CN103735845A - Traditional Chinese medicine external preparation for treating pediatric secretory otitis media and preparation method thereof - Google Patents

Abstract

The invention discloses a traditional Chinese medicine external preparation for treating pediatric secretory otitis media. The external preparation comprises the following raw materials in parts by weight: 10-20 parts of centipeda minima, 10-20 parts of schizonepeta, 10-20 parts of radix sophorae flavescentis, 10-20 parts of toosendan fruit, 10-20 parts of borneol, 10-20 parts of phellodendron amurense, 10-20 parts of scutellaria, 10-20 parts of rhizoma bletillae, 10-20 parts of mint, 10-20 parts of indigo naturalis, 10-20 parts of lithospermum, 10-20 parts of salvia miltiorrhiza, 10-20 parts of dandelion, 10-20 parts of rhizoma atractylodis and 10-20 parts of radix angelicae. The medicine provided by the invention has good functions of clearing away heat and toxic materials, eliminating dampness and astringing sores, removing necrotic tissue and promoting granulation and exorcising evil and relieving pain, and has the effects of being quick to dry ears, short in treatment course and free of side effect. If being dosed to secretory otitis media patients, the medicine can promote degradation and absorption of secretion, repair perforated tympanic membrane and recover the audition. The traditional Chinese medicine external preparation disclosed by the invention has such functions as resisting inflammation and bacteria, convergence, dehumidification, dredging aperture, relieving pain, etc.

Description

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

Technical field

The present invention relates to contain the medicinal preparation that derives from plant, animal or mineral component, particularly a kind of Chinese medicine for external application for the treatment of Pediatric secretory otitis media and preparation method thereof.

Background technology

Secretory otitis media (otitis media with effusion) is the middle ear apyetous inflammatory diseases take middle ear effusion and auditory dysesthesia as feature, is one of otorhinolaryngology common disease.Child is common.After upper respiratory tract infection take the vexed swollen sense of ear and auditory dysesthesia as cardinal symptom.Because otalgia is not obvious, child main suit is unclear, and when children's's audition is affected, the head of a family just finds to go to a doctor, usually delay diagnosis and treatment.Secretory otitis media can cause child's hearing loss, affects speech development of speech, answers highly vigilant of and observes in time treatment.For adults with unilateral pathological changes person, the clear and definite cause of disease as early as possible, the occupancy tumor of eliminating nasopharynx part and peripheral clearance thereof, relief of symptoms, the quality of making the life better as early as possible.

Secretory otitis media is take middle ear effusion and auditory dysesthesia as the middle ear apyetous inflammatory diseases of feature, is called again 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 be gelatin person, be called again secretory otitis media.After upper respiratory tract infection take the vexed swollen sense of ear, listen the remote and auditory dysesthesia of sound as cardinal symptom.Because otalgia is not obvious, child main suit is unclear, and when children's's audition is affected, the head of a family just finds to go to a doctor, 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.Can cause child's hearing loss, affect speech development of speech, answer highly vigilant of and observe in time treatment.For adults with unilateral pathological changes person, the clear and definite cause of disease as early as possible, the occupancy tumor of eliminating nasopharynx part and peripheral clearance thereof, relief of symptoms, the quality of making the life better as early as possible.

The preschooler of research discovery about 90% was suffered from secretory otitis media, and 25% school age population is suffered from secretory otitis media.Be most commonly in June～4 year old child.The child who suffered from secretory otitis media during by 1 years old exceedes 50%, during by 2 years old, is increased to 60%.Many outbreaks were disappeared voluntarily at 3 months, and approximately 30%～40% children with otitis media with effusion can recur.5%～10% infant secretory otitis media continues more than 1 year.In the U.S., there are every year 22000000 infants that are diagnosed as secretory otitis media, the direct and consequential damage causing is every year estimated to reach 4,000,000,000 dollars.

It is relevant that infant is easily suffered from the secretory otitis media anatomical structure special with infant.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.The neonate of doing artificial respiration when difficult labour during childbirth, breech presentation, chamber breath, amniotic fluid Chang Yi enters middle in ear.Parent is suffered 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 contrary breast of neonatal nursing, the dorsal position of particularly making even is not manually fed person with feeding bottle, and during contrary breast, milk pool amasss in cavum nasopharyngeum, enters middle ear cause otitis media through pharyngotympanic tube.

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

Infant shows as ambient sound Low Response, grabs ear, and sleep is easily waken up, irritability.Baby does not react sound around, head can not be turned to sound source exactly; Even if infant does not have main suit's auditory dysesthesia, household finds that infant is careless, behavior change, reactionless to normal dialog, when seeing TV or using hearing device, always sound is opened very large; For repeatedly outbreak acute otitis media, should watch out for outbreak the intermission may be lasting secretory otitis media; School grade is poor; Balanced capacity is poor, the clumsiness of unknown cause; Speech development of speech is slow.

Infant and children with otitis media with effusion should be differentiated 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, mainly with ear vexed be cardinal symptom, otalgia is discontinuity, lighter, even without otalgia, shows.

Because secretory otitis media is self-limited disease, there is certain spontaneous recovery rate, before having wound to treat, patient should tightly observe March.Secretory otitis media whether spontaneous recovery depends on the length of the cause of disease and hydrops time.The patients with secretory otitis media of being left over by acute otitis media, approximately 75%～90% can spontaneous recovery when March, and tympanogram transfers A to by B, C type.Approximately 55% patients with secretory otitis media can spontaneous recovery when March, and still, approximately 1/3 infant may increase the weight of.In ominous 2～4 years old infant of onset time, approximately 25% infant spontaneous recovery time is 3 months.Baby and children's's spontaneous recovery rate is higher.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 in observing the non-high-risk infant in stage, be no matter hundred evils and none profit is observed and waited for non-high-risk infant without harm of medicine or surgical intervention; Need to inform that household's infant audition is poor, especially ears patients with secretory otitis media; Formulation improves infant and listens to and measure and the scheme of academic environment; 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, not recommendation.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 can show as tympanum hyperemia) of antibiotic application, do not advocate to combine and use antihistaminic and Decongestant, because their side effect is obvious.Do not advocate life-time service oral hormone treatment at large, unless indivedual case yet.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, and main cause is, curative effect is not remarkable, and some treatment cycle reach several weeks.In prior art, treating the medicine of otitis media, is mostly to use Western medicine antiinflammatory, and concerning children's, side effect is many, not recommendation; Chinese medicine decoction is oral, and mouthfeel is poor, and infant is not also accepted.Only have Chinese medicine for outer use the properest, through focus.The new drug that exploitation is applicable to the treatment secretory otitis media of children's's use is exactly the present task of top priority.

Summary of the invention

Technical problem to be solved by this invention is, treats the medicine of secretory otitis media in prior art, is mostly to use Western medicine antiinflammatory, and concerning children's, side effect is many, and not recommendation is larger to human injury; Chinese medicine decoction is oral, and mouthfeel is poor, and infant is not also accepted.Only have Chinese medicine for outer use the properest, through focus.The new drug that exploitation is applicable to the treatment secretory otitis media of children's's use is exactly the present task of top priority.

For solving these technical barriers, the invention provides a kind of Chinese medicine for external application for the treatment of Pediatric secretory otitis media, described in it, in external preparation, the parts by weight of various raw materials are: 10～20 parts of Herba Centipedae, 10～20 parts of Herba Schizonepetae, 10～20 parts of Radix Sophorae Flavescentiss, 10～20 parts of Fructus Toosendans, 10～20 parts of Borneolum Syntheticums, 10～20 parts of Cortex Phellodendris, 10～20 parts of Radix Scutellariaes, 10～20 parts of Pseudobulbus Bletillae (Rhizoma Bletillae), 10～20 parts of Herba Menthaes, 10～20 parts of Indigo Naturaliss, 10～20 parts of Radix Arnebiae (Radix Lithospermi)s, 10～20 parts of Radix Salviae Miltiorrhizaes, 10～20 parts of Herba Taraxacis, 10～20 parts of Rhizoma Atractylodis, 10～20 parts of the Radixs Angelicae Dahuricae.

The Chinese medicine for external application of described treatment Pediatric secretory otitis media, described in it, in external preparation, the parts by weight of various raw materials can be: 10～15 parts of Herba Centipedae, 10～15 parts of Herba Schizonepetae, 10～15 parts of Radix Sophorae Flavescentiss, 10～15 parts of Fructus Toosendans, 10～15 parts of Borneolum Syntheticums, 10～15 parts of Cortex Phellodendris, 10～15 parts of Radix Scutellariaes, 10～20 parts of Pseudobulbus Bletillae (Rhizoma Bletillae), 10～20 parts of Herba Menthaes, 10～20 parts of Indigo Naturaliss, 10～20 parts of Radix Arnebiae (Radix Lithospermi)s, 10～20 parts of Radix Salviae Miltiorrhizaes, 10～20 parts of Herba Taraxacis, 10～20 parts of Rhizoma Atractylodis, 10～20 parts of the Radixs Angelicae Dahuricae.

The Chinese medicine for external application of described treatment Pediatric secretory otitis media, described in it, in external preparation, the parts by weight of various raw materials can also be: 10～20 parts of Herba Centipedae, 10～20 parts of Herba Schizonepetae, 10～20 parts of Radix Sophorae Flavescentiss, 10～20 parts of Fructus Toosendans, 10～20 parts of Borneolum Syntheticums, 10～20 parts of Cortex Phellodendris, 10～20 parts of Radix Scutellariaes, 10～15 parts of Pseudobulbus Bletillae (Rhizoma Bletillae), 10～15 parts of Herba Menthaes, 10～15 parts of Indigo Naturaliss, 10～15 parts of Radix Arnebiae (Radix Lithospermi)s, 10～15 parts of Radix Salviae Miltiorrhizaes, 10～15 parts of Herba Taraxacis, 10～15 parts of Rhizoma Atractylodis, 10～15 parts of the Radixs Angelicae Dahuricae.

For solving the problems of the technologies described above, the present invention also provides a kind of preparation method of Chinese medicine for external application for the treatment of Pediatric secretory otitis media, and described in it, the dosage form of preparation is drop, and preparation method comprises:

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

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

C, by said extracted thing mix be condensed into pasty state, add Oleum sesami, bottling.

In step a, can first Herba Centipedae, Herba Menthae, Indigo Naturalis, Borneolum Syntheticum and Pseudobulbus Bletillae (Rhizoma Bletillae) be distilled with steam method, obtain crystal, be then ground into fine powder; Standby as component 1.

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

In described step c, the component of distillation extraction 1 can be put into the medicinal residues extractum component 2 of ethanol extraction, add Oleum sesami and soak the use of can bottling for 5-10 days.

For solving the problems of the technologies described above, the present invention also provides a kind of preparation method of Chinese medicine for external application for the treatment of Pediatric secretory otitis media, and the preparation process that described external used medicine dosage form is spray comprises:

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

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

C, above-mentioned two kinds of extracts are merged, decompression recycling ethanol concentrated sucking filtration absorption, obtain medicated powder solubilizer and pack in Aerosol Products for Medical Use.

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

The Chinese medicine for external application of described treatment Pediatric secretory otitis media, described in it, 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, a little spraying of the powder that medicine of the present invention is made or brush the in ear to patient, make its mucomembranous surface gently cover one deck powder, so can not cause auditory meatus to stop up, be conducive to suffer from ear mucosa part and fully absorb the drug, the curative effect obtaining.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, the analgesic effect that exorcises evil spirits, and has the effect that dry ear is fast, curative effect is short, have no side effect.For patients with secretory otitis media, can impel the secretions absorption of disappearing, the tympanum reparation of perforation, makes auditory rehabilitation.The multiple effects such as that the present invention has is antibacterial, antiinflammatory, convergence, dehumidifying, sensible, pain relieving.Toxic and side effects of the present invention is little, antimicrobial spectrum is wider, be difficult for producing drug resistance, Ear is without overt toxicity effect, responsive especially to otitis media pus antimicrobial spectrum, can anti-bacteria protein synthetic and reach the object of sterilization, has avoided after some Chinese medicine preparation local application, produce cerumen and be difficult to the feature of eliminating, have that dry ear is fast, curative effect is high, a short treating period, side effect is little, medicine source is wide feature.

Chinese medicine composition safety of the present invention, toxic and side effects is little, is applicable to children's and uses, and there is no dependency.Its using method is simple, and healing time is short, after curing, is difficult for recurrence.Can create good social value and economic interests.

The specific embodiment

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

Modern medicine about the theory of otitis media is: primary disease is on eustachian tube obstruction basis, or due to being infected on this basis, is divided into mechanicalness and struvite two kinds, and inflammation is divided into again infective inflammation and allergy.Therefore treatment adopts antibiotic, antihistaminic, nasal cavity is convenient to MEV and excretion with vaso-excitor material, 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 due to poly-ear key.Because middle ear drainage does not freely wait many reasons, make the touching difficulty of primary disease more.Motherland's medical science is classified as " glue ear ", thinks 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 due to 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 goes out key clearly on defeated clear sun, < < Compendium of medicine > > meaning: " taste one void; knowledge nine orifices is all sick ", weakness of the spleen and stomach is clear YANG failing to ascend, and ear key loses its warm supporting, and the more double insufficiency of the spleen water of not changing wets, the wet tired knot ear key of water, therefore in ear pus is for years dry, therefore clear YANG failing to ascend is dizziness and tinnitus and become deaf quickly, and shallow complexion is simple and unadorned is resembling for insufficiency of the spleen insufficiency of vital energy and blood; Lack of appetite abdominal distention, half congealed during stool, be also insufficiency of the spleen wet the levying that have.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, the effect that the 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, the 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, understand things pain-stopping, detumescence and apocenosis, dampness leukorrhagia stopping.< < Japan hanako materia medica > >: control conjunctival congestion bulbar conjunctiva polyp, and tire patching leaks 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, goes face Shao-defect scar.

Radix Sophorae Flavescentis hardship, cold.GUIXIN, liver, stomach, large intestine, urinary bladder channel 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 being combined with Hedyotidis Diffusae, is the external good medicine for the treatment of dermatomycosis.

Radix Scutellariae: Radix Scutellariae has heat clearing and damp drying, 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 used in fungal culture miscellaneous bacteria and infect special severity by the strong feature of broad-spectrum antibacterial action, fine by Radix Scutellariae extracting solution effect.< < Bencao Jingshu > >: Radix Scutellariae, its property is respectful clearly, so evil removing: so bitter in the mouth dampness; So YIN-cold victory heat, therefore main all heat.All hot persons, pathogenic heat with all over heat also, jaundice, intestinal be out-of-the-way, let out dysentery, the disease of all damp and hot victory also, is analysed it, all diseases are from recover.Bitter cold can be except damp and hot, thus small intestinal profit and water from by, source is clearly flowed also clean.The blood person of closing, excess-heat is at blood system, and amenorrhea is made us obstructed in instant heating human blood chamber, damp and hot solution, Ying Qi is clearly and voluntarily also.Malignant boil cellulitis erosion person, heat in blood is stayed knot, and is that carbuncle stain is also rotten: acute scleritis person, fire of moxibustion blood trouble also, removing heat from blood heat extraction, spontaneous recovery also.Radix Scutellariae has antiallergic action and antiinflammatory action: the contained baicalin of Radix Scutellariae and baicalin can obviously suppress the anaphylaxis contractile response that sensitized guinea pig rat small intestine in vitro and isolated tracheal produce antigen, passive general allergy to Cavia porcellus and mice and Cavia porcellus passivity skin allergic reaction, baicalin and baicalin also have inhibitory action.Radix Scutellariae has refrigeration function, most evidences, and the active ingredient baicaligenin of Radix Scutellariae has refrigeration function.Radix Scutellariae has Detoxication, and baicalin has obvious Detoxication, and this may be that baicalin decomposites glucuronic acid due under the effect of glucuronidase, and due to being combined with multiple poisonous substance.10 milligrams of LD50 that can improve strychnine of baicalin reach 2.5 times, and the hepatic glycogen content of carbon tetrachloride poisoning mice is increased.

Fructus Toosendan is cold in nature, and 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 except damp and hot, clearing away liver-fire, pain relieving, parasite killing.Except damp and hot, 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, regulates the flow of vital energy, dampness, stopping vomiting is against acid regurgitation, headache due to JUE YIN disorder, 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, enters liver, spleen, stomach, large intestine, kidney channel.External has obvious pain relieving and therapeutic effect.< < Thunder God is concocted 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, and pain relieving, cough with dyspnea cold and heat, dehumidifying 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 damp and hot as good take except the part of the body cavity below the umbilicus, housing the bladder, kidneys and bowels.

Radix Salviae Miltiorrhizae hardship, is slightly cold.GUIXIN, Liver Channel.Stasis-dispelling and pain-killing, promoting blood circulation to restore menstrual flow, relieving restlessness clears away heart-fire.For menoxenia, amenorrhea dysmenorrhea, lump in the abdomen, breast ventral spine pain, pyretic arthralgia pain, skin infection swells and ache, dysphoria and insomnia.For costa sternales hypochondriac pain, rheumatic arthralgia, lump in the abdomen caking, skin infection swells and ache, the tumbling down pain of injury, menoxenia, amenorrhea dysmenorrhea, puerperal stasis of blood pain etc.Treatment costa sternales pain, lump in the abdomen caking, and menoxenia, amenorrhea dysmenorrhoea have good effect.< < detailed outline > > carries: Radix Salviae Miltiorrhizae, press the sensible opinion of < < married woman > > cloud, SIWU TANG is controlled gynecopathy, pay no attention to antenatal puerperal, how many through water, all can be general, only taste Radix Salviae Miltiorrhizae is loose, cures mainly identical with it.Lid Radix Salviae Miltiorrhizae can break stagnated blood, mends fresh blood, peaceful tire, the stillborn fetus that falls, only metrorrhagia dysentery, regulating menstruation arteries and veins.

Herba Menthae is one of Chinese conventional Chinese medicine.It is pungent cool property sweating antipyretic medicine, controls influenza, headache, conjunctival congestion, fever of the body, throat, the dental bed disease such as swell and ache.Place with can training the mind dysmenorrhoea, skin pruritus, erythra and eczema etc.The Herba Menthae of light friend 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, improving eyesight clears away heart-fire.Herba Menthae has extremely strong sterilization antibacterial action, often drinks its energy preventing viral flu, oral disease, makes breath freshening.Gargle with mint tea juice, can be anti-halitosis in advance.With mint tea mist steaming face, also has the effect of shrinking pore.By the blade that steeped tea, apply and on eyes, can feel refrigerant, can remove eyestrain.It is said that Herba Menthae also has the another name of " eyes grass ", can be used for treating ophthalmic.

Herba Schizonepetae taste is flat, and warm in nature, nontoxic, faint scent is dense.Herba Schizonepetae is diaphoresis, and antipyretic is one of conventional medical herbs of China.Energy town expectorant, timid wind, removing heat from blood.Control influenza, the diaphoresis of headache cold and heat, 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 flu, headache, measles, rubella, skin infection from the beginning of.< < detailed outline > >: loose wind heat, refresh oneself, throat, the skin ulcer that disappears is swollen.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, and removing toxic substances rash.For heat in blood poison contain, 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, loose conjunctival congestion is swollen, nebula, deafness, headache olic acid, controls Tan Nve Snore clam, has a stuffy nose obstructed, and plug breath is from falling, and loose skin ulcer is swollen again.< < detailed outline > >: food grass in goose, above reaches brains, and control top pain order disease, stuffy nose relieving gas and the flat meat that falls; Inside reach lung meridian Er Zhi Snore clam, intermittent fever due to phlegm, loose skin ulcer is swollen; It is especially aobvious wonderful except the merit of nebula.By the former machine of Ni Wei moral < <, open micro-collection > > cloud: control corneal nebula nose, BIYUNSAN is monarch with Herba Centipedae removing toxic substances, Indigo Naturalis is reduced phlegm and internal heat as assistant, and the pungent broken of Sichuan Cordyceps stays evil removing for making, and the medicine rising also.On the whole as boiled, cover method, often want evil poison and do not close, order has outlet.So power is little and sharp, suitable its power of Chang Yiju, and all diseases in all orders, all can, with it, give birth to more refreshing.

Pseudobulbus Bletillae (Rhizoma Bletillae) astringing to arrest bleeding, detumescence and promoting granulation.For hemoptysis, spit blood, traumatic hemorrhage, sore swollen toxin, chapped skin; Pulmonary tuberculosis hemoptysis, ulcer haemorrhage.1. anastalsis: Pseudobulbus Bletillae (Rhizoma Bletillae) can strengthen platelet factor III activity, significantly shortens clotting time and thrombinogen formation time, suppresses plasmin enzymatic activity, and local hemorrhage is had to 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; To anesthetized dog, experimental Stomach duodenum perforation has therapeutical effect.3. antibacterial, antifungic action: the immersion of Pseudobulbus Bletillae (Rhizoma Bletillae) ethanol has inhibitory action to staphylococcus aureus, bacillus subtilis, Bacillus tuberculosis; Water logging agent has inhibitory action to microsporon audouini; Contained 3 biphenyl classes and 2 the luxuriant and rich with fragrance compounds of two hydrogen of Pseudobulbus Bletillae (Rhizoma Bletillae) have inhibitory action to staphylococcus aureus, bacillus subtilis, Candida albicans ATCC1057 and Trichophyton QM248.

Rhizoma Atractylodis are pungent, bitter, temperature.Return spleen, stomach, Liver Channel.Function cures mainly: drying damp and strengthening spleen, and expelling wind and cold, improving eyesight.For distension and fullness in the abdomen, the edema of having loose bowels, beriberi flaccidity of feet with lamenness, 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; Heavy sensation of the body pain; Arthromyodynia warm nature; Podomere is ached and is being weighed; Flaccidity folds in a garment.Antibacterial: Rhizoma Atractylodis extract has the effect of eliminating drug resistance shigella flexneri R plasmid, can reduce the generation of bacterial drug resistance.Utilize 95% soak with ethanol Rhizoma Atractylodis 10 hours, take out Rhizoma Atractylodis, be placed on the floor of operating room of preparing sterilization, light, until Rhizoma Atractylodis turn to ash, after sterilization, than clump count in air before sterilization, obviously reduce.But early stage in vitro study does not find that Rhizoma Atractylodis decocting liquid has obvious antibacterial action.< < medicineization justice > >: Rhizoma Atractylodis, acrid in the mouth master is loose, warm in nature and dry, dry drying, specially enters taste, cures mainly anemofrigid-damp arthralgia, epidemic pathogenic factors from mountains, hydroderma, all pungent strong merit by heresy is also.Rule three wetting, if wet at the part of the body cavity above the diaphragm housing the heart and lungs, easily raw damp-phlegm, with this dampness row expectorant; Wet middle Jiao, stagnant gas rushes down, with this alleviating distention in middle-JIAO spleen invigorating; Wet in bottom, sufficient knee joint flaccidity is soft, with this, with Cortex Phellodendri, controls flaccidity, can make sufficient knee joint strong; Get its pungent loose gas hero, the loose evil diaphoresis of using, extremely happy.Close six god loose, general solution spring and summer damp-heat disease; Assistant decoction for dispelling pathogens from superficial muscles, the loose malaria of table from the beginning of; If after under calentura antiperspirant, deficiency-heat is not understood, and adds Baihu Tang, then separates it, perspiration stopped cool skin with this.Miao Zhongchun with this simply for end, control insufficiency of the spleen distention of the abdomen caused by various parasites.

Herba Taraxaci is the Chinese medicine of commonly using 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 Materia Medica > > records: " Detoxicating food-poisoning, loose stagnant gas, heat clearing away poison, relieving dyspepsia poison, disappear dislike swollen, tuberculosis, furuncle is swollen." Herba Taraxaci hides sweet flatly, its property is nontoxic.When being enters stomach into liver, the key medicine of antipyretic removing heat from blood.

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, with steam method distillation, obtain crystal, is then ground into fine powder, standby as component 1, again will, get medicinal residues and surplus stock Herba Schizonepetae 1000g after distillation, 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% soak with ethanol 1-2 hour that Radix Angelicae Dahuricae 1000g adds 5-10 doubly to measure, heating extraction 2 times, each 1-2 hour, remove supernatant, merge extractive liquid, 80-120 order filters, through the molecular weight that dams, be the ultrafiltration post ultrafiltration of 5000-10000 again, 1.36 extractum when ultrafiltrate concentrating under reduced pressure relative density is 80 ℃, heating is concentrated, 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 of distillation extraction 1 is put into the medicinal residues extractum component 2 of ethanol extraction, added Oleum sesami and soak the use of can bottling for 5-10 days.

The manufacturing process of spray of the present invention is: will first Herba Centipedae 1200g, Herba Menthae 1300g, Indigo Naturalis 1300g, Borneolum Syntheticum 1200g and Pseudobulbus Bletillae (Rhizoma Bletillae) 1100g distillation be crystallized into powder; Medicinal residues be will distill and other surplus stock Herba Schizonepetae 1200g, Radix Scutellariae 1200g, Radix Sophorae Flavescentis 1300g mixed, 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 puts into 10 times of amount ethanol, heating and refluxing extraction 2 times, each 1～2 hour, 2 extracting solution are merged to filtering and standing; Extracted twice thing is merged, and decompression recycling ethanol to be concentrated into liquor strength be 0.4g crude drug/mL, after sucking filtration, when the relative density of filtrate is about 20 ℃ 1.06; The macroporous adsorptive resins that above-mentioned filtrate is 10L through volume, first use deionized water or the distilled water eluting of 10 times of resin column volumes, use again 95% ethanol elution of 5 times of resin column volumes, collect ethanol elution, remove solvent, obtain raw material medicated powder and mix the distillation crystalline powder that abovementioned steps obtains, solubilizer, packs in Aerosol Products for Medical Use

The manufacturing process of external pulvis of the present invention is: get first Herba Centipedae 1100g, Herba Menthae 1300g, Indigo Naturalis 1300g, Borneolum Syntheticum 1200g and Pseudobulbus Bletillae (Rhizoma Bletillae) 1100g distillation are crystallized into powder, to distill medicinal residues and mix other surplus stock Herba Schizonepetae 1200g, 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 mixes by proportioning, drop into pulverizer and be ground into fine powder, after sieving, puts into fine powder acid and alkali-resistance infusion kettle, at normal temperatures, flood 10～20 days with ethanol is common, the liquid having flooded and medicinal residues are carried out to squeeze and filter, after separation, get filtrate, heating is concentrated into pasty state, put into baking oven, be controlled at 100 ℃, cooling after drying, directly become powder, directly use.

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

According to described umber, Herba Centipedae 1200g, Herba Menthae 1300g, Indigo Naturalis 1300g, Borneolum Syntheticum 1400g and Pseudobulbus Bletillae (Rhizoma Bletillae) 1200g are become to crystallization with steam distillation, 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% soak with ethanol 1-2 hour that adds 5-10 doubly to measure, heating extraction 2 times, each 1-2 hour, remove supernatant, merge extractive liquid, 80-120 order filters, through the molecular weight that dams, be the ultrafiltration post ultrafiltration of 5000-10000 again, 1.36 extractum when ultrafiltrate concentrating under reduced pressure relative density is 80 ℃, heating is concentrated, 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, by putting into the component 2 of ethanol extraction after the component of distillation extraction 1 and Radix Scutellariae 1200g pulverizing, mix vaseline and make unguentum.

The ointment that also can obtain with said method soaks absorbent cotton, becomes suppository, directly fills in sufferer ear.

Pharmacology's toxicity test

Acute toxicity testing data

1, experimental technique

Guinea pig back spinal column both sides are evenly coated depilatory, make approximately 40 square centimeters of unhairing scopes.Clean depilatory returns cage to observe 24 hours, every group of Cavia porcellus is coated with respectively Chinese medicine preparation external drop 0.2,0.4 of the present invention and 0.8ml, respectively containing crude drug 92mg, 184mg and 368mg), another group is coated with the every twice-daily of solvent 0.8ml, and continuous one week, after experiment finishes, 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 activity, histopathologic examination, the administration group heart, liver, kidney and depilation skin with contrast more also no significant difference of word.

Results suggest, 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 is used safety.

Long term toxicity test data

1, experimental technique

By random Cavia porcellus part, become 4 groups, 15 every group.In guinea pig back spinal column both sides, depilatory is evenly coated, made approximately 40 square centimeters of its depilation scopes.Clean depilatory, observe every group of Cavia porcellus after 24 hours and be coated with respectively external drop 0.2,0.4 of the present invention and 0.8ml, respectively containing crude drug 92,184 and 368mg), another group is coated with the every twice-daily of solvent 0.8ml, continuous 30 days, observe the ordinary circumstance of Cavia porcellus, experiment finishes rear execution animal and carries 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 activity, 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, Chinese medicine preparation long-term prescription of the present invention is showed no obvious toxic action to local skin and whole body important organ.Result of the test shows: Chinese medicine preparation experiment safety of the present invention.

Aggregate toxicity experiment:

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

Pharmacological experiment explanation:

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

1 materials and methods

1.1 laboratory animal

By 6～8 weeks 21 of healthy BALB/C mice (being provided by University Of Qingdao's animal center), body weight 22～30g, was divided into 3 groups at random: 7 of experimental grouies, matched group I7,7 of control Group II.Before experiment, all through endoscopy of ear, confirm without external auditory meatus and middle ear infection.

1.2 modeling method

Experimental group gives 1.2mg OVA (sigma company, the U.S.) be dissolved in 0.6ml phosphate buffer (PBS), take 5.14mg aluminium hydroxide (rising chemical industry preparation factory purchased from east, Wenzhou City) as the capable lumbar injection of immunological adjuvant, 1 time weekly, continuous 2 weeks, this was the whole body sensitization stage.After 2 weeks, with the capable intraperitoneal injection of anesthesia of 20% urethane 5m1/kg, under sterile working, 1m1/kg OVA/PBS mixed liquor 15L1 is injected to 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 detection index

Mice is 2d after secondary excitation, and being breaked end lives kills, and gets bilateral otic capsule, fixes with 4% paraformaldehyde, 5% aqueous solution of nitric acid decalcification, after dehydration, specimens paraffin embedding slices, conventional hematoxylin-eosin staining, light Microscopic observation mucosa of tympanic cavity hypertrophy situation, counting eosinophilic granulocyte.Immunohistochemical staining detects the expression (all purchased from Wuhan doctor's moral company) of IL-4, IL-5, IL-12, IFN-C, and DAB developer is purchased from Beijing Zhong Shan Bioisystech Co., Ltd, and step is undertaken by test kit explanation.

1.4 method for cell count

On eyepiece, join counting lattice, under low power lens, under middle-ear mucosa, in lamina propria, tympanum transudate, choose the region that 5 positive cells are many, under high power lens, count cell number, get the average under 5 high power lens visuals field (HP), result represents with-x ± s, and mucosa thickness is measured under light microscopic with micrometer.

1.5 statistical procedures

Adopt onew ay variance analysis and the check of pearson rectilinear correlation in SPSS11.0 statistical package, P < 0.05 is for there being statistical significance.

2 results

2.1 modeling results

After all BALB/C mice row in ear injection OVA/PBS mixed liquors or PBS liquid every day row endoscopy of ear, experimental group is after 24h, there is erythema in tympanum and surrounding tissue, and tympanum has the stria vascularis of radial expansion in various degree; After 36h, tympanum loses normal gloss, is 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 in tympanums have faint yellow transparent wash, measure less, approximately 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, and puncture is without hydrops, and visible tympanum is dry, without congested.

2.2 light microscopy checking results

Two matched group mucosa of tympanic cavity are simple squamous epithelium or simple cuboidal epithelium, without obviously 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 take serosity as main; thin in water sample; to be faint yellow; mucosa of tympanic cavity hyperemia, edema, and blood capillary increases; permeability increases; epithelium cilium comes off, and the eosinophilic granulocyte, plasma cell, the lymphocytic infiltration that under mucosa, occur in the middle of lamina propria, medullary cavity and exudate are main, and mastocyte, mononuclear cell are also more common.Experimental group and two matched groups more all have statistical significance (all P < 0.05, table 1), and two matched groups are compared, difference not statistically significant.

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 are multiformity, visible lymphocyte, plasma cell, eosinophilic granulocyte, epithelial cell, vascular endothelial cell and fibroblast various kinds of cell are expressed, be expressed in Cytoplasm, be brown yellow granule, mainly be distributed among lamina propria under mucosal epithelium, medullary cavity and tympanum transudate, and matched group is weak positive or without expression.In experimental group, the expression of 4 kinds of cytokines all has statistical significance (P < 0.05, table 2) compared with two matched groups, and two matched groups are compared difference not statistically significant.

The expression of Th2 type cytokines IL-4, IL-5 is compared with the expression of Th1 type cytokines IFN-C, IL-12, and difference has statistical significance (P < 0.05).

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

3, the impact of experimental example on Guinea Pigs otitis media

1, experimental technique

After modeling success.After 30 minutes, one group of Cavia porcellus auris dextra injects 0.08ml (46.6mg/ only) Chinese medicine preparation solution of the present invention, and another group is injected equivalent solvent, continuous 12 days.Then solvent group is only used Chinese medicine preparation of the present invention (external drop) 21.3mg/ instead, and medication group continues administration, then within continuous six days, observes impact and the subacute toxicity of medicine on acute inflammation and hypertrophy variation.It is the same that another batch of test causes scorching method.Cause scorching latter 48 hours, one group of Cavia porcellus is only injected Chinese medicine preparation 42.6mg/ of the present invention in auris dextra, another group is injected 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 finishes, get external ear, tympanum, auditory ossicles and the heart, liver, kidney is done histopathologic examination.

2, result

Scorching latter 30 minutes of caused by dimethylbenzene xylene, in every Cavia porcellus auris dextra, inject Chinese medicine preparation of the present invention (external drop) 0.08ml (42.6mg), with matched group comparison, administration has no obvious transudate after 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 has obvious histopathology to change, and solvent disappears to impinging upon to latter 120 hours rednesses of inflammation, there is scar tissue in road, auditory meatus narrows, and middle in ear is shown in that a large amount of focus neutrophilic leukocyte invades profit.Cause scorching latter the 12 day, this group is used Chinese medicine preparation of the present invention instead, (42.6mg) once a day, continuous six, see that auditory meatus is tending towards 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, are reactive hyperplasia and change.The above results prompting: Chinese medicine preparation of the present invention not only has inhibitory action but also hypertrophy is also had to certain antagonism acute transudate, this medicine continuous application 18 days, do 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 42.6mg/ in peak period (48 hours), and Chinese medicine preparation of the present invention is treated two days later, and transudate and cell number obviously reduce (P < 0.05) redness and disappear.Cavia porcellus in ear transudate antibacterial culturing and count of bacteria result show, before administration, (ooze out peak period), in the Cavia porcellus ear transudate of test group, take golden Portugal bacterium as main, bacterial population is (1,600 ten thousand, 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 obviously 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 10,000 19 ten thousand and 450,000/ml) that cause scorching latter 48 hours

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

Clinical pharmacology drug effect:

Illustrate: Pediatric secretory otitis media patient 96 examples that in October, 2008-2012, the court are accepted for medical treatment year November are used Chinese medicine for external application treatment, and choose 60 examples (68 ear) patient who accepts for medical treatment the same period and as a control group, with antibiotic medicine, treat.And clinical data is carried out to review formula analysis contrast.Result: treatment group patient all successfully leaves hospital, audition on average improves 19.6dB.And compared with matched group patient, all there is remarkable significant difference in treatment group aspect cure rate and total effective rate.Chinese medicine external is treated children's acute secretory otitis media, have that therapeutic modality is easy, side effect is little, curative effect is short and eutherapeutic clear superiority, easily by infant, accepted, can be used as safe, effective, economic auxiliary treating method and spread out extensively at basic hospital.

Pediatric secretory otitis media (otitis media with effusion, OME) the children's's secretory otitis media that is otherwise known as, it refers at tympanum and contains from the apyetous hydrops that spills, oozes out and secrete, and children's OME is apt to occur in 6 years old following underage child.Its pathogenic factor is various, mainly contains Eustachian tube disfunction; Upper respiratory tract infection; Hypersecretion; Nasopharynx part kitchen range amygdala inflammation, nasal sinusitis and the hyperplasia of the adenoid; Ambient pressure sudden change; Other for vegetative nerve function be the reasons such as cleft palate, endocrinopathy.For improving the clinical Level of first-aid treatment to Pediatric secretory otitis media patient, comprehensive survey and analysis, existing report is as follows.

1 data and method

1.1 physical data

Selecting in October, 2008-2,012 96 examples (109 ear) the Pediatric secretory otitis media patient that my institute accepts for medical treatment year November is object of study treatment group.Patient age is 2～8 years old, average 5.4 years old, and wherein boy's 59 examples, girl's 37 examples.Left ear 45 examples of infant, auris dextra 41 examples, ears 13 examples.The average 4.5d of the infant course of disease.Patient is carried out to acoustic immitance test.Choose in addition 60 examples (68 ear) patient that accepts for medical treatment the same period as a control group, two groups of age, the course of disease, ears of asking infant are suffered from situation and the equal no difference of science of statistics of the anti-test case of sound channel, have comparability.

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.Acoustic immitance test is used Denmark MADSENZODLAC901 type otitis media functional analysis instrument to carry out tympanometry inspection, tympanogram Type B 78 ears, and C type 31 ears, wherein the visible liquid of 26 ear is flat, without acoustic stapedial reflex.

1.3 Therapeutic Method

Treatment group: make drop by the embodiment of the present invention 1, side uses: 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, makes drop.Every day three times.7d was 1 course for the treatment of.

Matched group: give the each 5mg/kg of patient's Administration of roxithromycin dispersible tablet, the each 5mg of prednisone, all day takes twice, Decongestant nasal drop collunarium, 1 week course for the treatment of for the two.

1.4 efficacy determination

Recovery from illness: clinical symptom disappearance, it is normal that tympanum recovers, and pure tone test threshold reverts to and returns to normal range in 25dB, and tympanum is anti-leads figure and is A type or As type.Effective: transference cure or alleviate to some extent, otopiesis makes moderate progress, more than the pure tone test threshold of audibility recovers 10～15dB.Tympanogram result upgrading, as C type transfers A type to or Type B turns C type.Invalid: symptom improves not obvious 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 remarkable significant difference in treatment group aspect cure rate and total effective rate.Concrete relatively 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, may cause a disease due to reasons such as antibacterial, viral infection, immunoreation or Eustachian tube disfunctions.The cardinal principle for the treatment of and preventing child secretory otitis media is: focus on child's spleen invigorating and support lung, carry out body function adjustment, thereby strengthen the resistance that infant infects outside.In addition, for preventing the generation of secreting type otitis media or repeating, occur, tackle in treating pharyngotympanic tube organ lesion around and impose treatment timely and effectively.State's internal therapy mainly contains the methods such as Drug therapy, operation tympanum catheterization and He-Ne laser therapy at present.

Traditional therapy is treated children's acute secretory otitis media, have that therapeutic modality is easy, side effect is little, curative effect is short and eutherapeutic clear superiority, easily by infant, accepted, can be used as safe, effective, economic auxiliary treating method and carry out promotion at basic hospital.

The specific embodiment:

Embodiment 1, Feng, female, 2 years old, medical 2010 dates JIUYUE 6 days, head of a family's readme sick child after upper respiratory tract infection take the vexed swollen sense of ears, listen the remote and auditory dysesthesia of sound as cardinal symptom.Because otalgia is not obvious, child main suit is unclear, and when children's's audition is affected, the head of a family just finds to go to a doctor, 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, makes drop.Every day three times.7d was 1 course for the treatment of.Clean left survey middle ear canals, by Chinese medicine drop of the present invention splash into middle ear canals with in, advise outpatient service check after 3 days, be in and observe 2 days, infant secretions disappears, and body temperature starts normally, continues to use a week, and in ear, secretion disappears, audition starts to recover, and continues to use 1 month, and audition takes a turn for the better gradually.

Embodiment 2: Liu, man, 6 years old, in November, 2011 was medical.Upper respiratory tract infection causes the vexed swollen sense first quarter moon of auris dextra.Once in outer court, with " upper respiratory tract infection ", treated 5 weeks, symptom is without alleviation.The vexed swollen sense of head of a family's readme ears, to listen the remote and auditory dysesthesia of sound be cardinal symptom.Look into tympanum complete, cave in and be lark; Auris dextra conductive deafness is shown in electric audiometry, conductance decline 40db; Row tympanum drawing liquid has secretions.Red tongue, moderate pulse.Be diagnosed as 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, Radix Angelicae Dahuricae 13g, makes drop.Every day three times.7d was 1 course for the treatment of.Clean left survey middle ear canals, by Chinese medicine drop of the present invention splash into middle ear canals with in, treat after 3 days, external auditory meatus secretions reduces, pain slowly disappears, audition is recovered normally gradually, external auditory meatus is dried, and without secretions, flows out.After 10 days, pain disappears, and auditory rehabilitation is normal, and external auditory meatus is dry, without secretions, flows out.Follow up a case by regular visits to, do not recur half a year.

Claims (10)

1. a Chinese medicine for external application for the treatment of Pediatric secretory otitis media, is characterized in that, in described external preparation, the parts by weight of various raw materials comprise: 10～20 parts of Herba Centipedae, 10～20 parts of Herba Schizonepetae, 10～20 parts of Radix Sophorae Flavescentiss, 10～20 parts of Fructus Toosendans, 10～20 parts of Borneolum Syntheticums, 10～20 parts of Cortex Phellodendris, 10～20 parts of Radix Scutellariaes, 10～20 parts of Pseudobulbus Bletillae (Rhizoma Bletillae), 10～20 parts of Herba Menthaes, 10～20 parts of Indigo Naturaliss, 10～20 parts of Radix Arnebiae (Radix Lithospermi)s, 10～20 parts of Radix Salviae Miltiorrhizaes, 10～20 parts of Herba Taraxacis, 10～20 parts of Rhizoma Atractylodis, 10～20 parts of the Radixs Angelicae Dahuricae.

2. treat according to claim 1 the Chinese medicine for external application of Pediatric secretory otitis media, it is characterized in that, in described external preparation, the parts by weight of various raw materials comprise: 10～15 parts of Herba Centipedae, 10～15 parts of Herba Schizonepetae, 10～15 parts of Radix Sophorae Flavescentiss, 10～15 parts of Fructus Toosendans, 10～15 parts of Borneolum Syntheticums, 10～15 parts of Cortex Phellodendris, 10～15 parts of Radix Scutellariaes, 10～20 parts of Pseudobulbus Bletillae (Rhizoma Bletillae), 10～20 parts of Herba Menthaes, 10～20 parts of Indigo Naturaliss, 10～20 parts of Radix Arnebiae (Radix Lithospermi)s, 10～20 parts of Radix Salviae Miltiorrhizaes, 10～20 parts of Herba Taraxacis, 10～20 parts of Rhizoma Atractylodis, 10～20 parts of the Radixs Angelicae Dahuricae.

3. treat according to claim 1 the Chinese medicine for external application of Pediatric secretory otitis media, it is characterized in that, in described external preparation, the parts by weight of various raw materials are: 10～20 parts of Herba Centipedae, 10～20 parts of Herba Schizonepetae, 10～20 parts of Radix Sophorae Flavescentiss, 10～20 parts of Fructus Toosendans, 10～20 parts of Borneolum Syntheticums, 10～20 parts of Cortex Phellodendris, 10～20 parts of Radix Scutellariaes, 10～15 parts of Pseudobulbus Bletillae (Rhizoma Bletillae), 10～15 parts of Herba Menthaes, 10～15 parts of Indigo Naturaliss, 10～15 parts of Radix Arnebiae (Radix Lithospermi)s, 10～15 parts of Radix Salviae Miltiorrhizaes, 10～15 parts of Herba Taraxacis, 10～15 parts of Rhizoma Atractylodis, 10～15 parts of the Radixs Angelicae Dahuricae.

4. a preparation method for the treatment of the Chinese medicine for external application of Pediatric secretory otitis media as described in any one in claim 1～3, is characterized in that, the dosage form of described preparation is drop, and preparation method comprises:

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

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

C, by said extracted thing mix be condensed into pasty state, add Oleum sesami, bottling.

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

6. according to the preparation method of Chinese medicine for external application for the treatment of Pediatric secretory otitis media described in claim 4, it is characterized in that, in described step b, get the 60-90% soak with ethanol 1-2 hour that medicinal residues after distillation and surplus stock add 5-10 doubly to measure, heating extraction 2 times, each 1-2 hour, remove supernatant, merge extractive liquid, 80-120 order filters, through the molecular weight that dams, be the ultrafiltration post ultrafiltration of 5000-10000 again, 1.36 extractum when ultrafiltrate concentrating under reduced pressure relative density is 80 ℃, heating is concentrated, 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.

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

8. according to the preparation method of Chinese medicine for external application for the treatment of Pediatric secretory otitis media described in any one in claim 1～3, it is characterized in that, the preparation process that described external used medicine dosage form is spray comprises:

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

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

C, above-mentioned two kinds of extracts are merged, decompression recycling ethanol concentrated sucking filtration absorption, obtain medicated powder solubilizer and pack in Aerosol Products for Medical Use.

9. the preparation method for the treatment of according to claim 8 the Chinese medicine for external application of Pediatric secretory otitis media, is characterized in that, in described step b, by distilling medicinal residues, put into 10 times of amount ethanol, heating and refluxing extraction 2 times, each 1～2 hour, merges filtering and standing by 2 extracting solution; In described step c, it is characterized in that, extracted twice thing is merged, decompression recycling ethanol to be concentrated into liquor strength be 0.4g crude drug/mL, after sucking filtration, when the relative density of filtrate is about 20 ℃ 1.06; The macroporous adsorptive resins that above-mentioned filtrate is 10L through volume, first use deionized water or the distilled water eluting of 10 times of resin column volumes, use again 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, packs in Aerosol Products for Medical Use.

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