CN101524388B

CN101524388B - Pharmaceutical composition for curing rhinitis and preparation method thereof

Info

Publication number: CN101524388B
Application number: CN2009101196615A
Authority: CN
Inventors: 白玛卓玛; 朱建英
Original assignee: Gansu Qizheng Tibetan Medicine Co Ltd
Current assignee: Gansu Qizheng Tibetan Medicine Co Ltd
Priority date: 2009-01-21
Filing date: 2009-03-25
Publication date: 2011-12-07
Anticipated expiration: 2029-03-25
Also published as: CN101524388A

Abstract

The invention discloses a pharmaceutical composition for curing rhinitis, nasal sinusitis and allergic rhinitis and a preparation method thereof. The pharmaceutical composition comprises the following bulk drugs: auckandia root, embelia laeta, benzoin and butein and further comprises centipede, myrobalan fruit or liquorice. The preparation method adopts an alcohol-extraction and water precipitation or water extraction and alcohol precipitation method and the like, the bulk drugs are prepared into conventional and clinically acceptable preparations according to the conventional process, and the preparations include but are not limited to spraying agent, powder spray, gelata, granula, and the like. The experimental results show that the pharmaceutical composition has better effects of curing the rhinitis, the nasal sinusitis and the allergic rhinitis.

Description

A kind of pharmaceutical composition and preparation method thereof with the effect of treatment rhinitis

Technical field

The present invention relates to a kind of pharmaceutical composition, particularly relate to a kind of pharmaceutical composition and preparation method thereof with treatment rhinitis, sinusitis and allergic rhinitis effect with the effect of treatment rhinitis.

Background technology

Rhinitis be nose section clinical in a most common class disease, the pathogenic factors complexity, clinical symptoms is different, when influencing the physiological function of nasal cavity, respiratory disorder can appear, and cause blood oxygen concentration and reduce, influence the function and the metabolism of other tissue and organ, and some appear as headache, dizzy, hypomnesis, chest pain, uncomfortable in chest, listlessness etc., in addition can concurrent emphysema, severe complications such as pulmonary heart disease, asthma.And fail to get timely medical treatment when rhinitis, when influencing the olfactory sensation mucosa, olfactory disorder will appear, cause hearing not good and foul smells grade for abnormal smells from the patient.Even more serious is, inflammation will diffuse to adjacent organs, tissue, and concurrent as multiple critical emergency cases such as osteomyelitis of frontal bone, socket of the eye bone wall osteitis and periostitis, subperiosteal orbital abscess, orbital cellulitis, retrobulbar neuritis, spinal epidural absceess, subdural abscess, purulent meningitis, brain abscess, cavernous sinus thrombophlebitiss.

Rhinitis is human a kind of disease common, occurred frequently, in the medical prophylaxis treatment, do not paid attention in the past, there are not corresponding methods of treatment and medicine in addition, the general anti-inflammatory treatment of still continuing to use over when making it to treat clinically can not be obtained good curative effect, the disease of chronic rhinitis has much relations with people's spirit, emotion again in addition, so antiinflammatory simply, antibiotic, only the meeting delay treatment causes damage to health.

Sinusitis often is secondary to sense or acute rhinitis, and fear of cold, heating, inappetence, constipation, whole body discomfort etc. appear at this moment original sx.Chronic sinusitis also has hyposmia or disappearance except that symptoms such as nasal obstruction, watery nasal discharge, headache.

Allergic rhinitis can be divided into seasonal and long-term property two big classes according to the difference of duration of seizure.The former is caused that by seasonal sensitizer modal is exactly pollen, claims pollinosis again by pollenogenic allergic rhinitis; The latter causes by long-term sensitizer, and is how relevant with acarid, fungus etc., the title catarrhus perennialis.The symptom of allergic rhinitis is to show effect repeatedly, and the intranasal that takes place is very itched suddenly, continuous sneeze, and volume clear water sample nasal mucus, nasal obstruction, duration of seizure is of short duration.To send out author's WA in early morning symptom obvious throughout the year, and seasonal to send out the author many in the flowers are in blossom season.There is considerable asthmatic patient that the allergic rhinitis symptom is arranged before asthma attack, if can in time takes therapy measure, can avoid the outbreak of asthma allergic rhinitis.

Now rhinitis medicine on the market can both be alleviated the surface symptoms such as nasal obstruction, rhinocnesmus, sneeze of rhinitis greatly, and various rhinitis are had certain curative effect, still, still has various weak points.Contain Herba Ephedrae mostly as existing nose external preparation, and long-term practical Herba Ephedrae has and causes drug resistance.

Summary of the invention

One object of the present invention is to disclose a kind of pharmaceutical composition with treatment rhinitis, sinusitis and allergic rhinitis effect; Another object of the present invention is to disclose this preparation of drug combination method.

The present invention seeks to be achieved through the following technical solutions:

Pharmaceutical composition of the present invention is mainly made by following crude drug:

Radix Aucklandiae 1-55 weight portion Fructus embeliae laetae 1-40 weight portion

Benzoinum 0.1-25 weight portion ZIMAOZI 1-40 weight portion.

The crude drug composition of pharmaceutical composition of the present invention is preferably:

The Radix Aucklandiae 50 weight portion Fructus embeliae laetaes 30 weight portions

Benzoinum 20 weight portion ZIMAOZI 30 weight portions.

The Radix Aucklandiae 45 weight portion Fructus embeliae laetaes 15 weight portions

Benzoinum 5 weight portion ZIMAOZI 35 amount parts.

The Radix Aucklandiae 20 weight portion Fructus embeliae laetaes 35 weight portions

Benzoinum 15 weight portion ZIMAOZI 15 weight portions.

The Radix Aucklandiae 5 weight portion Fructus embeliae laetaes 5 weight portions

Benzoinum 1 weight portion ZIMAOZI 5 weight portions.

The above-mentioned raw materials medicine can also increase one or several in the following crude drug:

Herba Centipedae 1-30 weight portion Fructus Chebulae 1-50 weight portion Radix Glycyrrhizae 1-30 weight portion.

The above-mentioned raw materials medicine can also preferably increase one or several in the following crude drug:

Herba Centipedae 28 weight portion Fructus Chebulaes 5 weight portion Radix Glycyrrhizaes 3 weight portions.

Herba Centipedae 3 weight portion Fructus Chebulaes 45 weight portion Radix Glycyrrhizaes 28 weight portions.

Herba Centipedae 15 weight portion Fructus Chebulaes 25 weight portion Radix Glycyrrhizaes 15 weight portions.

Get pharmaceutical composition crude drug of the present invention, add conventional adjuvant, according to common process, make nasal cavity administrated preparation, tablet, capsule, powder, soft capsule, drop pill, honeyed pill, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparations such as nasal mist, nasal cavity powder spray, gel for nose, nasal drop

Preparation of drug combination method of the present invention can also comprise the steps:

Get the above-mentioned composition crude drug, cleaning, drying are ground into fine powder, and particle diameter is 150 μ m-200 μ m, makes micropowders through micronizing again, and particle diameter is 5 μ m-20 μ m, this micropowders add conventional adjuvant routinely technology make above-mentioned dosage form;

Or get the above-mentioned composition crude drug, the water that adds the 5-10 times of weight, extract 1-3 time, and extracting solution is condensed into per 1 parts by volume is equivalent to medical material 1-2 weight portion, add 95% ethanol and reach 60%～70% to containing the alcohol amount, leave standstill 24h, remove impurity, obtain clarifying liquid, again through concentrate, drying obtains extract dry powder, this extract dry powder add conventional adjuvant routinely technology make above-mentioned dosage form;

Or get the above-mentioned composition crude drug, ethanol extraction 1-3 time that adds 5-10 times of weight 60-90%, alcohol extract reclaims ethanol, the water that adds medicinal liquid 1-3 times of weight stirs, complete post precipitation elimination impurity is treated in cold preservation, obtains clarifying liquid, again through concentrate, drying obtains extract dry powder, this extract dry powder add conventional adjuvant routinely technology make above-mentioned dosage form;

Or get the above-mentioned composition crude drug, the water that adds the 5-10 times of weight, extract 1-3 time, and extracting solution is concentrated upward macroporous resin column absorption of back, after washing with water, the ethanol elution of reuse 60%-95%, eluent is reclaimed ethanol, concentrate drying, obtain extract dry powder, with extract dry powder add conventional adjuvant routinely technology make above-mentioned dosage form;

Or get the above-mentioned composition crude drug, add 5-10 times of weight 60-90% ethanol extraction 1-3 time, extracting solution reclaims ethanol and obtains extractum, and extractum is gone up macroporous adsorptive resins after with water dissolution, after washing with water, the ethanol elution of reuse 60%-95%, eluent is reclaimed ethanol, concentrate drying, obtain extract dry powder, with extract dry powder add conventional adjuvant routinely technology make above-mentioned dosage form.

Preparation of drug combination method of the present invention can also preferably include following steps:

Get the above-mentioned composition crude drug, cleaning, drying are ground into fine powder, and particle diameter is 190 μ m, makes micropowders through micronizing again, and particle diameter is 10 μ m, this superfine powder add conventional adjuvant routinely technology make above-mentioned dosage form;

Or get the above-mentioned composition crude drug, water extract respectively three times as follows: add the water of 10 times of weight, extracted 2 hours; The water that adds 8 times of weight extracted 1 hour; The water that adds 6 times of weight extracted 0.5 hour; Merge three times decocting liquid, shorten per 1 parts by volume into and be equivalent to medical material 2 weight portions extracting solution is suitable, the ethanol of adding 95% is 60% to containing the alcohol amount, leave standstill 24h, remove impurity, obtain clarifying liquid, through concentrate, drying obtains extract dry powder, this extract dry powder add conventional adjuvant routinely technology make above-mentioned dosage form;

Or get the above-mentioned composition crude drug, ethanol with 75% extract respectively three times as follows: 75% ethanol extraction 2 hours that adds 10 times of weight, 75% ethanol extraction 1 hour that adds 8 times of weight, 75% ethanol extraction 0.5 hour that adds 6 times of weight, filter merging filtrate respectively, reclaim ethanol, the water that adds medicinal liquid 2 times of weight, mixing leaves standstill 24h, gets supernatant and filters, reclaim ethanol, obtain clarifying medicinal liquid, through concentrate, drying obtains extract dry powder, this extract dry powder add conventional adjuvant routinely technology make above-mentioned dosage form;

Or get the above-mentioned composition crude drug, with decocting extract respectively 3 times as follows: the water extraction 2 hours that adds 10 times of weight; The water extraction 1 hour that adds 8 times of weight; The water extraction 0.5 hour that adds 6 times of weight, and extracting solution is concentrated the back go up macroporous resin column absorption, after washing with water, the ethanol elution of reuse 90% reclaims ethanol with eluent, concentrates, drying obtains extract dry powder, with extract dry powder add conventional adjuvant routinely technology make above-mentioned dosage form;

Or get the above-mentioned composition crude drug, with 75% ethanol extract respectively 3 times as follows: 75% ethanol extraction 2 hours that adds 10 times of weight; 75% ethanol extraction 1 hour that adds 8 times of weight; The 75% ethanol extraction 0.5h that adds 6 times of weight, extracting solution reclaims ethanol and obtains extractum, extractum is gone up macroporous adsorptive resins after with water dissolution, after washing with water, reuse 90% ethanol elution reclaims ethanol with eluent, concentrate, drying obtains extract dry powder, with extract dry powder add conventional adjuvant routinely technology make above-mentioned dosage form.

The preparation method of pharmaceutical composition nasal mist of the present invention comprises the steps:

Get crude drug, mix, use water extraction 2h, 1h and the 0.5h of 10 times of weight, 8 times of weight, 6 times of weight respectively, filter, get filtrate and be concentrated into the concentrated solution that relative density is 1.01-1.30, preferred relative density is 1.01-1.10,1.10-1.20 or 1.20-1.30, adopts the method for accelerating slowly to stir to add ethanol in concentrated solution, make the alcohol amount of containing reach 50%-70%, preferred 60%, cold preservation 10-48 hour, preferred 24 hours, filter, reclaim ethanol; With 50-200 weight portion distilled water diluting filtrate, preferably use 150 weight portion distilled water diluting filtrates, add conventional adjuvant, pour into spray bottle, make nasal mist;

Or get crude drug, mix, use water extraction 2h, 1h and the 0.5h of 10 times of weight, 8 times of weight, 6 times of weight respectively, filter, filtrate is concentrated into 1: 1-1: 2 (ml: cross macroporous adsorbent resin g), wash with water,, preferably use 90% ethanol elution with the ethanol elution of 60%-95%, collect eluent, evaporate to dryness obtains active component, with this active component of 50-200 weight portion distilled water diluting, preferably use 150 these active components of weight portion distilled water diluting, add conventional adjuvant again, pour into spray bottle, make nasal mist;

Or get crude drug, and mixing, the ethanol extraction with 10 times of weight, 8 times of weight, 6 times of weight 60%～90% extracts 2h, 1h and 0.5h respectively, leaves standstill filtration; Reclaim ethanol, cold preservation filters again; With 50-200 weight portion distilled water diluting filtrate, preferably use 150 weight portion distilled water diluting filtrates, add conventional adjuvant, pour into spray bottle, make nasal mist;

Or get crude drug, and mixing, the ethanol extraction with 10 times of weight, 8 times of weight, 6 times of weight 60%～90% extracts 2h, 1h and 0.5h respectively, leaves standstill filtration; Reclaim ethanol, cold preservation filters again; Filtrate is concentrated into 1: 1-1: 2 (ml: cross macroporous adsorbent resin g), wash with water,, preferably use 90% ethanol elution with the ethanol elution of 60%-95%, collect eluent, evaporate to dryness obtains active component, with this active component of 50-200 weight portion distilled water diluting, preferably use 150 these active components of weight portion distilled water diluting, add conventional adjuvant again, pour into spray bottle, make nasal mist.

Wherein, described adjuvant is meant osmotic pressure regulator, pH regulator agent, antiseptic, penetration enhancer, wherein penetration enhancer comprise in cyclodextrin and derivant, phospholipid and derivant, Borneolum Syntheticum, Camphora, the Mentholum any or several.

The preparation method of pharmaceutical composition nasal cavity powder spray of the present invention comprises the steps:

Get crude drug, cleaning, drying are ground into fine powder, and particle diameter is 150 μ m-200 μ m, makes micropowders through micronizing again, and particle diameter is 5 μ m-20 μ m, this micropowders add conventional adjuvant routinely technology make the nasal cavity powder spray;

Or get crude drug, and mix, use the water of 10 times of weight, 8 times of weight, 6 times of weight or ethanol extraction 3 times respectively, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is condensed into extractum, the spray-dried dry powder that obtains of extractum, and dry powder and adjuvant mixed grinding make the nasal cavity powder spray;

Or get crude drug, and mix, use the water of 10 times of weight, 8 times of weight, 6 times of weight or ethanol extraction 3 times respectively, extract 2h, 1h, 0.5h respectively, filter, filtrate is concentrated into 1: 1-1: 2 (ml: cross macroporous adsorbent resin g), wash with water, ethanol elution with 60%-95%, preferably use 90% ethanol elution, collect eluent, evaporate to dryness, obtain active component, this active component and adjuvant mixed grinding make the nasal cavity powder spray.

Wherein, described adjuvant comprises lubricant, fluidizer and pharmaceutical carrier; Wherein pharmaceutical carrier comprises cellulose derivative, chitosan, lactose and carbomer.

The preparation method of pharmaceutical composition gel for nose of the present invention comprises the steps:

Get crude drug, mix, use the water of 10 times of weight, 8 times of weight, 6 times of weight or ethanol extraction 3 times respectively, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is condensed into extractum, and this extractum adds hydrophilic gel, and acceptable accessories is made gel for nose;

Or get crude drug, with the water of 10 times of weight, 8 times of weight, 6 times of weight or ethanol extraction 3 times, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is concentrated into 1: 1-1: 2 (ml: g), cross macroporous adsorbent resin, obtain medicine activity component, add hydrophilic gel, and acceptable accessories is made gel for nose.

Wherein, described hydrophilic gel is carbomer 934, Acritamer 940, one or more in Carbopol 941, carbomer 974P, Polycarbophil, methylcellulose, sodium carboxymethylcellulose or antelope third methylcellulose; Other adjuvant be pH regulator agent, wetting agent, antiseptic, solubilizing agent and cosolvent one or more; The pH regulator agent is one or more in monoethanolamine, two isopropanolamine, triethanolamine, sodium hydroxide, potassium hydroxide, hydrochloric acid, phosphoric acid, citric acid or the sodium citrate; Antiseptic is oxybenzene esters, chlorobutanol, benzyl alcohol, phenethanol, disodiumedetate, chlorhexidine acetate, thimerosal or season by in the compounds cationic surfactant one or more; Solubilizing agent and cosolvent are one or more in ethanol, polyethylene glycols, propylene glycol, TC, Labrasol, poly-Pyrusussuriensis phenols or the cyclodextrin.

The relation of weight portion of the present invention and parts by volume is the relation of g/ml.

The invention provides the proved recipe that a kind of Tibetan medicine of application treats rhinitis, sinusitis and allergic rhinitis, determined curative effect, but administering mode is original, and dosage is big, and strictness of the present invention by the pharmacy codes and standards with former pharmaceutical composition be developed to efficiently, high-quality, safety, novel formulation stable, taking convenience make easy received nasal mist and nasal cavity powder spray.A kind of preparation of the treatment of Tibetan medicine safely and effectively rhinitis, sinusitis and allergic rhinitis is provided for rhinitis, sinusitis and Allergic Rhinitis.Its preferred formulation is a nasal cavity administrated preparation, and nasal-cavity administration has the following advantages: 1. do not have the gastrointestinal tract Degradation: 2. do not have liver first-pass effect; 3. drug absorption is rapid, and onset time is fast after the administration; 4. directly enter blood circulation after the drug absorption, reach the purpose of treatment; 5. good patient compliance.The used medical material of the present invention is Tibetan medicine commonly used, has no side effect.Treat the rhinitis medicine on the market and contain ephedrine hydrochloride mostly, life-time service can cause cardiopalmus, anxious, insomnia etc., does not contain ephedrine hydrochloride in this prescription, does not have above-mentioned side effect.The treatment of doctor trained in Western medicine common antibiotics, but the antibiotic usage and dosage is difficult to grasp, easily causes recurrence and drug resistance.Glucocorticoid is as assist control sinunasal mucosal inflammation in addition, and it mainly act as antiinflammatory, edema.Medicinal liquid directly is distributed on the nasal membrane equably during the used aerosol spray administration of the present invention, does not resemble need rely on flowing of drop to be distributed to mucosa gradually the nasal drop to get on, do not need head to swing back so can reduce chemical liquid consumption.Therefore convenient drug administration not only, and medicinal liquid can not occur and flow to bottleneck throat and produce bitterness and medicinal liquid and suck trachea and bring complication.And powder agent Chinese medicine stability and microbial stability are than liquid dosage form height.No matter be that spray or powder spray all do not need propellant, can not cause the environmental pollution of aerosol sample.

In addition, the Radix Aucklandiae in this Tibetan medicine compositions contains constuslactone, has the bibliographical information constuslactone that the human body nasopharyngeal carcinoma cell is had cytotoxicity.Wherein the main component of Radix Glycyrrhizae is triterpenoid saponin compounds and flavone compounds such as glycyrrhizin, isoliquiritigenin such as glycyrrhizic acid, have effects such as relieving cough and expelling phlegm, heat-clearing and toxic substances removing, spleen reinforcing stomach function regulating, coordinating the actions of various ingredients in a prescription, can antiinflammatory, antiviral, antiallergic action, raising body antineoplastic ability.ZIMAOZI and Fructus embeliae laetae be the Tibetan medicine use always have a medicine antibiotic, itching-relieving action.

Following experimental example is used to further specify but is not limited to the present invention.

Experimental example 1 pharmaceutical composition of the present invention causes the influence of Cavia porcellus allergic rhinitis model to TDI

1 material

1.1 medicine

Pharmaceutical composition first of the present invention (making) according to embodiment 1; Pharmaceutical composition second of the present invention (making) according to embodiment 22; Levocabastine nasal spray (10mL props up); 0.5mgmL ^-1Levocabastine.

1.2 animal

Cavia porcellus, Lanzhou Institute of Biological Products's Experimental Animal Center provides, the quality certification number: the moving word 14-001 of doctor.

1.3 main agents and instrument

Toluene-2,4-diisocyanate, 4-vulcabond (TDI) are the production of Shanghai chemical reagent company limited, face with the TDI olive oil solution that before is mixed with 10%; MIAS2000 type computer picture work system.

2 methods

2.1 model preparation and grouping

Get 90 of Cavia porcelluss, male and female half and half, body weight (273.6 ± 21.7) g is divided into 9 groups by sex, body weight stratified random, 10 every group.Except that the normal control group, all the other each group splashes into nasal cavity before the Cavia porcellus bilateral with micro sample adding appliance with the olive oil solution of 10%TDI, and every side nasal cavity splashes into 5 μ L time ^-1, 1 d ^-1, 7d altogether, the next day of changing into after the 7th day 1 time, normal control group Cavia porcellus replaces the TDI processing with isopyknic olive oil solution.Since the 7th day, each group dripped medicine, is respectively normal saline 0.32mLkg ^-1D ^-1(normal control group and model control group), invention medicine first low dose group (25mgkg ^-1D ^-1), dosage group (50mgkg in the invention medicine first ^-1D ^-1), invention medicine first high dose group (75mgkg ^-1D ^-1); Invention medicine second low dose group (25mgkg ^-1D ^-1), dosage group (50mgkg in the invention medicine second ^-1D ^-1), invention medicine second high dose group (75mgkg ^-1D ^-1); Levocabastine nasal spray 0.16mgkg ^-1D ^-1(positive controls), every day 2 times, successive administration 15d.

2.2 observation index

From administration the 1st day, behind the TDI collunarium in the 30min, (rhinocnesmus dabbed nose several times, 1 minute to observe the nose outward appearance symptom of Cavia porcellus and scoring respectively; Scratching nose, face is more than, friction everywhere, 2 minutes; Sneeze, 1～3,1 minute; 4～10,2 minutes; More than 11,3 minutes; Thin nasal discharge flow to anterior nares, 1 minute; Surpass anterior nares, 2 minutes; Watery nasal discharge is had one's face covered with, 3 minutes).After the last administration is observed, femoral artery sacrificed by exsanguination Cavia porcellus, open bridge of the nose rapidly, get the nasal septum mucosa, 10% neutral formalin is fixed, paraffin embedding, conventional section, the thick 4 μ m of sheet, HE dyeing, light microscopy checking, and measure to calculate inflammatory cell area, average optical, integral optical density and average blackness with MIAS2000 type computer picture work system.

2.3 statistical analysis

(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Relatively carry out one factor analysis of variance between organizing more, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group.P＜0.05 expression difference has significance.

3 results

3.1 invention medicine first, second causes the influence of allergic rhinitis model symptom to TDI

Compare with the normal control group, in 2 weeks, the symptom of rhinocnesmus, sneeze and thin nasal discharge obviously increases the weight of the model control group Cavia porcellus before administration and after the administration, and symptom score is more than 6 minutes.Compare with model control group, beginning on the 5th after the administration of invention medicine first, second, Cavia porcellus rhinocnesmus, sneeze and thin nasal discharge symptom all obviously alleviate, and the prolongation allergic symptom scoring reduction gradually along with treatment time the results are shown in Table 1.

Table 1 couple TDI cause Cavia porcellus allergic rhinitis model symptom score influence (x ± s, n=10)

Compare with the normal control group, ^##P＜001

Compare with model control group, ^*P＜005, ^*P＜001

3.2 invention medicine first, second is to the morphologic influence of Cavia porcellus nasal mucosa histopathology

Light microscopic is observed down, and TDI causes the visible a large amount of inflammatory cells that soak into of Cavia porcellus allergic rhinitis model nasal septum mucosal epithelium, and inflammatory cell is based on acidophilia, neutrophilic leukocyte, and soaks in mucosal epithelium.With the normal control group relatively, model control group nasal septum mucositis sexual cell sum, inflammatory cell area summation, inflammatory cell average optical summation, inflammatory cell integral optical density summation and the average blackness summation of inflammatory cell have significantly and increase.Compare with model control group, the basic, normal, high dosage group of invention medicine first, second all can make These parameters significantly reduce, and is dose-effect relationship, and prompting invention medicine first and second all can significantly alleviate the infiltration degree of nasal mucosa epithelitis sexual cell.The results are shown in Table 2.

Table 2 couple TDI cause Cavia porcellus allergic rhinitis model inflammatory cell influence (x ± s, n=10)

Compare with the normal control group, ^##P＜001

Compare with model control group, ^*P＜005, ^*P＜001

This experimental result shows, invention medicine first and second all can alleviate Cavia porcellus allergic rhinitis model rhinocnesmus, sneeze and thin nasal discharge symptom, inflammatory cell sum, inflammatory cell area summation, inflammatory cell average optical summation, inflammatory cell integral optical density summation, the average blackness summation of inflammatory cell are all obviously reduced, prompting invention medicine first and second can obviously alleviate the infiltration degree of nasal mucosa epithelitis sexual cell, and allergic rhinitis is had therapeutical effect preferably.

Experimental example 2 pharmaceutical compositions of the present invention are to the preventive and therapeutic effect of acute bacterial rhinitis rat model

1 material

1.1 medicine and reagent

Pharmaceutical composition first of the present invention (making) according to embodiment 1; Pharmaceutical composition second of the present invention (making) according to embodiment 22; SHUANGHUANGLIAN KOUFUYE is that Harbin No.4 Traditional Chinese Pharmaceutical Factory produces; Dried yeast powder is produced by Shanghai yeast factory; Staphylococcus aureus liquid MRSAI is provided by Beijing 301 Hospital of the Chinese People's Liberation Army, and microbial room cultivates, 18g * 109cfumL ^-1Complement C ₃, C ₄And c reactive protein (CRP) detection kit, available from Beijing Bai Ding biological engineering company limited.

1.2 laboratory animal

Male 90 of SD rat, body weight (250 ± 20) g purchases the animal center in Nat'l Pharmaceutical ﹠ Biological Products Control Institute, the animal grade is a secondary, approval number (accurate word 99001 is moved in the capital), and animal is raised in the court's cleaning level animal center, healthy anosis behind quarantine 4d, test.

2 methods

2.1 animal grouping

Rat is divided into 9 groups at random by body weight, 10 every group.Be divided into: normal control group, model control group, invention medicine first low dose group (25mgkg ^-1D ^-1), dosage group (50mgkg in the invention medicine first ^-1D ^-1), invention medicine first high dose group (75mgkg ^-1D ^-1); Invention medicine second low dose group (25mgkg ^-1D ^-1), dosage group (50mgkg in the invention medicine second ^-1D ^-1), invention medicine second high dose group (75mgkg ^-1D ^-1); SHUANGHUANLIAN matched group (1mLkg ^-1).

2.2 preparation of rhinitis model and administration are handled

Adopt the staphylococcus aureus yeast to increase the venom nasal drip and prepare rat rhinitis model, staphylococcus aureus strain MRSAI cultivates in microbial room, faces fresh preparation of time spent, gets 10mL bacterium liquid and adds the 1g dry yeast.The high, medium and low dosage group of invention medicine, SHUANGHUANLIAN matched group, the 3d of prevention administration earlier.All the other are respectively organized rat and give the staphylococcus aureus yeast and increase venom 120 μ Ld except that the normal control group ^-1Collunarium, continuously collunarium 4d modeling gives the medicinal liquid of matched doses simultaneously respectively, and normal control group, model control group give the water of equivalent.Continue administration 3d again after the modeling of last collunarium, the 0.5h femoral artery is got blood after the last administration, and separation of serum uses the AU-560Olympus automatic biochemistry analyzer to adopt immunoturbidimetry to detect CRP level in the serum.Put to death animal, get nasal mucosa and bronchial tissue, 5% formalin fixed, HE dyeing is observed nasal mucosa epithelium and bronchiolar epithelium histopathology form and is changed.

2.3 statistical analysis

(x ± s) expression adopts the SPSS11.5 statistical software to carry out date processing to all data with mean ± standard deviation.Relatively carry out one factor analysis of variance between group, check with LSD when variance has homogeneous, heterogeneity of variance Dunnett ' s T3 check is carried out comparing between each group.P＜0.05 expression difference has significance.

3 results

3.1 the general symptom performance of rat after the modeling

Rat increases venom collunarium bacterial infection through the antibacterial yeast, can comparatively fast cause bacterial infection, drips back 1h rat disturbance uneasiness, painful sense is arranged, and rat is refused to grab during the 2d collunarium, and the 3rd, bacterial infection increases the weight of behind the 4d collunarium, rat uneasiness, Chang Youyong fore paw are grabbed nose action and rhinorrhea.And the rat of invention medicine first and second group will obviously be better than model control group from state, and minority has rhinorrhea.

3.2 invention medicine first and second are to the influence of rhinitis rat blood serum c reactive protein (CRP) level

CRP is a kind of albumen when acute in the serum, can with the endobacillary C-mucopolysaccharide of some pneumonia streptococcus generation precipitation.Nearly all acute bacterial infection and pulmonary tuberculosis and all types of tissue injury, operation wound, radiation damage etc. all can make CRP raise.When pathological changes is alleviated, then reduce to normal level rapidly.After the modeling of model control group rat, inflammatory reaction is strong, and CRP obviously increases, and invention medicine first and the high, medium and low dosage group of second, the CRP value of SHUANGHUANLIAN matched group of modeling are starkly lower than model control group again behind the prevention administration 3d; Illustrate that invention medicine first and second all can lower the infringement that the staphylococcus yeast increases venom, alleviate inflammatory reaction, reduce the degree of bacterial infection, the results are shown in Table 3.

The influence of table 3 pair rhinitis rat blood serum CRP level (x ± s)

Annotate: compare with model control group, ^*P＜0.05, ^*P＜0.01

3.3 invention medicine first and second are to the influence of rhinitis rat model nasal mucosa and bronchial mucosa histopathology form

Rats in normal control group nasal mucosa structure is normal, and nasal mucosa stratified ciliated columnar epithelium cell is clear, and mucosa is not seen hyperemia and inflammatory cell infiltration; The bronchial mucosa epithelial structure is normal, and ciliated columnar epithelial cells is clear, and mucosa is not seen hyperemia.And model control group rat nasal mucosa exuviation is obvious, the light moderate hyperemia of mucosa, and neutrophilic leukocyte, lymphocytic infiltration are arranged, bronchial mucosa the Ciliated epithelium partly come off, obvious lymphocytic infiltration in the mucosa.Invention medicine first and second height, middle dosage group rat nasal mucosa epithelial structure are normal, and the Ciliated epithelium is clear, do not see to come off rare leukocyte, lymphocytic infiltration in the mucosa; The bronchial mucosa epithelial structure is normal, and the Ciliated epithelium is clear, does not see to come off a small amount of lymphocytic infiltration in the mucosa.SHUANGHUANLIAN control rats nasal mucosa epithelium partly comes off, and sees obviously neutrophilic leukocyte, lymphocytic infiltration in the mucosa; The bronchial mucosa epithelium partly comes off, a small amount of lymphocytic infiltration in the mucosa.

4 sum up

Rat increases venom collunarium bacterial infection through the staphylococcus aureus yeast in this experiment, can comparatively fast cause bacterial infection, and invention medicine first and second are respectively organized rat, will obviously be better than model control group from state.This experiment increases the venom per nasal with the staphylococcus aureus yeast and splashes into and make the rat acute bacterial infection cause inflammatory reaction, and CRP obviously raises, and has outstanding performance with model control group; And each dosage group of invention medicine first and second and SHUANGHUANLIAN matched group CRP level do not raise, and with the model control group ratio highly significant statistical significance are arranged, and illustrate that invention medicine first and second all have bacteriostasis, all have the effectiveness of bacterial-infection resisting.

The histopathology observed result shows: modeling treated animal nasal mucosa and bronchial mucosa histologic lesion, congested in nasal mucosa epithelium and bronchial mucosa epithelial cell shedding, the epithelial tissue cell, a large amount of neutrophilic leukocytees, lymphocytic infiltration are arranged, and two groups of rat nasal mucosas of invention medicine first and second and bronchial mucosa structure are normal substantially, and be near with the normal control winding.The prompting of histopathology result of study: invention medicine first and second all have the bacterial-infection resisting ability, can obviously lower the antibacterial yeast and increase the infringement of venom to nasal mucosa and bronchial mucosa.

Result of study prompting: invention medicine first and second can alleviate obviously all that acute bacterial infection causes to nasal mucosa, the infringement of bronchial mucosa epithelium.Can lower the rapid rising of the CRP level that causes because of bacterial infection, have tangible bacterial-infection resisting and render a service.Prompting invention medicine first and second all have the better prevention effect to rhinitis.

The test of pesticide effectiveness of experimental example 3 medicine composite for curing sinusitis of the present invention

1 material

1.1 animal

100 of SD rats, body weight 200-250g, male and female half and half, Lanzhou Institute of Biological Products's Experimental Animal Center provides.Indoor temperature is controlled at 20 ℃-25 ℃.

1.2 medicine, reagent, important apparatus and other material

Pharmaceutical composition first of the present invention (making) according to embodiment 1; Pharmaceutical composition second of the present invention (making) according to embodiment 22; Gelomyrtol (Gelomyrtol Forte capsule): the big pharmaceutical factory of German Bao Shijia; Ketaject injection (production of Shanghai first pharmaceutical factory); Epinephrine (Shanghai Hefeng Pharmaceutical Co., Ltd.'s production); Lidocaine hydrochloride injection (production of Beijing ten thousand brightness Pharmaceutical groups); Staphylococcus aureus reference culture (ATCC): Pathogen Biology teaching and research room of preclinical medicine institute of Lanzhou University preparation; The PH reagent paper: reagent three factories in Shanghai produce; Test kit (malonaldehyde, glutathion peroxidase): bio-engineering research institute is built up in Nanjing; Caspase3H-277 (clone number) one is anti-available from Santa Cruz Biotechnology, and corresponding two anti-and test kits are available from Beijing Zhong Shan Bioisystech Co., Ltd.

Full automatic biochemical apparatus (7020 types, Japan); Low-temperature and high-speed centrifuge (Pico.Heraeus, Germany); CO ₂Critical point drying machine (CPD030, Germany); Atomic Absorption Spectrometer (BH5100 type, the Bohui Innovation Photoelectric Technology Co. Ltd., Beijing produces); Scanning electron microscope (SEM): AMRAY-1000B, Chinese Academy of Sciences's assembling; Electronic clinical thermometer (GFJY type, Tianjin medical apparatus instrument factory is produced); Microscope: OLYMPUS AX80 type, Japan produces; MIAS-2000 type graph image analytical system; Electronic balance (FA1194 type, Shanghai balance equipment head factory is produced); Pipettor; Scalpel, tissue are cut, eye scissors, needle holder, ophthalmology tweezer (straight forceps, curved tweezer), ophthalmology drag hook; Dermal needle; Silk thread; Gelfoam; Disinfecting cotton swab; 75% ethanol, povidone iodine; 0.9% sodium chloride injection; Shaver; Disposable syringe (5ml, 1ml); 2.5% glutaraldehyde; The medical aseptic glove.

2 methods

2.1 modeling

After freely feeding a week, by body weight, 90 rat modelings of sex picked at random, wherein 10 false model group of conduct remain 10 rats and organize as blank with rat.Totally 100.

The modeling process is as follows:

1. lumbar injection ketalar 5mg/100g (calculating by the rat ABW) repeats once with a half-value dose in case of necessity.

2. use 0.5% lidocaine hydrochloride 1.5-2ml (20mg/ml), join epinephrine 0.0125mg, make infiltration anesthesia under the bridge of the nose.

3. shave hair, use the iodophor disinfection preserved skin.Rat head is fixed in laboratory table, and under operating microscope, 1/3 intersection is other on center line opens 3mm and make otch with miter angle, enlarges surgical field of view, fills in gelfoam that the Semen Sesami size has staphylococcus aureus then in interior, sews up the incision.

4. false model group modeling method is the same, but what inject gelfoam is not staphylococcus aureus, but normal saline.

The standard of model success: the rat nasal obstruction, nasal vestibule has purulent secretion; Fervescence, the nose of scratching, sneeze, diet reduces, and the mental status is not good enough.

2.2 grouping

After freely feeding a week, laboratory animal is divided into blank group, model group, false model group, the high, medium and low dosage group of invention medicine first, the high, medium and low dosage group of invention medicine second, gelomyrtol group at random.Every group 10, totally 100.

2.3 medication

Modeling began administration after 7 days, and the administration persistent period is 7 days, and is specific as follows:

1. blank group: do not irritate stomach;

2. model group: every day is to irritate stomach with the normal saline of capacity such as medication group;

3. false model group: every day is to irritate stomach with the normal saline of capacity such as medication group;

4. the high, medium and low dosage group of invention medicine first: dosage is respectively 75mg/kgd, 50mg/kgd, 25mg/kgd irritates stomach.

5. the high, medium and low dosage group of invention medicine second: dosage is respectively 75mg/kgd, 50mg/kgd, 25mg/kgd irritates stomach.

6. gelomyrtol group: irritate stomach with the gelomyrtol (being equivalent to gelomyrtol 75mg/kgd) that is equivalent to 5 times of clinical adult's dosage every day, divides sooner or later every day to gavage for twice.

2.4 index and detection method

2.4.1 ordinary circumstance is observed

From modeling second day, observe the behavior of animal, state, sign, amount of drinking water, the situation of ingesting, the defecation situation, body temperature, body weight is observed sniffle emphatically, the amount that has that it's too late of nasal discharge, color, matter situation.

2.4.2 nasal discharge pH value

Try clean rat nasal vestibule with disinfecting cotton swab, (scope 6.4-8.0) is cut into 2 * 0.1cm with precision test paper ^-2Size stretches into the rat nasal cavity with the tweezers gripping, is close to the Mus nasal membrane, takes out after 30 seconds, reads this side nasal discharge pH value.

2.4.3 zinc ion Zn ²⁺Content

Medication 7 days takes femoral artery to get blood after finishing, centrifugal after, get serum, measure the Zn in serum ion Zn with chemical colorimetry ²⁺Content.

2.4.4 malonaldehyde (malonaldehyde, malondialdehyde, MDA) content

Medication 7 days takes femoral artery to get blood after finishing, centrifugal after, get serum, measure malonaldehyde (MDA) content in the serum with automatic biochemistry analyzer.

2.4.5 glutathion peroxidase (glutathione peroxidase, GSH-Px) vigor

Medication 7 days takes femoral artery to get blood after finishing, centrifugal after, get serum, measure glutathion peroxidase (GSH-Px) vigor in the serum with automatic biochemistry analyzer.

2.5 statistical analysis

3 results and analysis thereof

3.1 ordinary circumstance is observed

Beginning in the 3rd day after the modeling, nasal obstruction appears in most of animal, nasal vestibule hydroderma or flushing, nasal secretion transfers sticking purulence or purulence to gradually by the clear water sample, and the nose of scratching is frequent.After the modeling 7 days, above symptom all appears in all animals of antibacterial modeling group, and spirit is poor slightly, and the body temperature major part all has rising in various degree.Have several modeling treated animals loose stool to occur, mental status is relatively poor.False model group has several a little clear water sample secretions is arranged a little.Blank group no abnormality seen.

After the medication 7 days, model group rat rhinorrhea pus symptom does not have obviously and changes, and other medication group rat rhinorrhea pus disease all has and alleviates to some extent or disappear.False model group, blank group are not seen the Rhinorrhea symptom.

Medication is respectively organized rat body weight recruitment (Δ W=W before and after 1 week _After-W _Before) to relatively more obvious, model group weight increase amount is minimum, and blank group is maximum with false model group weight increase amount.In addition, two groups of invention medicine first, second and gelomyrtol group weight increase amount do not have significant difference each other.

After the medication 7 days, the model group rat temperature still maintains high level.The height of invention medicine first and second, middle dosage group body temperature descend to some extent, and its value occupy between blank group and model group.Rat temperature due to the gold Portugal bacterium raises, and still can not recover voluntarily in 7 days.The temperature recovery that the basic, normal, high dosage group of invention medicine first and second all can make rat raise is extremely normal.

3.2 nasal discharge pH value

Table 4 shows: model group rat nasal discharge pH value is the highest, compares with blank group, two groups of invention medicine first, second and other medication group, and significant difference (P＜0.01) is arranged.But the nasal discharge pH value of gelomyrtol group is still higher, compares with the blank group, and significant difference (P＜0.05) is arranged.

Nose mucus or secretions pH value (acid-base value) can influence the activity and the activity of lysozyme of nose mucomembranous cilium.It is generally acknowledged that the snotter pH value is in a reference index of conduct diagnosis sinusitis more than 7.5 or 7.5.Suitable snotter pH value not only can keep nasal mucosa ciliary movement function, but also activity of lysozyme is continued in higher level.

Mucociliary still contains the chemical substance destroy microorganisms except mechanically removing the microorganism with rete malpighii, kills and divides most by airborne antibacterial as lysozyme.And lysozyme is the most active in weak acid environment, could keep its most effective function.

This result of the test is shown: normal rat snotter pH value is alkalescence, and modeling group rat nasal discharge pH value significance increases.Invention medicine first and second all can reduce the nasal secretion pH value that rat raises, thereby infer and cause the best acid or alkali environment that is fit to rat nasal mucosa ciliary movement, help mucociliary the carrying out in transmission time.Simultaneously the relatively low lysozyme etc. of may impelling of pH value plays a role, and collaboratively promotes disappearing of rat hole transmucosal inflammation.

Experiment shows that invention medicine first and second all can make the nasal secretion pH value descend after treatment, nasal cavity is transformed to the normal range of neutral slant acidity from the alkaline environment of morbid state.

Rat nasal discharge pH value (x ± s) is respectively organized in table 4 medication after 7 days

Annotate: compare with the blank group: ^*P＜0.05, ^*P＜0.01 is compared with model group ^▲P＜0.05, ^{▲ ▲}P＜0.01

3.3 invention medicine first and second are to serum zinc ion (Zn ²⁺) influence

Each organizes rat except that the middle and high dosage group of invention medicine first and second, between all the other each group, comprises blank group, model group, false model group and other each medication group serum Zn ²⁺Concentration all more approaching, do not have significant difference.But the middle and high dosage group Zn of invention medicine first and second ²⁺Content is but apparently higher than other each group, and other respectively all has significant difference (P＜0.05) between group.Illustrate that certain density invention medicine first and second are by replenishing or having stimulated Zn in the body ²⁺Level, the metabolism of integrally-regulated body and immunologic function, thus reach the purpose of disease cured.The results are shown in Table 5.

Invention medicine first and second all can improve Zn in serum content, certain density invention medicine first and second have stimulated the commutative zinc pond of body, have used part zinc wherein and have made it be discharged into the activation that tissue and body fluid participate in relevant enzyme.Give full play to self-regulation mechanism in the body, impel benign cycle and the dynamic equilibrium of keeping organism metabolism.

Rat blood serum Zn is respectively organized in table 5 medication after 7 days ²⁺The content comparison (x ± s)

3.4 invention medicine first and second are to the influence of serum malonaldehyde (MDA)

From this experimental result data as can be seen, the model group rat is not because its inflammation is controlled artificially, and its Content of MDA occupies each experimental group peak, has compared notable difference (P＜0.05) with other experimental group.Illustrate when sinusitis is inflamed, produced too much free radical and lipid peroxidation has taken place.After Drug therapy, each organizes rat blood serum MDA value all in various degree decline, and wherein 6 invention medicine groups descend particularly evident.Illustrate that medicine first of the present invention and second all have the obvious suppression lipid peroxidation, the protection body is avoided the damage of free radical.The results are shown in Table 6.

Relatively (x ± s) of rat MDA is respectively organized in table 6 medication after 7 days

3.5 invention medicine first and second are to glutathion peroxidase in the serum (glutathione peroxidase, GSH-P _x) influence

Table 7 shows: after 1 week of medication, and model group rat blood serum GSH-P _xSignificantly reduce (P＜0.05), 3 dosage group rat blood serum GSH-P of invention medicine first and second _xCompare with model group, all significantly rise, significant difference (P＜0.05) is arranged, and suitable with the blank group, there was no significant difference (P＞0.05).

By GSH-P in the table 7 _xWith the contrast of MDA value, as can be seen, MDA numerical value basically and GSH-P _xThe relation of being inversely proportional to, GSH-P _xBe worth greatly more, the MDA value is just more little.Result of study explanation medicine first of the present invention of this experiment and second can both reach the purpose of removing excessive free radicals by the intravital relevant enzyme of activation machine system.

Rat blood serum glutathion peroxidase GSH-P is respectively organized in table 7 medication after 7 days _xRelatively (x ± s)

3.6 respectively organize rat rhinitis apoptosis situation after the administration

Under 10 * 20 times of light microscopics, observe rat rhinitis apoptosis situation, inflammatory cell apoptosis situation utilization Mias-2000 image analysis system is analyzed, for of the influence of other factorses such as erythrocyte among the eliminating Caspase-3 (SABC), add the integral optical density of surveying apoptosis to inflammatory cell apoptosis result of calculation.The results are shown in Table 8.

Apoptosis situation (the x ± s) of rat rhinitis cell is respectively organized in table 8 medication after 7 days

Annotate: compare with model group ^▲P＜0.05, ^{▲ ▲}P＜0.01

Table 8 shows: medication is after 7 days, and visible model group animal rhinitis apoptosis is not obvious, and 6 dosage groups, the gelomyrtol treated animal inflammatory cell apoptosis of invention medicine are more obvious.Each medication group rat rhinitis apoptosis area and apoptosis integral optical density all increase, and compare variant (P＜0.05) with model group, wherein, the middle and high dosage group increasing degree maximum of invention medicine first and second is compared with model group, and there were significant differences (P＜0.01).

Experimental result shows: invention medicine first and second all can be induced the apoptosis of inflammatory cell, alleviate or stop the generation of inflammatory reaction.

Following embodiment is used to further specify but is not limited to the present invention.

The specific embodiment

Embodiment 1: pharmaceutical composition nasal mist of the present invention

Radix Aucklandiae 50kg Fructus embeliae laetae 30kg

Benzoinum 20kg ZIMAOZI 30kg;

Get crude drug, mix, use water extraction 2h, 1h and the 0.5h of 10 times of weight, 8 times of weight, 6 times of weight respectively, filter, get filtrate and be concentrated into the concentrated solution that relative density is 1.01-1.10, adopt the method for accelerating slowly to stir in concentrated solution, to add ethanol, make and contain alcohol amount and reach 60%, cold preservation 24 hours filters, and reclaims ethanol; With 100kg distilled water diluting filtrate, add osmotic pressure regulator, pH regulator agent, antiseptic, penetration enhancer, pour into spray bottle, make nasal mist.

Embodiment 2: pharmaceutical composition nasal mist of the present invention

Radix Aucklandiae 45kg Fructus embeliae laetae 15kg

Benzoinum 5kg ZIMAOZI 35kg

Herba Centipedae 28kg Fructus Chebulae 5kg

Radix Glycyrrhizae 3kg;

Get crude drug, mix, use water extraction 2h, 1h and the 0.5h of 10 times of weight, 8 times of weight, 6 times of weight respectively, filter, filtrate is concentrated into 1: 1-1: 2 (ml: cross macroporous adsorbent resin g), wash with water, ethanol elution with 90%, collect eluent, evaporate to dryness obtains active component, with this active component of 150kg distilled water diluting, add osmotic pressure regulator, pH regulator agent, antiseptic, penetration enhancer again, pour into spray bottle, make nasal mist.

Embodiment 3: pharmaceutical composition nasal mist of the present invention

Radix Aucklandiae 20kg Fructus embeliae laetae 35kg

Benzoinum 15kg ZIMAOZI 15kg

Herba Centipedae 3kg Fructus Chebulae 45kg;

Get crude drug, mix, the ethanol extraction with 10 times of weight, 8 times of weight, 6 times of weight 80% extracts 2h, 1h and 0.5h respectively, leaves standstill filtration; Reclaim ethanol, cold preservation filters again; Filtrate is concentrated into 1: 1-1: 2 (ml: cross macroporous adsorbent resin g), wash with water, the ethanol elution with 90%, collection eluent, evaporate to dryness obtains active component, with this active component of 100kg distilled water diluting, add conventional adjuvant again, pour into spray bottle, make nasal mist.

Embodiment 4: pharmaceutical composition nasal cavity powder spray of the present invention

Radix Aucklandiae 5kg Fructus embeliae laetae 5kg

Benzoinum 1kg ZIMAOZI 5kg

Herba Centipedae 15kg;

Get crude drug, mix, use the water extraction 3 times of 10 times of weight, 8 times of weight, 6 times of weight respectively, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is condensed into extractum, the spray-dried dry powder that obtains of extractum, dry powder and lubricant, fluidizer and lactose mixed grinding make the nasal cavity powder spray.

Embodiment 5: pharmaceutical composition gel for nose of the present invention

Radix Aucklandiae 45kg Fructus embeliae laetae 15kg

Benzoinum 5kg ZIMAOZI 35kg

Herba Centipedae 28kg Fructus Chebulae 5kg;

Get crude drug, with the water extraction of 10 times of weight, 8 times of weight, 6 times of weight 3 times, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is concentrated into 1: 1-1: 2 (ml: g), cross macroporous adsorbent resin, obtain medicine activity component, add the hydrophilic gel carbomer 934, add the poly-Pyrusussuriensis phenol of pH regulator agent monoethanolamine, wetting agent, antiseptic chlorobutanol, solubilizer polyethylene glycol and cosolvent again, make gel for nose.

Embodiment 6: pharmaceutical composition tablet of the present invention

Radix Aucklandiae 20kg Fructus embeliae laetae 35kg

Benzoinum 15kg ZIMAOZI 15kg;

Get the above-mentioned composition crude drug, water extract respectively three times as follows: add the water of 10 times of weight, extracted 2 hours; The water that adds 8 times of weight extracted 1 hour; The water that adds 6 times of weight extracted 0.5 hour; Merge three times decocting liquid, shorten every 1L into and be equivalent to medical material 2kg extracting solution is suitable, adding 95% ethanol is 60% to containing the alcohol amount, leave standstill 24h, remove impurity, obtain clarifying liquid, through concentrate, drying obtains extract dry powder, this extract dry powder add conventional adjuvant routinely technology make tablet.

Embodiment 7: medicament composition capsule agent of the present invention

Radix Aucklandiae 45kg Fructus embeliae laetae 15kg

Benzoinum 5kg ZIMAOZI 35kg

Herba Centipedae 28kg Fructus Chebulae 5kg

Radix Glycyrrhizae 3kg;

Get the above-mentioned composition crude drug, with decocting extract respectively 3 times as follows: the water extraction 2 hours that adds 10 times of weight; The water extraction 1 hour that adds 8 times of weight; The water extraction 0.5 hour that adds 6 times of weight, and extracting solution is concentrated the back go up macroporous resin column absorption, after washing with water, the ethanol elution of reuse 90% reclaims ethanol with eluent, concentrates, drying obtains extract dry powder, with extract dry powder add conventional adjuvant routinely technology make capsule.

Embodiment 8: medicament composition granule agent of the present invention

Radix Aucklandiae 20kg Fructus embeliae laetae 35kg

Benzoinum 15kg ZIMAOZI 15kg;

Get the above-mentioned composition crude drug, with 75% ethanol extract respectively 3 times as follows: 75% ethanol extraction 2 hours that adds 10 times of weight; 75% ethanol extraction 1 hour that adds 8 times of weight; The 75% ethanol extraction 0.5h that adds 6 times of weight, extracting solution reclaims ethanol and obtains extractum, extractum is gone up macroporous adsorptive resins after with water dissolution, after washing with water, reuse 90% ethanol elution reclaims ethanol with eluent, concentrate, drying obtains extract dry powder, with extract dry powder add conventional adjuvant routinely technology make above-mentioned dosage form.

Embodiment 9: pharmaceutical composition nasal cavity powder spray of the present invention

Radix Aucklandiae 55kg Fructus embeliae laetae 33kg

Benzoinum 17kg ZIMAOZI 33kg

Radix Glycyrrhizae 11kg;

Get crude drug, cleaning, drying are ground into fine powder, and particle diameter is 150 μ m-200 μ m, makes micropowders through micronizing again, and particle diameter is 5 μ m-20 μ m, and this micropowders and lubricant, fluidizer and cellulose derivative mixed grinding make the nasal cavity powder spray.

Embodiment 10: pharmaceutical composition nasal cavity powder spray of the present invention

Radix Aucklandiae 30kg Fructus embeliae laetae 25kg

Benzoinum 12kg ZIMAOZI 15kg

Radix Glycyrrhizae 20kg Fructus Chebulae 30kg

Get crude drug, mix, use 65% ethanol extraction 3 times of 10 times of weight, 8 times of weight, 6 times of weight respectively, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is condensed into extractum, the spray-dried dry powder that obtains of extractum, dry powder and lubricant, fluidizer and lactose mixed grinding make the nasal cavity powder spray.

Embodiment 11: pharmaceutical composition gel for nose of the present invention

Radix Aucklandiae 20kg Fructus embeliae laetae 35kg

Benzoinum 15kg ZIMAOZI 15kg

Radix Glycyrrhizae 15kg;

Get crude drug, with 65% ethanol extraction of 10 times of weight, 8 times of weight, 6 times of weight 3 times, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is concentrated into 1: 1-1: 2 (ml: g), cross macroporous adsorbent resin, obtain medicine activity component, add the hydrophilic gel carbomer 934, add the poly-Pyrusussuriensis phenol of pH regulator agent monoethanolamine, wetting agent, antiseptic chlorobutanol, solubilizer polyethylene glycol and cosolvent again, make gel for nose.

Embodiment 12: pharmaceutical composition gel for nose of the present invention

Radix Aucklandiae 50kg Fructus embeliae laetae 30kg

Benzoinum 20kg ZIMAOZI 30kg

Herba Centipedae 30kg Fructus Chebulae 10kg;

Get crude drug, with the water extraction of 10 times of weight, 8 times of weight, 6 times of weight 3 times, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is concentrated into 1: 1-1: 2 (ml: g), the ethanol of adding 95% is 60% to containing the alcohol amount, leave standstill 24h, remove precipitation, supernatant adds the hydrophilic gel carbomer 934, add the poly-Pyrusussuriensis phenol of pH regulator agent monoethanolamine, wetting agent, antiseptic chlorobutanol, solubilizer polyethylene glycol and cosolvent again, make gel for nose.

Embodiment 13: pharmaceutical composition nasal drop of the present invention

Radix Aucklandiae 45kg Fructus embeliae laetae 30kg

Benzoinum 15kg ZIMAOZI 30kg

Herba Centipedae 20kg

Get crude drug, with 65% ethanol extraction of 10 times of weight, 8 times of weight, 6 times of weight 3 times, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is concentrated into 1: 1-1: 2 (ml: g), cross macroporous adsorbent resin, obtain medicine activity component, medicine activity component is combined with the pharmaceutics acceptable auxiliary, and make nasal drop by the routine techniques of galenic pharmacy.

Embodiment 14: pharmaceutical composition ointment of the present invention

Radix Aucklandiae 40kg Fructus embeliae laetae 30kg

Benzoinum 15kg ZIMAOZI 30kg

Radix Glycyrrhizae 10kg

Get crude drug, mix, use the water extraction 3 times of 10 times of weight, 8 times of weight, 6 times of weight respectively, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is condensed into extractum, extractum add conventional adjuvant routinely technology make ointment.

Embodiment 15: medicament composition dropping pills of the present invention

Radix Aucklandiae 30kg Fructus embeliae laetae 25kg

Benzoinum 12kg ZIMAOZI 15kg

Radix Glycyrrhizae 20kg Fructus Chebulae 30kg

Get crude drug, mix, use 65% ethanol extraction 3 times of 10 times of weight, 8 times of weight, 6 times of weight respectively, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is condensed into extractum, and extractum combines with the pharmaceutics acceptable auxiliary, and makes drop pill by the routine techniques of galenic pharmacy.

Embodiment 16: medicinal composition powders of the present invention

Radix Aucklandiae 20kg Fructus embeliae laetae 25kg

Benzoinum 12kg ZIMAOZI 30kg

Radix Glycyrrhizae 10kg Fructus Chebulae 30kg

Herba Centipedae 15kg

Getting crude drug adds conventional adjuvant and makes powder according to common process.

Embodiment 17: drug composition oral liquid of the present invention

Radix Aucklandiae 40kg Fructus embeliae laetae 25kg

Benzoinum 10kg ZIMAOZI 25kg

Radix Glycyrrhizae 10kg Fructus Chebulae 30kg

Herba Centipedae 20kg

Get crude drug, with the water extraction of 10 times of weight, 8 times of weight, 6 times of weight 3 times, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate concentrates, add conventional adjuvant after the ultrafiltration, adds pure water and makes oral liquid.

Embodiment 18: pharmaceutical composition honeyed pill of the present invention

Radix Aucklandiae 50kg Fructus embeliae laetae 30kg

Benzoinum 20kg ZIMAOZI 30kg

Radix Glycyrrhizae 30kg Fructus Chebulae 10kg;

Get crude drug, with the water extraction of 10 times of weight, 8 times of weight, 6 times of weight 3 times, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is concentrated into 1: 1-1: 2 (ml: g), adding 95% ethanol is 60% to containing the alcohol amount, leave standstill 24h, remove precipitation, supernatant concentration adds conventional adjuvant, and technology is made honeyed pill routinely.

Embodiment 19: medicine composition injection of the present invention

Radix Aucklandiae 10kg Fructus embeliae laetae 5kg

Benzoinum 1kg ZIMAOZI 15kg

Radix Glycyrrhizae 5kg Fructus Chebulae 10kg;

Get crude drug, with the water extraction of 10 times of weight, 8 times of weight, 6 times of weight 3 times, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is concentrated into 1: 1-1: 2 (ml: g), cross macroporous adsorbent resin, obtain medicine activity component, medicine activity component is combined with the pharmaceutics acceptable auxiliary, and make injection by the routine techniques of galenic pharmacy.

Embodiment 20: pharmaceutical composition nasal mist of the present invention

Radix Aucklandiae 50kg Fructus embeliae laetae 30kg

Benzoinum 20kg ZIMAOZI 30kg;

Get crude drug, mix, use water extraction 2h, 1h and the 0.5h of 10 times of weight, 8 times of weight, 6 times of weight respectively, filter, get filtrate and be concentrated into the concentrated solution that relative density is 1.10-1.20, adopt the method for accelerating slowly to stir in concentrated solution, to add ethanol, make and contain alcohol amount and reach 60%, cold preservation 24 hours filters, and reclaims ethanol; With 100kg distilled water diluting filtrate, add osmotic pressure regulator, pH regulator agent, antiseptic, penetration enhancer, pour into spray bottle, make nasal mist.

Embodiment 21: pharmaceutical composition nasal mist of the present invention

Radix Aucklandiae 50kg Fructus embeliae laetae 30kg

Benzoinum 20kg ZIMAOZI 30kg;

Get crude drug, mix, use water extraction 2h, 1h and the 0.5h of 10 times of weight, 8 times of weight, 6 times of weight respectively, filter, get filtrate and be concentrated into the concentrated solution that relative density is 1.20-1.30, adopt the method for accelerating slowly to stir in concentrated solution, to add ethanol, make and contain alcohol amount and reach 60%, cold preservation 24 hours filters, and reclaims ethanol; With 100kg distilled water diluting filtrate, add osmotic pressure regulator, pH regulator agent, antiseptic, penetration enhancer, pour into spray bottle, make nasal mist.

Embodiment 22: pharmaceutical composition nasal cavity powder spray of the present invention

Radix Aucklandiae 50kg Fructus embeliae laetae 30kg

Benzoinum 20kg ZIMAOZI 30kg

Radix Glycyrrhizae 10kg Fructus Chebulae 50kg;

Get crude drug, mix, use 70% ethanol extraction 3 times of 10 times of weight, 8 times of weight, 6 times of weight respectively, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is condensed into extractum, the spray-dried dry powder that obtains of extractum, dry powder and lubricant, fluidizer and lactose mixed grinding make the nasal cavity powder spray.

Claims

1. one kind has the pharmaceutical composition for the treatment of rhinitis, sinusitis and allergic rhinitis effect, it is characterized in that the crude drug of this pharmaceutical composition consists of:

Benzoinum 0.1-25 weight portion ZIMAOZI 1-40 weight portion.

2. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:

Benzoinum 20 weight portion ZIMAOZI 30 weight portions.

3. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:

Benzoinum 5 weight portion ZIMAOZI 35 weight portions.

4. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:

Benzoinum 15 weight portion ZIMAOZI 15 weight portions.

5. pharmaceutical composition as claimed in claim 1 is characterized in that the crude drug of this pharmaceutical composition consists of:

Benzoinum 1 weight portion ZIMAOZI 5 weight portions.

6. as the arbitrary described pharmaceutical composition of claim 1-5, it is characterized in that also adding in the crude drug of this pharmaceutical composition in the following crude drug one or more:

7. pharmaceutical composition as claimed in claim 6 is characterized in that also adding in the crude drug of this pharmaceutical composition in the following crude drug one or more:

Herba Centipedae 28 weight portion Fructus Chebulaes 5 weight portion Radix Glycyrrhizaes 3 weight portions;

Or Herba Centipedae 3 weight portion Fructus Chebulaes 45 weight portion Radix Glycyrrhizaes 28 weight portions;

Or Herba Centipedae 15 weight portion Fructus Chebulaes 25 weight portion Radix Glycyrrhizaes 15 weight portions.

8. as claim 1-5 or 7 arbitrary described preparation of drug combination methods, it is characterized in that this method comprises the steps:

Get the above-mentioned composition crude drug, clean, dry, be ground into fine powder, particle diameter is 150 μ m-200 μ m, make micropowders through micronizing again, particle diameter is 5 μ m-20 μ m, this micropowders add conventional adjuvant routinely technology make nasal mist, nasal cavity powder spray, gel for nose, nasal drop, tablet, capsule, powder, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation;

Or get the above-mentioned composition crude drug, the water that adds the 5-10 times of weight, extract 1-3 time, and extracting solution is condensed into per 1 parts by volume is equivalent to medical material 1-2 weight portion, add 95% ethanol and reach 60%～70% to containing the alcohol amount, leave standstill 24h, remove impurity, obtain clarifying liquid, again through concentrating, drying obtains extract dry powder, this extract dry powder add conventional adjuvant routinely technology make nasal mist, the nasal cavity powder spray, gel for nose, nasal drop, tablet, capsule, powder, pill, granule, the soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation;

Or get the above-mentioned composition crude drug, ethanol extraction 1-3 time that adds 5-10 times of weight 60-90%, alcohol extract reclaims ethanol, the water that adds medicinal liquid 1-3 times of weight stirs, cold preservation, treat complete post precipitation elimination impurity, obtain clarifying liquid, again through concentrate, drying obtains extract dry powder, this extract dry powder add conventional adjuvant routinely technology make nasal mist, nasal cavity powder spray, gel for nose, nasal drop, tablet, capsule, powder, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation;

Or get the above-mentioned composition crude drug, the water that adds the 5-10 times of weight, extract 1-3 time, and with the upward macroporous resin column absorption of the concentrated back of extracting solution, after washing with water, the ethanol elution of reuse 60%-95%, eluent is reclaimed ethanol, concentrate, dry, obtain extract dry powder, with extract dry powder add conventional adjuvant routinely technology make nasal mist, nasal cavity powder spray, gel for nose, nasal drop, tablet, capsule, powder, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation;

Or get the above-mentioned composition crude drug, add 5-10 times of weight 60-90% ethanol extraction 1-3 time, extracting solution reclaims ethanol and obtains extractum, extractum is gone up macroporous adsorptive resins after with water dissolution, after washing with water, the ethanol elution of reuse 60%-95%, eluent is reclaimed ethanol, concentrate, dry, obtain extract dry powder, with extract dry powder add conventional adjuvant routinely technology make nasal mist, the nasal cavity powder spray, gel for nose, nasal drop, tablet, capsule, powder, pill, granule, the soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation.

9. preparation of drug combination method as claimed in claim 8 is characterized in that capsule described in this method is a soft capsule, and pill is honeyed pill or drop pill.

10. preparation of drug combination method as claimed in claim 8 is characterized in that this method comprises the steps:

Get the above-mentioned composition crude drug, clean, dry, be ground into fine powder, particle diameter is 190 μ m, make micropowders through micronizing again, particle diameter is 10 μ m, this superfine powder add conventional adjuvant routinely technology make nasal mist, nasal cavity powder spray, gel for nose, nasal drop, tablet, capsule, powder, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation;

Or get the above-mentioned composition crude drug, water extract respectively three times as follows: add the water of 10 times of weight, extracted 2 hours; The water that adds 8 times of weight extracted 1 hour; The water that adds 6 times of weight extracted 0.5 hour; Merge three times decocting liquid, extracting solution is condensed into per 1 parts by volume is equivalent to medical material 2 weight portions, the ethanol of adding 95% is 60% to containing the alcohol amount, leave standstill 24h, remove impurity, obtain clarifying liquid, through concentrate, drying obtains extract dry powder, this extract dry powder add conventional adjuvant routinely technology make nasal mist, nasal cavity powder spray, gel for nose, nasal drop, tablet, capsule, powder, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation;

Or get the above-mentioned composition crude drug, ethanol with 75% extract respectively three times as follows: 75% ethanol extraction 2 hours that adds 10 times of weight, 75% ethanol extraction 1 hour that adds 8 times of weight, 75% ethanol extraction 0.5 hour that adds 6 times of weight, filter merging filtrate respectively, reclaim ethanol, the water that adds medicinal liquid 2 times of weight, mixing, leave standstill 24h, getting supernatant filters, reclaim ethanol, obtain clarifying medicinal liquid, through concentrating, drying obtains extract dry powder, this extract dry powder add conventional adjuvant routinely technology make nasal mist, the nasal cavity powder spray, gel for nose, nasal drop, tablet, capsule, powder, pill, granule, the soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation;

Or get the above-mentioned composition crude drug, with decocting extract respectively 3 times as follows: the water extraction 2 hours that adds 10 times of weight; The water extraction 1 hour that adds 8 times of weight; The water extraction 0.5 hour that adds 6 times of weight, and with the upward macroporous resin column absorption of the concentrated back of extracting solution, after washing with water, the ethanol elution of reuse 90%, eluent is reclaimed ethanol, concentrate, dry, obtain extract dry powder, with extract dry powder add conventional adjuvant routinely technology make nasal mist, nasal cavity powder spray, gel for nose, nasal drop, tablet, capsule, powder, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation;

Or get the above-mentioned composition crude drug, with 75% ethanol extract respectively 3 times as follows: 75% ethanol extraction 2 hours that adds 10 times of weight; 75% ethanol extraction 1 hour that adds 8 times of weight; The 75% ethanol extraction 0.5h that adds 6 times of weight, extracting solution reclaims ethanol and obtains extractum, extractum is gone up macroporous adsorptive resins after with water dissolution, after washing with water, reuse 90% ethanol elution, eluent is reclaimed ethanol, concentrate, dry, obtain extract dry powder, with extract dry powder add conventional adjuvant routinely technology make nasal mist, nasal cavity powder spray, gel for nose, nasal drop, tablet, capsule, powder, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation.

11. preparation of drug combination method as claimed in claim 10 is characterized in that capsule described in this method is a soft capsule, pill is honeyed pill or drop pill.

12. preparation of drug combination method as claimed in claim 6 is characterized in that this method comprises the steps:

13. preparation of drug combination method as claimed in claim 12 is characterized in that capsule described in this method is a soft capsule, pill is honeyed pill or drop pill.

14. preparation of drug combination method as claimed in claim 12 is characterized in that this method comprises the steps:

Or get the above-mentioned composition crude drug, water extract respectively three times as follows: add the water of 10 times of weight, extracted 2 hours; The water that adds 8 times of weight extracted 1 hour; The water that adds 6 times of weight extracted 0.5 hour; Merge three times decocting liquid, shorten per 1 parts by volume into and be equivalent to medical material 2 weight portions extracting solution is suitable, the ethanol of adding 95% is 60% to containing the alcohol amount, leave standstill 24h, remove impurity, obtain clarifying liquid, through concentrate, drying obtains extract dry powder, this extract dry powder add conventional adjuvant routinely technology make nasal mist, nasal cavity powder spray, gel for nose, nasal drop, tablet, capsule, powder, pill, granule, soft extract with bee honey agent, slow releasing preparation, quick releasing formulation, controlled release preparation, oral liquid or ejection preparation;

15. preparation of drug combination method as claimed in claim 14 is characterized in that capsule described in this method is a soft capsule, pill is honeyed pill or drop pill.

16., it is characterized in that the preparation method of pharmaceutical composition nasal mist comprises the steps: as claim 1-5 or 7 arbitrary described preparation of drug combination methods

Get crude drug, mix, use water extraction 2h, 1h and the 0.5h of 10 times of weight, 8 times of weight, 6 times of weight respectively, filter, get filtrate and be concentrated into the concentrated solution that relative density is 1.01-1.30, adopt the method for accelerating slowly to stir in concentrated solution, to add ethanol, make the alcohol amount of containing reach 50%-70%, cold preservation 10-48 hour, filter, reclaim ethanol; With 50-200 weight portion distilled water diluting filtrate, add conventional adjuvant, pour into spray bottle, make nasal mist;

Or get crude drug, and mix, use water extraction 2h, 1h and the 0.5h of 10 times of weight, 8 times of weight, 6 times of weight respectively, filter, filtrate is concentrated into ml: g is 1: 1-1: macroporous adsorbent resin is crossed in 2 backs, washes with water, ethanol elution with 60%-95%, collect eluent, evaporate to dryness obtains active component, with this active component of 50-200 weight portion distilled water diluting, add conventional adjuvant again, pour into spray bottle, make nasal mist;

Or get crude drug, and mixing, the ethanol extraction with 10 times of weight, 8 times of weight, 6 times of weight 60%～90% extracts 2h, 1h and 0.5h respectively, leaves standstill filtration; Reclaim ethanol, cold preservation filters again; With 50-200 weight portion distilled water diluting filtrate, add conventional adjuvant, pour into spray bottle, make nasal mist;

Or get crude drug, and mixing, the ethanol extraction with 10 times of weight, 8 times of weight, 6 times of weight 60%～90% extracts 2h, 1h and 0.5h respectively, leaves standstill filtration; Reclaim ethanol, cold preservation filters again; Filtrate is concentrated into ml: g is 1: 1-1: macroporous adsorbent resin is crossed in 2 backs, wash with water, ethanol elution with 60%-95%, collect eluent, evaporate to dryness obtains active component, with this active component of 50-200 weight portion distilled water diluting, add conventional adjuvant again, pour into spray bottle, make nasal mist.

17. preparation of drug combination method as claimed in claim 16 is characterized in that the preparation method of pharmaceutical composition nasal mist comprises the steps:

Get crude drug, mix, use water extraction 2h, 1h and the 0.5h of 10 times of weight, 8 times of weight, 6 times of weight respectively, filter, get filtrate and be concentrated into the concentrated solution that relative density is 1.01-1.10,1.10-1.20 or 1.20-1.30, adopt the method for accelerating slowly to stir in concentrated solution, to add ethanol, make and contain alcohol amount and reach 60%, cold preservation 24 hours filters, and reclaims ethanol; With 150 weight portion distilled water diluting filtrates, add conventional adjuvant, pour into spray bottle, make nasal mist;

Or get crude drug, and mix, use water extraction 2h, 1h and the 0.5h of 10 times of weight, 8 times of weight, 6 times of weight respectively, filter, filtrate is concentrated into ml: g is 1: 1-1: macroporous adsorbent resin is crossed in 2 backs, washes with water, ethanol elution with 90%, collect eluent, evaporate to dryness obtains active component, with 150 these active components of weight portion distilled water diluting, add conventional adjuvant again, pour into spray bottle, make nasal mist;

Or get crude drug, and mixing, the ethanol extraction with 10 times of weight, 8 times of weight, 6 times of weight 60%～90% extracts 2h, 1h and 0.5h respectively, leaves standstill filtration; Reclaim ethanol, cold preservation filters again; With 150 weight portion distilled water diluting filtrates, add conventional adjuvant, pour into spray bottle, make nasal mist;

Or get crude drug, and mixing, the ethanol extraction with 10 times of weight, 8 times of weight, 6 times of weight 60%～90% extracts 2h, 1h and 0.5h respectively, leaves standstill filtration; Reclaim ethanol, cold preservation filters again; Filtrate is concentrated into ml: g is 1: 1-1: macroporous adsorbent resin is crossed in 2 backs, washes with water, and the ethanol elution with 90% is collected eluent, evaporate to dryness obtains active component, with 150 these active components of weight portion distilled water diluting, add conventional adjuvant again, pour into spray bottle, make nasal mist.

18. as claim 16 or 17 arbitrary described preparation of drug combination methods, it is characterized in that wherein said adjuvant is meant osmotic pressure regulator, pH regulator agent, antiseptic, penetration enhancer, wherein penetration enhancer comprise in cyclodextrin, phospholipid, Borneolum Syntheticum, Camphora, the Mentholum any or several.

19. preparation of drug combination method as claimed in claim 6 is characterized in that the preparation method of pharmaceutical composition nasal mist comprises the steps:

20. preparation of drug combination method as claimed in claim 19 is characterized in that the preparation method of pharmaceutical composition nasal mist comprises the steps:

21. as claim 19 or 20 arbitrary described preparation of drug combination methods, it is characterized in that wherein said adjuvant is meant osmotic pressure regulator, pH regulator agent, antiseptic, penetration enhancer, wherein penetration enhancer comprise in cyclodextrin, phospholipid, Borneolum Syntheticum, Camphora, the Mentholum any or several.

22., it is characterized in that the preparation method of this pharmaceutical composition nasal cavity powder spray comprises the steps: as claim 1-5 or 7 arbitrary described preparation of drug combination methods

Or get crude drug, mix, use the water of 10 times of weight, 8 times of weight, 6 times of weight or ethanol extraction 3 times respectively, extract 2h, 1h, 0.5h respectively, filter, filtrate is concentrated into ml: g is 1: 1-1: macroporous adsorbent resin is crossed in 2 backs, washes with water, with the ethanol elution of 60%-95%, collect eluent, evaporate to dryness obtains active component, and this active component and adjuvant mixed grinding make the nasal cavity powder spray.

23. preparation of drug combination method as claimed in claim 6 is characterized in that the preparation method of this pharmaceutical composition nasal cavity powder spray comprises the steps:

Get crude drug, cleaning, drying are ground into fine powder, and particle diameter is 150 μ m-200 μ m, makes micropowders through micronizing again, and particle diameter is 5 μ m-20 μ m, and this micropowders and adjuvant mixed grinding make the nasal cavity powder spray;

24., it is characterized in that wherein said adjuvant comprises lubricant, fluidizer and pharmaceutical carrier as claim 22 or 23 arbitrary described preparation of drug combination methods; Wherein pharmaceutical carrier comprises cellulose, chitosan, lactose and carbomer.

25., it is characterized in that the preparation method of this pharmaceutical composition gel for nose comprises the steps: as claim 1-5 or 7 arbitrary described preparation of drug combination methods

Or get crude drug, with the water of 10 times of weight, 8 times of weight, 6 times of weight or ethanol extraction 3 times, extract 2h, 1h, 0.5h respectively, filter, remove residue, filtrate is concentrated into ml: g is 1: 1-1: 2, cross macroporous adsorbent resin, and obtain medicine activity component, add hydrophilic gel, and acceptable accessories is made gel for nose.

26. preparation of drug combination method as claimed in claim 6 is characterized in that the preparation method of this pharmaceutical composition gel for nose comprises the steps:

27. as claim 25 or 26 arbitrary described preparation of drug combination methods, it is characterized in that wherein said hydrophilic gel is carbomer 934, Acritamer 940, one or more in Carbopol 941, carbomer 974P, Polycarbophil, methylcellulose, sodium carboxymethylcellulose or antelope third methylcellulose; Other adjuvant be pH regulator agent, wetting agent, antiseptic, solubilizing agent and cosolvent one or more; The pH regulator agent is one or more in monoethanolamine, two isopropanolamine, triethanolamine, sodium hydroxide, potassium hydroxide, hydrochloric acid, phosphoric acid, citric acid or the sodium citrate; Antiseptic is oxybenzene ester, chlorobutanol, benzyl alcohol, phenethanol, disodiumedetate, chlorhexidine acetate, thimerosal or season by in the compounds cationic surfactant one or more; Solubilizing agent and cosolvent are one or more in ethanol, Polyethylene Glycol, propylene glycol, TC, Labrasol or the cyclodextrin.

28. the application in preparation treatment rhinitis, sinusitis medicine as claim 1-5 or 7 arbitrary described pharmaceutical compositions.

29. the application in preparation treatment of allergic rhinitis medicine as claim 1-5 or 7 arbitrary described pharmaceutical compositions.

30. the application of pharmaceutical composition as claimed in claim 6 in preparation treatment rhinitis, sinusitis medicine.

31. the application of pharmaceutical composition as claimed in claim 6 in preparation treatment of allergic rhinitis medicine.