CN103735845B - A kind of Chinese medicine for external application treating Pediatric secretory otitis media and preparation method thereof - Google Patents

Abstract

A kind of Chinese medicine for external application treating Pediatric secretory otitis media, in described external preparation, the parts by weight of various raw materials are: Herba Centipedae 10～20 parts, Herba Schizonepetae 10～20 parts, Radix Sophorae Flavescentis 10～20 parts, Fructus Toosendan 10～20 parts, Borneolum Syntheticum 10～20 parts, Cortex Phellodendri 10～20 parts, Radix Scutellariae 10～20 parts, Pseudobulbus Bletillae (Rhizoma Bletillae) 10～20 parts, Herba Menthae 10～20 parts, Indigo Naturalis 10～20 parts, Radix Arnebiae (Radix Lithospermi) 10～20 parts, Radix Salviae Miltiorrhizae 10～20 parts, Herba Taraxaci 10～20 parts, Rhizoma Atractylodis 10～20 parts, the Radix Angelicae Dahuricae 10～20 parts。Medicine of the present invention has good heat-clearing and toxic substances removing, eliminating dampness and astringing sores, removing the necrotic tissue and promoting granulation, exorcise evil spirits analgesic effect, and has effect that dry ear is fast, curative effect is short, have no side effect。For patients with secretory otitis media, it is possible to promote secretions to disappear absorption, the tympanum reparation of perforation, make auditory rehabilitation。The present invention has the multiple effects such as antibacterial, antiinflammatory, convergence, dehumidifying, sensible, pain relieving。

Description

A kind of Chinese medicine for external application treating Pediatric secretory otitis media and preparation method thereof

Technical field

The present invention relates to containing the medicinal preparation deriving from plant, animal or mineral component, particularly to a kind of Chinese medicine for external application treating Pediatric secretory otitis media and preparation method thereof。

Background technology

The middle ear apyetous inflammatory diseases that secretory otitis media (otitismediawitheffusion) is is feature with middle ear effusion and auditory dysesthesia, for one of otorhinolaryngology common disease。Child is common。With the vexed swollen sense of ear and auditory dysesthesia for cardinal symptom after upper respiratory tract infection。Owing to otalgia is inconspicuous, child main suit is unclear, and when children's's audition is affected, the head of a family just finds medical, usually delay diagnosis and treatment。Secretory otitis media can cause the hearing loss of child, affects verbal language and grows, answers highly vigilant of and observe treatment in time。For adults with unilateral pathological changes person, should the clear and definite cause of disease as early as possible, get rid of the occupancy tumor of nasopharynx part and peripheral clearance thereof, as early as possible relief of symptoms, quality of making the life better。

The middle ear apyetous inflammatory diseases that secretory otitis media is is feature with middle ear effusion and auditory dysesthesia, is also called secretory otitis media, non-suppurative otitis media, MOM, catarrhal otitis media, hydrotympanum, otitis media serosa, serosity one MOM, aseptic otitis media。If hydrops and thickness and in gelatin person, be also called secretory otitis media。With the vexed swollen sense of ear after upper respiratory tract infection, listen sound remote and auditory dysesthesia is for cardinal symptom。Owing to otalgia is inconspicuous, child main suit is unclear, and when children's's audition is affected, the head of a family just finds medical, usually delay diagnosis and treatment。The visible tympanum of otology training inspection is amber or crocus, also visible air fluid level or bubble, and tympanum mobility reduces。Secretory otitis media child is common。The hearing loss of child can be caused, affect verbal language and grow, answer highly vigilant of and observe treatment in time。For adults with unilateral pathological changes person, should the clear and definite cause of disease as early as possible, get rid of the occupancy tumor of nasopharynx part and peripheral clearance thereof, as early as possible relief of symptoms, quality of making the life better。

Research finds that the preschooler of about 90% suffered from secretory otitis media, and the school age population of 25% suffers from secretory otitis media。It is most commonly in June～4 year old child。Suffer from the child of secretory otitis media during by 1 years old more than 50%, during by 2 years old, increase to 60%。Many outbreaks were disappeared voluntarily at 3 months, and the children with otitis media with effusion of about 30%～40% can recur。The infant secretory otitis media of 5%～10% continues more than 1 year。In the U.S., the infant having 2,002,000,000 diagnosis to be secretory otitis media every year, the direct and consequential damage caused every year is estimated to reach 4,000,000,000 dollars。

The anatomical structure that infant is susceptible to suffer from secretory otitis media special with infant is relevant。Neonatal pharyngotympanic tube is short, wide and straight, and secretions The book of Changes pharyngotympanic tube of nasopharynx part enters middle ear and causes inflammation。Made the neonate of artificial respiration when difficult labour during childbirth, breech presentation, room breath, amniotic fluid often easily enter in ear。Parent suffers from hypertensive state of pregnancy, preeclampsia or antepartum hemorrhage person, and amniotic fluid also easily enters middle ear generation infection and causes otitis media。The improper easily inverse breast of neonatal nursing, person manually do not fed by dorsal position of particularly making even feeding bottle, and during inverse breast, milk pool amasss in cavum nasopharyngeum, enters middle ear through pharyngotympanic tube and causes otitis media。

The clinical manifestation of secretory otitis media is mainly auditory dysesthesia, can change with position chanP, slight otalgia, tinnitus, sense that ear is vexed swollen and inaccessible, the audible underwater sound of shaking the head。The visible otopiesis of otology training inspection, in amber or color and luster obfuscation, also visible air fluid level or bubble, tympanum mobility reduces。

Infant then shows as ambient sound Low Response, grabs ear, and sleep is easily waken up, irritability。The sound of surrounding is not reacted by baby, it is impossible to head turns to sound source exactly；Even if infant does not have main suit's auditory dysesthesia, household then finds that infant is careless, behavior change, normal dialog is reactionless, always sound is opened very big when seeing TV or using hearing device；For the acute otitis media of recurrent exerbation, should watch out for and be likely to lasting secretory otitis media in the outbreak intermission；School grade is poor；Balanced capacity is poor, the clumsiness of unknown cause；Verbal language hypoevolutism。

Infant and children with otitis media with effusion should differentiate mutually with acute otitis media。Acute otitis media treatment thoroughly or protracted course of disease can be exchanged into secretory otitis media。Many courses of disease are shorter, and patient can have the symptoms such as violent otalgia, discharging ear, and the many courses of disease of secretory otitis media are longer, how vexed for cardinal symptom with ear, and otalgia is discontinuity, gentlier, even show without otalgia。

Because secretory otitis media is self-limited disease, having certain spontaneous recovery rate, before giving invasive treatment, patient should close observation March。Whether the cause of disease and the length of hydrops time are depended in spontaneous recovery to secretory otitis media。The patients with secretory otitis media left over by acute otitis media, about 75%～90% when March can spontaneous recovery, tympanogram is transferred to A, C type by B。About 55% patients with secretory otitis media can the spontaneous recovery when March, but, the infant of about 1/3 is likely to increase the weight of。In 2～4 years old infant that the onset time is ominous, the infant spontaneous recovery time of about 25% is 3 months。The spontaneous recovery rate of baby and children's is higher。Within more than 2 years old, ears secretory otitis media, the course of disease are at above infant in March, and when 6～December, its spontaneous recovery person is about 30%。

For being in the non-high-risk children in observation stage, it is no matter medicine or surgical intervention then hundred evils and none is sharp, observes and wait non-high-risk children then without harm；Need to inform that household's infant audition is poor, especially ears patients with secretory otitis media；Formulation improves infant and listens to the measure with academic environment and scheme；Periodic review, go forward side by side circulation of qi promoting clamp lug mirror and tympanogram inspection。

For child, curative effect of medication is of short duration and limited, and side effect is many, does not recommend。Do not advocate life-time service antibiotic therapy secretory otitis media, tympanum hyperemia should not become the indication (having 5% children with secretory otitis media also to can behave as tympanum hyperemia) of antibiotic application, do not advocate antihistaminic and Decongestant are used in combination, because their side effect is obvious。Life-time service oral hormone treatment at large is not advocated yet, unless single cases。There is no evidence and support the therapeutical effect of pharyngotympanic tube ventilation, oral or Injection in Tympanic Cavity mucus eccritic and other drug。

The medicine of existing treatment by Chinese herbs secretory otitis media is less, main reason is that, curative effect is not notable, and some treatment cycle are up to several weeks。Treating the medicine of otitis media in prior art, be mostly use Western medicine antiinflammatory, for children's, side effect is many, does not recommend；Chinese medicine decoction is administered orally, and mouthfeel is poor, and infant does not also accept。Only Chinese medicine for outer use is the properest, through focus。The new drug of the treatment secretory otitis media that the applicable children's of exploitation uses is exactly the present task of top priority。

Summary of the invention

The technical problem to be solved is in that, treats the medicine of secretory otitis media in prior art, is mostly use Western medicine antiinflammatory, and for children's, side effect is many, does not recommend, and human injury is relatively larger；Chinese medicine decoction is administered orally, and mouthfeel is poor, and infant does not also accept。Only Chinese medicine for outer use is the properest, through focus。The new drug of the treatment secretory otitis media that the applicable children's of exploitation uses is exactly the present task of top priority。

For solving these technical barriers, the invention provides a kind of Chinese medicine for external application treating Pediatric secretory otitis media, in its described external preparation, the parts by weight of various raw materials are: Herba Centipedae 10～20 parts, Herba Schizonepetae 10～20 parts, Radix Sophorae Flavescentis 10～20 parts, Fructus Toosendan 10～20 parts, Borneolum Syntheticum 10～20 parts, Cortex Phellodendri 10～20 parts, Radix Scutellariae 10～20 parts, Pseudobulbus Bletillae (Rhizoma Bletillae) 10～20 parts, Herba Menthae 10～20 parts, Indigo Naturalis 10～20 parts, Radix Arnebiae (Radix Lithospermi) 10～20 parts, Radix Salviae Miltiorrhizae 10～20 parts, Herba Taraxaci 10～20 parts, Rhizoma Atractylodis 10～20 parts, the Radix Angelicae Dahuricae 10～20 parts。

The Chinese medicine for external application of described treatment Pediatric secretory otitis media, in its described external preparation, the parts by weight of various raw materials can be: Herba Centipedae 10～15 parts, Herba Schizonepetae 10～15 parts, Radix Sophorae Flavescentis 10～15 parts, Fructus Toosendan 10～15 parts, Borneolum Syntheticum 10～15 parts, Cortex Phellodendri 10～15 parts, Radix Scutellariae 10～15 parts, Pseudobulbus Bletillae (Rhizoma Bletillae) 10～20 parts, Herba Menthae 10～20 parts, Indigo Naturalis 10～20 parts, Radix Arnebiae (Radix Lithospermi) 10～20 parts, Radix Salviae Miltiorrhizae 10～20 parts, Herba Taraxaci 10～20 parts, Rhizoma Atractylodis 10～20 parts, the Radix Angelicae Dahuricae 10～20 parts。

The Chinese medicine for external application of described treatment Pediatric secretory otitis media, in its described external preparation, the parts by weight of various raw materials can also be: Herba Centipedae 10～20 parts, Herba Schizonepetae 10～20 parts, Radix Sophorae Flavescentis 10～20 parts, Fructus Toosendan 10～20 parts, Borneolum Syntheticum 10～20 parts, Cortex Phellodendri 10～20 parts, Radix Scutellariae 10～20 parts, Pseudobulbus Bletillae (Rhizoma Bletillae) 10～15 parts, Herba Menthae 10～15 parts, Indigo Naturalis 10～15 parts, Radix Arnebiae (Radix Lithospermi) 10～15 parts, Radix Salviae Miltiorrhizae 10～15 parts, Herba Taraxaci 10～15 parts, Rhizoma Atractylodis 10～15 parts, the Radix Angelicae Dahuricae 10～15 parts。

For solving above-mentioned technical problem, the preparation method that present invention also offers a kind of Chinese medicine for external application treating Pediatric secretory otitis media, the dosage form of its described preparation is drop, and preparation method includes:

A, first by Herba Centipedae, Herba Menthae, Indigo Naturalis, Borneolum Syntheticum and Pseudobulbus Bletillae (Rhizoma Bletillae) distillation crystallize into powder；For component 1,

B, again the medicinal residues after distillation and all the other raw materials being put into soak with ethanol, heat is extracted, and becomes extractum shape, for component 2；

C, by said extracted thing mixing be condensed into pasty state, add Oleum sesami, bottling。

In step a, it is possible to first Herba Centipedae, Herba Menthae, Indigo Naturalis, Borneolum Syntheticum and Pseudobulbus Bletillae (Rhizoma Bletillae) steam method is distilled, obtain crystal, be then comminuted into fine powder；Standby as component 1。

In described step b, the medicinal residues after distillation and surplus stock can be taken and add 60-90% soak with ethanol 1-2 hour of 5-10 times amount, heating extraction 2 times, each 1-2 hour, remove supernatant, united extraction liquid, 80-120 order filters, the ultrafiltration post ultrafiltration that molecular weight is 5000-10000 then through damming, the extractum of 1.36 when ultrafiltrate concentrating under reduced pressure relative density is 80 DEG C, heating concentration, 30 minutes～45 minutes, extracts active ingredient, concentrated solution is settled into extractum shape, mass continues heating and is concentrated into extractum shape, stand for standby use, becomes component 2。

In described step c, it is possible to the component 1 of distillation extraction is put in the medicinal residues extractum component 2 of ethanol extraction, add Oleum sesami and soak use of can bottling for 5-10 days。

For solving above-mentioned technical problem, the preparation method that present invention provides a kind of Chinese medicine for external application treating Pediatric secretory otitis media, the preparation process that described external drug dosage forms is spray includes:

A, will first by Herba Centipedae, Herba Menthae, Indigo Naturalis, Borneolum Syntheticum and Pseudobulbus Bletillae (Rhizoma Bletillae) distillation crystallize into powder；For component；

B, again medicinal residues mixing surplus stock is added alcohol heating reflux extract；

C, being merged by above two extract, decompression recycling ethanol also concentrates sucking filtration absorption, obtains medicated powder solubilizer and loads in Aerosol Products for Medical Use。

In described step b, it is possible to put in 10 times amount ethanol by distilling medicinal residues, heating and refluxing extraction 2 times, each 1～2 hour, 2 extracting solution are merged filtering and standing；In described step c, it is characterised in that twice extract merged, decompression recycling ethanol to be concentrated into liquor strength be 0.4g crude drug/mL, after sucking filtration, the relative density of filtrate is about when 20 DEG C 1.06；Above-mentioned filtrate is the macroporous adsorptive resins of 10L through volume, first with the deionized water of 10 times of resin column volumes or distilled water eluting, again with 95% ethanol elution of 5 times of resin column volumes, collect ethanol elution, remove solvent, obtain the distillation crystalline powder that raw material medicated powder mixing abovementioned steps obtains, solubilizer, load in Aerosol Products for Medical Use。

The Chinese medicine for external application of described treatment Pediatric secretory otitis media, its described external preparation dosage form can be: drop, spray, ointment, tincture, irrigation and absorbent cotton suppository, powder, powder, ointment, suppository, plaster and cream。

Using method: before use, patient's in ear pus is cleaned up, after drying, the powder made by medicine of the present invention sprays a little or brushes to patient's in ear, its mucomembranous surface is made gently to cover one layer of powder, so do not result in auditory meatus blocking, be conducive to suffering from ear mucosa local and fully absorb medicine, the curative effect obtained。Medication every day 1 time, 1-7 days is a course for the treatment of。

Medicine of the present invention has good heat-clearing and toxic substances removing, eliminating dampness and astringing sores, removing the necrotic tissue and promoting granulation, exorcise evil spirits analgesic effect, and has effect that dry ear is fast, curative effect is short, have no side effect。For patients with secretory otitis media, it is possible to promote secretions to disappear absorption, the tympanum reparation of perforation, make auditory rehabilitation。The present invention has the multiple effects such as antibacterial, antiinflammatory, convergence, dehumidifying, sensible, pain relieving。Toxic and side effects of the present invention is little, antimicrobial spectrum is wider, it is not likely to produce drug resistance, to internal ear without overt toxicity effect, otitis media pus antimicrobial spectrum is especially sensitive, the synthesis of bacterioprotein can be suppressed, it is to avoid after some Chinese medicine preparation local application to reach the purpose of sterilization, produce cerumen and be difficult to the feature that eliminates, have that dry ear is fast, curative effect is high, short treating period, side effect is little, medicine source is a wide feature。

Chinese medicine composition safety of the present invention, toxic and side effects is little, is suitable for children's and uses, and does not have dependency。Its using method is simple, and healing time is short, controls difficulty in relapse after healing。Good social value and economic interests can be created。

Detailed description of the invention

Primary disease is called " otopyosis ", " chronic suppurative otitis media " by the traditional Chinese medical science, it is believed that be cause because dampness-heat in the liver and gallbladder (fire) pathogen is prevailing。Otitis media is often shown effect winter, and itself does not have infectiousness, but a flu can be propagated in the middle of a lot of children and cause their generation ear infection。Tcm theory is thought, otalgia, discharging ear liquid, the symptom such as fester, and for the fire of upper inflammation, fascia then eardrum severe pain of burning, retention and fumigation of damp-heat inside the body, then degenerates gathering。Technical scheme is exactly according to above-mentioned theory, and the effect put on flesh according to heat-clearing and toxic substances removing, eliminating dampness and astringing sores, granulation promoting is to prepare medical material。Chinese medicine think otitis media and yin-Yang lack of proper care, disharmony between QI and blood relevant, it is its Etiological pathogenesis that damp invasion, internal body fluid run imbalance, effective determination for the treatment of based on pathogenesis obtained through differentiation of symptoms and signs can be carried out according to the different times of disease, different pathological situation, as acute stage is sensible with wind dispelling heat clearing away, try hard to eliminate pharyngotympanic tube and middle-ear mucosa edema, congestive state；When middle ear effusion is more, then based on promoting diuresis to eliminate damp pathogen, try hard to adjust eustachian tube function, improve ciliary movement function, to promote fluid removal；Later stage, based on promoting flow of QI and blood, tries hard to stop pathological changes to develop to adhesive otitis media, and regulating functions of ZANG FU-organs, reinforcing body resistance, reduces the chance of secretory otitis media recurrence。

Modern medicine about the theory of otitis media is: primary disease is on eustachian tube obstruction basis, or caused by being infected on this basis, be divided into mechanicalness with struvite two kinds, inflammation is divided into again infective inflammation and allergy。Therefore treatment adopts antibiotic, antihistaminic, nasal cavity vaso-excitor material is easy to MEV and excretion, tympanum drawing liquid or injection hormone therapy。

The traditional Chinese medical science thinks that this disease mostly is wind attacking the lung, and through flatulence due to stagnation of QI plug, it is obstructed that inhibited pulmonary QI causes water channel, and turbid damp stops caused by poly-ear key。Freely do not wait many reasons due to middle ear drainage, make the touching difficulty of primary disease more。Motherland's medical science is classified as " glue ear ", it is believed that be that deficiency of spleen and stomach, turbid damp fire-toxin accumulate for a long time and cause。The traditional Chinese medical science thinks that the pathogenesis of primary disease is caused by stagnation of dampness due to deficiency of the spleen, Committed obsessed ears。Children's have the physiological characteristics of the spleen tending to insufficiency usually, the kidney being always deficient。The spleen being the foundation of acquired constitution, main transmitting and distributing the fluids and biochemical QI and blood, defeated clear sun goes out clear key, and " Compendium of medicine " is called: " taste one are empty; knowledge nine orifices is all sick ", weakness of the spleen and stomach is clear YANG failing to ascend then, ear key lose its warm support, more double insufficiency of the spleen do not change water wet, the wet tired knot ear key of water, therefore in ear pus is for years does not do, clear YANG failing to ascend therefore dizziness and tinnitus and become deaf quick, shallow complexion is simple and unadorned be for insufficiency of the spleen insufficiency of vital energy and blood as；Lack of appetite abdominal distention, half congealed during stool, also there is wet levying for insufficiency of the spleen。Therefore the suitable spleen invigorating eliminating dampness by diuresis for the treatment of, dispersion by invigorating evacuation of pus。

External Radix Sophorae Flavescentis, Herba Centipedae, bactericidal antiphlogistic, Cortex Phellodendri removing heat from blood toxin expelling, Indigo Naturalis antiphlogistic antibacterial；Herba Menthae cool blood and remove dampness, Radix Scutellariae and Borneolum Syntheticum evacuation of pus, expelling pus and promoting granulation；Herba Schizonepetae anti-inflammation and sterilization, effect that foster skin of invigorating blood circulation, heat-clearing and toxic substances removing, Radix Angelicae Dahuricae granulation promoting are put on flesh。All medicines have share spleen invigorating eliminating dampness by diuresis, effect that heat-clearing and toxic substances removing, eliminating dampness and astringing sores, granulation promoting are put on flesh。

Radix Angelicae Dahuricae meridian distribution of property and flavor: pungent, temperature。Attach to the lung and stomach meridians。Expelling wind and cold, sensible pain relieving, detumescence and apocenosis, dampness leukorrhagia stopping。" Japan hanako materia medica ": control conjunctival congestion bulbar conjunctiva polyp and tire patching leakage landing, broken stagnated blood, mend fresh blood, acute mastitis, carbuncle on the back, scrofula, hemorrhoidal hamorrhage, hemorrhoid complicated by anal fistula, evacuation of pus, desolation, scabies, pain relieving granulation promoting, go face defect scar。

Radix Sophorae Flavescentis is bitter, cold。GUIXIN, liver, stomach, large intestine, bladder are through heat clearing and damp drying, parasite killing, diuresis。For hematodiarrhoea, have blood in stool, jaundice urine retention, leucorrhea with red and white discharge, swelling of the vulva pudendal pruritus, dermatomycosis, eczema, skin pruritus, scabies leprosy；Often be combined use with Hedyotidis Diffusae, be the external good medicine for the treatment of dermatomycosis。

Radix Scutellariae: Radix Scutellariae has heat clearing and damp drying, and removing heat from blood is antiabortive, detoxicating functions。Cure mainly the diseases such as epidemic febrile disease, upper respiratory tract infection, cough due to lung-heat, damp and hot jaundice, pneumonia, dysentery, hemoptysis, conjunctival congestion, frequent fetal movement, hypertension, carbuncle furuncle。The clinical practice of Radix Scutellariae is antibacterial not worse than Rhizoma Coptidis, and does not develop immunity to drugs。We are by the strong feature of broad-spectrum antibacterial action, are used in fungal culture miscellaneous bacteria and infect special severe, fine by Radix Scutellariae extracting solution effect。" Bencao Jingshu ": Radix Scutellariae, its property is respectful clearly, so evil removing: bitter in the mouth is so dampness；YIN-cold is so victory is hot, therefore main all heat。All hot persons, pathogenic heat are with all over heat also, and jaundice, intestinal are out-of-the-way, let out dysentery, and the disease of all damp and hot victory also, analyses it, then all diseases are from recover。Bitter cold can dehumidify heat, thus small intestinal profit and water from by, source clearly then flow clean also。The blood person of closing, excess-heat is in blood system, instant heating human blood room, and it is obstructed to make us amenorrhea, and damp and hot solution, then Ying Qi is clearly and voluntarily also。Malignant boil cellulitis erosion person, heat in blood then stays knot, and is that carbuncle stain is rotten also: acute scleritis person, and also, removing heat from blood heat extraction, then spontaneous recovery is also for fire of moxibustion blood trouble。Radix Scutellariae has antiallergic action and antiinflammatory action: baicalin contained by Radix Scutellariae and baicalin can substantially suppress sensitized guinea pig rat small intestine in vitro and isolated tracheal to anaphylaxis contractile response produced by antigen, passive general allergy and Cavia porcellus passivity skin allergic reaction to Cavia porcellus and mice, baicalin and baicalin also have inhibitory action。Radix Scutellariae has a refrigeration function, most it have been experienced that, the active ingredient baicaligenin of Radix Scutellariae has refrigeration function。Radix Scutellariae has Detoxication, baicalin to have obvious Detoxication, and this is likely due under the effect of glucuronidase, and baicalin decomposites glucuronic acid, and caused by being combined with multiple poisonous substance。10 milligrams of LD50 that can improve strychnine of baicalin reach 2.5 times, and make the hepatic glycogen content of carbon tetrachloride poisoning mice increase。

Fructus Toosendan is cold in nature, bitter in the mouth, is the one of qi-activating drug。Mainly enter Liver Channel, catharsis liver-heat, promoting the circulation of QI to relieve pain, have the function of dehumidifying heat, clearing away liver-fire, pain relieving, parasite killing。Dehumidifying heat, clearing away liver-fire, pain relieving, parasite killing。Control epigastric pain with cold limbs due to adverseness of heat, hypochondriac pain, colic, abdominal pain due to worm stagnation。" herbal classic ": " main temperature disease, typhoid fever are too hot tired mad, kill three scabies and steal, diuresis water channel。"

Indigo Naturalis is hot in nature, warming middle-JIAO, and pain relieving is regulated the flow of vital energy, dampness, and stopping vomiting is against acid regurgitation, headache due to JUE YIN disorder, and the coldness of ZANG-organ is vomited and diarrhoea, abdominal distention, abdominal pain during menstruation, Diarrhoea, vascular hypertension, beriberi, hernia, aphthous ulcer, toothache, dermatomycosis。Acrid in the mouth, hardship, dispersing cold for relieving pain, enter liver, spleen, stomach, large intestine, kidney channel。External has obvious pain relieving and therapeutic effect。" Thunder God concocts property of medicine solution ": warming middle-JIAO, pain relieving, regulates the flow of vital energy, dampness。" herbal classic " carries: main warming the middle warmer and descending qi, pain relieving, cough with dyspnea cold and heat, and dehumidify arthralgia due to stagnation of blood, by ailment said due to cold or exposure, loosing the interspaces of skin and muscles, is the good medicine for the treatment of dermatosis external。

Cortex Phellodendri heat clearing and damp drying, pathogenic fire purging is except steaming, detoxification sore treatment。For damp-heat dysentery, jaundice, leukorrhagia, pyretic stranguria, beriberi, flaccidity is warded off, hectic fever due to YIN-deficiency consumptive fever, night sweat, seminal emission, sore swollen toxin, eczema pruritus。Cortex Phellodendri nourishing YIN to lower pathogenic fire。For hyperactivity of fire caused by deficiency of YIN, night sweat hectic fever due to YIN-deficiency。" Chinese Pharmacopoeia " carries the power of Cortex Phellodendri heat clearing and damp drying, similar to Radix Scutellariae, Rhizoma Coptidis, but to be preferred except the damp and hot of the part of the body cavity below the umbilicus, housing the bladder, kidneys and bowels。

Radix Salviae Miltiorrhizae is bitter, is slightly cold。GUIXIN, Liver Channel。Stasis-dispelling and pain-killing, promoting blood circulation to restore menstrual flow, clear away heart-fire relieving restlessness。For menoxenia, amenorrhea dysmenorrhea, lump in the abdomen, chest and abdomen twinge, pyretic arthralgia pain, skin infection swells and ache, dysphoria and insomnia。For costa sternales hypochondriac pain, rheumatic arthralgia, lump in the abdomen lumps, and skin infection swells and ache, and tumbling down is grieved, menoxenia, amenorrhea dysmenorrhea, puerperal stasis of blood pain etc.。Treatment costa sternales pain, lump in the abdomen caking, and menoxenia, amenorrhea dysmenorrhoea has good effect。" detailed outline " carries: Radix Salviae Miltiorrhizae, and by " the sensible opinion of married woman " cloud, SIWU TANG controls gynecopathy, pays no attention to antenatal puerperal, how many through water, and all generally applicable, only taste Radix Salviae Miltiorrhizae dissipates, and cures mainly same。Lid Radix Salviae Miltiorrhizae can break stagnated blood, mends fresh blood, peaceful tire, and fall stillborn fetus, only metrorrhagia dysentery, regulating menstruation arteries and veins。

Herba Menthae is one of China's conventional Chinese medicine。It is pungent cool property sweating antipyretic medicine, controls influenza, the disease such as headache, conjunctival congestion, fever of the body, throat, dental bed swell and ache。Place is with can training the mind dysmenorrhoea, skin pruritus, erythra and eczema etc.。The Herba Menthae of light friend's Greenhouse Fruit Picking is again the fresh vegetable on dining table in the Spring Festival。Clearly good to eat。Usually with Herba Menthae for tea, clear away heart-fire improving eyesight。Herba Menthae has extremely strong sterilization antibacterial action, often drinks its energy preventing viral flu, oral disease, makes breath freshening。Gargle by Herba Menthae tea juice, it is possible to anti-halitosis in advance。Steam face with mint tea mist, also have the effect of shrinking pore。Take and steeped the blade of tea and apply and may feel that refrigerant on eyes, eyestrain can be released。It is said that Herba Menthae also has the another name of " eyes grass ", can be used for treating ophthalmic。

Herba Schizonepetae taste is put down, and warm in nature, nontoxic, faint scent is dense。Herba Schizonepetae is diaphoresis, antipyretic, is one of conventional medical herbs of China。Can town expectorant, timid wind, removing heat from blood。Control influenza, headache cold and heat diaphoresis, vomiting。Dispel the wind；Induce sweat；Rash；Hemostasis。Main cold, fever；Headache；Eye itching；Cough；Laryngopharynx swelling and pain；Measles；Carbuncle；Skin ulcer scabies；Epistaxis；Spit blood；Have blood in stool；Metrorrhagia；Puerperal blood faints。For catching a cold, headache, measles, rubella, skin infection from the beginning of。" detailed outline ": dissipating wind heat, refresh oneself, throat, the skin ulcer that disappears swells。Control stiffness of the nape, black flower in order, and raw skin ulcer, cloudy ruined, spit blood, epistaxis, hematochezia, dysentery, metrorrhagia, anal fistula。

Radix Arnebiae (Radix Lithospermi) is cold in nature, sweet in the mouth, one-tenth。GUIXIN, Liver Channel。Function cures mainly removing heat from blood, invigorates blood circulation, rash of detoxifying。Contain for heat in blood poison, macule purple is black, measles without adequate eruption, skin infection, eczema, burn due to hot liquid or fire。Clearing away heat and cooling blood, for measles, calentura skin eruption, eczema, hematuria, stranguria with blood, dysentery, skin infection, erysipelas, burn, constipation with heat retention。

Herba Centipedae dispersing wind-cold, clearing the nasal passage, cough-relieving, removing toxic substances。" detailed outline ": removing toxic substances, improving eyesight, scattered conjunctival congestion is swollen, nebula, deaf, and olic acid of having a headache is controlled intermittent fever due to phlegm clam, had a stuffy nose obstructed, and plug breath falls certainly, dissipates again skin ulcer and swells。" detailed outline ": food grass in goose, is up to brains, and it is sick to control top pain order, stuffy nose relieving gas and the flat meat that falls；Inside reach lung meridian and control clam, intermittent fever due to phlegm, dissipate skin ulcer and swell；It is except the merit of nebula, outstanding aobvious wonderful。By Ni Weide " former machine opens micro-collection " cloud: control corneal nebula nose, BIYUNSAN is monarch with Herba Centipedae removing toxic substances, and Indigo Naturalis is reduced phlegm and internal heat as helping, and the pungent broken of Sichuan Cordyceps stays evil removing for making, and the medicine risen is also。On the whole as boiled lid method, being often intended to evil poison and do not close, order has outlet。Right power is little and sharp, suitable its power of Chang Yiju, all diseases in all orders, all can with it, and life is more refreshing。

Pseudobulbus Bletillae (Rhizoma Bletillae) astringing to arrest bleeding, detumescence and promoting granulation。Spit blood for hemoptysis, traumatic hemorrhage, sore swollen toxin, chapped skin；Pulmonary tuberculosis hemoptysis, ulcer haemorrhage。1. anastalsis: Pseudobulbus Bletillae (Rhizoma Bletillae) can strengthen platelet factor III activity, and notable shortening clotting time and thrombinogen form the time, it is suppressed that plasmin enzymatic activity, and local hemorrhage is had anastalsis；Zoopery shows, external haemostatic effect is quite good to parenchymatous organ's (liver, spleen), muscle vascular be hemorrhage etc. for Pseudobulbus Bletillae (Rhizoma Bletillae) water extraction。2. protection gastric mucosa: 1% Pseudobulbus Bletillae (Rhizoma Bletillae) decoct gavage, the rat pipe film injury that hydrochloric acid is caused has protective effect；The experimental Stomach duodenum perforation of anesthetized dog had therapeutical effect。3. antibacterial, antifungic action: staphylococcus aureus, bacillus subtilis, Bacillus tuberculosis are had inhibitory action by Pseudobulbus Bletillae (Rhizoma Bletillae) ethanol immersion；Microsporon audouini is had inhibitory action by water logging agent；Staphylococcus aureus, bacillus subtilis, Candida albicans ATCC1057 and Trichophyton QM248 are had inhibitory action by 3 biphenyl classes and 2 double; two hydrogen phenanthrene compounds contained by Pseudobulbus Bletillae (Rhizoma Bletillae)。

Rhizoma Atractylodis are pungent, bitter, temperature。Return spleen, stomach, Liver Channel。Function cures mainly: drying damp and strengthening spleen, expelling wind and cold, improving eyesight。For distension and fullness in the abdomen, edema of having loose bowels, beriberi flaccidity, rheumatic arthralgia, anemofrigid cold, nyctalopia。Main the spleen and stomach being stranded by dampness；Asthenia drowsiness；Born of the same parents' painful abdominal mass abdominal distention；Inappetence；Tell and have loose bowels；Phlegm retention；Damp-edema；Exterior syndrome folder is wet；Head heavy sensation of the body pain；Arthromyodynia warm nature；Podomere is ached and is weighed；Flaccidity folds in a garment。Antibacterial: Rhizoma Atractylodis extract has the effect eliminating drug resistance shigella flexneri R plasmid, can reduce the generation of bacterial drug resistance。Utilizing 95% soak with ethanol Rhizoma Atractylodis 10 hours, take out Rhizoma Atractylodis, be positioned ready on the floor of operating room of sterilization, light, until Rhizoma Atractylodis turn to ash, after sterilization, than in air before sterilization, clump count significantly reduces。But, initial in vitro research does not find that Rhizoma Atractylodis decocting liquid has obvious antibacterial action。" medicineization justice ": Rhizoma Atractylodis, acrid in the mouth master dissipates, warm in nature and dry, dry dries, and specially enters taste, cures mainly anemofrigid-damp arthralgia, epidemic pathogenic factors from mountains, hydroderma, and all pungent strong merit by heresy is also。Rule three wet, if wetting at the part of the body cavity above the diaphragm housing the heart and lungs, easily raw damp-phlegm, with this dampness row expectorant；Wetting middle Jiao, stagnant gas rushes down, with this alleviating distention in middle-JIAO spleen invigorating；Wetting in bottom, foot knee joint flaccidity is soft, controls flaccidity with this with Cortex Phellodendri, and foot knee joint can be made strong；Take its pungent scattered gas male, the scattered evil diaphoresis of use, extremely freely。Close six god to dissipate, general solution spring and summer damp-heat disease；Assistant decoction for dispelling pathogens from superficial muscles, table dissipate malaria from the beginning of；If after under calentura antiperspirant, deficiency-heat is not understood, and adds Baihu Tang with this, then solves it, perspiration stopped cool skin。Miao Zhongchun is end simply with this, controls insufficiency of the spleen distention of the abdomen caused by various parasites。

Herba Taraxaci is the Chinese medicine commonly used simply, and its medical value is loaded various medical books early。Its all herbal medicine, containing compositions such as taraxasterol, taraxerol, taraxacin, caffeic acid, choline, inulin。The flat sweet and slightly bitter taste of property。Can heat-clearing and toxic substances removing, dispersing swelling and dissipating binds。Compendium of Material Medica is recorded: " Detoxicating food-poisoning, dissipates stagnant gas, heat clearing away poison, relieving dyspepsia poison, and the evil that disappears is swollen, tuberculosis, furuncle are swollen。" Herba Taraxaci hides sweet flat, its property is nontoxic。When being enter stomach, the key medicine of antipyretic removing heat from blood into liver。

The manufacturing process of drop of the present invention is: by Herba Centipedae 1000g, Herba Menthae 1000g, Indigo Naturalis 1000g, Borneolum Syntheticum 1000g and Pseudobulbus Bletillae (Rhizoma Bletillae) 1000g, distills with steam method, obtains crystal, be then comminuted into fine powder；Standby as component 1, again will, take the medicinal residues after distillation and surplus stock Herba Schizonepetae 1000g, Radix Scutellariae 1000g, Radix Sophorae Flavescentis 1000g, Fructus Toosendan 1000g, Cortex Phellodendri 1000g, Radix Arnebiae (Radix Lithospermi) 1000g, Radix Salviae Miltiorrhizae 1000g, Herba Taraxaci 1000g, Rhizoma Atractylodis 1000g, the 60-90% of Radix Angelicae Dahuricae 1000g addition 5-10 times amount soak with ethanol 1-2 hour, heating extraction 2 times, each 1-2 hour, remove supernatant, united extraction liquid, 80-120 order filters, the ultrafiltration post ultrafiltration that molecular weight is 5000-10000 then through damming, the extractum of 1.36 when ultrafiltrate concentrating under reduced pressure relative density is 80 DEG C, heating concentration, 30 minutes～45 minutes, extract active ingredient, concentrated solution is settled into extractum shape, mass continues heating and is concentrated into extractum shape, stand for standby use, become component 2；The component 1 of distillation extraction is put in the medicinal residues extractum component 2 of ethanol extraction, add Oleum sesami and soak use of can bottling for 5-10 days。

The manufacturing process of spray of the present invention is: first Herba Centipedae 1200g, Herba Menthae 1300g, Indigo Naturalis 1300g, Borneolum Syntheticum 1200g and Pseudobulbus Bletillae (Rhizoma Bletillae) 1100g distillation will be crystallized into powder；Other surplus stocks Herba Schizonepetae 1200g, Radix Scutellariae 1200g, Radix Sophorae Flavescentis 1300g was mixed by distilling medicinal residues, Fructus Toosendan 1200g, Cortex Phellodendri 1100g, Radix Arnebiae (Radix Lithospermi) 1200g, Radix Salviae Miltiorrhizae 1300g, Herba Taraxaci 1400g, Rhizoma Atractylodis 1200g, Radix Angelicae Dahuricae 1300g put in 10 times amount ethanol, heating and refluxing extraction 2 times, each 1～2 hour, 2 extracting solution are merged filtering and standing；Twice extract being merged, decompression recycling ethanol to be concentrated into liquor strength be 0.4g crude drug/mL, after sucking filtration, the relative density of filtrate is about when 20 DEG C 1.06；Above-mentioned filtrate is the macroporous adsorptive resins of 10L through volume, first with the deionized water of 10 times of resin column volumes or distilled water eluting, again with 95% ethanol elution of 5 times of resin column volumes, collect ethanol elution, remove solvent, obtain the distillation crystalline powder that raw material medicated powder mixing abovementioned steps obtains, solubilizer, load in Aerosol Products for Medical Use

The manufacturing process of external pulvis of the present invention is: takes and first Herba Centipedae 1100g, Herba Menthae 1300g, Indigo Naturalis 1300g, Borneolum Syntheticum 1200g and Pseudobulbus Bletillae (Rhizoma Bletillae) 1100g distillation is crystallized into powder；Other surplus stocks Herba Schizonepetae 1200g was mixed by distilling medicinal residues, Radix Scutellariae 1400g, Radix Sophorae Flavescentis 1100g, Fructus Toosendan 1300g, Cortex Phellodendri 1200g, Radix Arnebiae (Radix Lithospermi) 1400g, Radix Salviae Miltiorrhizae 1300g, Herba Taraxaci 1400g, Rhizoma Atractylodis 1200g, Radix Angelicae Dahuricae 1300g is by proportioning mixing, put into pulverizer and be ground into fine powder, fine powder puts into acid and alkali-resistance infusion kettle after sieving, at normal temperatures, jointly impregnate with ethanol 10～20 days, the liquid impregnated and medicinal residues are carried out squeeze and filter, filtrate is taken after separation, heating is concentrated into pasty state, put into baking oven, control at 100 DEG C, cool down after drying, directly become powder, directly use。

The preparation method of externally used paste of the present invention:

According to described number, Herba Centipedae 1200g, Herba Menthae 1300g, Indigo Naturalis 1300g, Borneolum Syntheticum 1400g and Pseudobulbus Bletillae (Rhizoma Bletillae) 1200g steam distillation are become crystallization, become component 1 standby；Again by medicinal residues and Herba Schizonepetae 1200g, Radix Scutellariae 1200g, Radix Sophorae Flavescentis 1100g, Fructus Toosendan 1300g, Cortex Phellodendri 1200g, Radix Arnebiae (Radix Lithospermi) 1400g, Radix Salviae Miltiorrhizae 1300g, Herba Taraxaci 1400g, Rhizoma Atractylodis 1300g, the Radix Angelicae Dahuricae 1, 400g, the 60-90% of addition 5-10 times amount soak with ethanol 1-2 hour, heating extraction 2 times, each 1-2 hour, remove supernatant, united extraction liquid, 80-120 order filters, the ultrafiltration post ultrafiltration that molecular weight is 5000-10000 then through damming, the extractum of 1.36 when ultrafiltrate concentrating under reduced pressure relative density is 80 DEG C, heating concentration, 30 minutes～45 minutes, concentrated solution is settled into extractum shape, mass continues heating and is concentrated into extractum shape, stand for standby use, become component 2；Putting in the component 2 of ethanol extraction after the component 1 of distillation extraction and Radix Scutellariae 1200g being pulverized, unguentum made by mixing vaseline。

The ointment that can also obtain in aforementioned manners soaks absorbent cotton, becomes suppository, is directly plugged in sufferer ear。

Pharmacological toxicity is tested

Acute toxicity testing data

1, experimental technique

Depilatory is uniformly coated with by guinea pig back spinal column both sides, makes unhairing scope about 40 square centimeters。Clean depilatory returns cage to observe 24 hours, often group Cavia porcellus is coated with Chinese medicine preparation external drop 0.2,0.4 of the present invention and 0.8ml respectively, respectively containing crude drug 92mg, 184mg and 368mg), another group is coated with the every twice-daily of solvent 0.8ml, continuous one week, after experiment terminates, Cavia porcellus is put to death, the heart, liver, kidney and depilation skin do pathological examination。

2, result

Above-mentioned three groups of medication Cavia porcellus trunks depilation district, having no local skin has edema, hyperemia, erythema, petechia and ulcer。Medication group Cavia porcellus chroma of hair, ingest, the matched group no significant difference such as extremity are movable, histopathologic examination, the administration group heart, liver, kidney and depilation skin compare also no significant difference with compareing word。

Result is pointed out, and Chinese medicine for external application of the present invention, without local irritant effect, also has no general toxicity performance。Show that Chinese medicine for external application of the present invention uses safety。

Long term toxicity test data

1, experimental technique

Random for Cavia porcellus part is become 4 groups, often group 15。In guinea pig back spinal column both sides, depilatory is uniformly coated with so that it is depilation scope about 40 square centimeters。Clean depilatory, often organize Cavia porcellus after observing 24 hours and be coated with external drop 0.2,0.4 of the present invention and 0.8ml respectively, respectively containing crude drug 92,184 and 368mg), another group is coated with the every twice-daily of solvent 0.8ml, continuous 30 days, observing the ordinary circumstance of Cavia porcellus, experiment is put to death animal after terminating and is carried out hematology, blood biochemical and pathological examination。

2, result

Above-mentioned three groups of medication Cavia porcellus trunk unhairing districts, having no local skin has edema, hyperemia, erythema, petechia and ulcer。Medication group and control animals chroma of hair, ingest, the matched group no significant difference such as extremity are movable, blood biochemistry checking, medication group and matched group are all in normal range。Histopathologic examination, tests each group of heart, liver, kidney and local skin and is showed no obvious pathological changes。Prompting, local skin and whole body important organ are showed no obvious toxic action by Chinese medicine preparation long-term prescription of the present invention。Result of the test shows: Chinese medicine preparation experiment safety of the present invention。

Aggregate toxicity is tested:

Mice is pressed 7.69,19.18 and 43.21g crude drug/kg continuous use 15 weeks (1.0ml/100g body weight by Chinese medicine external spray of the present invention, every day 2 times) and drug withdrawal 3 weeks after, result shows: the indexs such as the hair of rat, behavior, defecation, body weight, organ weights, hemogram, hepatic and renal function, blood glucose, blood fat are all had no significant effect by Chinese medicine preparation of the present invention, internal organs naked eyes do not find that difference change and histological indications show, after medication 15 weeks and drug withdrawal 3 weeks, each internal organs of rat are all without substantially changing。Illustrate that Chinese medicine preparation oral capsule of the present invention is little to toxicity after rat long-term prescription, react also without difference after drug withdrawal, application safety。

Pharmacological experiment illustrates:

Secretory otitis media (OME) cause of disease is still not clear, and therefore, Therapeutic Principle exists dispute。There are some researches show, ibid exhale mucous membrane the same when middle-ear mucosa is subject to antigenic stimulus, become immunocompetence organ, thus supporting such hypothesis: OME is a kind of result of allergy。This experiment, with BALB/C mice for object of study, adopts oralbumin (OVA) sensitization in ear to excite mice to make OME model, inquires into I allergic reaction type, relation between Th1, Th2 type cytokines and OME。

1 materials and methods

1.1 laboratory animals

With 6～8 weeks healthy BALB/C mice 21 (being provided by University Of Qingdao's animal center), body weight 22～30g, it is randomly divided into 3 groups: experimental group 7, matched group I7, control Group II 7。All confirm without external auditory meatus and middle ear infection through endoscopy of ear before experiment。

1.2 modeling methods

Experimental group gives 1.2mgOVA (sigma company, the U.S.) it is dissolved in 0.6ml phosphate buffer (PBS), with 5.14mg aluminium hydroxide (rising chemical industry preparation factory purchased from east, Wenzhou City) for immunological adjuvant row lumbar injection, 1 time weekly, continuous 2 weeks, this was whole body sensitisation phase。After 2 weeks, with 20% urethane 5m1/kg row intraperitoneal injection of anesthesia, under sterile working, 1m1/kgOVA/PBS mixed liquor 15L1 is injected tympanum through tympanum front lower place, after 24h, mice is anaesthetized again, observes tympanum state, and duplicate injection the 2nd time, this is in ear excitation phase, makes OME model。Matched group I is OVA/PBS whole body sensitization, and PBS liquid in ear excites；Control Group II is PBS liquid whole body sensitization, and OVA/PBS liquid in ear excites。

1.3 specimen samplings and Testing index

Mice is 2d after secondary excitation, and being breaked end lives kills, and takes bilateral otic capsule, fixes with the paraformaldehyde of 4%, 5% aqueous solution of nitric acid decalcification, after dehydration, specimens paraffin embedding slices, conventional hematoxylin-eosin stains, light Microscopic observation mucosa of tympanic cavity proliferative conditions, count eosinophilic granulocyte。The expression (all purchased from Wuhan doctor's moral company) of immunohistochemical staining detection IL-4, IL-5, IL-12, IFN-C, DAB developer is purchased from Beijing Zhong Shan Bioisystech Co., Ltd, and step illustrates to carry out by test kit。

1.4 method for cell count

Eyepiece is joined counting lattice, lamina propria, tympanum transudate are chosen 5 many regions of positive cell under low power lens under middle-ear mucosa, cell number is counted under high power lens, take the average under 5 high power lens visuals field (HP), result represents with-x ± s, and mucosa thickness micrometer is measured under light microscopic。

1.5 statistical procedures

Adopting the oneway variance analysis in SPSS11.0 statistical package and pearson linear correlation inspection, P < 0.05 is statistically significant。

2 results

2.1 modeling results

Row endoscopy of ear every day after all BALB/C mice row in ear injection OVA/PBS mixed liquor or PBS liquid, after 24h, there is erythema to experimental group in tympanum and surrounding tissue, and tympanum has the stria vascularis of radial expansion in various degree；After 36h, tympanum loses normal gloss, in faint yellow or amber。Siegle otoscopy tympanum limitation of activity, but fail to peep clear liquid plane, 2 animals of experimental group are because anaesthetizing excessive death, in 14 ears, 12 ears find there is pale yellow transparent wash in tympanum, measure less, about 5～8L, 1 average 6.5L, 1 success rate is 85.0% (12/14)。Two matched group tympanum gloss compared with normals are slightly dark, puncture without hydrops, it is seen that tympanum dries, without congested。

2.2 light microscopy checking results

Two matched group mucosa of tympanic cavity are simple squamous epithelium or simple cuboidal epithelium, without substantially destroying, only see that a small amount of inflammatory cell and a little Ciliated epithelium come off。The visible tympanum sepage of experimental group is based on serosity; thin in water sample; in faint yellow; mucosa of tympanic cavity is congested, edema, and blood capillary increases; permeability increases; epithelial cilia comes off, and under mucosa, in the middle of lamina propria, medullary cavity and exudate, the eosinophilic granulocyte of appearance, plasma cell, lymphocytic infiltration are main, and mastocyte, mononuclear cell are also more common。Experimental group and two matched groups more statistically significant (equal P < 0.05, table 1), two matched groups are compared, no significant difference。

The comparison of table 1 experimental group and two matched group mucosa of tympanic cavity thickness and eosinophilic granulocyte ,-x ± s

Group	Ear number	Mucosa of tympanic cavity thickness/Lm	, eosinophilic granulocyte/
				Experimental group	14	0.9321±0.078	36.55±1.22
Matched group I	14	0.0623±0.017	62.51±0.34
				Control Group II	14	0.0624±0.85	72.42±0.52

2.3 immunohistochemical detection results

Experimental group IL-4, IL-5, IFN-C, IL-12 positive cell is multiformity, visible lymphocyte, plasma cell, eosinophilic granulocyte, epithelial cell, vascular endothelial cell and fibroblast various kinds of cell are expressed, it is expressed in Cytoplasm, in brown yellow granule, be distributed mainly under mucosal epithelium lamina propria, among medullary cavity and tympanum transudate, and matched group is the weak positive or without expression。The expression of 4 kinds of cytokines all statistically significant compared with two matched groups (P < 0.05, table 2) in experimental group, and two matched groups compare no significant difference。

The expression of the expression of Th2 type cytokines IL-4, IL-5 relatively Th1 type cytokines IFN-C, IL-12, difference statistically significant (P < 0.05)。

The religion of IL-4, IL-5, IFN-C, IL-12 positive cell ,-x ± s in table 2 experimental group and two matched group middle-ear mucosa tissues

3, the experimental example impact on Guinea Pigs otitis media

1, experimental technique

After modeling success。Within 30 minutes, later group Cavia porcellus auris dextra injects 0.08ml (46.6mg/ is only) Chinese medicine preparation solution of the present invention, and another group injects equivalent solvent, continuous 12 days。Then solvent group uses Chinese medicine preparation of the present invention (external drop) 21.3mg/ instead only, and medication group continues administration, then within continuous six days, observes medicine to the impact of acute inflammation and Hypertrophic change and subacute toxicity。Another batch of test causes scorching method ibid。Cause scorching latter 48 hours, one group of Cavia porcellus only injects Chinese medicine preparation 42.6mg/ of the present invention in auris dextra, another group injects equivalent solvent, and within continuous 4 days once a day, observation index is that inflammatory different time oozes out liquid measure total white blood cells and classification, antibacterial number and the general performance of kind and inflammation。When experiment terminates, take external ear, tympanum, auditory ossicles and the heart, liver, kidney and make histopathologic examination。

2, result

Scorching latter 30 minutes of caused by dimethylbenzene xylene, Chinese medicine preparation of the present invention (external drop) 0.08ml (42.6mg) is injected in every Cavia porcellus auris dextra, compare with matched group, obvious transudate is had no after being administered 4 hours, red and swollen cancellation, auditory meatus normal in size, continuous use 18 days, also have no tympanum, auditory ossicles and the heart, liver, kidney have obvious Histopathologic changes, and Vehicle controls is disappearing to scorching latter 120 hours rednesses, there is scar tissue in road, and auditory meatus narrows, and middle in ear is shown in that profit is invaded in a large amount of Focal neutrophilic leukocyte。Cause after inflammation the 12nd day, this group uses Chinese medicine preparation of the present invention instead, once a day (42.6mg), continuous six, see that auditory meatus tends to normal size, scar tissue reduces, histopathologic examination shows, the appearance of external ear and tympanum and cartilage have no obvious pathological changes, and intradermal is shown in two lymph nodes, change in reactive hyperplasia。The above results is pointed out: acute transudate is not only had inhibitory action but also hypertrophy also has certain antagonism by Chinese medicine preparation of the present invention, this medicine continuous application 18 days, does not regard sb. as an outsider middle ear and the heart, liver, kidney have obvious histopathology to change。After caused by dimethylbenzene xylene inflammation, middle ear only ooze out the right injection in peak period (48 hours) 42.6mg/, and Chinese medicine preparation of the present invention is treated two days later, and transudate and cell number significantly reduce (P < 0.05) redness and disappear。Cavia porcellus in ear transudate antibacterial culturing and count of bacteria result show, (peak period is namely oozed out) before administration, in the Cavia porcellus ear transudate of test group, based on S. aureus L-forms, bacterial population is (16,000,000,3360000 and 100,000,000/ml) and medication two days (causing scorching latter 96 hours), the bacterial population in transudate is (without bacterial growth, 34 and 170,000/ml)。After medication compared with before medication, bacterial population significantly reduces。And the bacterial population of matched group Cavia porcellus ear transudate is risen to (4,400,000,1,200,000 and 85.6 ten thousand/ml) of 96 hours by (23.5 ten thousand 19 ten thousand and 450,000/ml) that cause scorching latter 48 hours

The above results is pointed out, and Chinese medicine for external application of the present invention can not only reduce and oozes out and treat acute inflammation and the cell infection after causing inflammation is also had obvious bacteriostasis。

Clinical pharmacology drug effect:

Illustrate: Pediatric secretory otitis media patient 96 example that the court is accepted for medical treatment in November ,-2012 in October, 2008 uses Chinese medicine for external application treatment, and choose 60 examples (68 ear) patient that accepts for medical treatment the same period as a control group, with antibiotic medication。And clinical data is carried out review formula analysis contrast。Result: treatment group patient all successfully leave hospital, audition on average improves 19.6dB。And compared with matched group patient, all there is notable significant difference in treatment group in cure rate and total effective rate。Children's acute secretory otitis media is treated by Chinese medicine external, have therapeutic modality simplicity, side effect is little, curative effect is short and eutherapeutic clear superiority, easily accepted by infant, it is possible to as safely, effectively, that economic auxiliary treating method carries out stand at basic hospital is wide。

Pediatric secretory otitis media (otitismediawitheffusion, OME) be otherwise known as children's's secretory otitis media, it refers to and is contained within from the apyetous hydrops spilling, ooze out and secreting at tympanum, and children's OME is apt to occur in less than 6 years old underage child。Its pathogenic factor is various, mainly has Eustachian tube disfunction；Upper respiratory tract infection；Hypersecretion；Nasopharynx part stove amygdala inflammation, nasal sinusitis and the hyperplasia of the adenoid；Ambient pressure suddenlys change；Other is the reasons such as vegetative nerve function system cleft palate, endocrinopathy。For improving the clinical economics level to Pediatric secretory otitis media patient, comprehensive survey and analysis, existing report is as follows。

1 data and method

1.1 physical data

Selecting 96 examples (109 ear) the Pediatric secretory otitis media patient that in November ,-2012 in October, 2008, my institute accepted for medical treatment is object of study treatment group。Patient age is 2～8 years old, average 5.4 years old, wherein boy 59 example, girl 37 example。Infant left ear 45 example, auris dextra 41 example, ears 13 example。The average 4.5d of the infant course of disease。Patient is carried out Impedance audiometry。Additionally choose 60 examples (68 ear) patient that accepts for medical treatment the same period as a control group, ask that the age of infant, the course of disease, ear suffer from situation and the equal no difference of science of statistics of the anti-test case of sound channel, there is comparability for two groups。

1.2 clinical symptoms

There is the clinical manifestations such as the vexed otalgia tinnitus of ear, auditory dysesthesia, snoring, nose choked flow tears in infant, tympanum is creamy white or dusty blue, and light cone disappears, limitation of activity。Impedance audiometry uses Denmark MADSENZODLAC901 type otitis media functional analysis instrument to carry out tympanometry inspection, tympanogram Type B 78 ear, C type 31 ear, and wherein the 26 visible liquid of ear are put down, without acoustic stapedial reflex。

1.3 Therapeutic Method

Treatment group: make drop by the embodiment of the present invention 1, Fang Yong: Herba Centipedae 10g, Herba Schizonepetae 12g, Radix Sophorae Flavescentis 11g, Fructus Toosendan 12g, Borneolum Syntheticum 12g, Cortex Phellodendri 12g, Radix Scutellariae 11g, Pseudobulbus Bletillae (Rhizoma Bletillae) 12g, Herba Menthae 13g, Indigo Naturalis 12g, Radix Arnebiae (Radix Lithospermi) 12g, Radix Salviae Miltiorrhizae 12g, Herba Taraxaci 12g, Rhizoma Atractylodis 11g, Radix Angelicae Dahuricae 12g, make drop。Every day three times。7d was 1 course for the treatment of。

Matched group: to the patient each 5mg/kg of Administration of roxithromycin dispersible tablet, each 5mg of prednisone, both days take twice, Decongestant nasal drop collunarium, 1 week course for the treatment of。

1.4 efficacy determinations

Recovery from illness: clinical symptom disappearance, tympanum recovers normal, and pure tone test threshold reverts to and namely returns within 25dB normal range, and tympanum is anti-, and to lead figure be A type or As type。Effective: transference cure or alleviate to some extent, otopiesis makes moderate progress, and the pure tone test threshold of audibility recovers 10～more than 15dB。Tympanogram result is upgraded, and transfers A type to such as C type or Type B turns C type。Invalid: symptom improves inconspicuous or substantially without improving, audiometry is without raising, and otopiesis is difficult to activity, and sound channel tympanogram is still Type B。

2 results

The equal successful surgery for the treatment of group patient is left hospital, and audition on average improves 19.6dB。And compared with matched group patient, all there is notable significant difference in treatment group in cure rate and total effective rate。Specifically compare such as table 1。

Table 1 otitis media infant treatment group and matched group Comparison of therapeutic [ear (%)]

3 discuss

So far, the concrete cause of disease of secretory otitis media is still uncertain, it is possible to owing to the reasons such as antibacterial, viral infection, immunoreation or Eustachian tube disfunction are caused a disease。The cardinal principle for the treatment of and preventing child secretory otitis media is: will focusing on child's spleen invigorating and support lung, carrying out body function adjustment, thus strengthening the infant resistance to external infections。In addition, for preventing the generation of secreting type otitis media or repeating to occur, tackle to impose in the organ lesion treated around pharyngotympanic tube and treat timely and effectively。Current state internal therapy mainly has the methods such as Drug therapy, operation tympanic pressure treatment and He-Ne laser therapy。

Children's acute secretory otitis media is treated by traditional therapy, have therapeutic modality simplicity, side effect is little, curative effect is short and eutherapeutic clear superiority, easily accepted by infant, it is possible to as safely, effectively, economic auxiliary treating method carry out promotion at basic hospital。

Detailed description of the invention:

Embodiment 1, Feng, female, 2 years old, medical 2010 dates JIUYUE 6 days, head of a family readme sick child after upper respiratory tract infection with the vexed swollen sense of ears, listen sound remote and auditory dysesthesia is for cardinal symptom。Owing to otalgia is inconspicuous, child main suit is unclear, and when children's's audition is affected, the head of a family just finds medical, and the visible tympanum of otology training inspection is amber or crocus, also visible air fluid level or bubble, and tympanum mobility reduces。Affect speech, development of speech, treatment: external preparation is: Herba Centipedae 12g, Herba Schizonepetae 12g, Radix Sophorae Flavescentis 11g, Fructus Toosendan 12g, Borneolum Syntheticum 12g, Cortex Phellodendri 12g, Radix Scutellariae 11g, Pseudobulbus Bletillae (Rhizoma Bletillae) 12g, Herba Menthae 13g, Indigo Naturalis 12g, Radix Arnebiae (Radix Lithospermi) 12g, Radix Salviae Miltiorrhizae 12g, Herba Taraxaci 12g, Rhizoma Atractylodis 11g, Radix Angelicae Dahuricae 12g, make drop。Every day three times。7d was 1 course for the treatment of。Clean left survey middle ear canals, in same for Chinese medicine drop of the present invention instillation middle ear canals, outpatient service check after advising 3 days, observation 2 days of being in, infant secretions disappears, and body temperature starts normally, is continuing with a week, and in ear, secretion disappears, audition starts to recover, and is continuing with 1 month, and audition takes a turn for the better gradually。

Embodiment 2: Liu, man, 6 years old, in November, 2011 went to a doctor。Upper respiratory tract infection causes the vexed swollen sense first quarter moon of auris dextra。Once treating 5 weeks with " upper respiratory tract infection " in outer court, symptom is without alleviation。The vexed swollen sense of head of a family's readme ears, listen sound remote and auditory dysesthesia is cardinal symptom。Look into tympanum complete, cave in lark；Auris dextra conductive deafness, conductance decline 40db are shown in electric audiometry；Row tympanum drawing liquid has secretions。Red tongue, moderate pulse。Diagnosis is secretion otitis media。Treatment: external preparation is: Herba Centipedae 11g, Herba Schizonepetae 13g, Radix Sophorae Flavescentis 11g, Fructus Toosendan 12g, Borneolum Syntheticum 12g, Cortex Phellodendri 12g, Radix Scutellariae 11g, Pseudobulbus Bletillae (Rhizoma Bletillae) 12g, Herba Menthae 13g, Indigo Naturalis 12g, Radix Arnebiae (Radix Lithospermi) 12g, Radix Salviae Miltiorrhizae 12g, Herba Taraxaci 12g, Rhizoma Atractylodis 11g, and Radix Angelicae Dahuricae 13g makes drop。Every day three times。7d was 1 course for the treatment of。Clean left survey middle ear canals, in same for Chinese medicine drop of the present invention instillation middle ear canals, after treating 3 days, external auditory meatus secretions reduces, and pain slowly disappears, and audition recovers normal gradually, and external auditory meatus dries, and flows out without secretions。After 10 days, pain disappears, and auditory rehabilitation is normal, and external auditory meatus dries, and flows out without secretions。Following up a case by regular visits to, half a year does not recur。

Claims (9)

1. the Chinese medicine for external application treating Pediatric secretory otitis media, it is characterised in that described external preparation is made up of the crude drug of following parts by weight: Herba Centipedae 10～20 parts, Herba Schizonepetae 10～20 parts, Radix Sophorae Flavescentis 10～20 parts, Fructus Toosendan 10～20 parts, Borneolum Syntheticum 10～20 parts, Cortex Phellodendri 10～20 parts, Radix Scutellariae 10～20 parts, Pseudobulbus Bletillae (Rhizoma Bletillae) 10～20 parts, Herba Menthae 10～20 parts, Indigo Naturalis 10～20 parts, Radix Arnebiae (Radix Lithospermi) 10～20 parts, Radix Salviae Miltiorrhizae 10～20 parts, Herba Taraxaci 10～20 parts, Rhizoma Atractylodis 10～20 parts, the Radix Angelicae Dahuricae 10～20 parts。

2. treat the Chinese medicine for external application of Pediatric secretory otitis media according to claim 1, it is characterized in that, described external preparation is made up of the crude drug of following parts by weight: Herba Centipedae 10～15 parts, Herba Schizonepetae 10～15 parts, Radix Sophorae Flavescentis 10～15 parts, Fructus Toosendan 10～15 parts, Borneolum Syntheticum 10～15 parts, Cortex Phellodendri 10～15 parts, Radix Scutellariae 10～15 parts, Pseudobulbus Bletillae (Rhizoma Bletillae) 10～20 parts, Herba Menthae 10～20 parts, Indigo Naturalis 10～20 parts, Radix Arnebiae (Radix Lithospermi) 10～20 parts, Radix Salviae Miltiorrhizae 10～20 parts, Herba Taraxaci 10～20 parts, Rhizoma Atractylodis 10～20 parts, the Radix Angelicae Dahuricae 10～20 parts。

3. treat the Chinese medicine for external application of Pediatric secretory otitis media according to claim 1, it is characterized in that, described external preparation is made up of the crude drug of following parts by weight: Herba Centipedae 10～20 parts, Herba Schizonepetae 10～20 parts, Radix Sophorae Flavescentis 10～20 parts, Fructus Toosendan 10～20 parts, Borneolum Syntheticum 10～20 parts, Cortex Phellodendri 10～20 parts, Radix Scutellariae 10～20 parts, Pseudobulbus Bletillae (Rhizoma Bletillae) 10～15 parts, Herba Menthae 10～15 parts, Indigo Naturalis 10～15 parts, Radix Arnebiae (Radix Lithospermi) 10～15 parts, Radix Salviae Miltiorrhizae 10～15 parts, Herba Taraxaci 10～15 parts, Rhizoma Atractylodis 10～15 parts, the Radix Angelicae Dahuricae 10～15 parts。

4. the preparation method of the Chinese medicine for external application treating Pediatric secretory otitis media as according to any one of claims 1 to 3, it is characterised in that the dosage form of described preparation is drop, and preparation method includes:

A, first by Herba Centipedae, Herba Menthae, Indigo Naturalis, Borneolum Syntheticum and Pseudobulbus Bletillae (Rhizoma Bletillae) distillation crystallize into powder；For component 1,

B, again by the medicinal residues after distillation with put into soak with ethanol outside all the other raw materials, heat is extracted, and becomes extractum shape, for component 2；

C, said components 1 and component 2 are mixed it is condensed into pasty state, add Oleum sesami, bottling。

5. the preparation method treating the Chinese medicine for external application of Pediatric secretory otitis media according to claim 4, it is characterized in that, in step a, first Herba Centipedae, Herba Menthae, Indigo Naturalis, Borneolum Syntheticum and Pseudobulbus Bletillae (Rhizoma Bletillae) steam method are distilled, obtain crystal, be then comminuted into fine powder；Standby as component 1。

6. the preparation method treating the Chinese medicine for external application of Pediatric secretory otitis media according to claim 4, it is characterized in that, in described step c, the component 1 of distillation extraction is put in the medicinal residues extractum component 2 of ethanol extraction, add Oleum sesami and soak use of can bottling for 5-10 days。

7. the preparation method of the Chinese medicine for external application treating Pediatric secretory otitis media as according to any one of claims 1 to 3, it is characterised in that described external drug dosage forms is spray, and its preparation process includes:

A, by first by the distillation of Herba Centipedae, Herba Menthae, Indigo Naturalis, Borneolum Syntheticum and Pseudobulbus Bletillae (Rhizoma Bletillae), to crystallize into powder be component 1；

B, again medicinal residues mixing surplus stock is added alcohol heating reflux extract;

C, being merged by above two extract, decompression recycling ethanol also concentrates sucking filtration absorption, obtains medicated powder solubilizer and loads in Aerosol Products for Medical Use。

8. the preparation method treating the Chinese medicine for external application of Pediatric secretory otitis media according to claim 7, it is characterised in that in described step b, put in 10 times amount ethanol by distilling medicinal residues, 2 extracting solution each 1～2 hour, are merged filtering and standing by heating and refluxing extraction 2 times；In described step c, it is characterised in that twice extract merged, decompression recycling ethanol to be concentrated into liquor strength be 0.4g crude drug/mL, after sucking filtration, the relative density of filtrate is about when 20 DEG C 1.06；Above-mentioned filtrate is the macroporous adsorptive resins of 10L through volume, first with the deionized water of 10 times of resin column volumes or distilled water eluting, again with 95% ethanol elution of 5 times of resin column volumes, collect ethanol elution, remove solvent, obtain raw material medicated powder mixing abovementioned steps and obtain component 1, solubilizer, load in Aerosol Products for Medical Use。

9. the Chinese medicine for external application treating Pediatric secretory otitis media according to any one of claims 1 to 3, it is characterized in that, described external preparation dosage form is: drop, spray, tincture, irrigation and absorbent cotton suppository, powder, powder, ointment, suppository, plaster or cream。