result is shown in table 33, preparation nose Shu Kang of the present invention is in vitro to staphylococcus aureus, and bacillus pyocyaneus, escherichia coli, beta hemolytic streptococcus, streptococcus pneumoniae, Bacillus proteus all have certain bacteriostasis.
Table 33 preparation in-vitro antibacterial of the present invention experimental result
The therapeutical effect of 3.5 pairs of egg albumen sensitization guinea pig experimental rhinitis
3.5.1 method: get 60 of Cavia porcelluss, every animal lumbar injection ovalbumin 20 μ g, and Al (0H) 35mg, every other day once, totally 3 times, after whole body sensitization, every animal nasal cavity each perfusion morning and afternoon every day 0.5%OVA 0.1ml, totally 5 days; After local sensitization, animal is divided into preparation nose Shu Kang high dose of the present invention (1.0g/kg), middle dosage (0.5g/kg), low dose group (0.25g/kg) at random, positive controls aspirin (0.15g/kg), sinusitis capsule group (1.2g/kg), 10 every group, totally 7 days; Within after last administration the 2nd day, rise, the OVA solution of every animal nasal cavity perfusion 0.5% excites, and every day 1 time, carries out altogether 7 times.
3.5.2 observation item: sniffle sign: in antigen (or normal saline) collunarium 30 minutes, collunarium is observed after 2 hours 30 minutes again.Sniffle standards of grading, rhinocnesmus: 1 point, dab nose several times; 2 points, scratching nose, face is more than, scouring everywhere.Sneeze: 1 point, l～3; 2 points, 4～10; 3 points, on 11.1 point of thin nasal discharge, flow to anterior nares; 2 points, exceed anterior nares; 3 points, watery nasal discharge is had one's face covered with.While record, score with the addition method, total score exceedes 5 points of person's model successes.Nasal obstruction: before being stimulated for the 7th time respectively at Cavia porcellus and excite its respiratory frequency of rear mensuration.Histological observation: then animal subject is put to death, retain viscerocranium, insert and fix the nitric acid decalcification with 5% after 7d in l% formalin solution.Routine is prepared tissue slice, in light Microscopic observation.According to nasal mucosa edema, hyperemia, inflammatory cell infiltration degree and eosinophilic granulocyte's quantity etc. press degree of inflammation scoring (standards of grading: 0: feminine gender, without above-mentioned positive pathological characters; 1: slight, tissue edema is not obvious, and inflammatory cell and acidophil are few: 2: moderate, tissue edema is obvious, and inflammatory cell and acidophil amount are medium: 3: severe, tissue edema is serious, the expansion of blood vessel height, inflammatory cell and acidophil amount are many.
3.5.3 result:
(1) sniffle, sign scoring dynamic change: the results are shown in Table 34.The each dosage group of preparation of the present invention is compared with negative control group, and from the 2nd day, all there were significant differences (P < 0.05).
The each group of table 34 sniffle, sign scoring
(2) nasal obstruction symptom: after exciting for the 7th time, the decline for the treatment of group respiratory frequency is obviously delayed in model group (P < 0.05), the results are shown in Table 35.
The contrast of the each group of table 35 respiratory frequency
(3) on the histological impact of guinea-pig nasal: compared with model control group, the each dosage group of preparation of the present invention histo pathological change degree score compared with negative control group obviously reduces (P < 0.05), acidophil obviously reduces (P < 0.05), the results are shown in Table 36.
The impact of table 36 on guinea-pig nasal mucosal tissue pathological change
4, conclusion
The high, medium and low dosage of 4.1 preparation nose Shu Kang of the present invention all can reduce rat granuloma quality (P < 0.01), shows good antiphlogistic effects.
The 4.2 high, medium and low dosage of preparation nose Shu Kang of the present invention and positive control drug all can significantly suppress dimethylbenzene induced mice auricle edema rate, relatively there is statistical significance (P < 0.01) with blank group, point out preparation of the present invention to there is good antiphlogistic effects.
The high, medium and low dosage of 4.3 preparation nose Shu Kang of the present invention can significantly reduce acetic acid induced mice abdominal cavity capillary permeability and raise (P<0.01), points out the good antiphlogistic effects of preparation nose Shu Kang of the present invention.
To models of passive skin irritability of rats, reaction all has significant inhibitory action (P < 0.01) to the high, medium and low dosage of 4.4 preparation nose Shu Kang of the present invention, points out preparation nose Shu Kang of the present invention to have good antiallergic effect.
The mouse writhing reaction that the high, medium and low dosage group of 4.5 preparation nose Shu Kang of the present invention Dichlorodiphenyl Acetate causes all has significant inhibitory action, relatively there is statistical significance (P < 0.01) with blank group, show that preparation of the present invention has certain analgesic activity.
The high, medium and low dosage of 4.6 preparation nose Shu Kang of the present invention all can significantly suppress hot plate stimulates the mice pain reaction of induction, shows that preparation of the present invention has certain analgesic activity.
4.7 preparation nose Shu Kang of the present invention are in vitro to staphylococcus aureus, and bacillus pyocyaneus, escherichia coli, beta hemolytic streptococcus, streptococcus pneumoniae, Bacillus proteus all have certain bacteriostasis.Point out preparation of the present invention to have certain inhibitory action to control upper respiratory tract pathogenic bacterium.
To egg albumen sensitization guinea pig experimental rhinitis, experiment shows 4.8 preparations of the present invention, and preparation of the present invention can improve rhinitis inflammation shape, sign, histopathology, points out preparation of the present invention to have certain preventive and therapeutic effect to rhinitis.
In sum, preparation of the present invention has good antiinflammatory, analgesia, antiallergic, the effect such as antibacterial, for its clinical experiment and use provide experimental basis.
five, toxicity test research
acute toxicity testing
1. experiment material
1.1 animal Kunming mouses, body weight 18～22g.The quality certification number: SCXK(Chongqing is provided by Animal Experimental Study chamber, Chongqing Institute of Chinese Medicine) 20020004.
1.2 medicine medicated powder of the present invention.Wear into fine powder with mortar, be mixed with suspension with distilled water for subsequent use.
2, method
2.1 measure median lethal dose(LD 50) (LD 50): 40 of female mices, body weight 18～22g, is divided into 4 groups (10/group): be respectively medicine 18g/kg.d of the present invention at random -1, 20g/kg.d -1, 22g/kg.d -1, 24g/kg.d -1(maximum suspendible concentration), fasting (can't help water) single gastric infusion after 12 hours, each 0.4ml/10g, ordinary circumstance (body weight change, diet, fur, behavior, secretions, Excreta etc.) and poisoning, the death condition of observing mice, Continuous Observation 14 days.
2.2 maximum dosage-feeding experiments: 20 of female mices, body weight 18～22g, administration volume 0.4ml/10g, 90g/kg.d divides gastric infusion three times, observes general activity situation and the death toll of mice, Continuous Observation 14 days.
3, result
3.1 medicines of the present invention have no dead during respectively organizing mouse test, and general status good (body weight, diet, fur, behavior, secretions, Excreta etc.), cannot obtain LD 50.
3.2 adopt maximum dosage-feeding 90g/kg.d(to be approximately equivalent to 300 times of clinical every day of dosage) gavage, duration of test Mice Body weight average increases (in table 37), diet and movable normal, fur is smooth, the no abnormality seen secretions such as mouth, nose, eye, after administration, only within the 1st day, be brown soft stool, urine no abnormality seen.
4. the experiment of conclusion maximum dosage-feeding shows that medicine of the present invention is very low to chmice acute toxicity.
The comparison of table 37 medicine maximum dosage-feeding of the present invention experiment mice body weight
Brief description of the drawings
Fig. 1 is preparation process thereof flow chart of the present invention.
below in conjunction with detailed description of the invention, the present invention is further illustrated.
Detailed description of the invention
Embodiment 1: get Caulis et folium pavettae hongkongensis 15g, Herba Centipedae 10g, Serissa foetida 20g, Herba Polygoni cymosi 20g, the Radix Angelicae Dahuricae 10.Adding decocting becomes decoction to take.Usage and dosage: 1 dose of every day, point 3 clothes.
Embodiment 2: get Caulis et folium pavettae hongkongensis 15g, Herba Centipedae 10g, Radix Codonopsis 15g, Serissa foetida 20g, Herba Polygoni cymosi 20g, Flos Chrysanthemi Indici 10g, Radix Angelicae Dahuricae 10g.Adding decocting becomes decoction to take.Usage and dosage: 1 dose of every day, point 3 clothes.
Embodiment 3: get Caulis et folium pavettae hongkongensis 300g, Herba Centipedae 200g, Serissa foetida 400g, Herba Polygoni cymosi 400g, Radix Angelicae Dahuricae 200g.Decoct with water twice, add water 10 times at every turn, decoct 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.35(60 DEG C) extractum, add starch appropriate, mix, granulate, dry, add magnesium stearate appropriate, mix, tabletting, coating, makes 1000, obtains tablet of the present invention.Specification: every heavy 0.25g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 4: get Caulis et folium pavettae hongkongensis 6kg, Herba Centipedae 4kg, Serissa foetida 8kg, Herba Polygoni cymosi 8kg, Radix Angelicae Dahuricae 4kg.Decoct with water twice, add water 10 times at every turn, decoct 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.35(60 DEG C) extractum, add starch appropriate, mix, granulate, dry, add magnesium stearate appropriate, mix, tabletting, coating, makes 20000, obtains tablet of the present invention.Specification: every heavy 0.25g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 5: get Caulis et folium pavettae hongkongensis 600g, Herba Centipedae 150g, Serissa foetida 300g, Herba Polygoni cymosi 300g, Radix Angelicae Dahuricae 150g.Decoct with water 3 times, add water 5 times at every turn, decoct 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 DEG C) extractum, add starch appropriate, mix, granulate, dry, add magnesium stearate appropriate, mix, tabletting, coating, makes 1000, obtains tablet of the present invention.Specification: every heavy 0.25g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 6: get Caulis et folium pavettae hongkongensis 150g, Herba Centipedae 225g, Serissa foetida 450g, Herba Polygoni cymosi 450g, Radix Angelicae Dahuricae 225g.Decoct with water 1 time, add water 12 times at every turn, decoct 4 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.30(60 DEG C) extractum, add starch appropriate, mix, granulate, dry, add magnesium stearate appropriate, mix, tabletting, coating, makes 1000, obtains tablet of the present invention.Specification: every heavy 0.25g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 7: get Caulis et folium pavettae hongkongensis 300g, Herba Centipedae 200g, Serissa foetida 400g, Herba Polygoni cymosi 400g, Radix Angelicae Dahuricae 200g.Decoct with water 3 times, add water 8 times at every turn, decoct 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 DEG C) extractum, add right amount of auxiliary materials, mix, dry, make 1000, obtain capsule of the present invention, specification: every dress 0.3g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 8: get Caulis et folium pavettae hongkongensis 120g, Herba Centipedae 80g, Serissa foetida 160g, Herba Polygoni cymosi 160g, Radix Angelicae Dahuricae 80g.Decoct with water 3 times, add water 8 times at every turn, decoct 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 DEG C) extractum, add right amount of auxiliary materials, mix, granulate, dry, make 300g(Sugarless type), 1000g(sugar-containing type), obtain granule of the present invention, specification: every packed 3g(Sugarless type), 10g(sugar-containing type).Usage and dosage: oral, one time 1 bag, 3 times on the one.
Embodiment 9: get Caulis et folium pavettae hongkongensis 1200g, Herba Centipedae 800g, Serissa foetida 1600g, Herba Polygoni cymosi 1600g, Radix Angelicae Dahuricae 80g.Decoct with water 2 times, add water 10 times at every turn, decoct 2 hours at every turn, filter, merging filtrate, hold over night, gets supernatant and is evaporated to about 800ml, adds right amount of auxiliary materials, mixes, and adds water and makes 10000ml, obtains oral liquid of the present invention, specification: every bottled 10ml.Usage and dosage: oral, one time 1 bottle, 3 times on the one.
Embodiment 10: get Caulis et folium pavettae hongkongensis 3000g, Herba Centipedae 2000g, Serissa foetida 4000g, Herba Polygoni cymosi 4000g, Radix Angelicae Dahuricae 2000g.Decoct with water 3 times, add water 8 times at every turn, decoct 1 hour at every turn, filter, it is 1.25～1.35(60 DEG C that filtrate decompression is concentrated into relative density) extractum, dry, pulverize into fine powder, add right amount of auxiliary materials, grind well, be pressed into 10000, obtain soft capsule of the present invention, specification: every dress 0.4g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 11: get Caulis et folium pavettae hongkongensis 6000g, Herba Centipedae 1500g, Serissa foetida 3000g, Herba Polygoni cymosi 3000g, Radix Angelicae Dahuricae 1500g.Decoct with water 2 times, add water 12 times at every turn, decoct 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 DEG C) extractum, add starch appropriate, mix, granulate, dry, add magnesium stearate appropriate, mix, tabletting, coating, makes 10000, obtains tablet of the present invention.Specification: every heavy 0.25g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 12: get Caulis et folium pavettae hongkongensis 3kg, Herba Centipedae 2kg, Serissa foetida 4kg, Herba Polygoni cymosi 4kg, Radix Angelicae Dahuricae 2kg.Decoct with water 2 times, add water 10 times at every turn, decoct 1.5 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.30(60 DEG C) extractum, add right amount of auxiliary materials, mix, dry, make 10000, obtain capsule of the present invention, specification: every dress 0.25g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 13: get Caulis et folium pavettae hongkongensis 300g, Herba Centipedae 200g, Radix Codonopsis 300g, Serissa foetida 400g, Herba Polygoni cymosi 400g, Flos Chrysanthemi Indici 200g, Radix Angelicae Dahuricae 200g.Decoct with water 2 times, add water 10 times at every turn, decoct 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.35(60 DEG C) extractum, add starch appropriate, mix, granulate, dry, add magnesium stearate appropriate, mix, tabletting, coating, makes 1000, obtains tablet of the present invention.Specification: every heavy 0.3g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 14: get Caulis et folium pavettae hongkongensis 6000g, Herba Centipedae 4000g, Radix Codonopsis 6000g, Serissa foetida 8000g, Herba Polygoni cymosi 8000g, Flos Chrysanthemi Indici 4000g, Radix Angelicae Dahuricae 4000g.Decoct with water 2 times, add water 10 times at every turn, decoct 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.35(60 DEG C) extractum, add starch appropriate, mix, granulate, dry, add magnesium stearate appropriate, mix, tabletting, coating, makes 20000, obtains tablet of the present invention.Specification: every heavy 0.3g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 15: get Caulis et folium pavettae hongkongensis 1000g, Herba Centipedae 2200g, Radix Codonopsis 3600g, Serissa foetida 4400g, Herba Polygoni cymosi 4400g, Flos Chrysanthemi Indici 2200g, Radix Angelicae Dahuricae 2200g.Decoct with water 3 times, add water 8 times at every turn, decoct 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 DEG C) extractum, add starch appropriate, mix, granulate, dry, add magnesium stearate appropriate, mix, tabletting, coating, makes 10000, obtains tablet of the present invention.Specification: every heavy 0.3g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 16: get Caulis et folium pavettae hongkongensis 6000g, Herba Centipedae 1600g, Radix Codonopsis 2400g, Serissa foetida 3400g, Herba Polygoni cymosi 3400g, Flos Chrysanthemi Indici 1600g, Radix Angelicae Dahuricae 1600g.Decoct with water 1 time, add water 12 times at every turn, decoct 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 DEG C) extractum, add starch appropriate, mix, granulate, dry, add magnesium stearate appropriate, mix, tabletting, coating, makes 10000, obtains tablet of the present invention.Specification: every heavy 0.3g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 17: get Caulis et folium pavettae hongkongensis 3000g, Herba Centipedae 2000g, Radix Codonopsis 3000g, Serissa foetida 4000g, Herba Polygoni cymosi 4000g, Flos Chrysanthemi Indici 2000g, Radix Angelicae Dahuricae 2000g.Decoct with water 4 times, add water 6 times at every turn, decoct 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.30(60 DEG C) extractum, add starch appropriate, mix, granulate, dry, add magnesium stearate appropriate, mix, tabletting, coating, makes 10000, obtains tablet of the present invention.Specification: every heavy 0.3g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 18: get Caulis et folium pavettae hongkongensis 300g, Herba Centipedae 200g, Radix Codonopsis 300g, Serissa foetida 400g, Herba Polygoni cymosi 400g, Flos Chrysanthemi Indici 200g, Radix Angelicae Dahuricae 200g.Decoct with water 2 times, add water 10 times at every turn, decoct 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.35(60 DEG C) extractum, add right amount of auxiliary materials, mix, dry, make 1000, obtain capsule of the present invention, specification: every dress 0.3g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 19: get Caulis et folium pavettae hongkongensis 2000g, Herba Centipedae 4000g, Radix Codonopsis 6000g, Serissa foetida 8000g, Herba Polygoni cymosi 8000g, Flos Chrysanthemi Indici 4000g, Radix Angelicae Dahuricae 4000g.Decoct with water 3 times, add water 8 times at every turn, decoct 2 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 DEG C) extractum, add right amount of auxiliary materials, mix, dry, make 20000, obtain capsule of the present invention, specification: every dress 0.3g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 20: get Caulis et folium pavettae hongkongensis 1200g, Herba Centipedae 800g, Radix Codonopsis 1200g, Serissa foetida 1600g, Herba Polygoni cymosi 1600g, Flos Chrysanthemi Indici 800g, Radix Angelicae Dahuricae 800g.Decoct with water 3 times, add water 8 times at every turn, decoct 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.30～1.35(60 DEG C) extractum, add right amount of auxiliary materials, mix, granulate, dry, make 5000g(Sugarless type), 10000g(sugar-containing type), obtain granule of the present invention, specification: every packed 5g(Sugarless type), 10g(sugar-containing type).Usage and dosage: oral, one time 1 bag, 3 times on the one.
Embodiment 21: get Caulis et folium pavettae hongkongensis 120g, Herba Centipedae 80g, Radix Codonopsis 120g, Serissa foetida 160g, Herba Polygoni cymosi 160g, Flos Chrysanthemi Indici 80g, Radix Angelicae Dahuricae 80g.Decoct with water 2 times, add water 10 times at every turn, decoct 2 hours at every turn, filter, merging filtrate, hold over night, gets supernatant and is evaporated to about 800ml, adds right amount of auxiliary materials, mixes, and adds water and makes 1000ml, obtains oral liquid of the present invention, specification: every bottled 10ml.Usage and dosage: oral, one time 1 bottle, 3 times on the one.
Embodiment 22: get Caulis et folium pavettae hongkongensis 3000g, Herba Centipedae 2000g, Radix Codonopsis 3000g, Serissa foetida 4000g, Herba Polygoni cymosi 4000g, Flos Chrysanthemi Indici 2000g, Radix Angelicae Dahuricae 2000g.Decoct with water 3 times, add water 8 times at every turn, decoct 1 hour at every turn, filter, it is 1.25～1.35(60 DEG C that filtrate decompression is concentrated into relative density) extractum, dry, pulverize into fine powder, add right amount of auxiliary materials, grind well, be pressed into 10000, obtain soft capsule of the present invention, specification: every dress 0.5g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 23: get Caulis et folium pavettae hongkongensis 300g, Herba Centipedae 200g, Radix Codonopsis 300g, Serissa foetida 400g, Herba Polygoni cymosi 400g, Flos Chrysanthemi Indici 200g, Radix Angelicae Dahuricae 200g.Decoct with water twice, add water 10 times at every turn, decoct 3 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25(60 DEG C) extractum, add starch, add suitable quantity of water and mix thoroughly agglomeratingly to what hold, faling apart for degree of pressureing, cuts pill.Molding, capping, coating, makes 1000 balls, obtains pill of the present invention, specification: every heavy 0.4g.Usage and dosage: oral, 4 balls, 3 times on the one.
Embodiment 23: get Caulis et folium pavettae hongkongensis 750g, Herba Centipedae 500g, Radix Codonopsis 750g, Serissa foetida 1000g, Herba Polygoni cymosi 1000g, Flos Chrysanthemi Indici 500g, Radix Angelicae Dahuricae 500g.8 times of decoctings that add the total amount of writing out a prescription boil 2 times, decoct 1 hour at every turn, and hold over night, gets supernatant and filter, and merging filtrate, being evaporated to relative density is 1.20(20 DEG C) clear paste, spraying is dry, fine powder is for subsequent use; Add in the polyethylene glycol 6000 of melting, stir evenly, splash in methyl-silicone oil, take out, drop pill is absorbed condensed fluid, dry, makes 20000, obtains drop pill of the present invention.Specification: every heavy 40mg.Usage and dosage: oral, one time 10,3 times on the one.
Embodiment 24: get Caulis et folium pavettae hongkongensis 120g, Herba Centipedae 80g, Radix Codonopsis 120g, Serissa foetida 160g, Herba Polygoni cymosi 160g, Flos Chrysanthemi Indici 80g, Radix Angelicae Dahuricae 80g.Decoct with water twice, add water 10 times at every turn, decoct 3 hours at every turn, filter, merging filtrate, is evaporated to about 800ml, add sucrose 100g, Mel 100g, sodium benzoate 2g, stir evenly, be heated to boil, put to room temperature, then add Fructus Citri tangerinae essence 1ml, add water to 1000ml, stir evenly, filter fill, obtain syrup of the present invention, specification: every bottled 100ml.Usage and dosage: oral, a 10ml, 3 times on the one.
Embodiment 25: get Caulis et folium pavettae hongkongensis 1000g, Herba Centipedae 2200g, Radix Codonopsis 3600g, Serissa foetida 4400g, Herba Polygoni cymosi 4400g, Flos Chrysanthemi Indici 2200g, Radix Angelicae Dahuricae 2200g.Decoct with water 3 times, add water 8 times at every turn, decoct 1 hour at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.35(60 DEG C) extractum, add right amount of auxiliary materials, mix, dry, make 10000, obtain capsule of the present invention, specification: every dress 0.3g.Usage and dosage: oral, one time 4,3 times on the one.
Embodiment 26: get Caulis et folium pavettae hongkongensis 6000g, Herba Centipedae 1600g, Radix Codonopsis 2400g, Serissa foetida 3400g, Herba Polygoni cymosi 3400g, Flos Chrysanthemi Indici 1600g, Radix Angelicae Dahuricae 1600g.Decoct with water 2 times, add water 12 times at every turn, decoct 2 hours at every turn, filter, merging filtrate, being evaporated to relative density is 1.25～1.35(60 DEG C) extractum, add right amount of auxiliary materials, mix, dry, make 10000, obtain capsule of the present invention, specification: every dress 0.3g.Usage and dosage: oral, one time 4,3 times on the one.

Claims (7)

1. prevent and treat a pharmaceutical preparation for rhinitis, it is characterized in that: it is to be made up of the crude drug of following weight ratio example: Caulis et folium pavettae hongkongensis 10%～40%, Herba Centipedae 10%～15%, Serissa foetida 20%～30%, Herba Polygoni cymosi 20%～30%, the Radix Angelicae Dahuricae 10%～15%.
2. according to the pharmaceutical preparation that prevents and treats rhinitis described in claim 1, it is characterized in that: the consumption of each crude drug is: Caulis et folium pavettae hongkongensis 20%, Herba Centipedae 13.3%, Serissa foetida 26.7%, Herba Polygoni cymosi 26.7%, the Radix Angelicae Dahuricae 13.3%.
3. prevent and treat the pharmaceutical preparation of rhinitis for one kind, it is characterized in that: be by crude drug: Caulis et folium pavettae hongkongensis, Herba Centipedae, Serissa foetida, Herba Polygoni cymosi, the Radix Angelicae Dahuricae, Radix Codonopsis, Flos Chrysanthemi Indici are made, the consumption of each component is: Caulis et folium pavettae hongkongensis 15%, Herba Centipedae 10%, Radix Codonopsis 15%, Serissa foetida 20%, Herba Polygoni cymosi 20%, Flos Chrysanthemi Indici 10%, the Radix Angelicae Dahuricae 10%.
4. described in claim 1 or 2, prevent and treat the preparation method of the pharmaceutical preparation of rhinitis, it is characterized in that: get Caulis et folium pavettae hongkongensis, Herba Centipedae, Serissa foetida, Herba Polygoni cymosi, Radix Angelicae Dahuricae gomi herbs, 5～12 times of decoctings that add the total amount of writing out a prescription boil 1～4 time, each decoction 1～4 hour, filter, filtrate is concentrated into the extractum that 60 DEG C of relative densities are 1.20～1.40, and then preparation process is made different oral formulations routinely.
5. according to the pharmaceutical preparation that prevents and treats rhinitis described in claim 4, it is characterized in that: described oral formulations is decoction, granule, oral liquid, syrup, paste nourishing agent, pill, tablet, hard capsule, soft capsule or drop pill.
6. described in claim 3, prevent and treat the preparation method of the pharmaceutical preparation of rhinitis, it is characterized in that: get Caulis et folium pavettae hongkongensis, Herba Centipedae, Radix Codonopsis, Serissa foetida, Herba Polygoni cymosi, Flos Chrysanthemi Indici, Radix Angelicae Dahuricae seven flavor medicine material, 5～12 times of decoctings that add the total amount of writing out a prescription boil 1～4 time, each decoction 1～4 hour, filter, filtrate is concentrated into the extractum that 60 DEG C of relative densities are 1.20～1.40, and then preparation process is made different oral formulations routinely.
7. according to the pharmaceutical preparation that prevents and treats rhinitis described in claim 6, it is characterized in that: described oral formulations is decoction, granule, oral liquid, syrup, paste nourishing agent, pill, tablet, hard capsule, soft capsule or drop pill.
CN201010159712.XA 2010-04-29 2010-04-29 Medical preparation for preventing and treating rhinitis and preparation method thereof Expired - Fee Related CN101890079B (en)

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