CN107865966A

CN107865966A - The compound amino glycoside pharmaceutical composition being locally administered

Info

Publication number: CN107865966A
Application number: CN201610848780.4A
Authority: CN
Inventors: 刘力
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-09-23
Filing date: 2016-09-23
Publication date: 2018-04-03

Abstract

The present invention provide prepare effective dose Etimicin its pharmaceutically-acceptable salts or with have the steroid of anti-inflammatory effective dose or with non-steroidal antiinflammatory drugs or with the water conservation of effective dose or wetting agent or the composition of anti-dry eye drugs, and preparing prevention or the conjunctivitis for the treatment of people or mammal, application in the topical ophthalmics such as angular blepharitis, keratitis, sclerotitis, trachoma, scheroma, cataract, otitis externa, tympanitis, epifolliculitis, furuncle, impetigo or ear or nose use or external preparation for skin medicine, medicine of the present invention have the effect of more preferable or treatment compliance.

Description

The compound amino glycoside pharmaceutical composition being locally administered

Technical field

The present invention relates to pharmaceutical technology field, is specifically to provide prevention or treatment conjunctivitis, angular blepharitis, sand Eye, keratitis, dry eye syndrome, otitis externa, tympanitis, cataract, epifolliculitis, furuncle, impetigo, trauma infection contamination and eczema sense The Etimicin or its pharmaceutical salts and the dexamethasone of effective dose of dye or a kind of effective dose of dental ulcer treatment etc. or its The topical ophthalmic of derivative is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions and purposes.

Background technology

Etimicin is the aminoglycoside medicaments of domestic-developed, and it is semi-synthetic water-soluble to be classified as forth generation in the world at present Property aminoglycoside antibiotics (document：Chaudhary M1,Kesava Naidu G,Kumar S,Payasi A.Comparative antibacterial activity of a novel semisynthetic antibiotic: etimicin sulphate and other aminoglycosides.World J Microbiol Biotechnol.2012Dec；28(12):3365-71.), its mechanism of action is to suppress the normal protein synthesis of sensitive bacteria, its Ear renal toxicity is low.Other national research institutions do not find obvious toxicity to the sub-acute toxicity test of Etimicin yet.At present Drip-feed Etimicin treats some infectious diseases, recommended dose of being grown up：For normal renal function urinary infection or complete The patient of the sexy dye of body, a 0.l~0.15g, 2 times a day, or a 0.2~0.3g, 1 times a day, it is diluted in 0.9% chlorination Sodium injection or 5% glucose injection l00ml or 250ml iv drip, instil 1 hour every time, the course for the treatment of is 5~10. Clinical studies show this product to below infected with it is preferable the effect of：Respiratory tract infection：Such as acute bronchitis, chronic bronchitis Acute attack, community's pulmonary infection etc.；Kidney and urogenital infections：Such as acute pyelonephritis, cystitis, chronic renal plevis Ephritis or chronic cystitis acute attack etc.；Skin soft tissue and other infection：Such as skin and soft tissue infection, wound, wound Infection and the infection of other sensitive bacterias with operation postpartum.

Etimicin is Formulations for systemic administration at present, and to be easily caused whole body flora unbalance or be also easy to produce drug-fast bacteria for Formulations for systemic administration. It is worth noting that, germ also constantly changes to the drug resistance of aminoglycoside antibiotics, document also constantly reports such The drug resistance of medicine.163 plants of enterococcus that the detection such as Dan Zhiying is isolated from the sample of inpatient are to gentamicin and chain The height antibody-resistant bacterium (MICs >=2000mg/L) of mycin.As a result find, anti-109 plants of gentamicin height antibody-resistant bacterium (66.9%), anti-streptomycin height antibody-resistant bacterium 114 plants (69.9%).Total Test bacterial strain is to vancomycin sensitive.Prompting is faced Bed should use antibiotic with caution, select sensitive medicaments to be treated (document：Dan Zhiying, Wang Haiyi, Wu Hongfan, etc.；163 plants of intestines balls Bacterium is to high concentration aminoglycoside antibiotics resistance condition survey, Tianjin medicine, Tianjing Medical Journal, 1997,25(10)611-613；), Zheng is that gentle Shi Wei peaks agar dilution detects gentamicin, amikacin, to block that mould 6 kinds of element, TOB, Netilmicin and neomycin medicines are to the minimum inhibitory concentrations of 37 plants of ESBL-producing E.colis, to ammonia The resistant characterization and expression of drug resistance genes of base glucoside medicine are studied, and are detected 5 kinds of aminoglycoside drugs with PCR methods and are modified Enzyme gene, and being confirmed using DNA sequencing, as a result find gentamicin, amikacin, kanamycins, TOB and how 256mg/L is all higher than to 37 plants of EHECs MIC50, MIC90 for meter Xing, its resistant rate is respectively 78.4%, 45.9%, 72.9%th, 83.8% and 64.9%, and neomycin still has higher antibacterial activity (document：Zheng Weiping, Shi Weifeng；Production is super wide Compose beta-lactamase EHEC to study aminoglycoside drug drug resistance and drug resistant gene, international laboratory medicine magazine, International Journal of Laboratory Medicine,2009,3:220-222)。

Infected keratitis is still global common diseases causing blindness so far, it is estimated that annual 5000000 people in the whole world occurs each The infected keratitis of type, about 20% blind person is blinded because of ocular infection.China is used as developing country, particularly exists Many rural areas, because people life environment is poor and the backwardness of health care consciousness, the incidence of disease of infectious keratonosus It is higher.China's luscitas caused by disease of cornea and the blind patient of eyes, occupy the 2nd of ophthalmology blinding disease by about 2,000,000 Position.Therefore, it is not only in the case where the drug-fast bacteria of Formulations for systemic administration constantly increases, develops new local anti-infective medicine reply and constantly increase Drug-fast bacteria or the control or treatment of disease be highly desirable and be worth.

Ophthalmic infection disease also includes many, and harm is not shallow, for example, conjunctivitis be conjunctival tissue extraneous and body from The effect of body factor and the general designation of inflammatory reaction occurred.Although conjunctivitis is not serious to eyesight influence in itself, work as it When inflammation involves cornea or causes complication, the infringement of eyesight can be caused.Conjunctivitis has foreign body sensation, burn feeling, itched, photophobia, stream Tear.Important sign has conjunctival congestion, oedema, exudate, nipple hyperplasia, folliculus, pseudomembrane, true film, granuloma, lymphoglandulae auriculares anteriores Enlargement etc..Trachoma and complication account for the 3% of the inpairment of vision cause of disease.Lacrimal Passage Block is the common disease and frequently-occurring disease of ophthalmology, Obstruction of lacrimal passage often results in excessive tear, can develop into acute and chronic dacryocystitis, and excessive tear is hindered beauty to the dipping of face with tear in itself, given Patient causes body and psychological discomfort, and dacryocystitis can spread into eyeball and socket of the eye as the focus of infection of eye, cause bad Consequence, and [Liu Shuan, Tao Hai, Wang Wei, the epidemiological study of Lacrimal Passage Block are entered frequently as the contraindication of intraocular surgery Exhibition, international ophthalmology magazine, 2,008 8 (1):140-143].

Xerophthalmia is a kind of tear and ocular one kind disease caused by many factors, including ocular malaise symptoms, eyesight become Change and tear film is unstable and (or) the damage of ocular, and have potential ocular surface injury and visual disorder, with tear osmotic pressure Rise and ocular inflammatory reaction.The common sympton of xerophthalmia mainly has：Eyes are dry and astringent, foreign body sensation, pain burning heat sensation, tired, eye are itched, Sticky secretion, photophobia, severe patient affect one's power of vision, and are made troubles to work and life.And current document report polyethylene glycol, Trehalose, hyaluronic acid, chitosan, dexamethasone etc. have certain therapeutic action to xerophthalmia.

In recent years, with the aging of population, the increasingly exacerbation and a large amount of uses of various display screens of environmental pollution, do The quantity of eye patient is in obvious increase trend.Dry eyes are as a kind of common disease at present, it has also become global pandemic disease, both at home and abroad Epidemiological investigation shows that the incidence of disease of dry eyes is up to 7.8%~22.1%~33.7%, women illness rate apparently higher than Male, and its illness rate is in rising trend with the growth at age.According to statistics, there are dry eye patients in the U.S. more than 50,000,000, merely from Population calculates, thus it is speculated that Chinese dry eye patients are more than 300,000,000.The common sympton of xerophthalmia mainly has：Eyes are dry and astringent, foreign body sensation, pain Burning heat sensation, tired, eye are itched, sticky secretion, photophobia, severe patient affect one's power of vision, and are made troubles to work and life.Majority is dry Eye patient goes to a doctor repeatedly, and mood is urgent, and complaint dry eyes shape influences its quality of life；Half patient feels that dry eye disorders make its vision Quality is decreased obviously, and produces pessimistic idea, it is believed that can do by myself blinded because of dry eyes some day.The diagnosis and treatment work of xerophthalmia is more next More be taken seriously [document 1：Du Xianghong, Liang Qingfeng, the progress of dry eye patients mental handicape, Chinese Journal of Ophthalmology, 2016, 52(3):226-228；Document 2：Yang Yongming, Ma Linkun, the Advance of Epidemiological Research of dry eyes, international ophthalmology magazine, 2010,10 (10):1944-1946；Document 3：Chen Jian, Liu Xiaoyong, Chen Min, the Progress in Medication of dry eyes, Chinese Journal of Practical Ophthalmology, 2006,24(10):1014-1017；Document 4：Wan Pengxia, Wang Xiaoran, Song Yiyue, etc., Loteprednol treatment dry eyes the effect of see Examine, Chinese Journal of Ophthalmology, 2012,48 (2):142-147；Document 5：Chen Xingru, Gao Weiping, fluorometholone eye drops in treatment dry eyes Domestic and international progress, international ophthalmology magazine, 2016,16 (8):].

Gram or positive sensitive bacteria cause the impetigo of skin, scabies, epifolliculitis, eczema concurrent infection, trauma infection contamination, Tinea disease concurrent infection and other suppurative skin infections etc..

Tympanitis (OM) is North America and whole world baby, the common disease of children.Many researchers reported children in the world There are the incidence of disease and popularity of symptom and asymptomatic tympanitis.In these research work, the OM long-term incidence of disease is estimated as 4 ~62%, prevalence rate be 2~52% [Tian Jingfa, tympanitis epidemiology, foreign medical science Otolaryngology fascicle, 1992, 3:65-166]。

Tang Zhihui etc. is to investigate the Hong-Kong children with otitis media with effusion incidence of disease, and the further research knot with west Fruit is compared, and primary school, kindergarten (4~5 years old) and kindergarten are randomly selected within 1995~1998 years in Hong Kong (2~3 years old), 6872 2~7 years old children are checked, receive the otoscopy implemented by hals,Nasen und Ohrenheilkunde expert in the school And the Tympanometry performed by audiologist, in order to make the comparison of standardization with abroad studies result, according to their institutes The diagnostic criteria of use recalculates, and as a result finds, in the research object of 2~3 years old, 4~5 years old and 6~7 years old is divided into, if Standard is made with otoscope clinical diagnosis, incidence of otitis media with effusion rate is 5.2%~21.6%；If diagnosis mark is made with tympanogram Standard, the incidence of disease are 7.3%~30.7%.Either with which kind of method, as a result all with the incidence of disease difference of west research of the same age without Conspicuousness, and the incidence of disease increases and declined with the age.2~3 years old, 4~5 years old, conclusion Hong Kong, and point of 6~7 years old Children in China The secreting property tympanitis incidence of disease does not have significant difference [Tang Zhihui, Yu Weixiang, inscription of looking after one's family, etc. Hong-Kong with west reported literature With the comparison of Western Children incidence of otitis media with effusion rate, Chinese hals,Nasen und Ohrenheilkunde magazine, 2004,39 (7):429-432；].

Document report, heating children's complicated with acute tympanitis account for certain proportion in the children that generate heat, may be in clinic by mistake Examine, misdiagnosis [Zhou Jianye, Zhou Weidong, Zou Feng；Children's complicated with acute tympanitis of generating heat incidence investigation, Chinese Medicine guide, 12 phases in 2010:2029-2030；].Document also reports that the tinnitus incidence related to tympanitis is 19.75% [Chen Chuli, Liu It is fluffy, Chen Lihua, etc.；Tinnitus incidence and tinnitus the feature investigation of tympanitis patient, audiology and speech disease magazine, Journal of Audiology and Speech Pathology,2015,23(1):72-74；], clinical treatment is anxious at present Property the auristilla such as otitis media suppurative conventional chloramphenicol, neomycin, gentamicin, polymyxins there is interior ototoxicity, Long-term use can cause patient phonosensitive nerve deafness occur, be subject to certain restrictions otology local application.

RAU there is no specific treatment method at present, easily recurrence, closely related with bacterium infection etc., have celebrating big at present Mycin or dexamethasone are used for the treatment of the disease, but variety of problems or deficiency all be present.

One medicine may show different effects and toxic reaction after different way of administration or medicine-feeding part administration, It is effective with a kind of method of administration, but another method of administration is invalid or poor effect, or different pharmaceutical is in different way of administration Toxicity be different, this is very common in materia medica, and at present, the gatifloxacin of oral or intravenous administration and Moses are husky Magnitude can be clearly used for ophthalmology disease treatment [document 1, Chen Zuji, gatifloxacin ophthalmology application study be in progress, eye Optometry magazine, Chinese Journal of Optometry＆Ophthalmology, 2006,8 (6):400-402；Document 2nd, Chen Zuji；The new fluoroquinolone antibacterial agent MOXIFLOXACIN of broad-spectrum high efficacy and its application in ophthalmology, ophthalmology research, Chinese Ophthalmic Research, 06 phase in 2005:656-659；], however, cefalexin, cefadroxil can only Orally can not drug administration by injection or poor effect, Ceftriaxone Sodium, cefminox sodium etc. can only drug administration by injection can not be administered orally or Oral nearly unavailable, the topical treatment such as sodium cromoglycate eye-drop or spray conjunctivitis or allergy or asthma etc. are effective, are World's situation of selling well common medicine, but oral tablet easy to carry or capsule are valueless；More typically but to be generally known Example perhaps also has：The intravenous injection toxicity of the spectinomycin hydrochloride of aminoglycoside is far above toxicity during its intramuscular injection, Cause the medicine can not therapeutic dose upper vein be administered and can only intramuscular injection.However, any open source literature there is no to report at present The administering drug combinations such as Etimicin and dexamethasone are used for treatment or clinical efficacy or toxicity for being locally administered of ophthalmology disease etc., It is unknown its different dose profiles the effect of or the toxicity such as adverse reaction or retina or cornea or excitant etc., medicine is to eye Toxic action there is diversity and complexity.Eyes are the windows of people's soul, also one of most important organ of animal, eyes Cornea etc. is very sensitive to medicine, once the exposure to chemical substance is uncomfortable or causes serious adverse reaction, some fine differences The result of production likely results in serious adverse reaction or blindness etc., and in recent years, ophthalmically acceptable perfluoropropane gas is examining qualified feelings Still there is the serious blinding adverse reaction of unknown cause in condition, cause tens of people to blind.Therefore, it is reduction adverse reaction and raising Curative effect, tackle growing drug-fast bacteria, it is necessary to which can study Etimicin with steroidal or non-steroidal anti-inflammatory drug etc. Administering drug combinations of composition mode etc., to improve curative effect, shorten course for the treatment of etc..

The content of the invention

The present invention relates to pharmaceutical technology field, and in particular to the topical ophthalmic of people and mammal is used or ear is used or nose is used or skin Skin external application or oral cavity medicine compositions, the Etimicin Sulfate containing effective dose or Etimicin or its medicine in said composition It is any one or more of in acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound on, wherein The composition also has the steroid of the effective dose of anti-inflammatory or with non-steroidal antiinflammatory drugs or with anti-dry eye drugs (except ground Outside Sai meter Song or dexamethasone acetate or dexamethasone sodium phosphate) in it is any one or more of, remaining is pharmaceutically acceptable Carrier；

The topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin pharmaceutical composition, wherein the glucocorticoid selects From but be not limited to Rimexolone, fluorometholone, fluorometholone acetate, Econopred, prednisolone, prednisolone di(2-ethylhexyl)phosphate Sodium, prednisone acetate, metacortandracin, cortisone, hydrocortisone acetate, butyric acid hydrocortisone, hydrocortisone buteprate, Hydrocortisone valerate, the hydrocortisone of vinegar third, hydrocortisone sodium succinate, hydrocortisone sodium phosphate, hydrogenation can Pine, Rimexolone, Loteprednol, desonide, budesonide, ciclesonide, Halcinonide, Triamcinolone acetonide, Amcinonide, fluorine chlorine Nai De, alclometasone, Algestone, beclomeasone propionate, beclomethasone, betamethasone valerate, betamethasone sodium phosphate, times he Meter Song, betamethasone dipropionate, Clobetasol valerate, Clobetasol propionate, Chloroprednisone, clobetasol propionate, fourth Sour clobetasone, clobetasone, clocortolone, chlorine ripple Buddhist nun alcohol, deflazacort, Desoximetasone, diflorasone, diflucortolone, two Fluocortolone valerate, Difluprednate, flumethasone, flumethasone pivalate, flunisolide, Fluocinonide, FA ketal, FA, fluocortolone, fluperolone acetate, Fluprednidene acetate, fluprednisolone, fludroxycortide, fluticasone propionate, fluorine Can for Kathon CG, Cordran, clocortolone pivalate, Halobetasol Propionate, Halometasone, Halopredone acetate, hydrogen His ester, medrysone, meprednisone, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, furancarboxylic acid not rice Pine, Mometasone, method Buddhist nun's acid prednisolone ester, paramethasone, prednicarbate, ripple prednylidene 21-diethylaminoacetatte, mazipredone, Tixocortol, Qu An Siron, fluoxyprednisolone ketal, triamcinolone, Triamcinolone acetonide -21- phosphate, Triamcinolone acetonide -21- sulfate, betamethasone phosphate Basic salt in a kind of compound or their ester or its pharmaceutically acceptable salt or its different crystal forms or its solvent chemical combination Any one or a few in thing or their inclusion compound.

The topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin pharmaceutical composition, wherein the antiinflammatory is more preferably Including but not limited to Rimexolone, fluorometholone, fluorometholone acetate, Econopred, prednisolone, prednisolone di(2-ethylhexyl)phosphate Sodium, prednisone acetate, metacortandracin, cortisone, hydrocortisone acetate, butyric acid hydrocortisone, hydrocortisone buteprate, Hydrocortisone valerate, the hydrocortisone of vinegar third, hydrocortisone, Rimexolone, Loteprednol, desonide, budesonide, His rice of ciclesonide, Halcinonide, Triamcinolone acetonide, Amcinonide, Flucloronide, beclomeasone propionate, beclomethasone, valeric acid times Pine, betamethasone sodium phosphate, betamethasone, betamethasone dipropionate, Clobetasol valerate, Clobetasol propionate, chlorine Metacortandracin, clobetasol propionate, clobetasone butyrate, clobetasone, flumethasone, flumethasone pivalate, Fluocinonide, fluorine Light ketal, FA, fluocortolone, fluperolone acetate, Fluprednidene acetate, fluprednisolone, fludroxycortide, propionic acid fluorine Buddhist nun is sprinkled for Kathon CG, fluticasone, Cordran, clocortolone pivalate, medrysone, meprednisone, methylprednisolone, first The imperial acetate of pine, methylprednisolone sodium succinate, momestasone furoate, Mometasone, fluoxyprednisolone, fluoxyprednisolone ketal, triamcinolone Or its pharmaceutically acceptable salt or any of its different crystal forms or its solvated compounds or its inclusion compound or a variety of.

The present invention topical ophthalmic use or ear use nose use or external preparation for skin pharmaceutical composition, wherein the antiinflammatory include but Be not limited to non-steroidal antiinflammatory drugs, the non-steroidal antiinflammatory drugs be selected from prostaglandin synthase inhibitor, COX-1 inhibitor or Cox 2 inhibitor, COX-1 and cox 2 inhibitor or PAF antagonists and PDE IV inhibitor.

NSAID thing is selected from, but not limited to,：Prostaglandin synthase inhibitor (CoxI or Cox II), also by it Referred to as cyclooxygenase I types and II types inhibitor or its pharmaceutically acceptable salt or its isomers or solvated compoundses or its bag Compound, as Tet, benzydamine, bendazac lysine, Diclofenac, Flurbiprofen, flurbiprofen sodium, flurbiprofen axetil, (S)-(+)-Flurbiprofen, (S)-(+)-flurbiprofen axetil, ketorolac, suprofen, Ni Pafen sour (nepafenac), amfenac, Indocin, naproxen, brufen, (S)-ibuprofen, Ibuprofen Piconol, Bromfenac, the hydrate of bromfenac sodium 1.5, Ketoprofen, the right side That fragrant salt of rotation Ketoprofen, ketorolac, ketorolac tromethamine, dextrorotation ketorolac, dextrorotation Ketorolac Tromethamine, first chlorine, benzyl reach Bright, suprofen, piroxicam, sulindac, pranoprofen, mefenamic acid, Diflunisal, olsapozine, tolmetin, Fei Nuoluo Fragrant, benoxaprofens, Nabumetone, Etodolac, S- Etodolacs, aulin, piketoprofen, aniline ibuprofen, phenylbutazone, Ah This woods, Oxyphenbutazone, NCX-4016, HCT-1026, NCX-284, NCX-456, tenoxicam and Carprofen；Cyclooxygenase II types Selective depressant, such as NS-398, vioxx, celecoxib, SC 69124, imrecoxib, P54, L-804600 and S-33516； PAF antagonists, as SR-27417, A-137491, ABT-299, Apafant, Bepafant, minopafant, E-6123, BN-50727, Nupafant and Modipafant；PDE IV inhibitor, as ariflo, Torbafylline, rolipram, filaminast, piclamilast、cipamfylline、CG-1088、V-11294A、CT-2820、PD-168787、CP-293121、DWP- 205297th, CP-220629, SH-636, BAY-19-8004 and roflumilast；Cell factor formation inhibitor, CK-17, CK- 102, such as NFkB transcription factor inhibitors；Or other antiphlogistics well known by persons skilled in the art.

The topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin pharmaceutical composition, wherein the antiinflammatory-non-steroid Body anti-inflammatory drug includes but is not limited to Tet, benzydamine, bendazac lysine, Ni Pafen acid, paracetamol, Tuo Mei Fourth, naproxen, aulin, Flurbiprofen, flurbiprofen sodium, flurbiprofen axetil, (S)-(+)-Flurbiprofen, (S)-(+)-fluorine Than ibuprofen ester, piketoprofen, aniline ibuprofen, fenoprofen, fenoprofen calcium, non-rope ibuprofen, fenbufen, Ketoprofen, dextrorotation ketone Ibuprofen, Etodolac, S- Etodolacs, aulin, piketoprofen, Diclofenac, C14H10Cl2NNaO2 or Diclofenac Potassium or Diclofenac acid-choline or Diclofenac amino-acid salt or DICLOFENAC DIETHYLAMINE, the hydrate of bromfenac sodium 1.5, sulindac, pula Ibuprofen, brufen, (S)-ibuprofen, Ibuprofen Piconol, benzydamine, bendazac lysine, suprofen, piroxicam, chlorine promise happiness health, Celecoxib, rofecoxib, ketorolac, ketorolac tromethamine or dextrorotation ketorolac, dextrorotation ketorolac tromethamine, dextrorotation Ibuprofen lysinate, (S)-ibuprofen DL-Lys, (S)-ibuprofen arginine, (S)-ibuprofen L-arginine, plug carry out former times Cloth, SC 69124 or its pharmaceutically acceptable salt or its different crystal forms or amorphous article or its isomers or their solvation One or more in compound or its inclusion compound.

Bendazac lysine has been used for the treatment of cataract at present.

Contained steroid or or non-steroidal antiinflammatory drugs or antibacterials or anti-dry eye drugs in the present composition Concentration reagent and the inflammatory type treated selected by are changed.Its concentration should be to eye, ear or nose or skin histology Or oral cavity partial applies the composition and will be enough to mitigate the inflammation in these tissues afterwards.This amount herein is referred to as " effective dose " of " anti-inflammatory effective dose " or anti-inflammatory.

The composition of the present invention can typically contain one or more antiphlogistics, and its amount can be about 0.001~about 6.0wt%；Or per 1000ml or 1000g eye-drops preparations or ear nose section medicine or preparation for external application to skin in can contain 0.01g~ About 60g steroids or non-steroidal antiinflammatory drugs.

Typically, the ointment of 1-4 drops sterile liquid or suspension or comparable trial of strength is applied by part one and four times a day, coagulated The composition is given to impacted eye, ear or nose or skin histology or mouth by glue or other solids or semi-solid combination Chamber.But the composition can also be formulated into the flushing that impacted eye, ear or nose tissue are applied in surgical procedure Liquid.

Eye, ear, the nose of the present invention is used and skin composition contains in medicinal acceptable carrier and one or more The composition of anti-inflammatory agent simultaneously preferably comprises one or more antiphlogistics.The pH that the composition will typically have 5.0-8.0.Institute Stating ophthalmic composition must also be configured to have the osmotic value consistent with the aqueous humor in eye and ocular tissue.These osmotic values are usual It is about 200- about 400 milliosmols/kg water (" mOsm/kg "), it is preferred that about 300mOsm/kg.

Typically with multiple dose form packaging eye, ear, nose with and dermatologic product.Therefore preservative is needed to prevent Microorganism pollution during use.Suitable preservative includes：Polyquaternium -1, benzalkonium chloride, thimerosal, Acetochlorone, to hydroxyl Methyl benzoate, propylparaben, benzyl carbinol, disodium ethylene diamine tetraacetate, sorbic acid or those skilled in the art are The other reagents known.It is preferred that polyquaternium -1 is used to be used as anti-microbial preservative.Typically with the dense of 0.001%-1.0wt% Degree uses these preservatives.

The group of said composition can be improved by the way that surfactant or other suitable secondary solvents are added in this composition The solubility divided.These secondary solvents include polysorbate 20,60 and 80, polyethylene oxide/polypropylene oxide surfactant (such as Pluronic F-68, F-84 and P-103), VE succinic acid macrogol ester, cyclodextrin or people in the art Other reagents known to member.Typically to use these secondary solvents with 0.01%-2wt% concentration.

The wherein described composition also local anaesthetics containing effective dose, including be singly not limited to tetracaine hydrochloride, procaine, Chloroprocanine, lidocaine, oxybuprocaine, phenmethylol, menthol, Etidocaine, Bupivacaine, dyclonine, benzene assistant card Cause, Ropivacaine or its pharmaceutical salts or its inclusion compound etc., its weight of material or weight are than that can be the 5~50% of whole weight of formulation (w/w)；Remaining is pharmaceutically acceptable carrier.

The pharmaceutical composition of the present invention can be eye drops, gel for eye use, ophthalmic ointment, ophthalmically acceptable film on pharmaceutical preparation Agent, ophthalmically acceptable dripping pill, external-use gel, ointment, emulsifiable paste, plastics, film, auristilla, oral cavity adhesion tablet, buccal tablets etc..

Aforementioned pharmaceutical compositions can be used for preparing prevention or the conjunctivitis for the treatment of people and mammal, angular blepharitis, sand Eye, keratitis, severe conjunctival scorching (vernal keratoconjunctivitis), sclerotitis, episcleritis, retinal vasculitis, sensitive bacterial sense The eye medicinal of eye disease, xerophthalmia or the scheroma of dye or dry eye syndrome etc., the illness of otitis externa and tympanitis or white Skin soft-tissue infection caused by cataract or glaucoma, the topical drug of the ear of ear or nasa surgery operation patient or nose, sensitive bacterial Property disease, such as epifolliculitis, furuncle, impetigo, trauma infection contamination and eczema infection；Convergence burn, scald, the part on the pernio surface of a wound Dermal drug, or canker sore or recurrent oral ulceration medicine.

The expression way of the present composition can have different modes to describe, or per 1000ml or 1000g or 1000cm² Ophthalmically acceptable or ear use or nose use preparation for external application to skin or oral preparations in the Etimicin Sulfate containing effective dose or according to For any in rice star or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. One or more, wherein the composition also steroid of the effective dose containing anti-inflammatory or with non-steroidal antiinflammatory drugs or dry with resisting It is any one or more of in eye disease drug；Remaining is pharmaceutically acceptable carrier；

Wherein, the steroidal anti-inflammatory agents more preferably include but is not limited to Rimexolone, fluorometholone, fluorometholone acetate, vinegar Sour prednisolone, prednisolone, prednisolone disodium hydrogen phosphate, prednisone acetate, metacortandracin, cortisone, hydrocortisone acetate, Butyric acid hydrocortisone, hydrocortisone buteprate, hydrocortisone valerate, the hydrocortisone of vinegar third, hydrocortisone How are sodium succinate, hydrocortisone sodium phosphate, hydrocortisone, Rimexolone, Loteprednol, desonide, budesonide, strop Moral, Halcinonide, Triamcinolone acetonide, Amcinonide, Flucloronide, beclomeasone propionate, beclomethasone, betamethasone valerate, times Ta meter Song sodium phosphates, betamethasone, betamethasone dipropionate, Clobetasol valerate, Clobetasol propionate, chlorine sprinkle Buddhist nun Pine, clobetasol propionate, clobetasone butyrate, clobetasone, flumethasone, flumethasone pivalate, Fluocinonide, FA Ketal, FA, fluocortolone, fluperolone acetate, Fluprednidene acetate, fluprednisolone, fludroxycortide, propionic acid fluorine are for card Pine, fluticasone, Cordran, clocortolone pivalate, two vinegar Diflorasones, medrysone, meprednisone, meprednisone Dragon, the contracting of methylprednisolone acetate, methylprednisolone sodium succinate, momestasone furoate, Mometasone, fluoxyprednisolone, fluoxyprednisolone Ketone, triamcinolone or its pharmaceutically acceptable salt or any of its different crystal forms or its solvated compounds or its inclusion compound or It is a variety of.

Wherein, antiinflammatory-nonsteroidal anti-inflammatory drug is preferably but not limited to Tet, benzydamine, bendazac lysine, Ni Pa Fragrant acid, paracetamol, tolmetin, naproxen, aulin, Flurbiprofen, flurbiprofen axetil, (S)-(+)-fluorine compare Lip river Sweet smell, (S)-(+)-flurbiprofen axetil, piketoprofen, aniline ibuprofen, fenoprofen, fenoprofen calcium, non-rope ibuprofen, fenbufen, Ketoprofen, dexketoprofen, Etodolac, S- Etodolacs, aulin, piketoprofen, Diclofenac, C14H10Cl2NNaO2 or Diclofenac Potassium or diclofenac acid-choline or Diclofenac amino-acid salt or DICLOFENAC DIETHYLAMINE, the hydrate of bromfenac sodium 1.5, Sulindac, pranoprofen, brufen, (S)-ibuprofen, Ibuprofen Piconol, benzydamine, bendazac lysine, suprofen, pyrrole sieve former times Health, chlorine promise happiness health, celecoxib, rofecoxib, ketorolac, ketorolac tromethamine or dextrorotation ketorolac, dextrorotation Ketoralac ammonia Butantriol, dexibuprofen lysine, (S)-ibuprofen DL-Lys, (S)-ibuprofen arginine, (S)-ibuprofen L- essence ammonia Acid, celecoxib, SC 69124 or its pharmaceutically acceptable salt or its different crystal forms or amorphous article or its isomers or it Solvated compoundses or its inclusion compound in one or more.

The present invention the compound amino glycoside pharmaceutical composition being locally administered, containing Etimicin or its can pharmaceutically connect It is any one or more of in the salt or different crystal forms or amorphous article or its solvate received or its inclusion compound, wherein the combination The Etimicin concentration that thing contains is 0.05~5.0wt%, wherein steroid of the composition also containing anti-inflammatory effective dose or With it is any one or more of in non-steroidal antiinflammatory drugs and anti-dry eye drugs；Remaining is pharmaceutically acceptable carrier；Or can It is expressed as：Per 1000ml or 1000g or 1000cm²Preparation for external application to skin or oral preparations in contain Etimicin or sulfuric acid Appoint in Etimicin or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. What is one or more, and 0.01~50g is calculated as or in terms of the potency of Etimicin or Etimicin Sulfate by the weight of Etimicin For the unit of 100,000 units~50,000,000, wherein steroid or and nonsteroidal anti-inflammatory agent of the composition also containing anti-inflammatory effective dose It is any one or more of in thing and anti-dry eye drugs；Remaining is pharmaceutically acceptable carrier.

The present invention the compound amino glycoside pharmaceutical composition being locally administered, containing Etimicin or its can pharmaceutically connect It is any one or more of in the salt or different crystal forms or amorphous article or its solvate received or its inclusion compound, wherein the combination The weight or ratio of weight and number for the Etimicin that thing contains are 0.010-1.0wt%, wherein the composition also has containing anti-inflammatory Imitate dosage steroid or with it is any one or more of in non-steroidal antiinflammatory drugs and anti-dry eye drugs；Remaining is that can pharmaceutically connect The carrier received；Or it can be expressed as：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose is used or preparation for external application to skin Or containing Etimicin or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms in oral preparations or without fixed It is any one or more of in type thing or its solvate or its inclusion compound etc., 0.05~10g is calculated as with the weight of Etimicin, its Described in steroid of the composition also containing anti-inflammatory effective dose or with non-steroidal antiinflammatory drugs and anti-dry eye drugs any one Kind is a variety of；Remaining is pharmaceutically acceptable carrier.

The present invention the compound amino glycoside pharmaceutical composition being locally administered, containing Etimicin or its can pharmaceutically connect It is any one or more of in the salt or different crystal forms or amorphous article or its solvate received or its inclusion compound, wherein the combination The weight or ratio of weight and number for the Etimicin that thing contains are 0.010-1.0wt%, wherein the composition also has containing anti-inflammatory Imitate dosage steroid or with it is any one or more of in non-steroidal antiinflammatory drugs and anti-dry eye drugs；Remaining is that can pharmaceutically connect The carrier received；Or it can be expressed as：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose is used or preparation for external application to skin Or containing Etimicin or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms in oral preparations or without fixed It is any one or more of in type thing or its solvate or its inclusion compound etc., 0.05~10g is calculated as with the weight of Etimicin, its Described in steroid of the composition also containing anti-inflammatory effective dose or with non-steroidal antiinflammatory drugs and anti-dry eye drugs any one Kind or a variety of weight are calculated as 0.01~50g；Remaining is pharmaceutically acceptable carrier.

The present invention the compound amino glycoside pharmaceutical composition being locally administered, wherein the steroid or with non-steroid anti-inflammatory Medicine or its different crystal forms or amorphous article or its solvate or its inclusion compound.

The compound amino glycoside pharmaceutical composition being locally administered of the present invention, wherein the antiinflammatory includes betamethasone Or betamethasone acetate or cortisone acetate or its different crystal forms or amorphous article or its solvate or its inclusion compound.Times his rice The inclusion compound of loose or hydrocortisone or cortisone acetate etc. has many documents to record, for example [the document 1 of the document in bracket： By force, beta-schardinger dextrin and its derivative are to the solubilizing effect of betamethasone, Scientific and Technical Communication, and 2011, (7):105-106；Document 2：Ginger Vertical group, Zhai Suodi, Yang Li, the research of hydrocortisone-hydroxypropyl-beta-cyclodextrin inclusion preparation technology, Chinese Journal of New Drugs, 2003,12(10):837-839；Document 3：Bao Huike, Ma Yinhu, Yuan Dongchao, hydroxypropyl-β-cyclodextrin and cortisone acetate bag Tie preparation and the sign of thing, University Of Science and Technology Of Tianjin's journal, 2009,24 (6):13-15；].

In the compound amino glycoside drug combination preparation being locally administered of the present invention, pharmaceutically acceptable carrier can Including water, pharmaceutically acceptable thickener, pH adjusting agent and or pharmaceutically acceptable preservative or bacteriostatic agent, antioxygen Agent, stabilizer, isotonic regulator, sorbefacient, solubilizer, excipient, diluent, NMF etc. or any one in them It is or a variety of.

In the composition of invention, its pharmaceutically acceptable salt of Etimicin or different crystal forms or amorphous article or its is molten Agent compound or its inclusion compound rise in eye drops or gel for eye use or topical ophthalmic with Etimicin Sulfate or Etimicin To same treatment and prevention effect.

The Etimicin being locally administered or its pharmaceutically acceptable salt or different crystal forms or amorphous article of the present invention or Its solvate or its include medicine composition, the sodium of antiinflammatory ophthalmic solution four that can be containing effective dose, Lifitegrast, cyclosporin etc. or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or Any of its inclusion compound is a variety of, wherein the weight for the anti-dry eyes agent that the composition contains can be 0.0010- 6.0wt%.

, can also polyethylene glycol, the sea of the anti-xerophthalmia containing effective dose or wetting agent simultaneously in the composition of invention Algae sugar, hyaluronic acid, Sodium Hyaluronate, chitosan, overstate ground phosphorus Suo Si sodium, lifitegrast, polysaccharide, glucan, chondroitin sulfate Element, poloxamer, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, Any of sodium carboxymethylcellulose, cellulose derivative etc. are a variety of, wherein the anti-dry eyes agent that the composition contains Weight can be 0.0010-6.0wt%.

The described compound amino glycoside pharmaceutical composition being locally administered of the present invention, can include：A kind of topical ophthalmic With or ear use or nose use or external preparation for skin or oral cavity medicine compositions, contain Etimicin Sulfate or Etimicin or its pharmacy Upper acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound, wherein the composition is also containing anti- The steroid of scorching effective dose or with it is any one or more of in non-steroidal antiinflammatory drugs and anti-dry eye drugs, remaining is pharmaceutically Acceptable carrier, wherein the Etimicin concentration that the composition contains is 0.10-0.8wt%；Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in containing Etimicin or Etimicin Sulfate or It is any or more in its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. Kind, 1.0~8.0g is calculated as with the weight of Etimicin or the unit of 1,000,000 units~8,000,000 is calculated as with Etimicin potency, wherein Steroid of the composition also containing anti-inflammatory effective dose or with it is any in non-steroidal antiinflammatory drugs and anti-dry eye drugs It is or a variety of；Remaining is pharmaceutically acceptable carrier；Pharmaceutically acceptable carrier includes water, pharmaceutically acceptable thickening Agent, pH adjusting agent and or pharmaceutically acceptable preservative or bacteriostatic agent, antioxidant, stabilizer, isotonic regulator, absorption Accelerator, solubilizer, excipient, diluent, NMF or they in it is any one or more of.

The described topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can be with Including：Per 1000ml or 1000g or 1000cm²Preparation in containing Etimicin or Etimicin Sulfate or its pharmaceutically may be used It is any one or more of in the salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. of receiving, with according to for rice The weight of star is calculated as 1.0~6g or is calculated as the unit of 1,000,000 units~6,000,000 with Etimicin potency, wherein the composition is also Dexamethasone or the pharmaceutically acceptable derivates of dexamethasone or its inclusion compound containing anti-inflammatory effective dose；Remaining is medicine Acceptable carrier on；

The described topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can be with Including：Per 1000ml or 1000g or 1000cm²Preparation in containing Etimicin or Etimicin Sulfate or its can pharmaceutically connect It is any one or more of in the salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. received, with Etimicin Weight be calculated as 2.0~6.0g or the unit of 2,000,000 units~6,000,000 be calculated as with Etimicin potency, wherein the composition is also Steroid containing anti-inflammatory effective dose or with it is any one or more of in non-steroidal antiinflammatory drugs and anti-dry eye drugs；Remaining is Pharmaceutically acceptable carrier；

Pharmaceutically acceptable carrier includes water, pharmaceutically acceptable thickener, pH adjusting agent and or pharmaceutically may be used The preservative or bacteriostatic agent of receiving, antioxidant, stabilizer, isotonic regulator, sorbefacient, solubilizer, excipient, dilution Agent, NMF, attenuation agent or they in it is any one or more of.Generally, in addition to water, these compounds are used in eye drops Weight range typically can be 0.0001~30.0%.

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 1.0g is calculated as with the weight of Etimicin or 1,000,000 units are calculated as with Etimicin potency, Steroid of the wherein described composition also containing anti-inflammatory effective dose or with it is any in non-steroidal antiinflammatory drugs and anti-dry eye drugs It is one or more；Remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 3.0g is calculated as with the weight of Etimicin or 3,000,000 units are calculated as with Etimicin potency, Steroid of the wherein described composition also containing anti-inflammatory effective dose or with it is any in non-steroidal antiinflammatory drugs and anti-dry eye drugs It is one or more；Remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention with or ear with nose with or the pharmaceutical composition in external preparation for skin or oral cavity, can wrap Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its bag It is any one or more of in compound etc., 5.0g is calculated as with the weight of Etimicin or 5,000,000 units are calculated as with Etimicin potency, Steroid of the wherein described composition also containing anti-inflammatory effective dose or with it is any in non-steroidal antiinflammatory drugs and anti-dry eye drugs It is one or more；Remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, in terms of the weight or parts by weight of Etimicin For 0.1~10g, wherein steroid of the composition also containing anti-inflammatory effective dose or with non-steroidal antiinflammatory drugs and anti-xerophthalmia Any one or more of weight or parts by weight are calculated as 0.01~50g in medicine, and remaining is pharmaceutically acceptable carrier；Its In, the weight of Etimicin can be 100,000-1,000 ten thousand units in terms of Etimicin potency.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also Including：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to For rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight or parts by weight of Etimicin Be calculated as 1~10g, wherein steroid of the composition also containing anti-inflammatory effective dose or with non-steroidal antiinflammatory drugs and anti-xerophthalmia Any one or more of weight or parts by weight are calculated as 0.1~50g in medicine, and remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, in terms of the weight or parts by weight of Etimicin For 1~10g, wherein steroid of the composition also containing anti-inflammatory effective dose or with non-steroidal antiinflammatory drugs and anti-xerophthalmia medicine Any one or more of weight or parts by weight are calculated as 0.1~30g in thing, and remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, in terms of the weight or parts by weight of Etimicin For 1~10g, wherein steroid of the composition also containing anti-inflammatory effective dose or with non-steroidal antiinflammatory drugs and anti-xerophthalmia medicine Any one or more of weight or parts by weight are calculated as 0.1~10g in thing, and remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, be calculated as 1.5 with the weight of Etimicin~ 8.0g, or 1,500,000-1,000 ten thousand units are calculated as with Etimicin potency, wherein the composition is also containing anti-inflammatory effective dose Steroid or with weight or parts by weight any one or more of in non-steroidal antiinflammatory drugs and anti-dry eye drugs be calculated as 0.1~ 8.0g, remaining is pharmaceutically acceptable carrier；

The described aminoglycoside medicaments composition being locally administered, can include：Per 1000ml or 1000g or 1000cm²Preparation in containing Etimicin or its pharmaceutically acceptable salt or its different crystallization or its solvate or its Inclusion compound or they in it is any one or more of, 0.01~10g, Rimexolone, fluorometholone, fluorine are calculated as with the weight of Etimicin Any one or more of 0.1~5g in the imperial acetate of rice, momestasone furoate, Mometasone, remaining is pharmaceutically acceptable carrier.

The described aminoglycoside medicaments composition being locally administered, can include：Per 1000ml or 1000g or 1000cm²Preparation in containing Etimicin or its pharmaceutically acceptable salt or its different crystallization or its solvate or its Inclusion compound or they in it is any one or more of, 0.01~10g is calculated as with the weight of Etimicin, Econopred, sprinkles Buddhist nun Song Long, prednisolone disodium hydrogen phosphate, prednisone acetate, metacortandracin, cortisone, hydrocortisone acetate, butyric acid hydrocortisone, Hydrocortisone buteprate, hydrocortisone valerate, hydrocortisone, Rimexolone, Loteprednol, according to carbonic acid chlorine for sprinkle Any one or more of 0.1~10g in promise, desonide, remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 1.0g or 3.0g or 5.0g, betamethasone or betamethasone valerate or betamethasone sodium phosphate or its pharmaceutically acceptable salt or its solvent One or more of 0.1g or 0.25g or 0.5g or 1g in compound or its inclusion compound, remaining is pharmaceutically acceptable carrier；

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 3.0g or 5.0g, betamethasone or betamethasone valerate or betamethasone sodium phosphate or its pharmaceutically acceptable salt or its solvate or One or more of weight in its inclusion compound are calculated as 0.5g or 1g, and remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 3.0g or 5.0g, the hydrocortisone acetate containing anti-inflammatory effective dose, butyric acid hydrocortisone, hydrocortisone buteprate, hydrogenation Cortisone valerate, the hydrocortisone of vinegar third, hydrocortisone, hydrocortisone sodium succinate, fludrocortisone acetate or its One or more of weight in pharmaceutically acceptable salt or its solvate or its inclusion compound are calculated as 0.25g or 0.5g or 1g Or 2g or 10g or 20g or 25g or 50g, remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 3.0g or In 5.0g, Fluocinonide, FA ketal, FA or its pharmaceutically acceptable salt or its solvate or its inclusion compound One or more of weight be calculated as 0.1g or 0.25g or 0.5g or 1g, remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 3.0g or 5.0g, momestasone furoate, Mometasone, Rimexolone, fluorometholone, desonide, budesonide, Triamcinolone acetonide, fluticasone propionate, Fluticasone, beclomeasone propionate, beclomethasone, betamethasone valerate, betamethasone sodium phosphate, clobetasol propionate or its medicine One or more of weight in acceptable salt or its solvate or its inclusion compound are calculated as 0.1g or 0.2g or 0.25g Or 0.5g or 1g, remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 3.0g or 5.0g, Econopred, prednisolone, prednisolone disodium hydrogen phosphate, prednisone acetate, metacortandracin, cortisone, medrysone, Meprednisone, methylprednisolone, methylprednisolone acetate, methylprednisolone sodium succinate, medrysone, diflucortolone, difluoro Can imperial valerate, halogen Mei Tasong, two vinegar Diflorasones, Loteprednol, method Buddhist nun acid prednisolone ester or its pharmaceutically acceptable salt Or one or more of weight in its solvate or its inclusion compound are calculated as 0.5g or 1g or 2.5g or 5g or 10g or 14g, Remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 3.0g or 5.0g, Tet, benzydamine, bendazac lysine, Flurbiprofen, flurbiprofen axetil, (S) containing anti-inflammatory effective dose- (+)-Flurbiprofen, (S)-(+)-flurbiprofen axetil, piketoprofen, fenoprofen, fenoprofen calcium, non-rope ibuprofen, fenbufen, Ketoprofen, dexketoprofen, Etodolac, S- Etodolacs, aulin, piketoprofen, Diclofenac, C14H10Cl2NNaO2 or Diclofenac Potassium or diclofenac acid-choline or Diclofenac amino-acid salt or DICLOFENAC DIETHYLAMINE, the hydrate of bromfenac sodium 1.5, Sulindac, pranoprofen, brufen, (S)-ibuprofen, suprofen, piroxicam, chlorine promise happiness health, celecoxib, Rofe former times Cloth, ketorolac, ketorolac tromethamine or dextrorotation ketorolac, dextrorotation ketorolac tromethamine, dexibuprofen lysine, the right side Revolve brufen DL-Lys, (S)-ibuprofen arginine, (S)-ibuprofen L-arginine, celecoxib, SC 69124 or its medicine One or more of weight in acceptable salt or its solvate or its inclusion compound be calculated as 0.25g or 0.5g or 1g or 2g or 10g or 20g or 25g or 50g, remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its is pharmaceutically acceptable Salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 3.0g or 5.0g, wherein anti-dry eyes agent or the weight of NMF that the composition also contains can be 0.0010-6.0wt%, remaining is Pharmaceutically acceptable carrier；

Wherein, the polyethylene glycol of the anti-xerophthalmia containing effective dose or wetting agent, trehalose, hyaluronic acid, hyalomitome Sour sodium, chitosan, overstate ground phosphorus Suo Si sodium, lifitegrast, cyclosporin, polysaccharide, glucan, chondroitin sulfate, Bo Luosha Nurse, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, carboxymethyl are fine Any of plain sodium, cellulose derivative etc. or a variety of are tieed up, wherein the weight for the anti-dry eyes agent that the composition contains can be with For 0.0010-6.0wt%.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its solvate or its pharmaceutically acceptable salt or its inclusion compound or It is any one or more of in them, 3.0g or 5.0g are calculated as with the weight of Etimicin, wherein the composition also contain it is anti- Scorching anti-dry eyes agent or NMF overstate ground phosphorus Suo Si sodium, lifitegrast or its pharmaceutically acceptable different crystallization or its is molten Agent compound or its pharmaceutically acceptable salt or its inclusion compound or weight any one or more of in them be 5g or 10g or 15g or 20g or 25g or 30g or 35g or 40g or 45g or 50g, remaining is pharmaceutically acceptable carrier.

Topical ophthalmic of the present invention is used or ear is used or nose is used or external preparation for skin or oral cavity medicine compositions, can also be wrapped Include：Per 1000ml or 1000g or 1000cm²Ophthalmically acceptable or ear use or nose use or external preparation for skin or oral preparations in contain according to for Rice star or its pharmaceutically acceptable different crystallization or its solvate or its pharmaceutically acceptable salt or its inclusion compound or It is any one or more of in them, 3.0g or 5.0g, momestasone furoate, Mometasone, Li Meisuo are calculated as with the weight of Etimicin Dragon, fluorometholone, desonide, budesonide, Triamcinolone acetonide, fluticasone propionate, fluticasone, beclomeasone propionate, times chlorine rice Pine, betamethasone, betamethasone valerate, betamethasone sodium phosphate, clobetasol propionate, Loteprednol, method Buddhist nun's acid prednisolone One or more of weight in ester or its pharmaceutically acceptable salt or its solvate or its inclusion compound be calculated as 0.1g or 0.2g or 0.25g or 0.5g or 1g or 2.5g or 5g or 10g or 14g, wherein the anti-dry eyes agent of anti-inflammatory that the composition also contains NMF overstate ground phosphorus Suo Si sodium, lifitegrast or its pharmaceutically acceptable different crystallization or its solvate or its Pharmaceutically acceptable salt or its inclusion compound or weight any one or more of in them be 5g or 10g or 15g or 20g or 25g or 30g or 35g or 40g or 45g or 50g, remaining is pharmaceutically acceptable carrier.

In topical ophthalmic use or ear use of the present invention or nose use or external preparation for skin or oral cavity medicine compositions preparation, Etimicin or its pharmaceutically acceptable different crystallization or its pharmaceutically acceptable solvate or its can pharmaceutically connect The salt received or its pharmaceutically acceptable inclusion compound or in them it is any one or more of with the steroid of anti-inflammatory effective dose or and The composition of non-steroidal antiinflammatory drugs, and non-hormone or non-prostaglandin synthase inhibitor, COX-1 inhibitor or COX-2 Anti- dry eye drug (polyethylene glycol, the marine alga of inhibitor, COX-1 and cox 2 inhibitor or PAF antagonists and PDE IV inhibitor Sugar, hyaluronic acid, Sodium Hyaluronate, chitosan, chondroitin sulfate, poloxamer, polyvinyl alcohol, polyvinylpyrrolidone, first Any in base cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, cellulose derivative etc. Kind is a variety of) new composition can be formed with composition.

Local skin externally-applied medicinal composition of the present invention, can also include：Per 1000ml or 1000g or 1000cm²Containing Etimicin or its pharmaceutically acceptable different crystallization or its is pharmaceutically acceptable in preparation for external application to skin Solvate its pharmaceutically acceptable salt or its pharmaceutically acceptable inclusion compound or they in it is any one or more of, 1.0~30g is calculated as with the weight of Etimicin, the steroid of effective dose or with non-steroidal antiinflammatory drugs and anti-dry eye drugs etc. 0.1~50g, remaining is pharmaceutically acceptable carrier；

Pharmaceutically acceptable carrier or sorbefacient or NMF etc. are selected from but are not limited only to：Water, chirality or racemization Or D- or L- or the amino acid of racemization or its salt, such as D- or L- or DL-Lys, Lysine Acetate, cysteine, egg ammonia Acid, arginine or acetic arginine or L-aminobutanedioic acid or Monosodium L-aspartate, glutamic acid, glycine, taurine, alanine, figured silk fabrics ammonia Acid, leucine, isoleucine, serine, threonine, cysteine, cystine, methionine, asparagine, glutamine, 5- Oxylysine, histidine, phenylalanine, tyrosine, tryptophan, 3- hydroxy-prolines, 4- hydroxy-prolines, proline, height Cysteine, homocystine, homoserine, ornithine, citrulling, creatine, 3- alanine, theanine, 2-amino-butyric acid, 4- ammonia Base butyric acid, 2- amino-2-methyls propionic acid, 2- methyl -3- alanines, 2,6- diaminopimelic acids, 2- amino -3- phenyl fourths Acid, phenylglycine, canavanine, canaline, 4- hydroxyarginines, 4- hydroxyls ornithine, homoarginine, 4- hydroxyls are high Arginine, beta-lysine, 2,4-diamino-butanoic, 2,3- diaminopropionic acids, 2- methyl serines etc. or unit or polybasic carboxylic acid Or its pharmaceutical salts, gallic acid, propylgallate, progallin A, gallate, malic acid, butanedioic acid, Vitamin C Acid, L-AA, sodium ascorbate, arabo-ascorbic acid, sodium isoascorbate, nicotinic acid, niacinamide, pantothenic acid, sodium pantothenate, pantothenic acid Calcium, vitamin B1, vitamin B2, vitamin E, beta carotene, Pyridoxamine Hydrochloride, glutathione, allantoin, citric acid or lemon Lemon acid sodium or lactic acid, sodium lactate, lactobionic acid, sodium lactonic, gluconic acid, sodium gluconate or trehalose, urea, thiocarbamide, Or maltitol, sorbierite, mannitol, lactitol, xylitol, antierythrite, Hyaluronic Acid or sodium hyaluronate or its hydrate or One or more in their pharmaceutically acceptable salt or their isomers etc., sorbierite include D- D-sorbites, anhydrous One or more in sorbierite or the water thing of sorbierite half or 1 water sorbierite or sorbitol instant etc., it is above-mentioned to include its isomery Body；Generally, concentration range can be 0.000~5.0% used in these compounds.The group in the present invention such as above-mentioned wetting agent Contribute to reduce adverse reaction of the medicine to part in compound.

Pharmaceutically acceptable carrier can include pharmaceutically acceptable antioxidant and stabilizer, and they are selected from but not only It is limited to sulfurous acid and its salt, bisulfites, pyrosulfite, dithionite, TGA and its pharmaceutical salts, thio breast Acid and its pharmaceutical salts, thio-2 acid and salt, monohydroxy or multi-hydroxy carboxy acid and pharmaceutical salts, tartaric acid, sorbic acid or its is medicinal Salt, nitrate, acetic acid pharmaceutical salts, citrate, EDTA and edta salt including EDETATE SODIUM, the sodium of EDTA tetra-, mosatil Salt (including sodium ethylene diamine tetracetate calcium or the hydrate of sodium ethylene diamine tetracetate calcium 2, the hydrate of sodium ethylene diamine tetracetate calcium 4), N- Two (2- ethoxys) glycine, maltitol, xylitol, sorbierite, mannitol, vitamin E, beta carotene, hydrochloric acid pyrrole are more One or several kinds in amine, taurine, amino acid or their pharmaceutically acceptable salt etc..

Pharmaceutically acceptable carrier can be selected from comprising pharmaceutically acceptable chelating agent but be not limited only to EDTA and Edta salt including EDETATE SODIUM, the sodium of EDTA tetra- or its hydrate, Ca-EDTA sodium salt (including sodium ethylene diamine tetracetate calcium or second The hydrate of sodium ethylene diamine tetracetate calcium 2, the hydrate of sodium ethylene diamine tetracetate calcium 4), one in N- bis- (2- ethoxys) glycine etc. Kind is several.

It is thickener or stabilizer that the preparation of the present invention, which can include one or more pharmaceutically acceptable water soluble adjuvants, It may be selected from the composition being made up of water-soluble polymer and penetration enhancer and their mixture.The present invention eye drops or The water-soluble polymer that can be used in ophthalmically acceptable or skin use or oral preparations includes but is not limited to natural and synthesis gather Compound, polysaccharide, poly- aminoglycoside, cellulose derivative, guar gum, xanthans, glucan, carboxyl vinyl polymer, poly- third It is olefin(e) acid sodium, hyaluronidase, hyaluronic acid, Sodium Hyaluronate, chondroitin sulfate, locust bean gum, poloxamer, polyvinyl alcohol, poly- Vinylpyrrolidone, polyethylene glycol, gellan gum, alginic acid, methylcellulose, hydroxyethyl cellulose, hydroxypropyl methyl are fine Dimension element, sodium carboxymethylcellulose or derivative of dextrin and dextrin etc. and their mixture.It is dense used in these compounds Spending scope can be 0.00~15.0%.Above-mentioned water-soluble thickener in the present composition can coordinate controlling for xerophthalmia Treat or prevent.

Using viscosity enahncers the viscosity of the composition of the present invention can also be made to be more than the viscous of simple aqueous as needed Degree, so as to improve the eye absorption of reactive compound by the target tissue or increase the retention time in eye.These are viscous Spending reinforcing agent is included for example, polysaccharide, glucan, hyaluronic acid, poloxamer, polyvinyl alcohol, chondroitin sulfate, polyvinyl pyrrole Pyrrolidone, methylcellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, sea Algae is sugared or other reagents well known by persons skilled in the art.These reagents typically can be made with 0.01%-5wt% concentration With.

Thickener more preferably poloxamer, chondroitin sulfate, methylcellulose, hydroxypropyl methyl cellulose, exocellular polysaccharide Glue, hydroxyethyl cellulose, polyvinylpyrrolidone, polyethylene glycol, hyaluronic acid or Sodium Hyaluronate, trehalose etc., eye drops In the more excellent concentration with 0.02%-1wt% use.

In gel, the auxiliary gel matrix material for forming gel can be included, is selected from but is not limited only to poloxamer, Portugal Grape sugar phosphate, glucose phosphate ester derivant, xanthans, carboxyl vinyl polymer, Sodium Polyacrylate, cellulose derive Thing, polysaccharide, chondroitin sulfate, hyaluronic acid or Sodium Hyaluronate, guar gum, polyvinyl alcohol, alginic acid etc..

The excipient of hydrogel is also selected from but is not limited only to chitosan, poly- (hydroxyethyl meth acrylate), poly- (N- ethene Base pyrrolidones), polyvinyl alcohol, the polymer of acrylic acid, the one or more therein, wherein carbomer system such as carbomer series Row may include that carbomer 934, carbomer940, Acritamer 940, Carbopol 941, CARBOPOL 974P, Carbopol etc. are therein One or more, generally, concentration range can be in 0.001-25.0% used in these compounds.

Hyaluronic acid or Sodium Hyaluronate include but is not limited to macromolecular hyaluronic acid (molecular weight ranges 1,800,000~ 2200,000), middle molecular weight hyaluronic acid (molecular weight ranges 1,000,000~1,800,000), micromolecule hyaluronic acid (molecule Measure scope 200,000~1,000,000), more preferably in, micromolecule hyaluronic acid.

Also including solubilizer (including may include surfactant), solubilizer is selected from but not only pharmaceutically acceptable auxiliary material Be limited to polyethylene glycol oxide list oleic acid sorbitan ester, Tween-80, VE succinic acid macrogol ester (vitamin E TPGS), Glycerine-polyethylene glycol epoxide stearate, PEG-32 glyceryl palmitostearates, lauryl sodium sulfate, mono laurate mountain Pears alcohol acid anhydride ester, polyethylene glycol, polyethylene glycol 100-20000 (polyethylene glycol 200, polyethylene glycol 400, Macrogol 600, poly- second Glycol 4000, Macrogol 6000, PEG 8000 etc.), HS15, polyvinylpyrrolidine Ketone, polyvinyl alcohol, amino acid or its pharmaceutical salts, pharmaceutically acceptable alcohols, pharmaceutically acceptable polyalcohol, poloxamer, pool Luo Shamu 407, azone, laurocapram, cyclodextrin or cyclodextrin pharmaceutically acceptable derivates, amide-type or urea and spread out Biology, inorganic acid or inorganic acid salt, pharmaceutically acceptable organic acid or acylate, pharmaceutically acceptable carbohydrate or sugar lime, One or more in pharmaceutically acceptable amine etc. or their chiral isomer etc. or their pharmaceutically acceptable salt； Cyclodextrin includes alpha-cyclodextrin, beta-schardinger dextrin, gamma-cyclodextrin, hydroxypropyl-β-cyclodextrin etc..

The preparation of the pharmaceutical composition of the present invention with multiple dose form when being provided for preventing the preservative of contamination of products Or bacteriostatic agent, be selected from but be not limited only to pharmaceutically acceptable preservative or bacteriostatic agent, as organic acid bacteriostatic agent, benzoic acid, Sorbic acid or its pharmaceutical salts, dehydroactic acid sodium, the esters of oxybenzene esters compound or nipalgin, methyl hydroxybenzoate, para hydroxybenzene (Domiphen bromide, benzalkonium chloride, benzene are pricked for propyl formate, phenmethylol, benzyl carbinol, phenoxetol, anesin, quaternary ammonium derivative Bromine ammonium, hexadecyl ammonium methyl, cetylpyridinium chloride, Benzethonium etc.), polyquaternium (polyquaternium -1, PQ-1, Polidronium Chloride), organic Mercury derivatives (thiomersalate, thimerosal, phenylmercuric acetate and phenylmercuric nitrate etc.), pharmaceutically In acceptable phenol compound, o-phenyl phenol, chloreresol, chlorohexidene etc. or their pharmaceutically acceptable salt etc. It is one or more of.Generally, concentration range used in these compounds can be 0.0005-5.0%, and this depends on selected Preservative or bacteriostatic agent；More preferably use esters, sorbic acid or its pharmaceutical salts of nipalgin, thimerosal, the conduct of polyquaternium -1 Anti-microbial preservative；These preservatives are typically used with 0.001%-1.0wt% concentration；

The pharmaceutically acceptable isotonic regulator that uses can be included but not in the preparation of the pharmaceutical composition of the present invention It is limited to：Sodium chloride, potassium chloride, calcium chloride, sodium bromide, sodium phosphate, sodium sulphate, sodium nitrate, glucose, boric acid, borax, glycerine, It is propane diols, polyethylene glycol, PEG-400, PEG300, PEG-200, glucose, fructose, maltitol, xylitol, sorbierite, sweet Reveal the one or more in alcohol, inverted sugar, dextran, sodium lactate or sodium lactonic, gluconic acid or sodium gluconate etc.； Physiological saline (being usually the solution of sodium chloride)；Or isotonic regulation is carried out with cushioning liquid, cushioning liquid can include Sharpe phosphorus Phthalate buffer (is made up of, Acidic Liquid two kinds of storing solutions：8.4g/l containing AMSP, alkalies：Phosphoric acid disodium hydrogen 9.4g/l, in use, be obtained by mixing according to different proportion, if necessary plus appropriate sodium chloride is into isotonic), Palitzsch's buffer solution (it is made up of two kinds of storing solutions, Acidic Liquid：Boronic acid containing 12.4g/l, alkalies：Borax 19.1g/l, in use, according to not year-on-year Example is obtained by mixing, and if necessary plus appropriate sodium chloride is into isotonic), lucky Fei Shi buffer solutions, [buffer solution etc. is in medicament for borate buffer etc. It is described on：Tu Xide, the Zhang Jun longevity, Zhu Jiabi, pharmacy (third edition), 2002, Beijing, People's Health Publisher].

Eye, ear, the nose of the present invention is used, skin composition contains in medicinal acceptable carrier and resisted with one or more Scorching medicine.The pH that the composition will typically have 5.5-8.0.The ophthalmic composition must also be configured to have with eye and The consistent osmotic value of aqueous humor in ocular tissue.These osmotic values are typically about 200- about 400 milliosmols/kg water (" mOsm/kg "), it is preferred that about 300mOsm/kg.

The composition and recipe quantity of the pharmaceutically acceptable pH adjusting agent used in the preparation of the pharmaceutical composition of the present invention It is this area conventional selection, is selected from but is not limited only to pharmaceutically acceptable inorganic acid or organic acid or its pharmaceutical salts, inorganic Alkali or organic base or its pharmaceutical salts, the lewis acid or alkali of broad sense can also be included, one or several kinds can be contained, it includes But it is not limited to hydrochloric acid, sulfuric acid or its pharmaceutical salts, boric acid or its pharmaceutical salts, borax, phosphoric acid or its pharmaceutical salts, acetic acid or its is medicinal Salt, such as sodium acetate, lactic acid and lactic acid pharmaceutical salts, citric acid or its pharmaceutical salts, tartaric acid or citric acid or its pharmaceutical salts, phosphoric acid Disodium hydrogen, sodium dihydrogen phosphate, potassium dihydrogen phosphate, ascorbic acid, sodium ascorbate, arabo-ascorbic acid, sodium isoascorbate, hydrogen-oxygen Change sodium, potassium hydroxide, sodium carbonate, sodium acid carbonate, trihydroxy aminomethane, diethanol amine, monoethanolamine, diisopropanolamine (DIPA), 2- ammonia Base -2- (methylol) 1,3-PDs amine, N- methyl glucoses amine and their salt, multi-hydroxy carboxy acid and pharmaceutical salts, such as grape Uronic acid, gluconic acid, lactobionic acid, malic acid, threonic acid, glucoheptonic acid, amino acid or their pharmaceutically acceptable salt Or the one or several kinds in its hydrate etc..

The preparation of the topical ocular administration of the preparation of the present invention includes eye drops, situ-gel eye drops, heat-sensitive gel drop Ocular fluid, gel for eye use, eye ointment etc.；Eye drops can unit dose package or multiple-unit container.Wherein, situ-gel eye drops or temperature-sensitive Gel eyedrop, the pharmaceutically acceptable auxiliary material of gel for eye use may include thickener, surfactant, antioxidant, chelating Agent or metal ion couplant, preservative or bacteriostatic agent, pH adjusting agent, osmotic pressure regulator etc..

Etimicin or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its is molten In agent compound or its inclusion compound it is any one or more of with have anti-inflammatory effective dose steroid or with non-steroidal antiinflammatory drugs and resist The thermosensitive type situ-gel eye drops of any one or more of composition in dry eye drugs, its pharmaceutically acceptable auxiliary material can Including thickener, surfactant, antioxidant, chelating agent, preservative, pH adjusting agent, osmotic pressure regulator etc..

A kind of Etimicin Sulfate or its pharmaceutically acceptable salt etc. with have the steroid of anti-inflammatory effective dose or with non-steroid The thermosensitive type situ-gel eye drops of any one or more of composition or temperature-sensitive are coagulated in antiinflammatory drugs and anti-dry eye drugs The preparation method of glue eye drops, it may include following steps：(1) partial purification water is heated to 50 DEG C~60 DEG C, pharmaceutically will may be used The auxiliary material of receiving is dissolved in purified water, and room temperature is cooled to after dissolving；(2) main ingredient is added to the solution of gained in step (1) In, stirring is to being completely dissolved；(3) by thermosensitive type gel rubber material dispersing and dissolving in the partial purification water that water temperature is room temperature；(4) will The solution of step (2) and (3) is mixed, and solution ph is adjusted into 6.2~7.8, is settled to required volume, filtration sterilization, sterile point Loaded on eye drop bottle, produce.

The prescription of gel for eye use can include as follows：

The Etimicin or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms of effective dose or without fixed It is any one or more of with having the steroid of anti-inflammatory effective dose or resisting with non-steroid in type thing or its solvate or its inclusion compound It is any one or more of in scorching medicine and anti-dry eye drugs, gel-type vehicle (carbomer series, carbomer 934, carbomer 934P, Acritamer 940, Carbopol 941, CARBOPOL 974P etc., polyvinyl alcohol, chitosan, poloxamer, methylcellulose, hydroxyl Ethyl cellulose etc.), pharmaceutically acceptable thickener, stabilizer (antioxidant or stabilizer), preservative or bacteriostatic agent, infiltration Conditioning agent, pH adjusting agent etc., and pure water is pressed to add to 1000g.

Wherein, gel-type vehicle is usually 0.5~100.0g, more preferably 1~60.0g, more preferably 1~20.0g；

Stabilizer (antioxidant or stabilizer) is usually 0.05~200g, more preferably 1~150g, more preferably 1~120g；

Preservative or bacteriostatic agent are usually 0.005~20g, more preferably 0.01~2g；

Osmotic pressure regulator is usually 0.1~80.0g, more preferably 1~60.0g, more preferably 1~40.0g；

PH adjusting agent is usually 0.1~20.0g, more preferably 1~20.0g, more preferably 1~10.0g；

And supply 1000ml or 1000g with water.

Eye drops preparation method may include the following steps：

The preparation technology of eye drops or suspension：By Etimicin Sulfate or Etimicin be dissolved in distilled water or pure water or In water for injection or the pure water or water for injection of acidifying, there is the steroid of anti-inflammatory effective dose or done with non-steroidal antiinflammatory drugs with anti- Eye disease drug be dissolved in water or DL in water, by auxiliary material be dissolved in distilled water or pure water or water for injection or acidifying pure water or In water for injection, both are mixed, stirred and evenly mixed, (more preferably pH value is 6.0-7.5 to regulation solution ph between 5.8-7.8 Between), osmotic pressure is adjusted, adds water to full dose or filtering, filling, sterilizing, packaging.

Eye drops goes thermal source and bacteria remover filter type to include adding the activity with liquid measure 0.005~1% in preparing Charcoal removes thermal source, 0.20~0.8 μm of filtering with microporous membrane, pressure sterilizing, can also use ultrafiltration.In hyperfiltration process, ultrafilter can From flat, rolling, tubular type, hollow fiber form or circle boxlike etc., more preferably rolling and hollow fiber form ultrafilter, using cutting After staying the membrane filtration that relative molecular mass is 30,000 to 300,000, or again using retention relative molecular mass 4000~60000 The milipore filter of ultrafiltration membrance filter, preferably relative molecular mass 6000~30000.

The invention provides can be selected effective for the pharmaceutical preparation of topical treatment ocular infection disease and xerophthalmia The elementary sum symbol toxicity dosage range related to curative effect, these are not open before.

The preparation of the present invention prevent or treat the conjunctivitis of people or mammal, angular blepharitis, trachoma, keratitis, Severe conjunctival inflammation (vernal keratoconjunctivitis), sclerotitis, episcleritis, retinal vasculitis, the eye disease of sensitive bacterial infection When sick, xerophthalmia or scheroma or dry eye syndrome etc., the eye drops dosage of the method for the embodiment of the present invention 4 may generally be：One day 2-5 Secondary, each 1-3 drops, children can be with weight loss.The dosage of gel for eye use can suitably be adjusted according to the dosage of eye drops It is whole.

Auristilla preparation method may include the following steps：

The preparation technology of eye drops：By Etimicin Sulfate or Etimicin or its pharmaceutically acceptable salt or the non-isomorphous Type or amorphous article or its solvate or its inclusion compound and have anti-inflammatory effective dose steroid or with non-steroidal antiinflammatory drugs and In anti-dry eye drugs it is any one or more of be dissolved or suspended in water for injection or or glycerine or ethanol equal solvent in, it is appropriate to add Auxiliary material, stir and evenly mix, regulation solution ph for 5.0-7.8 between, or filtering, it is filling, sterilizing, pack.Auristilla dosage one As can include：One day 2-5 times, each 1-6 drops.

The preparation of ointment or emulsifiable paste

Etimicin or Etimicin Sulfate or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its is molten Agent compound or its inclusion compound with have the steroid of anti-inflammatory effective dose or with it is any in non-steroidal antiinflammatory drugs and anti-dry eye drugs One or more, mixed with the matrix and pharmaceutically acceptable bleeding agent of ointment or emulsifiable paste, emulsifying agent or surfactant etc. Uniformly obtain.The local skin outer used time can determine dosage according to size of skin infection etc., general one day 1-3 times.

The matrix and pharmaceutically acceptable bleeding agent of ointment or emulsifiable paste, emulsifying agent or surfactant etc. are selected from but not only limited In：Water, propane diols, glycerine, lanolin, vaseline, spermaceti, cera alba, paraffin, ceresine, vegetable oil, hydrogenated vegetable oil, axunge, Cholesterol, isopropyl myristate, hexadecanol, octadecyl alcolol, the fat of polyoxyethylene stearate 40, polyethylene glycol 100-20000, poly- second two It is alcohol -400, PEG-4000, PEG-4000, atoleine, sodium stearyl sulfate, glycerin monostearate, poly- Stearine, glycerin gelatine, sodium alginate, the series of polyethylene glycol, the series of poloxamer, polyvinyl alcohol, polyethylene Pyrrolidones, methylcellulose, carbomer, sodium carboxymethylcellulose, Tween-80, polyethylene glycol oxide list oleic acid sorbitan ester, VE succinic acid macrogol ester (vitamin E TPGS), glycerine-polyethylene glycol epoxide stearate, PEG-32 stearic acid Tripalmitin, lauryl sodium sulfate, Sorbitan monolaurate etc..

The purpose of the present invention also provides the pelliculae pro cavo oris of compound Etimicin, and pelliculae pro cavo oris can be made up of following components：Thing Expect weight than Etimicin or its pharmaceutically acceptable salt and its described in steroid of the composition also containing anti-inflammatory effective dose Or with any one or more of grade 10~50% (w/w) in non-steroidal antiinflammatory drugs and anti-dry eye drugs, filmogen 40~ 90% (w/w), flavouring 0~6% (w/w), colouring agent 0~5% (w/w)；The pelliculae pro cavo oris of the compound Etimicin of the present invention In the local anaesthetics containing effective dose, including be singly not limited to tetracaine hydrochloride, procaine hydrochloride, chloroprocanine, hydrochloric acid Lidocaine, oxybuprocaine, phenmethylol, menthol, Etidocaine, Bupivacaine, dyclonine, benzocainum, Ropivacaine Or the pharmaceutical salts of its parent compound or its inclusion compound etc., its weight of material ratio can be 5~50% (w/w)；

The filmogen is selected from but is not limited only to polyvinyl alcohol, IR, hypromellose Element, hydroxypropylcellulose, gelatin, pulullan polysaccharide, modified starch, HPMC K4M, HPMC E5, hydroxyl One or more in third methylcellulose E50, HPMC K100, cellulose family or natural macromolecular material etc.； The flavouring is sweetener, acid or aromatic；The colouring agent is natural pigment or artificial color.

The pelliculae pro cavo oris of described compound Etimicin, preferred ingredient composition are as follows：

Weight of material than for Etimicin or its pharmaceutically acceptable salt and have anti-inflammatory effective dose steroid or with it is non- Any one or more of grade 15~40% (w/w), (w/ of filmogen 60~80% in steroidal antiinflammatory drugs and anti-dry eye drugs W), flavouring 0.01~2% (w/w), colouring agent 0.01~1% (w/w)；

Flavouring used it is optional but be not limited only to lactose, Sucralose, aspartame, stevioside, acesulfame potassium, sorbierite, One or more in mannitol, saccharin sodium；Colouring agent used is optional but is not limited only to titanium dioxide, iron oxide, β-carrot Element, beet red, lac are red, red pigment of cowberry, capsanthin, red rice are red, carmine, amaranth, famille rose, erythrosine, newly red, lemon One or more in Huang, sunset yellow, indigo, light blue.

The purpose of the present invention, which lies also in provide, a kind of is used for respiratory tract, skin and soft tissue infection caused by treating sensitive bacteria Compound Etimicin or with dexamethasone plastics and preparation method thereof.

The present invention is achieved through the following technical solutions：A kind of compound Etimicin plastics, with 1000g weight or and 1000ml volumes represent, are done by the Etimicin of effective dose or with the steroid of effective dose or with non-steroidal antiinflammatory drugs with anti- Any one or more of in eye disease drug, chitosan, polyvinyl alcohol, the series of carbopol, hyaluronic acid, gelatin, Propiram are more Sugar, ethyl cellulose, sodium carboxymethylcellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, polyethylene kind, PP type, 10~80g of one or more, propane diols in the pharmaceutically acceptable filmogen such as cellulose family or natural macromolecular material Or one or more 20~200g, the pharmaceutically acceptable 0~30g of surfactant in glycerine, it is pharmaceutically acceptable 0~5g of bacteriostatic agent, 50~600g of purified water, ethanol are added to 1000g or 1000ml compositions.

Plastics made from the inventive method have that adhesive force is strong, stretchability is good, film forming is fast and it is difficult for drop-off, have it is certain Tearing toughness, it is heat-resisting, acid and alkali-resistance, easy cleaning the advantages that.

Embodiments of the invention into film test and cleaning

Embodiments of the invention coating liquid (embodiment 52) is dipped with banister brush and gently coats thin layer on a glass, is observed Film formation time is about within 3 minutes on a glass for film formation time result this plastics, while in back of people's hand of the present invention or pin One layer of this product of toe film, observation film formation time this plastics of result are about within 2 minutes in human body film formation time, and skin does not have red It is swollen to wait adverse reaction, illustrate that the film forming of this product is good.Rinsed with running water after ten minutes, washed away soon on glass plate Medicine film and human body trick on medicine film.

The purpose of the present invention also provides a kind of mouth paster of the treatment canker sore containing compound Etimicin, wherein often In single dose paster its adhesion layer can contain effective dose Etimicin or with the steroid of effective dose or and nonsteroidal anti-inflammatory agent Thing and anti-dry eye drugs etc.；Its adhesion layer can contain main ingredient Etimicin 0.1-5mg in wherein per single dose paster, more preferably Content is 0.5-3mg, steroid or with non-steroidal antiinflammatory drugs and anti-dry eye drugs 0.01-2mg, preferred content 0.05- 1mg, more preferably 0.1-0.6mg.

The compound Etimicin mouth paster of the present invention can be single-layer sheet or double-layer tablets, and single-layer sheet here is common list The tablet of the adhesion layer of synusia, only Etimicin containing main ingredient etc..

The preferred double-layer tablets of mouth paster described in the present invention, it is characterised in that the adhesion layer including Etimicin containing main ingredient etc. With protective layer or support layer not soluble in water.It can contain effective agent in the oral mucosa paster of the compound Etimicin of the present invention etc. The local anaesthetics of amount, including singly it is not limited to tetracaine hydrochloride, procaine, chloroprocanine, lidocaine, oxybuprocaine, benzene first Alcohol, menthol, Etidocaine, Bupivacaine, dyclonine, benzocainum, Ropivacaine or its pharmaceutical salts or its inclusion compound etc., Its weight of material than can be whole tablet weight 5~50% (w/w).

The compound Etimicin oral cavity adherent emplastrum of the present invention can be a kind of double-layer tablets, can be by medicated layer and protective layer or branch Hold layer composition.Medicine layer include active component Etimicin and effective dose steroid or with non-steroidal antiinflammatory drugs and anti-xerophthalmia One or several kinds among medicine etc., and filler, sustained-release matrix material, adhesive matrix, wetting agent and lubricant；Protective layer Or support layer includes the one or several kinds among filler, lubricant, wetting agent, adhesive, colouring agent.

Compound Etimicin mouth paster of the present invention, its adhesion material are selected from but are not limited only to one or more of Material：Hydroxypropyl methyl cellulose, the series of carbopol, sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP), hydroxypropyl Methylcellulose (HPC), polyvinyl alcohol (PVA), sodium carboxymethylcellulose (CMC-Na), hydroxypropyl cellulose (HPC), hydroxypropyl One or several kinds among methylcellulose (HPMC), chitosan, gelatin, starch, dextrin etc.；It is described viscous in each paster The gross weight of enclosure material can be 10-70mg.

Compound Etimicin mouth paster of the present invention, in addition to pharmaceutically acceptable filler, glidant Or lubricant, wherein, filler may be selected from but be not limited only to starch, amylum pregelatinisatum, dextrin, mannitol, xylitol, lactose etc. Central one or several kinds, preferable dextrin, lactose, the one or several kinds among microcrystalline cellulose；Glidant or lubricant can It is selected from but is not limited only to talcum powder, magnesium stearate, superfine silica gel powder, Compritol 888 ATO, lauryl sodium sulfate, dodecyl sulphur One or several kinds among sour sodium, VE succinic acid macrogol ester.Wetting agent may be selected from but be not limited only to ethanol, water.

Compound Etimicin mouth paster of the present invention, described protective layer not soluble in water is mainly with acrylic acid tree Ester or ethyl cellulose are that film forming agent is equipped with the solution spraying of appropriate pharmaceutical plasticizers and filler formation in drug containing (if necessary) The fish tail and waterproof layer that one surface of adhesion layer is formed.Described plasticizer may be selected from but be not limited only to dibutyl phthalate, One kind in diethyl phthalate, dioctyl phthalate, castor oil, epoxidized soybean oil, citric acid ester plasticizer Or it is several, the citric acid ester plasticizer can be enumerated but be not limited to citric acid tri-n-hexyl ester (THC), acetyl tributyl citrate three just Own ester (ATHC), trioctyl lemon acid (TOC), ATOC (ATOC), ATBC (TBC), acetyl lemon Lemon acid tributyl (ATBC), THC (THC), the own ester of acetyl tributyl citrate (ATHC), BTHC (BTHC), plasticizer optimization citric acid tributyl and/or tributyl 2-acetylcitrate.The plasticizer consumption can be protective layer weight The 5% to 30% of amount (dry weight), more preferably 8%~25%.

Appropriate flavouring or and colouring agent can be added as needed.Flavouring used is optional but is not limited only to lactose, three One or more in chlorine sucrose, aspartame, stevioside, acesulfame potassium, sorbierite, mannitol, saccharin sodium；Colouring agent used can Select but be not limited only to titanium dioxide, iron oxide, beta carotene, beet red, lac are red, red pigment of cowberry, capsanthin, red rice are red, kermes One or more in red, amaranth, famille rose, erythrosine, newly red, lemon yellow, sunset yellow, indigo, light blue.

Stickup tablet (above-mentioned individual layer, double layer adhesive sheet) of the present invention is prepared via a method which：By active component Dissolving, through granulation, whole grain after being mixed with filler, add tabletting after adhering to sustained release agent and magnesium stearate mixing and produce individual layer stickup Piece, then the solution spraying containing acrylic resin, plasticizer and pigment is made i.e. by protective layer in coat tablets by Membrane jetter Obtain double layer adhesive sheet.

The method of what the present invention narrated prepare compound Etimicin oral cavity adherent emplastrum also may be selected as follows：

1) can be micronized by Etimicin or with dexamethasone or steroidal or non-steroidal etc., remaining auxiliary material crosses 80~ 100 mesh sieves are standby or all solids to cross 80~100 mesh sieves standby.

2) medicated layer is pelletized：Weigh Etimicin steroidal or non-steroidal of medicated layer recipe quantity etc. and recipe quantity filler with The method that equivalent is progressively increased is mixed, then addition sustained-release matrix material is well mixed, with ethanol softwood, 20~40 mesh sieve whole grains； Obtained particle is put into baking oven with 45 DEG C~60 DEG C drying, 20~40 mesh sieve whole grains, and adds recipe quantity adhesive matrix, profit Lubrication prescription is well mixed, standby.

3) support layer is pelletized：The preparation of adhesive：It is added to by the flavouring of recipe quantity or with colouring agent containing adhesive Adhesive is used as in the aqueous solution.The filler of recipe quantity is weighed, is placed in wet granulator, addition adhesive softwood, 20~ 40 mesh are pelletized, and are dried in 45 DEG C~60 DEG C of baking oven, 20~40 mesh sieve whole grains, it is equal to be eventually adding recipe quantity mix lubricant It is even, it is standby.

4) detection of intermediate：Two kinds of particles is taken out and does determination of moisture, and does the assay of medicated layer.

5) tabletting：The piece weight of medicated layer is first regulated, then adjusts the piece weight of full wafer, double-layer tablets are pressed into bi-layer tablet press.

The usage of Etimicin betamethasone oral cavity adherent emplastrum or pelliculae pro cavo oris：General daily medication 1-3 times, affected part is each 1.

Study whether the medicine of the present invention can be used for topical treatment by following experiment

First, the excitant evaluation experimental of drug combination preparation of the invention to rabbit eyes

1st, test objective

The power that the pharmaceutical composition of the observation present invention is reacted after dosing eyes, to investigate pharmaceutical composition to rabbit eyes Whether eyeball occurs adverse reaction and its degree, bibliography (document：Qian Chen, Sun Baohai, Chen Zaixin, etc.；Besifloxacin hydrochloride Eye irritation acts on, West China pharmaceutical journal, 2013,28 (3):326-327).

2nd, test method：Every group takes body weight 2.5-3kg healthy rabbits 4 (male and female half and half, random packet), preselects animal flesh Eye observation：For cornea without muddy, conjunctiva without congested, oedema and secretion, pupil is circular, and both sides etc. are big, light is reflected good.

Ophthalmic slit lamp inspection：Corneal transparency, no cloudiness, spot screen, iris texture is clear, no congestion and edema.

Fluorescent staining：L0% fluorescence rope sodium injections, face the used time with 10 times of normal saline dilution, fixed rabbit, per rabbit Eye is clean with normal saline flushing after drip, and it is normal for cornea to observe cornea uncolored person, through it is above-mentioned it is pre- select anophthalmia disease and Healthy rabbits are used for this experiment.

3rd, single-dose Eye irritation is tested

Eye drops and the eye drops of dosage treatment control group 1 that in the present invention prepared by each embodiment method are instilled into every rabbit The eye conjunctiva of right eye is intracapsular, passively closes 10s, and physiological saline is added dropwise as blank control, after administration, lagophthalmos eyelid to left eye with method Passive closure about 10 seconds, 1,2,4,24,48,72 hour, 7 days eye local reaction situations after record administration.With reference to《Chemicals Excitant, anaphylaxis and hemolytic investigative technique guideline》Middle Eye irritation reaction standards of grading corneal, iris and conjunctiva point Do not scored (table 1), judges whether eye drops has excitant.

4th, multiple dosing Eye irritation is tested

First dyed before daily 1st dropwise addition eye drops with 2% Fluress and (use the l0% of 5 times of normal saline dilution Fluorescence rope sodium injection), then judge whether cornea is undermined degree of injury with ophthalmic slit lamp inspection, then use physiological saline After gently rinsing, eye drops and the eye drops of dosage treatment control group 1 prepared by each embodiment method instill every rabbit right eye Eye conjunctiva it is intracapsular, passively close 10s, give left eye that physiological saline is added dropwise as control with method, during the daily morning about 9 from every about 3h drops medicine 1 time, drip 3 times altogether, successive administration 7 days, reference《Chemical induced irritation, anaphylaxis and hemolytic investigative technique instruct Principle》Middle Eye irritation reaction standards of grading corneal, iris and conjunctiva are scored respectively, judge to give drop from its mean scores Whether ocular fluid has excitant.Corneal injury is checked with fluorescein sodium during observation, and with slit lamp examination corneal transparence and rainbow Film texture changes.

5th, experimental result (table 2) single-dose Eye irritation is tested：Standards of grading, the eye drip of embodiment are reacted according to Eye irritation Liquid stimulate the reaction synthesis mean scores are 0~3.

Multiple dosing Eye irritation is tested：The eye drops successive administration 7 days of the present invention, observe after each embodiment group single-dose To rabbit cornea it is transparent, without muddiness, iris is without congested, swelling, clean mark, without significant difference compared with left eye；It is each to implement The iris or conjunctiva mild hyperaemia or slight oedema of indivedual rabbit after the rabbit only multiple dosing of example group, but comprehensive mean scores Still within 3.Show that various embodiments of the present invention composition eye drops is nonirritant to lagophthalmos.In addition, experimental animal eye The tissue pathological slice HE dyeing detections of ball (including cornea, iris, conjunctiva), do not find notable difference.

Table 1, eye irritation laboratory strength standards of grading

Table 2, each embodiment single-dose, the irritant experiment result of multiple dosing

Sample	Single-dose mean scores	Multiple dosing overall average score value	As a result
				Embodiment 5	0	0.2	It is nonirritant
Embodiment 7	0	0.8	It is nonirritant
				Embodiment 9	0	0.2	It is nonirritant
Embodiment 15	0	0.3	It is nonirritant
				Embodiment 19	0	0.5	It is nonirritant
Embodiment 24	0	0.5	It is nonirritant
				Embodiment 29	0	0.3	It is nonirritant
Embodiment 33	0	0.5	It is nonirritant
				Embodiment 36	0	0.3	It is nonirritant
Embodiment 42	0	0.3	It is nonirritant

2nd, the treatment evaluation experimental of drug combination preparation of the invention to Bacteritic Keratitis in Rabbits

1st, in vivo studies rabbit eye injury type bacterial keratitis animal model

EHEC, staphylococcus aureus, Pseudomonas aeruginosa and the blood that will be inoculated on plain agar culture medium flat plate The micrococcus scarlatinae of agar plate is scraped with oese, and 2 × 10 are made into respectively with physiological saline⁹(photoelectricity is than turbid by CFU/ml Instrument determines concentration), reference literature method modeling type and progress pharmacodynamic experiment (document：Xiao Yi, Li Chen, Mei Qi Ping, etc.；Rabbit The foundation of eye injury type bacterial keratitis animal model, Shaanxi medical journal, 2003；32(2):187-188；Document 2：Grandson Boat, Yang Shuqun, Zhou Yuan great, etc., the pharmacodynamic study of levofloxacin eyedrops, Chongqing Medical, Chongqing Medical Journal,2004,33(7):1069-1071；), with 1.0g/kg urethane auricular vein injecting anesthetics rabbit (healthy rabbits, Body weight about 2.5-3kg, male and female half and half), rabbit cornea damage (eyes) is caused with corneal trephine, lagophthalmos palpebra inferior is pulled open, makes rabbit It is continuous to instill 2 days per four kinds of bacterium 0.1ml of ocular infections, eye discharge is taken with Sterile Saline cotton swab after 2d, it is sterile to be put into 4ml In normal saline bottle, Bacteria Culture is done to its liquid with agar plate method.

After modeling, there is obvious inflammatory reaction in lagophthalmos, and conjunctival hyperemia is serious, and corneal edema, superficial ulcer is formed, ulcer There is more secretion in face, and rabbit activity is reduced, and appetite reduces, and when checking lagophthalmos, scream is uneasy.

2nd, packet is set, and is grouped at random (in addition to Normal group and positive controls, every group of 5 rabbit)：

The method group of embodiment 12 (eye drops prepared by the method for bacterial infection+embodiment 12)；

The method group of embodiment 35 (eye drops of the method for bacterial infection+embodiment 35)；

The method group of embodiment 42 (eye drops of the method for bacterial infection+embodiment 42)；

Treat control group (eye drops of bacterial infection+Etimicin control group)；

Positive controls (bacterial infection+drop physiological saline), 3；

Normal group (normal rabbits, be uninfected by bacterium, only drip physiological saline) 3.

Different eye drops 0.2ml/d (eyes) in the treatment group drop present invention, Etimicin control group drop Etimicin Eye drops, positive controls and Normal group drop physiological saline 0.2ml/d (eyes), every 0.2ml, 4 times/d, continuity point medicine 6 days (d).Once scored every 24h eyes, Continuous Observation 6d, appraisal result, which takes statistics, learns t inspections processing.And in administration Preceding 1d, 5d takes discharge of eye to carry out Bacteria Culture with Sterile Saline cotton swab after administration, is placed in 37 DEG C of incubators after culture 48h Judge yin and yang attribute result.

Wherein, the preparation of Etimicin control group eye drops：

Etimicin Sulfate (in terms of Etimicin) 3g of recipe quantity is dissolved in 0.9% physiological saline 970ml, stirring is molten Solution, solution pH value is adjusted to 6.8 with 0.5M sodium hydroxide solutions and 0.5M hydrochloric acid solutions, adds 0.9% physiological saline extremely 1000ml, filling by 5ml/ bottles through 0.22 μm of filtering with microporous membrane, sealing, 100 DEG C sterilize 30 minutes, let cool, and examine, packaging.

3rd, result is shown (table 3)：

Rabbit discharge of eye bacteria cultivation results：After continuity point medicine 6 days, Normal group Bacteria Culture is feminine gender, positive Control group Bacteria Culture is the positive, and 12 groups of embodiment, 35 groups of embodiment, the method group Bacteria Culture of embodiment 42 are essentially feminine gender, Only 1-2 is only the positive, and more of the Bacteria Culture of the treatment control group of Etimicin is the positive；Compared with positive controls, respectively After the eye drops for the treatment of group is to EHEC, staphylococcus aureus, Pseudomonas aeruginosa, the administration of S. pyogenes infection group Positive total eye number has notable difference (P after treatment<0.01), compared with treating control group, positive for bacteria quantity always detects number It is low, there is obvious difference.

12 groups of embodiment, 35 groups of embodiment, the method group of embodiment 42 are respectively provided with the therapeutic effect of highly significant；Marked according to scoring Accurate is substantially 0 grade to rabbit eyes progress inflammatory score：Eyelid is clear without hyperemia, corneal transparency, iris texture without redness, conjunctiva Clear, eye is bright without secretion, belongs to healing or basic healing；The slightly show of the eyelid of only two swells, and is bisected into 0 grade to 0.5 grade, category In improvement or basic healing.

Treat control group and rabbit eyes are carried out with inflammatory score, 5 are 0 grade, and 5 are 0.5 grade to 1 grade：Conjunctiva slightly fills Blood, eye is slightly red and swollen, and secretion covering is less than 6mm；It is relatively each to implement although the eye drops for the treatment of control group is also effective Example method group has difference obvious.

The result of lagophthalmos secretion Bacteria Culture after table 3, eye drops in treatment

3rd, the experiment of composition attenuation

Bibliography method [document：Shi Ninghua, Miao Yian, Zhang Zhijian, etc., Etimicin ototoxicity test III, according to for The comparison that meter Xing Yu gentamicins, amikacin influence on vestibular function, Chinese antibiotic magazine, CHINESE J OF ANTIBIOTICS,1999,24(6):445-448；], observe the ototoxicity that can another component caused by antagonism Etimicin.Side Method：Health, hearing and the normal cavy of equilibrium function 64 are taken, 260~350g of body weight, male and female half and half, is randomly divided into 4 groups: 0.9% saline control group (16)；Etimicin Sulfate A groups 40mg/kg, 1ml solution Etimicin containing 40mg, 0.9% Physiological saline solution Etimicin Sulfate；According to for composition B groups [Etimicin Sulfate+betamethasone sodium phosphate (40mg/ 0.5mg/kg), 1ml liquid Etimicin containing 40mg and betamethasone sodium phosphate 0.5mg, 0.9% two kinds of physiological saline solution medicine Thing], according to for composition C groups (Etimicin Sulfate+hydrocortisone sodium succinate, 40mg/0.4mg/kg, 0.9% physiological saline Two kinds of medicines are dissolved, concentration is with B groups), each group Etimicin Sulfate is with Etimicin weight calculation amount；Daily intramuscular injection is once, common 28d, a vestibular function is checked weekly and after the completion of administration during administration, 0.9% physiological saline group daily administration volume with Etimicin Sulfate group is consistent.

Vestibular function is tested：Animal respectively before administration, administration 4 weeks after check vestibular function and nystagmus inhibiting rate change. Animal is placed in circulator, with 1 turn per second of the circle of rotating speed rotation 20, the nystagmus duration is observed immediately, calculates administration Nystagmus inhibiting rate (nystagmus inhibiting rate is the difference and the percentage of nystagmus time before administration of nystagmus time before and after administration) afterwards, nystagmus suppression The size of rate processed represents the impaired degree of vestibular function.

As a result it is as shown in table 4：Etimicin group has conspicuousness poor compared with physiological saline group compared with according to for composition group It is different, Etimicin group with according to the difference of the nystagmus inhibiting rate for composition B groups there is conspicuousness, according to for composition B groups and according to for Difference of the composition component C not with the poor absolute value of the nystagmus inhibiting rate of physiological saline group also has conspicuousness, it is seen that according to for group The trend that ototoxicity caused by the administration more single than Etimicin of compound group is reduced.

The each group animal of table 4 nystagmus inhibiting rate (%, n=16)

Group	Number of animals (n)	Nystagmus inhibiting rate
			Physiological saline group	16	8.85±5.73
Etimicin A groups	16	17.37±6.91
			According to for composition B groups	16	12.62±4.50
According to for composition C groups	16	12.96±4.83

4th, local application's irritation test

Body weight 2.5-3kg healthy rabbits 20 are taken, are divided into 4 groups, every group 5；44 groups of embodiment, 48 groups of embodiment, reality 49 groups of example and Normal group are applied, drips left and right ear with auristilla respectively, each 1-2 drops, 5 times a day, continuous 7d；Normal control Group does not drip any decoction.Observe and record animal whether there is restlessness, loses the appetite, grabs nose phenomenon.Used when last dose 24h The reflective spectroscopy White Rabbit ear-drum of ophthalmology, duct, the basal part of the ear (snail) whether there is hyperemia, oedema, red and swollen phenomenon.As a result 4 groups of animals are not Phenomena such as seeing ear-drum, duct, basal part of the ear hyperemia, oedema, redness, show to have no that embodiment group auristilla has local thorn through multiple dosing Swash property reaction.

5th, skin hypersensitivity is tested

Healthy guinea pig 64,250~350g of body weight is taken, male and female half and half, is randomly divided into 8 groups, bibliography method：(document： Zhang Meisong, He Xinjun, Chen Yu, the experimental study etc., purplish or white patches on the skin of dispelling secondary color ointment to animal skin allergic reaction, the Zhejiang traditional Chinese medical science are miscellaneous Will, 2013,48 (6):410-411；)

24h takes off guinea pig back diamond wool before experiment, depilation scope about 3cm × 3am per side, by the cavy after depilation It is randomly divided into DNFB positive controls, saline control group and the method group of embodiments of the invention 57, embodiment 64 method groups, the method group of embodiment 66, the method group of embodiment 76, the method group of embodiment 79, the method group of embodiment 83, DNFB is used Acetone sesame oil is made into 1% sensitization concentration and 0.1% and excites the concentration standby.

Sensitization contact：In each group cavy left dorsal portion, depilation skin embrocates 1%2,4- dinitrofluorobenzene, physiology salt respectively The preparation of water, each embodiment method group, every 0.5ml, then covered with 1 layer of oilpaper and 2 layers of gauze, piece adhesive plaster is gone with after determining 6h Except tested material.It is repeated 1 times with same method within 7th day and the 14th day.

Excite contact：The 14d after last coating, by 0.1%2,4- dinitrofluorobenzene, physiological saline and each embodiment group Substances are applied to hair removal section on the right side of guinea pig back respectively, remove tested material after 6h, observe at once, then in 24,48 and 72h again Observation skin whether there is the allergic reactions such as erythema, oedema.Erythema and oedema press following scale：Divide without erythema 0, slight erythema 1 Point, moderate erythema 2 is divided, and erythema 3 is divided once again, and edematous erythema 4 divides；Divide without oedema 0, Mild edema 1 is divided, and intermediate edema 2 is divided, weight Degree oedema 3 is divided；Whether also observation cavy there is the severe allergic reactions such as asthma, astasia or shock and changes of weight simultaneously, Sensitization rate=cavy number/tested cavy sum of erythema, oedema or systemic anaphylaxis occur.

The tested area of DNFB positive controls guinea pig skin excites rear 6h to start have slight erythema and oedema Occur, 24~48h erythema and oedema are obvious, have mitigated during 72h, and allergic reaction incidence is 100%, but without asthma, stand The systemic allergy such as shakiness；And saline control group and the method group of embodiment 57, the method group of embodiment 64, the method for embodiment 66 Group, the method group of embodiment 76, the method group of embodiment 79, the tested area of guinea pig skin of the method group of embodiment 83 have no the skins such as erythema, oedema The severe allergic reaction such as allergic reaction and asthma, astasia, sensitization rate are 0, the difference for having highly significant with positive controls. There are the local reactions such as erythema in the only indivedual guinea pig skins of the method group of embodiment 64, and its allergy incidence is about 3%, belongs to no mistake Quick property.

The skin hypersensitivity evaluation criterion of table 5

Allergic reaction incidence %	Classification	Allergic reaction intensity
			0~10	Ⅰ	Without sensitization
11~30	Ⅱ	Slight sensitization
			31~60	Ⅲ	Moderate sensitization
61~80	Ⅳ	Height sensitization
			81~100	V	Extreme sensitization

The pharmaceutical composition for demonstrating the present invention of skin irritation or the skin hypersensitivity experiment of embodiments of the invention Administering drug combinations safe foundation is provided.

6th, the irritant experiment of mucous membrane of mouth

Bibliography method observes the excitant [text of compound Etimicin sticking tablet and film to Golden Hamster mucous membrane of mouth Offer：Li Liang, Zheng Guoan, Guo Sheng, etc., Cydiodine buccal tablet mucous membrane of mouth irritation test, Inner Mongol traditional Chinese medicine, 2,009 28 (23): 62-63；].

Method：The male golden yellow gopher 24 of health is taken, body weight about 100-140g, 4 groups is randomly divided into, every group 6, distinguishes For the method group of embodiment 86 and the method group intact mucosa group of embodiment 87, the method group of embodiment 86, the method breakage mucous membrane group of embodiment 86, use Itself left and right sides mucous membrane compares, and left side administration, right side is as blank control；The sterile pins of 24h scratch damaged mucous membrane before administration Buccal mucous membrane at left and right sides of group Golden Hamster.

Medication：Dorsal position is taken to fix Golden Hamster, the method group of embodiment 86 accurately takes about 0.25 × 0.1cm film Piece is put on the left of its chamber in cheek pouch, and what medicine right side cheek pouch does not let alone；The method group of embodiment 87 weighs ten/a piece of dose It is put on the left of its chamber in cheek pouch, what medicine right side cheek pouch does not let alone, is administered daily 3 times, continuous 7d.Gross examination of skeletal muscle is evaluated：Often 1h before secondary administration and after administration, 1 after last dose, 24,48,72h, observe and record with the mucous membrane of medicament contact whether there is erythema, Situations such as rotten to the corn and oedema, and scored by literature method；If any other reactions, observe and record.

As a result show：Make gross examination of skeletal muscle evaluation and Histological evaluation after direct oral cavity mucosal drug delivery 7d, gross examination of skeletal muscle display is real Apply the method group of example 86 and the method group of embodiment 87 is nonirritant to the oral cavity intact mucosa of Golden Hamster and damaged mucous membrane；Pathological tissue Learn and check that the display method group of embodiment 86 and the method group intact mucosa of embodiment 87 and damaged mucous membrane do not produce the pathology such as inflammation and changed Become；Histopathology scoring shows, conclusion nonirritant to intact mucosa and damaged mucous membrane：The method group of embodiment 86 and embodiment 87 method groups are nonirritant to the mucous membrane of mouth of Golden Hamster.

The purposes of the present invention：Composition of the present invention be used to preparing the otitis externa that treats or prevents people or mammal and Illness, ear or the nasa surgery of tympanitis operate the application in the ear of patient or the topical drug of nose；The composition is used In the conjunctivitis for preparing treatment or prevention people or mammal, angular blepharitis, keratitis, dacryocystitis, sty, trachoma, eye In sterileization treatment, scheroma or the xerophthalmia or dry eye syndrome of section's peri-operation period or on the local eye medicinal of cataract Using；The composition is used to prepare skin soft-tissue infection's property caused by the sensitive bacterial for treating or preventing people or mammal Disease, such as epifolliculitis, furuncle, impetigo, trauma infection contamination and eczema infection；Convergence burn, scald, the local skin on the pernio surface of a wound Application on skin medicine or canker sore, RAU medicine.

There is provided medicine validity and security be medicament research and development eternal theme, not only facilitate reduce drug development into This, the treatment being more conducive under the different situations of disease, therefore, the present invention by for correlation treatment provide more effective approach or The effect of more preferable or better healing compliance are provided.

Embodiment

Except in embodiment and when indicated otherwise, all numerical value used should be by specification and claims It is interpreted as being modified with term " about " in all examples, therefore, unless the contrary indication, this specification and appended The numerical parameter gone out given in claims is approximation, the required property that it can be according to sought by by present disclosure Matter and change, at least, and not be intended to limit the application of doctrine of equivalents right, each numerical parameter takes an examination The number and routine for considering effective digital round up method to explain.

Although the number range and parameter that set the wide scope of disclosure are approximations.But institute in a particular embodiment The numerical value provided is reported as precisely as possible, and any number is substantially comprising some by finding in their own test The error that standard deviation is necessarily led to.

It is pointed out that unless in text clearly in addition explanation, used in this specification and the appended claims Singulative "one", " one kind " and "the" include the plural form of referring to thing, so, such as.If refer to containing " one Mixture including two or more compounds during the composition of kind compound ", it is further noted that unless herein clearly Ground illustrates that term "or" generally includes "and/or" in addition.

This " solvate " referred to herein as also include penetrating into crystal structure the molecule of solvent molecule, atom and/ Or the crystal formation of ion, the solvent molecule of solvate can be at regularly arranged and/or disorderly arranged, including hydrate.

Different crystal forms or polymorphic referred to herein as with identical chemical composition but formed the molecule of crystal, atom and/ Or the different crystal of space arrangement of ion.

Pharmaceutical composition

" pharmaceutical composition " used herein refers to the composition of medicine, and described pharmaceutical composition can contain at least one Pharmaceutically acceptable carrier.

" pharmaceutically acceptable excipient " used herein refers to the medicine that the compound for being applied to occasionally provide herein is administered With carrier or solvent, it includes, and well known to a person skilled in the art any examples of such carriers suitable for specific administration mode.

In the preparation technology of various embodiments of the present invention, the situation of the title of each component has been limited in the prescription of embodiment Under, for simplicity for each component in prescription, can carry out simplifying appellation or the property omitted address.

The concentration unit used in description of the invention has molar concentration (M) or (mol/L) or equivalent concentration (N), or hundred Divide specific concentration etc., chronomere can use second (s), minute (min), hour (h) etc., and volume unit, which can be used, rises (l or L), milli (ml), microlitre (μ l) are risen, mass unit can use gram (g), milligram (mg) etc..

" appropriate water for injection ", " appropriate sodium chloride ", appropriate each mean in " ethanol in proper amount " etc. can be by raw material or system Agent etc. is handled to the suitable less dosage or minimum dosage of required state or optimal dosage or preferable dosage.

In order to further appreciate that the present invention, the preferred embodiment of the invention is described with reference to embodiment, still It should be appreciated that these descriptions are simply further explanation the features and advantages of the present invention, rather than to the claims in the present invention Limitation.

Illustrate the effect of the present invention with specific embodiment below, but protection scope of the present invention is not limited by following examples System.

Specific embodiment

The preparation of the compound Etimicin situ-gel eye drops of embodiment 1

Prescription：Etimicin Sulfate (in terms of Etimicin) 3.0g, pranoprofen 0.5g, PLURONICS F87 50g, marine alga Sugared 10g, disodium hydrogen phosphate 4.2g, lysine 3g, natrium adetate 0.3g, 2M citric acid solution and appropriate sodium hydroxide solution, Water for injection is settled to 1000ml.

Preparation technology：The PLURONICS F87 for weighing recipe quantity is placed in the beaker of 700ml waters for injection, is stirred to dissolve, The Etimicin Sulfate of recipe quantity, pranoprofen, lysine, trehalose, disodium hydrogen phosphate are taken respectively in 200ml waters for injection In beaker, it is stirred to dissolve, two solution is mixed, adjusts the pH value of solution in right amount with 2M citric acid solutions and sodium hydroxide solution For 6.8, water for injection is added to be settled to 1000ml, by above-mentioned decoction through 2 μm of filtering with microporous membrane, after measure is qualified, by 10ml/ bottles It is filling, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

The preparation of the compound Etimicin gel eye drops of embodiment 2

Prescription：Etimicin Sulfate (in terms of Etimicin) 3.0g, hydrocortisone sodium succinate 0.25g, Acritamer 940 6g, polyvinyl alcohol 2g, trehalose 3g, taurine 5g, benzalkonium bromide 0.01g, natrium adetate 0.3g, polyoxyethylene sorbitan monoleate 1g, 2M Citric acid solution and 2M sodium hydroxide solutions are appropriate, and water for injection is settled to 1000g.

Preparation technology：Take recipe quantity Acritamer 940 and polyvinyl alcohol in beaker, add water about 850ml, stand, make it Swelling, pH value is adjusted to obtain matrix to neutrality, take Etimicin Sulfate, hydrogenation respectively with 2M citric acid solutions and 2M sodium hydroxides It is miscible that cortisone sodium succinate, trehalose, taurine, benzalkonium bromide, Tween-80 add appropriate amount of water stirring to make, and is slowly added into Into above-mentioned matrix, stir, add water to 1000g, vacuum outgas, be sub-packed in 10g flexible pipes, 100 DEG C of 30min sterilizings, i.e., .

The sulfated compound Etimicin (S)-ibuprofen eye drops of embodiment 3

Preparation technology：1) sodium dihydrogen phosphate (anhydrous) and disodium hydrogen phosphate (anhydrous) for weighing recipe quantity are put into stainless steel cask In, and 1000ml water for injection is added thereto, while stirring is allowed to fully dissolve, gained homogeneous solution is put at room temperature Put；2) in 3000ml waters for injection, the PVP K30, Etimicin Sulfate, dextrorotation cloth of recipe quantity are sequentially added Ibuprofen L-arginine, polyquaternium -1, sodium chloride, stirring are allowed to dissolve；3) two kinds of solution are well mixed, use citric acid solution It is 6.7 with NaOH solution regulation pH, benefit adds to the full amount of water for injection；4) resulting solution of filtration step 3, filtrate is filled into 5ml In plastics eye droppings bottle, and seal, examine, labeling.

The sulfated compound Etimicin Tet eye drops of embodiment 4

Preparation technology：1) sodium dihydrogen phosphate and disodium hydrogen phosphate, sodium chloride for weighing recipe quantity are put into stainless steel cask, and 1000ml water for injection is added thereto, is stirred to dissolve simultaneously, gained homogeneous solution is placed at room temperature；2) in 3000ml In water for injection, PVP K30, Etimicin Sulfate, hydrochloric acid Tet, the polyquaternary amine of recipe quantity are sequentially added Salt -1, stirring are allowed to dissolve；3) two kinds of solution are well mixed, are with 1mol/L citric acid solution and NaOH solution regulation pH 6.6, benefit adds to the full amount of water for injection；4) resulting solution of filtration step 3, filtrate is filled into 5ml plastics eye droppings bottles, and it is close Envelope, examine, labeling.

The Etimicin Sulfate Benzydalysine eye drop of embodiment 5

Preparation technology：1) trehalose, sodium dihydrogen phosphate and disodium hydrogen phosphate for weighing recipe quantity are put into stainless steel cask, and 1000ml water for injection is added thereto, is stirred to dissolve simultaneously, gained homogeneous solution is placed at room temperature；2) in 3000ml In water for injection, PVP K30, Etimicin Sulfate, bendazac lysine, the polyquaternary amine of recipe quantity are sequentially added Salt -1, sodium chloride, are stirred to dissolve；3) two kinds of solution are well mixed, pH is adjusted with 1mol/L citric acid and NaOH solution For 6.5, benefit adds to the full amount of water for injection；4) resulting solution of filtration step 3, filtrate is filled into 5ml plastics eye droppings bottles, and it is close Envelope, examine, labeling.The preparation of the compound Etimicin unit dose package eye drops of embodiment 6

Prescription：Etimicin Sulfate (in terms of Etimicin) 3.0g, dextrorotation Ketorolac Tromethamine are (with dextrorotation ketorolac Meter) 1g, hydroxypropyl methylcellulose 5g, boric acid 0.8g, borax 1.2g, taurine 10g, trehalose 1g, appropriate sodium chloride, 2M citric acids Solution and appropriate sodium citrate solution, water for injection are settled to 1000ml, obtain decoction.

Preparation technology：Weigh the Etimicin Sulfate of recipe quantity, dextrorotation Ketorolac Tromethamine is placed in 200ml waters for injection Beaker in, be stirred to dissolve, take the taurine, boric acid, borax of recipe quantity to add 200ml waters for injection to dissolve, precision weighs place The hydroxypropyl methylcellulose just measured is dissolved in 500ml waters for injection, two kinds of solution is mixed, with citric acid solution and sodium citrate The pH value that solution adjusts solution in right amount is 7.0, and the osmotic pressure that solution is adjusted with appropriate sodium chloride is about 300mOsmol/k, is added Water for injection is settled to 1000ml, obtains decoction；By above-mentioned decoction through 0.65 μm of filtering with microporous membrane, then through 0.45 μm of miillpore filter Filtering；After the assay was approved, the filling above-mentioned decoctions of 0.3ml sealing, are got product decoction into 1ml unit dose package plastic containers. The sulfated compound Etimicin Diclofenac sodium gutta of embodiment 7

Prescription：Etimicin Sulfate 3g, C14H10Cl2NNaO2 1g, disodium hydrogen phosphate (anhydrous) 5g, PVP K30 10g, trehalose 3g, appropriate sodium chloride, polyquaternium -1 0.01g, 1mol/L citric acid or appropriate with NaOH solution, injection 1000ml is added to water

Preparation technology：1) disodium hydrogen phosphate for weighing recipe quantity is put into stainless steel cask, and adds 300ml note thereto Penetrate and use water, be stirred to dissolve.Gained homogeneous solution is placed at room temperature；2) in 600ml waters for injection, recipe quantity is sequentially added PVP K30, trehalose, Etimicin Sulfate, C14H10Cl2NNaO2, polyquaternium -1, stirring be allowed to dissolve；3) Two kinds of solution are well mixed, is 6.8 with citric acid solution and NaOH solution regulation pH, adds appropriate sodium chloride to adjust solution Osmotic pressure is about 300mOsmol/k, and benefit adds to the full amount of water for injection；4) resulting solution of filtration step 3, filtrate is filled into 5ml In plastics eye droppings bottle, and seal, examine, labeling.

Preparation (the specification of the sulfated compound Etimicin Diclofenac Potassium unit dose package eye drops of embodiment 8：0.25ml/ Branch)

Prescription：Etimicin Sulfate (in terms of Etimicin) 5.0g, Diclofenac Potassium 1g, trehalose 3.78g, biphosphate Sodium 2.4g, disodium hydrogen phosphate 6.6g, taurine 10g, appropriate sodium chloride, water for injection are settled to 1000ml.

Preparation technology：Etimicin Sulfate, Diclofenac Potassium, trehalose, sodium dihydrogen phosphate, the phosphorus of recipe quantity are weighed respectively Sour disodium hydrogen adds 900mL waters for injection to dissolve, and stirs, and the osmotic pressure that solution is adjusted with appropriate sodium chloride is about 300mOsmol/k, 1000mL is settled to water for injection, obtains decoction；By above-mentioned decoction through 0.45 μm of filtering with microporous membrane, decoction After the assay was approved, the above-mentioned decoctions of filling 0.25ml sealing, produce into 1ml unit dose package plastic containers.

The Etimicin Sulfate bromfenac sodium DL eye drops (specification of embodiment 9：5ml/ bottles)

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, the hydrate 0.3g of bromfenac sodium 1.5, hydroxypropyl methylcellulose 20g, taurine 5g, appropriate sodium chloride, the 0.01g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, 1M citric acid or and Appropriate NaOH solution, water for injection add to 1000ml

Preparation technology：1) Etimicin Sulfate of recipe quantity, the hydrate of bromfenac sodium 1.5 of micronizing, edetic acid(EDTA) are weighed Disodium, taurine, polyquaternium -1, hydroxypropyl methylcellulose are dissolved in 920ml waters for injection, and 0.45 μm of filtering with microporous membrane will Two kinds of solution mixing, pH value are adjusted to 6.6 with citric acid solution and NaOH solution, appropriate sodium chloride adjusts the osmotic pressure of solution About 300mOsmol/k, add water for injection to be settled to 1000ml, be distributed into 5ml plastics eye droppings bottles, and seal, examine, i.e. .

The sulfated compound Etimicin sodium bromophenolate eye drops of embodiment 10

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, the hydrate 0.5g of bromfenac sodium 1.5, Macrogol 4000 5g, VE succinic acid macrogol ester 2g, appropriate sodium chloride, trehalose 4g, xylitol 1g, the 0.01g of polyquaternium -1, second Sodium ethylene diamine tetracetate 0.1g, 1M citric acid are appropriate with NaOH solution, and water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate, the hydrate of bromfenac sodium 1.5, trehalose, the edetic acid(EDTA) two of recipe quantity are weighed Sodium, xylitol, polyquaternium -1, Macrogol 4000, VE succinic acid macrogol ester are dissolved in 800ml waters for injection, Stir, it is standby through 0.65 μm of filtering with microporous membrane；Citric acid solution and NaOH solution adjust pH value to 6.6, add appropriate The osmotic pressure of sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, liquid is filled and is distributed into In 5ml plastics eye droppings bottles, and seal, examine, produce.

The Etimicin Sulfate sodium bromophenolate eye drops of embodiment 11

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, the hydrate 1g of bromfenac sodium 1.5, Macrogol 6000 3g, VE succinic acid macrogol ester 5g, Taurine 5g, trehalose 3g, the 0.005g of polyquaternium -1, ethylenediamine tetra-acetic acid Sodium 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with NaOH solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of recipe quantity, the hydrate of bromfenac sodium 1.5, Macrogol 6000, ox are weighed Yellow acid, trehalose, natrium adetate, polyquaternium -1, VE succinic acid macrogol ester, are dissolved in 900ml waters for injection In, stir, 0.65 μm of filtering with microporous membrane；Citric acid solution and NaOH solution adjust pH value to 6.5, with appropriate chlorination The osmotic pressure of sodium regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, and liquid is filled and is distributed into 5ml modelings In shots eye bottle, and seal, examine, produce.

The sulfated compound Etimicin pranoprofen eye drop of embodiment 12

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, pranoprofen 1g, L-arginine 5g, gallic acid 1g, gather Vinylpyrrolidone K30 12g, appropriate sodium chloride or are fitted at polyquaternium -1 0.01g, 1mol/L citric acid with NaOH solution Amount, water for injection add to 1000ml

Preparation technology：Gallic acid, L-arginine, PVP K30, the pranoprofen of recipe quantity are weighed successively It is put into 900ml water for injection stainless steel keg, is stirred to dissolve, sequentially adds the Etimicin Sulfate of recipe quantity, gathers Quaternary ammonium salt -1, stirring are allowed to dissolve；It is 6.8 with 1mol/L citric acid and NaOH solution regulation pH, is adjusted with appropriate sodium chloride The osmotic pressure for saving solution is about 300mOsmol/k, and benefit adds to the full amount of water for injection；Resulting solution is filtered, filtrate is filled into 5ml In plastics eye droppings bottle, and seal, examine, labeling.

The Etimicin Sulfate suprofen eye drops of embodiment 13

Prescription：Sulfuric acid according to for rice (in terms of Etimicin) star 3g, suprofen 10g, lysine 6g, (2- hydroxyethyls)-β- Cyclodextrin 10g, Macrogol 6000 3g, VE succinic acid macrogol ester 5g, trehalose 3g, polyquaternium -1 0.005g, sodium ethylene diamine tetracetate 0.1g, appropriate sodium chloride, 1M citric acid or appropriate, the injection with citric acid three sodium solution Water adds to 1000ml

Preparation technology：1) Etimicin Sulfate of recipe quantity, Macrogol 6000, trehalose, natrium adetate, poly- is weighed Quaternary ammonium salt -1, VE succinic acid macrogol ester, are dissolved in 580ml waters for injection, take the suprofen of recipe quantity, rely ammonia Acid, (2- hydroxyethyls)-beta-schardinger dextrin in 350ml waters for injection, add appropriate citric acid three sodium solution, are stirred to dissolve, 0.65 μm of filtering with microporous membrane；Two solution are well mixed, citric acid or adjust pH value to 6.9 with citric acid three sodium solution, are fitted The osmotic pressure of the sodium chloride regulation solution of amount is about 300mOsmol/k, adds water for injection to be settled to 1000ml, liquid is filled and dispensed Enter in 5ml plastics eye droppings bottles, and seal, examine, produce.

The sulfated compound Etimicin Flurbiprofen eye drops of embodiment 14

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, the hydrate of flurbiprofen sodium 2 (in terms of flurbiprofen sodium) 0.3g, Macrogol 4000 5g, VE succinic acid macrogol ester 0.5g, sodium chloride 5.2g, trehalose 4g, xylitol 1g, the 0.01g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, 1M citric acid or appropriate with NaOH solution, water for injection adds To 1000ml

Preparation technology：1) weigh the Etimicin Sulfate of recipe quantity, the hydrate of flurbiprofen sodium 2, sodium chloride, trehalose, Natrium adetate, xylitol, polyquaternium -1, Macrogol 4000, VE succinic acid macrogol ester are dissolved in 900ml Water for injection, stir, through 0.45 μm of filtering with microporous membrane, adjust pH value to 6.8 with citric acid solution and NaOH solution, add Water for injection is settled to 1000ml, and liquid is filled and is distributed into 5ml plastics eye droppings bottles, and seals, examine, produce.

The preparation of the sodium eye drops of 15 sulfated compound Etimicin ophthalmic solution of embodiment four

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, ophthalmic solution four sodium 30g, trehalose 5g, boric acid 0.5g, Cys 1g, 1B 4g, sodium pantothenate 1g, the 0.01g of polyquaternium -1, appropriate sodium chloride, 1M L-ASPARTIC ACIDs are molten Appropriate liquid, 1M sodium hydroxide solutions are appropriate, and water for injection adds to 1000ml

Preparation technology：The trehalose of recipe quantity is taken to be added in the stainless steel keg of 900ml waters for injection, stirring and dissolving, Sequentially add the Etimicin Sulfate of recipe quantity, the sodium of ophthalmic solution four, boric acid, cysteine, 1B, sodium pantothenate, poly- season Ammonium salt -1, it is stirred to dissolve, stirs, pH value is adjusted to 6.7 with L-ASPARTIC ACID solution and sodium hydroxide solution, with appropriate chlorine The osmotic pressure for changing sodium regulation solution is about 295mOsmol/k, adds water to full dose, through 0.45 μm of miillpore filter pressure filtration, measure It is filling by 8ml/ bottles after qualified, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

Take 10 bottles of above-mentioned sample lucifuges to be placed in 25 DEG C or so of room temperature, 6 are placed in the environment of relative humidity 75% ± 5% Month, solution keeps clear and bright, and the pH value for determining solution is 6.7.

The preparation of the sodium eye drops of 16 sulfated compound Etimicin ophthalmic solution of embodiment four

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, ophthalmic solution four sodium 20g, trehalose 10g, boric acid 0.3g, Niacinamide 4g, L-ASPARTIC ACID 3g, the 0.006g of polyquaternium -1, appropriate sodium chloride, 1M L-ASPARTIC ACID solution is appropriate, 1M hydrogen Appropriate sodium hydroxide solution, water for injection add to 1000ml

Preparation technology：The trehalose of recipe quantity is taken to be added in the stainless steel keg of 900ml waters for injection, stirring and dissolving, The Etimicin Sulfate of recipe quantity, the sodium of ophthalmic solution four, boric acid, niacinamide, L-ASPARTIC ACID, polyquaternium -1 are sequentially added, It is stirred to dissolve, stirs, adjusts pH value to 6.7 with L-ASPARTIC ACID solution and sodium hydroxide solution, adjusted with appropriate sodium chloride The osmotic pressure for saving solution is about 295mOsmol/k, adds water to full dose, through 0.65 μm of miillpore filter pressure filtration, after measure is qualified, It is filling by 8ml/ bottles, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

The preparation of the sodium unit dose package eye drops of 17 sulfated compound Etimicin ophthalmic solution of embodiment four

Prescription：Etimicin Sulfate (in terms of Etimicin) 3.0g, the sodium 15g of ophthalmic solution four, trehalose 3.78g, phosphoric acid Sodium dihydrogen 1.4g, disodium hydrogen phosphate 1.6g, taurine 5g, appropriate sodium chloride, water for injection are settled to 1000ml.

Preparation technology：Weigh respectively the Etimicin Sulfate of recipe quantity, the sodium of ophthalmic solution four, trehalose, sodium dihydrogen phosphate, Disodium hydrogen phosphate adds in the stainless steel keg of 900mL waters for injection, stirring and dissolving, after stirring, is adjusted with appropriate sodium chloride The osmotic pressure for saving solution is about 300mOsmol/k, is settled to 1000mL with water for injection, obtains decoction；By above-mentioned decoction through 0.65 μ M filtering with microporous membrane, after the assay was approved, the filling above-mentioned decoctions of 0.25ml are into 1ml unit dose package plastic containers, envelope for decoction Mouthful, produce.

The preparation of the sodium eye drops of 18 Etimicin ophthalmic solution of embodiment four

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, ophthalmic solution four sodium 10g, trehalose 10g, Boratex 2g, L MALIC ACID 1g, DL-Lys 4g, the 0.006g of polyquaternium -1, appropriate sodium chloride, 1M L-ASPARTIC ACID solution is appropriate, 1M Appropriate sodium hydroxide solution, water for injection add to 1000ml

Preparation technology：The trehalose of recipe quantity is taken to be added in the stainless steel keg of 900ml waters for injection, stirring and dissolving, Sequentially add the Etimicin Sulfate of recipe quantity, the sodium of ophthalmic solution four, Boratex, L MALIC ACID, DL-Lys, polyquaternium- 1, it is stirred to dissolve, stirs, pH value is adjusted to 6.7 with L-ASPARTIC ACID solution and sodium hydroxide solution, with appropriate sodium chloride The osmotic pressure for adjusting solution is about 295mOsmol/k, adds water to full dose, qualified through 0.65 μm of miillpore filter pressure filtration, measure Afterwards, it is filling by 8ml/ bottles, sealing, 121 DEG C of sterilizings, let cool, examine, packaging.

The preparation of the Etimicin lifitegrast eye drops of embodiment 19

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, lifitegrast 50g, trehalose 5g, 1B 10g, sodium citrate 2g, polyquaternium -1 0.006g, 1M L-ASPARTIC ACID solution is appropriate, and 1M sodium hydroxide solutions are appropriate, note Penetrate and add to 1000ml with water

Preparation technology：The trehalose of recipe quantity is taken to be added in the stainless steel keg of 900ml waters for injection, stirring and dissolving, Sequentially add Etimicin Sulfate, lifitegrast, lysine, sodium citrate, polyquaternium -1, the appropriate hydrogen of recipe quantity Sodium hydroxide solution, it is stirred to dissolve, stirs, adjusts pH value to 6.9 with L-ASPARTIC ACID solution and sodium hydroxide solution, add water to Full dose, it is filling by 8ml/ bottles after measure is qualified through 0.65 μm of miillpore filter pressure filtration, sealing, 121 DEG C of sterilizings, let cool, examine Test, pack.

The preparation of the Etimicin Sulfate lifitegrast eye drops of embodiment 20

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, lifitegrast 40g, trehalose 1g, Cys 1g, L-arginine 10g, tromethamine 5g, polyquaternium -1 0.006g, 1M L-aminobutanedioic acid solution is appropriate, 1M sodium hydroxide solutions In right amount, water for injection adds to 1000ml

Preparation technology：The trehalose of recipe quantity is taken to be added in the stainless steel keg of 900ml waters for injection, stirring and dissolving, Sequentially add the Etimicin Sulfate of recipe quantity, lifitegrast, cysteine, L-arginine, tromethamine, polyquaternium- 1st, appropriate sodium hydroxide solution, is stirred to dissolve, stirring, with L-aminobutanedioic acid solution and sodium hydroxide solution adjust pH value to 7.0, full dose is added water to, filling by 8ml/ bottles after measure is qualified through 0.65 μm of miillpore filter pressure filtration, sealing, 121 DEG C go out Bacterium, let cool, examine, packaging.

The preparation of the Etimicin lifitegrast unit dose package eye drops of embodiment 21

Prescription：Etimicin (in terms of Etimicin) 3g, lifitegrast 30g, trehalose 6g, lysine 10g, nicotinoyl Amine 2g, 2M citric acid solution and appropriate sodium citrate solution, water for injection 400ml, pH6.81 Sharpe phosphate buffer are determined Hold to 1000ml.

Preparation technology：The Etimicin Sulfate of recipe quantity, lifitegrast, lysine, niacinamide, marine alga are weighed respectively Sugar, proper amount of sodium citrate solution add in the stainless steel keg of 800ml waters for injection, stirring and dissolving, with 2M citric acid solutions and lemon The pH value that lemon acid sodium solution adjusts solution in right amount is that about 6.8, Jia Shashi phosphate buffers are settled to 1000ml, obtains decoction；Will Above-mentioned decoction is through 0.8 μm of filtering with microporous membrane, and decoction after the assay was approved, mould by the filling above-mentioned decoctions of 0.3ml to 1ml unit dose packages In material container, sealing, produce.

The preparation of the Etimicin lifitegrast unit dose package eye drops of embodiment 22

Prescription：Etimicin (in terms of Etimicin) 3g, lifitegrast 25g, trehalose 3g, borax 2.6g, ammonia fourth Triol 10g, appropriate sodium chloride, 2M citric acid solutions and appropriate sodium citrate solution, water for injection are settled to 1000ml.

Preparation technology：The Etimicin for weighing recipe quantity is placed in the beaker of 200ml waters for injection, adds appropriate citric acid Solution, makes dissolving, takes tromethamine, lifitegrast, trehalose, borax, the proper amount of sodium citrate solution of recipe quantity to add respectively In the stainless steel keg of 800ml waters for injection, it is stirred to dissolve, two solution is mixed, with 2M citric acid solutions and sodium citrate The pH value that solution adjusts solution in right amount is about 6.9, and the osmotic pressure that solution is adjusted with appropriate sodium chloride is about 300mOsmol/k, Add water for injection to be settled to 1000ml, obtain decoction；Above-mentioned decoction after the assay was approved, is filled through 0.8 μm of filtering with microporous membrane, decoction The above-mentioned decoctions of 0.4ml are filled into 1ml unit dose package plastic containers, sealing, are got product.

Preparation (the specification of the Etimicin lifitegrast unit dose package eye drops of embodiment 23：0.25ml/ branch)

Prescription：Etimicin Hydrochloride (in terms of Etimicin) 3.0g, lifitegrast 10g, Sodium Hyaluronate 1g, borax 2.0g, methionine 1g, tromethamine 6g, trehalose 3g, appropriate sodium chloride, 2M citric acid solutions and sodium citrate solution are fitted Amount, water for injection are settled to 1000ml.

Preparation technology：Take the Sodium Hyaluronate of recipe quantity be added in the stainless steel keg of 900ml waters for injection heat it is molten Solution is let cool, weigh respectively successively the Etimicin Hydrochloride of recipe quantity, tromethamine, methionine, lifitegrast, trehalose, Borax, proper amount of sodium citrate solution are added in above-mentioned solution, are stirred to dissolve, then molten with 2M citric acid solutions and sodium citrate The pH value that liquid adjusts solution in right amount is about 6.8, and the osmotic pressure of appropriate sodium chloride regulation solution is about 305mOsmol/k, filling Penetrate and be settled to 1000ml with water, obtain decoction；By above-mentioned decoction through 2 μm of filtering with microporous membrane, the filling above-mentioned decoctions of 0.25ml to 1ml In unit dose package plastic containers, sealing, produce.

The sulfated compound Etimicin eye drops of embodiment 24

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Loteprednol etabonate 5g, lifitegrast 20g, gather The 3g of ethylene glycol 4000, VE succinic acid macrogol ester 2g, trehalose 4g, Polyquaternium-10 .01g, ethylenediamine tetra-acetic acid Sodium 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with NaOH solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of recipe quantity, trehalose, natrium adetate, polyquaternium -1, poly- second are weighed Glycol 4000, VE succinic acid macrogol ester are stirred to dissolve, through 1 μ in the stainless steel keg of 850ml waters for injection M filtering with microporous membrane, it is standby；2) Loteprednol etabonate and lifitegrast of the micronizing of recipe quantity are weighed, is suspended in 100ml waters for injection, adding citric acid and NaOH solution adjust pH value to 6.9, and high-shearing dispersion emulsifying machine shears 10min (1000r/min), suspension is prepared into, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, it is molten with citric acid solution and NaOH Liquid adjusts pH value to 6.9, and the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection constant volume To 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 2.5ml plastics eye droppings bottles, and seals, examine Test, produce.

The sulfated compound Etimicin eye drops of embodiment 25

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Loteprednol etabonate 2g, lifitegrast 30g, gather The 3g of ethylene glycol 4000, VE succinic acid macrogol ester 2g, trehalose 4g, Polyquaternium-10 .01g, ethylenediamine tetra-acetic acid Sodium 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with NaOH solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of recipe quantity, trehalose, natrium adetate, polyquaternium -1, poly- second are weighed Glycol 4000, VE succinic acid macrogol ester are stirred to dissolve, through 1 μ in the stainless steel keg of 720ml waters for injection M filtering with microporous membrane, it is standby；2) Loteprednol etabonate and lifitegrast of the micronizing of recipe quantity are weighed, is suspended in 200ml waters for injection, pH value are adjusted to 6.8 with NaOH solution and citric acid solution, high-shearing dispersion emulsifying machine shears 10min (1200r/min), is prepared into suspension；3) 2) liquid is transferred to 1) liquid, stirs 10min, adjusted with citric acid solution and NaOH solution PH value is saved to 6.8, the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 2.5ml plastics eye droppings bottles, and seal, examine, Produce.

The sulfated compound Etimicin eye drops of embodiment 26

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Loteprednol etabonate 1g, lifitegrast 50g, gather The 3g of ethylene glycol 4000, VE succinic acid macrogol ester 2g, trehalose 4g, Polyquaternium-10 .01g, ethylenediamine tetra-acetic acid Sodium 0.1g, 2M citric acid are appropriate with 2M NaOH solution, and water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of recipe quantity, trehalose, natrium adetate, polyquaternium -1, poly- second are weighed Glycol 4000, VE succinic acid macrogol ester are stirred to dissolve, through 1 μ in the stainless steel keg of 700ml waters for injection M filtering with microporous membrane, it is standby；2) Loteprednol etabonate and lifitegrast of the micronizing of recipe quantity are weighed, is suspended in 200ml waters for injection, pH value are adjusted to 6.8 with NaOH solution and citric acid solution, high-shearing dispersion emulsifying machine shears 10min (1000r/min), suspension is prepared into, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, it is molten with citric acid solution and NaOH Liquid adjusts pH value to 6.9, adds water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and dispensed Enter in 2.5ml plastics eye droppings bottles, and seal, examine, produce.

The sulfated compound Etimicin eye drops of embodiment 27

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Loteprednol etabonate 2.5g, lifitegrast50g, Macrogol 4000 3g, VE succinic acid macrogol ester 2g, trehalose 4g, the 0.01g of polyquaternium -1, ethylenediamine tetraacetic Sodium acetate 0.1g, appropriate sodium chloride, 2M citric acid or appropriate with 2M NaOH solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of recipe quantity, lifitegrast, trehalose, natrium adetate, poly- is weighed Quaternary ammonium salt -1, Macrogol 4000, VE succinic acid macrogol ester stir in the stainless steel keg of 800ml waters for injection Mixing makes dissolving, standby through 1 μm of filtering with microporous membrane；2) Loteprednol etabonate of the micronizing of recipe quantity is weighed, is suspended in 100ml waters for injection, with citric acid solution regulation pH value to 6.6, high-shearing dispersion emulsifying machine shears 10min (1200r/min), Suspension is prepared into, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, with citric acid solution and NaOH solution adjust pH value to 6.6, the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, height is cut Dispersion emulsifying machine shearing 10min is cut, liquid is filled and is distributed into 2.5ml plastics eye droppings bottles, and seals, examine, produce.

The sulfated compound Etimicin eye drops of embodiment 28

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, desonide 0.5g, the sodium 15g of ophthalmic solution four, polyethylene glycol 4000 3g, VE succinic acid macrogol ester 2g, trehalose 4g, Polyquaternium-10 .01g, sodium ethylene diamine tetracetate 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with sodium citrate solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of the recipe quantity, sodium of ophthalmic solution four, trehalose, natrium adetate, poly- is weighed Quaternary ammonium salt -1, Macrogol 4000, VE succinic acid macrogol ester stir in the stainless steel keg of 800ml waters for injection Mixing makes dissolving, standby through 1 μm of filtering with microporous membrane；2) desonide of the micronizing of recipe quantity is weighed, is suspended in 100ml injections With water, pH value is adjusted to 6.6 with citric acid or with sodium citrate solution, high-shearing dispersion emulsifying machine shears 10min (1200r/ Min), suspension is prepared into, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, citric acid or adjusted with sodium citrate solution For pH value to 6.6, the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 2.5ml plastics eye droppings bottles, and seals, examine Test, produce.

The sulfated compound Etimicin eye drops of embodiment 29

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, desonide 0.5g, the sodium 30g of ophthalmic solution four, polyethylene glycol 4000 3g, VE succinic acid macrogol ester 2g, trehalose 4g, Polyquaternium-10 .01g, sodium ethylene diamine tetracetate 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with NaOH solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of the recipe quantity, sodium of ophthalmic solution four, trehalose, natrium adetate, poly- is weighed Quaternary ammonium salt -1, Macrogol 4000, VE succinic acid macrogol ester stir in the stainless steel keg of 800ml waters for injection Mixing makes dissolving, standby through 1 μm of filtering with microporous membrane；2) desonide of the micronizing of recipe quantity is weighed, is suspended in 100ml injections With water, pH value is adjusted to 6.6 with NaOH solution and citric acid solution, high-shearing dispersion emulsifying machine shears 10min (1200r/ Min), suspension is prepared into, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, adjusted with citric acid solution and NaOH solution For pH value to 6.6, the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 2.5ml plastics eye droppings bottles, and seal, examine, Produce.

The sulfated compound Etimicin eye drops of embodiment 30

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Loteprednol etabonate 5g, the sodium 30g of ophthalmic solution four, gather The 3g of ethylene glycol 4000, VE succinic acid macrogol ester 2g, trehalose 4g, the 0.01g of polyquaternium -1, ethylenediamine tetrem Sour sodium 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with NaOH solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of the recipe quantity, sodium of ophthalmic solution four, trehalose, natrium adetate, poly- is weighed Quaternary ammonium salt -1, Macrogol 4000, VE succinic acid macrogol ester stir in the stainless steel keg of 750ml waters for injection Mixing makes dissolving, standby through 1 μm of filtering with microporous membrane；2) Loteprednol etabonate of the micronizing of recipe quantity is weighed, is suspended in 150ml waters for injection, pH value are adjusted to 6.8 with NaOH solution and citric acid solution, high-shearing dispersion emulsifying machine shears 10min (1200r/min), suspension is prepared into, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, it is molten with citric acid solution and NaOH Liquid adjusts pH value to 6.8, and the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection constant volume To 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 2.5ml plastics eye droppings bottles, and seals, examine Test, produce.

The sulfated compound Etimicin eye drops of embodiment 31

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Loteprednol etabonate 5g, the sodium 20g of ophthalmic solution four, gather The 3g of ethylene glycol 4000, VE succinic acid macrogol ester 2g, trehalose 4g, the 0.01g of polyquaternium -1, ethylenediamine tetrem Sour sodium 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with sodium citrate solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of the recipe quantity, sodium of ophthalmic solution four, trehalose, natrium adetate, poly- is weighed Quaternary ammonium salt -1, Macrogol 4000, VE succinic acid macrogol ester stir in the stainless steel keg of 720ml waters for injection Mixing makes dissolving, standby through 1 μm of filtering with microporous membrane；2) Loteprednol etabonate of the micronizing of recipe quantity is weighed, is suspended in 200ml waters for injection, citric acid or adjust pH value to 6.2 with sodium citrate solution, high-shearing dispersion emulsifying machine shearing 10min (1200r/min), suspension is prepared into, it is standby；3) 2) liquid is transferred to 1) liquid, 10min is stirred, with citric acid or and sodium citrate Solution adjusts pH value to 6.6, and the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to determine Hold to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 2.5ml plastics eye droppings bottles, and seal, Examine, produce.

The sulfated compound Etimicin eye drops of embodiment 32

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Loteprednol etabonate 2.5g, the sodium 30g of ophthalmic solution four, Macrogol 4000 3g, VE succinic acid macrogol ester 2g, trehalose 4g, the 0.01g of polyquaternium -1, ethylenediamine tetraacetic Sodium acetate 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with sodium citrate solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of the recipe quantity, sodium of ophthalmic solution four, trehalose, natrium adetate, poly- is weighed Quaternary ammonium salt -1, Macrogol 4000, VE succinic acid macrogol ester stir in the stainless steel keg of 700ml waters for injection Mixing makes dissolving, standby through 1 μm of filtering with microporous membrane；2) Loteprednol etabonate of the micronizing of recipe quantity is weighed, is suspended in 200ml waters for injection, pH value are adjusted to 6.6 with citric acid or with sodium citrate solution, high-shearing dispersion emulsifying machine shears 10min (1200r/min), Loteprednol etabonate suspension is prepared into, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, use lemon Acid adjusts pH value to 6.6 with sodium citrate solution, and the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/ K, add water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 2.5ml plastics point In eye bottle, and seal, examine, produce.

The sulfated compound Etimicin eye drops of embodiment 33

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, fluorometholone 1g, the sodium 30g of ophthalmic solution four, polyethylene glycol 4000 3g, VE succinic acid macrogol ester 2g, trehalose 4g, Polyquaternium-10 .01g, sodium ethylene diamine tetracetate 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with NaOH solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of the recipe quantity, sodium of ophthalmic solution four, trehalose, natrium adetate, poly- is weighed Quaternary ammonium salt -1, Macrogol 4000, VE succinic acid macrogol ester stir in the stainless steel keg of 720ml waters for injection Mixing makes dissolving, standby through 1 μm of filtering with microporous membrane；2) fluorometholone of the micronizing of recipe quantity is weighed, is suspended in 200ml injections With water, pH value is adjusted to 6.2 with citric acid solution, high-shearing dispersion emulsifying machine shearing 10min (1200r/min), is prepared into fluorine The imperial suspension of rice, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, add dilute citric acid solution and NaOH solution adjust pH value to 6.6, the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, height is cut Dispersion emulsifying machine shearing 10min is cut, liquid is filled and is distributed into 2.5ml plastics eye droppings bottles, and seals, examine, produce.

The sulfated compound Etimicin eye drops of embodiment 34

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, fluorometholone 0.5g, the sodium 30g of ophthalmic solution four, polyethylene glycol 4000 3g, VE succinic acid macrogol ester 2g, trehalose 4g, Polyquaternium-10 .01g, sodium ethylene diamine tetracetate 0.1g, appropriate sodium chloride, 2M citric acid or appropriate with NaOH solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of the recipe quantity, sodium of ophthalmic solution four, trehalose, natrium adetate, poly- is weighed Quaternary ammonium salt -1, Macrogol 4000, VE succinic acid macrogol ester stir in the stainless steel keg of 750ml waters for injection Mixing makes dissolving, standby through 1 μm of filtering with microporous membrane；2) fluorometholone of the micronizing of recipe quantity is weighed, is suspended in 150ml injections With water, adding citric acid solution adjusts pH value to 6.6, high-shearing dispersion emulsifying machine shearing 10min (1200r/min), is prepared into fluorine The imperial suspension of rice, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, with citric acid solution and NaOH solution adjust pH value to 6.6, the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, height is cut Dispersion emulsifying machine shearing 10min is cut, liquid is filled and is distributed into 2.5ml plastics eye droppings bottles, and seals, examine, produce.

The sulfated compound Etimicin eye drops of embodiment 35

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, fluorometholone 1g, the sodium 15g of ophthalmic solution four, polyethylene glycol 4000 2g, VE succinic acid macrogol ester 2g, trehalose 4g, the 0.01g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, appropriate sodium chloride, 2M citric acid or appropriate with sodium citrate solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate of the recipe quantity, sodium of ophthalmic solution four, trehalose, natrium adetate, poly- is weighed Quaternary ammonium salt -1, Macrogol 4000, VE succinic acid macrogol ester stir in the stainless steel keg of 720ml waters for injection Mixing makes dissolving, standby through 1 μm of filtering with microporous membrane；2) fluorometholone of the micronizing of recipe quantity is weighed, is suspended in 200ml injections With water, pH value is adjusted to 6.7, high-shearing dispersion emulsifying machine shearing 10min (1200r/min) with citric acid or with sodium citrate, Fluor-Op is prepared into, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, adjusted with citric acid or with sodium citrate solution PH value is saved to 6.7, the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 2.5ml plastics eye droppings bottles, and seal, examine, Produce.

The Etimicin Sulfate fluorometholone eye drops of embodiment 36

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, fluorometholone 1g, hydroxypropyl methylcellulose 3g, tocopheryl succinate Acid polyethylene glycol ester 2g, appropriate sodium chloride, the 0.01g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, 1M citric acid or and Appropriate sodium citrate solution, water for injection add to 1000ml

Preparation technology：1) Etimicin Sulfate, natrium adetate, polyquaternium -1, the hypromellose of recipe quantity are weighed Element, VE succinic acid macrogol ester are dissolved in the beaker of 720ml waters for injection, and 0.45 μm of filtering with microporous membrane is standby With；2) fluorometholone of the micronizing of recipe quantity is weighed, is suspended in the beaker of 200ml waters for injection, citric acid or and citric acid Sodium adjusts pH value to 6.5, and high-shearing dispersion emulsifying machine shears 15min (1200r/min), is prepared into Fluor-Op, standby； 3) 2) liquid is transferred to 1) liquid, stirs 10min, adjusted pH value to 6.6 with citric acid or with sodium citrate solution, add appropriate chlorination The osmotic pressure of sodium regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 5ml plastics eye droppings bottles, and sealed, examine, produce.

The Etimicin Sulfate fluorometholone eye drops of embodiment 37

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, fluorometholone 0.5g, hydroxypropyl methylcellulose 5g, vitamin E amber Amber acid polyethylene glycol ester 2g, appropriate sodium chloride, the 0.01g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, 1M citric acid or Appropriate with sodium citrate solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate, natrium adetate, polyquaternium -1, the hypromellose of recipe quantity are weighed Element, VE succinic acid macrogol ester are dissolved in the beaker of 720ml waters for injection, and 0.45 μm of filtering with microporous membrane is standby With；2) fluorometholone of the micronizing of recipe quantity is weighed, is suspended in the beaker of 200ml waters for injection, with citric acid or and lemon Sour sodium adjusts pH value to 6.5, and high-shearing dispersion emulsifying machine shears 15min (1200r/min), is prepared into Fluor-Op, standby With；3) 2) liquid is transferred to 1) liquid, stirs 10min, adjusted pH value to 6.6 with citric acid or with sodium citrate solution, add appropriate The osmotic pressure of sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine 10min is sheared, liquid is filled and is distributed into 5ml plastics eye droppings bottles, and seals, examine, produce.

The Etimicin Sulfate fluorometholone eye drops of embodiment 38

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, fluorometholone 1g, hydroxypropyl methylcellulose 3g, tocopheryl succinate Acid polyethylene glycol ester 2g, appropriate sodium chloride, the 0.01g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, 2M citric acid or and Appropriate sodium citrate solution, water for injection add to 1000ml

Preparation technology：1) Etimicin Sulfate, natrium adetate, polyquaternium -1, the hypromellose of recipe quantity are weighed Element, VE succinic acid macrogol ester are dissolved in the beaker of 720ml waters for injection, and 0.45 μm of filtering with microporous membrane is standby With；2) fluorometholone of the micronizing of recipe quantity is weighed, is suspended in the beaker of 200ml waters for injection, citric acid or and citric acid Sodium solution adjusts pH value to 6.5, high-shearing dispersion emulsifying machine shearing 15min (1200r/min), is prepared into Fluor-Op, It is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, citric acid or adjust pH value to 6.6 with sodium citrate solution, added appropriate The osmotic pressure of sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine 10min is sheared, liquid is filled and is distributed into 5ml plastics eye droppings bottles, and seals, examine, produce.

The Etimicin Sulfate Rimexolone eye drops of embodiment 39

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Rimexolone 0.5g, hydroxypropyl methylcellulose 10g, vitamin E butanedioic acid macrogol ester 2g, appropriate sodium chloride, the 0.01g of polyquaternium -1, sodium ethylene diamine tetracetate 0.1g, 1M citric acid Or it is appropriate with sodium citrate solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate, natrium adetate, polyquaternium -1, the hypromellose of recipe quantity are weighed Element, VE succinic acid macrogol ester are dissolved in the beaker of 720ml waters for injection, and 2 μm of filtering with microporous membrane are standby；2) The Rimexolone of the micronizing of recipe quantity is weighed, is suspended in the beaker of 200ml waters for injection, citric acid or molten with sodium citrate Liquid adjusts pH value to 6.5, and high-shearing dispersion emulsifying machine shears 15min (1200r/min), is prepared into Rimexolone liquid, standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, citric acid or adjusts pH value to 6.5 with sodium citrate solution, adds appropriate sodium chloride to adjust The osmotic pressure for saving solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 5ml plastics eye droppings bottles, and sealed, examine, produce.

The Etimicin Sulfate hydrocortisone eye drops of embodiment 40

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, hydrocortisone acetate 25g, hydroxypropyl methylcellulose 15g, Tween-80 0.5g, VE succinic acid macrogol ester 2g, appropriate sodium chloride, the 0.01g of polyquaternium -1, ethylenediamine tetrem Sour sodium 0.1g, 2M citric acid or appropriate with sodium citrate solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate, natrium adetate, polyquaternium -1, the hypromellose of recipe quantity are weighed Element, Tween-80, VE succinic acid macrogol ester, are dissolved in the beaker of 700ml waters for injection, 0.45 μm of miillpore filter Filtering, it is standby；2) weigh the hydrocortisone acetate of the micronizing of recipe quantity, be suspended in 200ml waters for injection, citric acid or and Sodium citrate solution adjusts pH value to 6.5, high-shearing dispersion emulsifying machine shearing 15min (1000r/min), is prepared into acetic acid hydrogenation Cortisone suspension, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, citric acid or with sodium citrate solution adjust pH value to 6.5, the osmotic pressure for adding appropriate sodium chloride regulation solution is about 300mOsmol/k, adds water for injection to be settled to 1000ml, height is cut Dispersion emulsifying machine shearing 10min is cut, mixed rotary liquid is filled and is distributed into 5ml plastics eye droppings bottles, and seals, examine, produce.

The compound hydrochloric acid Etimicin eye drops of embodiment 41

Prescription：Etimicin Hydrochloride (in terms of Etimicin) 3g, betamethasone valerate 0.5g, Macrogol 4000 3g, dimension Raw plain E butanedioic acids macrogol ester 2g, trehalose 4g, xylitol 1g, Polyquaternium-10 .01g, sodium ethylene diamine tetracetate 0.1g, Sodium chloride and appropriate potassium chloride, 1M citric acid or appropriate with sodium citrate solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Hydrochloride of recipe quantity, trehalose, natrium adetate, xylitol, polyquaternary amine are weighed Salt -1, Macrogol 4000, VE succinic acid macrogol ester are dissolved in the beaker of 730ml waters for injection, and stirring is equal It is even, it is standby through 1 μm of filtering with microporous membrane；2) betamethasone valerate of the micronizing of recipe quantity is weighed, is suspended in 200ml injections With in the beaker of water, citric acid or pH value is adjusted to 6.6 with sodium citrate solution, high-shearing dispersion emulsifying machine shearing 10min (1200r/min), betamethasone valerate suspension is prepared into, it is standby；3) 2) liquid is transferred to 1) liquid, stirs 10min, citric acid or PH value is adjusted to 6.6 with sodium citrate solution, adds appropriate sodium chloride and potassium chloride adjusts the osmotic pressure of solution and is about 300mOsmol/k, add water for injection to be settled to 1000ml, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into In 2.5ml plastics eye droppings bottles, and seal, examine, produce.

The sulfated compound Etimicin eye drops of embodiment 42

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Loteprednol etabonate 5g, PVP K30 6g, VE succinic acid macrogol ester 3g, trehalose 4g, xylitol 2g, the 0.01g of polyquaternium -1, ethylenediamine tetra-acetic acid Sodium 0.1g, appropriate sodium chloride, 1M citric acid or appropriate with sodium citrate solution, water for injection adds to 1000ml

Preparation technology：1) Etimicin Sulfate, trehalose, natrium adetate, xylitol, the polyquaternary amine of recipe quantity are weighed Salt -1, PVP K30, VE succinic acid macrogol ester are dissolved in the beaker of 730ml waters for injection, are stirred Mix uniformly, it is standby through 2 μm of filtering with microporous membrane；2) Loteprednol etabonate of the micronizing of recipe quantity is weighed, is suspended in In the beaker of 200ml waters for injection, citric acid or with sodium citrate solution adjust pH value to 6.6, high-shearing dispersion emulsifying machine is cut 10min (1200r/min) is cut, is prepared into Loteprednol etabonate suspension, it is standby；3) 2) liquid is transferred to 1) liquid, stirred 10min, citric acid or with sodium citrate solution adjust pH value to 6.8, add water for injection to be settled to 1000ml, add appropriate chlorination The osmotic pressure of sodium regulation solution is about 300mOsmol/k, high-shearing dispersion emulsifying machine shearing 10min, liquid is filled and is distributed into 5ml In plastics eye droppings bottle, and seal, examine, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 43

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, hydrocortisone acetate 0.1g, natrium adetate 0.2g, 95% ethanol 500ml, glycerine 350ml, water for injection add to 1000ml.

Preparation technology：Take hydrocortisone acetate in 95%300ml ethanol in beaker, add glycerine and stir evenly and dissolve to obtain A Liquid；Take Etimicin Sulfate and natrium adetate to be placed in about 50ml water, make to dissolve to obtain B liquid；B liquid is poured into A liquid, with a small amount of Water for injection drip wash holds the utensil of B liquid, and washing lotion is poured into A liquid, stirred evenly, adds water to full dose, is stirred evenly, through 2 μm of miillpore filters Filtering, it is filling by 8ml/ bottles after measure is qualified, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 44

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, hydrocortisone acetate 1g, taurine 3g, edetic acid(EDTA) two Sodium 0.2g, 95% ethanol 500ml, glycerine 350ml, water for injection add to 1000ml.

Preparation technology：Hydrocortisone acetate is taken in the beaker of 95%300ml ethanol, glycerine is added and stirs evenly to obtain A liquid；Take Etimicin Sulfate, taurine and natrium adetate are placed in about 50ml water, make to dissolve to obtain B liquid；B liquid is poured into A liquid, with less Amount water for injection drip wash holds the utensil of B liquid, and washing lotion is poured into A liquid, stirred evenly, is added to the full amount of water for injection, is stirred evenly, through 2 μm Filtering with microporous membrane, it is filling by 8ml/ bottles after measure is qualified, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 45

Prescription：Etimicin Sulfate (in terms of Etimicin) 2g, hydrocortisone 0.25g, Tween-80 1g, edetic acid(EDTA) two Sodium 0.2g, ethanol 450ml, glycerine 350ml, water for injection add to 1000ml.

Preparation technology：Take Tween-80, hydrocortisone to be dissolved in the beaker of ethanol and glycerine, stir evenly to obtain A liquid；Take sulfuric acid Etimicin and natrium adetate are placed in about 200ml purified waters, make to dissolve to obtain B liquid；B liquid is poured into A liquid, with a small amount of injection The utensil of B liquid is held with water drip wash, washing lotion is poured into A liquid, stirred evenly, adds water to full dose, is stirred evenly, through 2 μm of filtering with microporous membrane, Determine it is qualified after, it is filling by 8ml/ bottles, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 46

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, betamethasone sodium phosphate 1g, natrium adetate 0.2g, third Glycol 50ml, glycerine 300ml, water 200ml, 70% ethanol add to 1000ml.

Preparation technology：Take Etimicin Sulfate, betamethasone sodium phosphate, natrium adetate to be dissolved in 200ml water respectively, add Enter propane diols, glycerine stirs evenly, after being cooled to room temperature, add 70% ethanol to stir evenly to scale, through 0.45 μm of filtering with microporous membrane, measure It is filling by 8ml/ bottles after qualified, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 47

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, betamethasone sodium phosphate 0.25g, natrium adetate 0.2g, Propane diols 50ml, glycerine 300ml, water 200ml, 70% ethanol add to 1000ml.

Preparation technology：Etimicin Sulfate, betamethasone sodium phosphate, natrium adetate is taken to be dissolved in the burning of 200ml water respectively In cup, addition propane diols, glycerine stir evenly, and after being cooled to room temperature, add 70% ethanol to be stirred evenly, through 0.45 μm of miillpore filter mistake to scale Filter, it is filling by 8ml/ bottles after measure is qualified, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 48

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, momestasone furoate 1g, tocopheryl succinate acid polyethylene glycol Ester 6g, natrium adetate 0.2g, ethanol 360ml, glycerine 400ml, water for injection add to 1000ml.

Preparation technology：The Etimicin Sulfate, VE succinic acid macrogol ester, edetic acid(EDTA) two of recipe quantity are taken respectively Sodium is dissolved in the beaker of 200ml water, takes the momestasone furoate, glycerine, ethanol of recipe quantity to be stirred evenly in beaker, by above-mentioned two liquid Mix, add to the full amount of water for injection, stir evenly, it is filling by 8ml/ bottles after measure is qualified, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 49

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, fluticasone propionate 0.5g, the poly- second of VE succinic acid Diol ester 3g, natrium adetate 0.2g, ethanol 350ml, glycerine 400ml, water for injection add to 1000ml.

Preparation technology：Etimicin Sulfate, VE succinic acid macrogol ester, natrium adetate is taken to be dissolved in respectively In the beaker of 200ml water；The fluticasone propionate, glycerine, ethanol of recipe quantity is taken to be stirred evenly in beaker, by above two solution Mix, add to the full amount of water for injection, stir evenly, it is filling by 8ml/ bottles, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 50

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, fluticasone propionate 0.5g, the poly- second of VE succinic acid Diol ester 10g, natrium adetate 0.2g, ethanol 350ml, glycerine 400ml, water for injection add to 1000ml.

Preparation technology：Etimicin Sulfate, VE succinic acid macrogol ester, natrium adetate is taken to be dissolved in respectively In the beaker of 200ml water；Take the fluticasone propionate, glycerine, ethanol of recipe quantity to be stirred evenly in beaker, above-mentioned two liquid mixed, Add to the full amount of water for injection, stir evenly, it is filling by 5ml/ bottles, sealing, produce.The sulfated compound Etimicin auristilla of embodiment 51 Prepare

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, clobetasol propionate 0.2g, the poly- second of VE succinic acid Diol ester 5g, Tween-80 0.5g, niacinamide 2g, natrium adetate 0.2g, ethanol 400ml, glycerine 450ml, water for injection add To 1000ml.

Preparation technology：Take respectively Etimicin Sulfate, VE succinic acid macrogol ester, Tween-80, niacinamide, according to Ground acid disodium is dissolved in the beaker of 100ml water；The clobetasol propionate, glycerine, ethanol of recipe quantity is taken to be stirred evenly in beaker, will Above-mentioned two liquid mixes, and adds to the full amount of water for injection, stirs evenly, filling by 8ml/ bottles, sealing, produces.

The preparation of the sulfated compound Etimicin auristilla of embodiment 52

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, flumethasone 1g, VE succinic acid macrogol ester 6g, Taurine 2g, natrium adetate 0.2g, ethanol 400ml, glycerine 420ml, water for injection add to 1000ml.

Preparation technology：Etimicin Sulfate, VE succinic acid macrogol ester, taurine, natrium adetate are taken respectively It is dissolved in the beaker of 100ml water；Take the flumethasone, glycerine, ethanol of recipe quantity to be stirred evenly in beaker, then above-mentioned two liquid mixed, Add to the full amount of water for injection, stir evenly, it is filling by 8ml/ bottles, sealing, produce.The sulfated compound Etimicin auristilla of embodiment 53 Prepare

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Loteprednol 5g, VE succinic acid macrogol ester 10g, glycine 3g, natrium adetate 0.2g, ethanol 400ml, glycerine 420ml, water for injection add to 1000ml.

Preparation technology：Etimicin Sulfate, VE succinic acid macrogol ester, glycine, natrium adetate are taken respectively It is dissolved in the beaker of 100ml water, makes dissolving, addition glycerine, ethanol stirs evenly, and add Loteprednol, and stirring makes mixing, adds injection Water is stirred evenly to full dose, filling by 8ml/ bottles, sealing, is produced.

The preparation of the sulfated compound Etimicin auristilla of embodiment 54

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Fluocinonide 0.25g, methionine 1g, vitamin E Butanedioic acid macrogol ester 6g, natrium adetate 0.2g, ethanol 380ml, glycerine 450ml, water for injection add to 1000ml.

Preparation technology：Etimicin Sulfate, VE succinic acid macrogol ester, methionine, edetic acid(EDTA) two are taken respectively For sodium in the beaker of 100ml water, stirring evenly makes dissolving；The Fluocinonide, glycerine, ethanol of recipe quantity is taken to be stirred in another beaker It is even, then above-mentioned two liquid is mixed, adds to the full amount of water for injection, stirs evenly, it is filling by 8ml/ bottles, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 55

Prescription：Etimicin Sulfate (in terms of Etimicin) 8g, desonide 0.25g, VE succinic acid macrogol ester 6g, natrium adetate 0.2g, glycine 10g, taurine 10g, ethanol 350ml, glycerine 500ml, water for injection add to 1000ml.

Preparation technology：Take Etimicin Sulfate, VE succinic acid macrogol ester, glycine respectively, taurine, according to Ground acid disodium is dissolved in the beaker of 100ml water, by the desonide, ethanol, glycerine of recipe quantity in another beaker, is stirred evenly, then Above-mentioned two liquid is mixed, adds to the full amount of water for injection, stirs evenly, it is filling by 8ml/ bottles, sealing, produce.

The preparation of the sulfated compound Etimicin auristilla of embodiment 56

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, betamethasone valerate 1g, the poly- second two of VE succinic acid Alcohol ester 6g, natrium adetate 0.2g, glycine 10g, taurine 10g, ethanol 350ml, glycerine 500ml, water for injection add to 1000ml。

Preparation technology：Take Etimicin Sulfate, VE succinic acid macrogol ester, glycine respectively, taurine, according to Ground acid disodium is dissolved in the beaker of 100ml water, by the betamethasone valerate, ethanol, glycerine of recipe quantity in another beaker, is stirred It is even, then above-mentioned two liquid is mixed, adds to the full amount of water for injection, stirs evenly, it is filling by 8ml/ bottles, sealing, produce.

The preparation (specification 10g/ branch) of the Etimicin Sulfate betamethasone sodium phosphate emulsifiable paste of embodiment 57

Preparation technology：1) stearic acid and octadecyl alcolol for weighing recipe quantity mix in beaker, and heating makes fusing, standby；2) Etimicin Sulfate, potassium sorbate, betamethasone sodium phosphate, polyquaternium -1, glycerine and the Tween 80 of recipe quantity is taken to add respectively In the container for entering 650ml water for injection, it is stirred to dissolve, is 6.5 with 1mol/L citric acid and NaOH solution regulation pH； 3) be stirred continuously it is lower will 1) be added in solution 2), benefit adds to the full amount of water for injection, emulsification, crosses 200 mesh nylon mesh, cooling, presses 10ml/ branch dispenses, and sealing, produces.

The preparation (specification 10g/ branch) of the Etimicin Sulfate method Buddhist nun's acid prednisolone ester ointment of embodiment 58

Prescription：Etimicin Sulfate 3g, method Buddhist nun's acid prednisolone ester 14g, beeswax 50g, glycerine 50g, lanolin 30g, in vain Vaseline adds to 1000g；

Preparation method：Vaseline 800g, the beeswax of recipe quantity, glycerine, lanolin are taken respectively in beaker, it is heated to 60~ 70 DEG C make to melt, and then sequentially add the Etimicin Sulfate of the recipe quantity of 100 mesh sieves, method Buddhist nun's acid prednisolone ester is sufficiently stirred Mix, dispense, seal, packaging.

The preparation (specification 10g/ branch) of the Etimicin Sulfate method Buddhist nun's acid prednisolone ester ointment of embodiment 59

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, method Buddhist nun acid prednisolone ester 10g, polyoxyethylene stearate 40 Fat 60g, glycerine 60g, lanolin 40g, albolene add to 1000g；

Preparation method：The fat of polyoxyethylene stearate 40, glycerine, the lanolin of vaseline 750g, recipe quantity is taken to be mixed in respectively In beaker, being heated to 60~70 DEG C makes to melt, and then sequentially adds Etimicin Sulfate, the method Buddhist nun acid of the recipe quantity of 100 mesh sieves Prednisolone ester is sufficiently stirred mixing, dispenses, and seals, packaging.

The preparation (specification 10g/ branch) of the Etimicin Sulfate Econopred ointment of embodiment 60

Prescription：Etimicin Sulfate 3g, Econopred 5g, spermaceti 50g, stearyl alcohol 30g, glycerine 50g, lanolin 30g, albolene add to 1000g；

Preparation method：Vaseline 820g, the spermaceti of recipe quantity, stearyl alcohol, glycerine, lanolin is taken to be mixed in beaker respectively In, being heated to 60~70 DEG C makes to melt, and then sequentially adds Etimicin Sulfate, the prednisone acetate of the recipe quantity of 100 mesh sieves Dragon stirs and evenly mixs, then adds albolene to stir and evenly mix to full dose, dispense, seal by the specification of 10g/ branch, pack.

The preparation (specification 20g/ branch) of the Etimicin Sulfate methylprednisolone acetate ointment of embodiment 61

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, methylprednisolone acetate 2.5g, polyoxyethylene stearate 40 Fat 50g, PEG-4000 60g, spermaceti 20g, atoleine 100g, lanolin 50g, Phenoxyethanol 3g, albolene add To 1000g；

Preparation method：Vaseline 630g and the recipe quantity fat of polyoxyethylene stearate 40, PEG-4000, whale are taken respectively Wax, atoleine, Phenoxyethanol, lanolin are mixed in beaker, and being heated to 60~70 DEG C makes to melt, and then sequentially adds 100 Etimicin Sulfate, the methylprednisolone acetate of the recipe quantity of mesh sieve stir and evenly mix, then add albolene mixed to full dose, stirring It is even, dispense, seal by the specification of 20g/ branch, packaging.The preparation of the Etimicin Sulfate diflucortolone valerate ointment of embodiment 62 (specification 10g/ branch)

Prescription：Etimicin Sulfate 6g, diflucortolone valerate 1g, the fat 50g of polyoxyethylene stearate 40, polyethylene glycol- 4000 60g, spermaceti 20g, atoleine 100g, lanolin 50g, albolene add to 1000g；

Preparation method：Vaseline 620g and the recipe quantity fat of polyoxyethylene stearate 40, PEG-4000, whale are taken respectively Wax, atoleine, lanolin are mixed in beaker, and being heated to 60~70 DEG C makes to melt, and then sequentially adds the prescription of 100 mesh sieves Etimicin Sulfate, the diflucortolone valerate of amount stir and evenly mix, then add albolene to be stirred and evenly mixed, by 10g/ branch to full dose Specification packing, seal, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate desonide ointment of embodiment 63

Prescription：Etimicin Sulfate 10g, desonide 0.25g, the fat 50g of polyoxyethylene stearate 40, PEG-4000 60g, spermaceti 20g, glycine 20g, atoleine 100g, lanolin 50g, albolene add to 1000g；

Preparation method：Vaseline 650g and the recipe quantity fat of polyoxyethylene stearate 40, PEG-4000, whale are taken respectively Wax, glycine, atoleine, lanolin are mixed in beaker, and being heated to 60~70 DEG C makes to melt, and then sequentially adds 100 mesh Etimicin Sulfate, the desonide of the recipe quantity of sieve stir and evenly mix, then add albolene to be stirred and evenly mixed, by 20g/ branch to full dose Specification packing, seal, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate desonide ointment of embodiment 64

Prescription：Etimicin Sulfate (in terms of Etimicin) 20g, desonide 0.25g, the fat 50g of polyoxyethylene stearate 40, gather The 60g of ethylene glycol -4000, spermaceti 20g, lysine 5g, glycine 20g, atoleine 100g, lanolin 50g, albolene add To 1000g；

Preparation method：Vaseline 620g and the recipe quantity fat of polyoxyethylene stearate 40, PEG-4000, whale are taken respectively Wax, glycine, atoleine, lanolin are mixed in beaker, and being heated to 60~70 DEG C makes to melt, and then sequentially adds 100 mesh Etimicin Sulfate, desonide, the lysine of the recipe quantity of sieve, are stirred and evenly mixed, then add albolene to stir and evenly mix to full dose, Dispense, seal by the specification of 20g/ branch, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate desonide ointment of embodiment 65

Prescription：Etimicin Sulfate (in terms of Etimicin) 30g, desonide 0.25g, lysine 6g, glycine 20g, firmly The poly- fat 50g of hydrocarbon oxygen 40 of resin acid, PEG-4000 60g, spermaceti 20g, atoleine 100g, lanolin 50g, albolene add To 1000g；

Preparation method：Vaseline 620g and the recipe quantity fat of polyoxyethylene stearate 40, PEG-4000, whale are taken respectively Wax, atoleine, lanolin are mixed in stainless steel keg, and being heated to 60~70 DEG C makes to melt, and then sequentially adds 100 mesh sieves Etimicin Sulfate, desonide, the lysine of recipe quantity stir and evenly mix, then add albolene to stir and evenly mix, press to full dose The specification packing of 20g/ branch, is sealed, packaging.

The preparation (specification 10g/ branch) of the Etimicin Sulfate Mometasonec of embodiment 66

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, momestasone furoate 1g, glycine 3g, paraffin 50g, 16 Alcohol 60g, lanolin 50g, vaseline add to 1000g；

Preparation method：Vaseline 700g and recipe quantity paraffin, hexadecanol are taken respectively, that lanolin is mixed in stainless steel is small In bucket, being heated to 60~70 DEG C makes to melt, and then sequentially adds the Etimicin Sulfate of the recipe quantity of 100 mesh sieves, furancarboxylic acid not rice Pine, glycine, are stirred and evenly mixed, then add albolene to stir and evenly mix, dispensed by the specification of 10g/ branch, sealing, packaging to full dose.

The preparation (specification 10g/ branch) of the Etimicin Sulfate Mometasone ointment of embodiment 67

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, Mometasone 1g, the fat 60g of polyoxyethylene stearate 40, glycerine 60g, lanolin 40g；Albolene adds to 1000g,

Preparation method：Vaseline 600g and the recipe quantity fat of polyoxyethylene stearate 40, glycerine, lanolin is taken to mix respectively In beaker, being heated to 60~70 DEG C makes to melt, and then sequentially adds Etimicin Sulfate, the Mometasone of the recipe quantity of 100 mesh sieves Mixing is sufficiently stirred, adds albolene to be stirred and evenly mixed, packing to 1000g.

The preparation (specification 20g/ branch) of the Etimicin Sulfate betamethasone ointment of embodiment 68

Prescription：Etimicin Sulfate 5g, betamethasone 1g, the fat 50g of polyoxyethylene stearate 40, PEG-4000 60g, Spermaceti 20g, atoleine 100g, lanolin 50g, albolene add to 1000g；

Preparation method：Vaseline 700g and the recipe quantity fat of polyoxyethylene stearate 40, PEG-4000, whale are taken respectively Wax, atoleine, lanolin are mixed in beaker, and being heated to 60~70 DEG C makes to melt, and then sequentially adds the prescription of 100 mesh sieves Etimicin Sulfate, the betamethasone of amount stir and evenly mix, then add albolene to be stirred and evenly mixed, the specification propped up by 20g/ to full dose Packing, seal, packaging.

The preparation of the Etimicin Sulfate desonide ointment of embodiment 69

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, desonide 0.5g, paraffin 50g, hexadecanol 60g, lanolin 50g, albolene add to 1000g；

Preparation method：Vaseline 700g and recipe quantity paraffin, hexadecanol are taken respectively, that lanolin is mixed in stainless steel is small In bucket, being heated to 65~70 DEG C makes to melt, and then sequentially adds Etimicin Sulfate, the desonide of the recipe quantity of 100 mesh sieves, Mixing is sufficiently stirred, then adds albolene to stir and evenly mix to full dose, dispense, seal by the specification of 10g/ branch, pack.

The preparation (specification 20g/ branch) of the Etimicin desonide ointment of embodiment 70

Prescription：Etimicin 5g, desonide 5g, the fat 50g of polyoxyethylene stearate 40, PEG-4000 60g, spermaceti 20g, atoleine 100g, lanolin 50g, the 0.01g of polyquaternium -1, albolene add to 1000g；

Preparation method：Vaseline 700g and the recipe quantity fat of polyoxyethylene stearate 40, PEG-4000, whale are taken respectively Wax, atoleine, polyquaternium -1, lanolin are mixed in stainless steel keg, and being heated to 60~70 DEG C makes to melt, and are then added successively Entered the Etimicin of the recipe quantity of 100 mesh sieves, desonide stirs and evenly mixs, then add albolene to full dose, stir and evenly mix, press The specification packing of 20g/ branch, is sealed, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate budesonide ointment of embodiment 71

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, budesonide 1g, paraffin 50g, hexadecanol 60g, lanolin 50g, albolene add to 1000g；

Preparation method：Vaseline 800g and recipe quantity paraffin, hexadecanol are taken respectively, that lanolin is mixed in stainless steel is small In bucket, being heated to 60~70 DEG C makes to melt, and then sequentially adds Etimicin Sulfate, the budesonide of the recipe quantity of 100 mesh sieves, Stir and evenly mix, then add albolene to be stirred and evenly mixed, packing to full dose.The Etimicin Sulfate propionic acid fluorine of embodiment 72 is for card The preparation (specification 20g/ branch) of soft cream

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, fluticasone propionate 0.5g, paraffin 50g, hexadecanol 60g, Lanolin 50g, albolene add to 1000g；

Preparation method：Vaseline 800g and recipe quantity paraffin, hexadecanol are taken respectively, that lanolin is mixed in stainless steel is small In bucket, being heated to 60~70 DEG C makes to melt, and then sequentially adds the Etimicin Sulfate of the recipe quantity of 100 mesh sieves, propionic acid fluorine replaces Kathon CG, stir and evenly mix, then add albolene to stir and evenly mix to full dose, dispense, seal by the specification of 20g/ branch, pack.

The preparation (specification 20g/ branch) of the Etimicin Sulfate Kin White of embodiment 73

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, Triamcinolone acetonide 0.25g, paraffin 50g, hexadecanol 60g, sheep Hair fat 50g, albolene add to 1000g；

Preparation method：Vaseline 750g and recipe quantity paraffin, hexadecanol are taken respectively, that lanolin is mixed in stainless steel is small In bucket, being heated to 60~70 DEG C makes to melt, and then sequentially adds Etimicin Sulfate, the Triamcinolone acetonide of the recipe quantity of 100 mesh sieves, Stir and evenly mix, then add albolene to stir and evenly mix to full dose, dispense, seal by the specification of 20g/ branch, pack.

The preparation (specification 20g/ branch) of the Etimicin Sulfate fluocinonide ointment of embodiment 74

Prescription：Etimicin Sulfate 5g, lidex 0.1g, paraffin 50g, hexadecanol 60g, lanolin 50g, Bai Fan Intellectual circle adds to 1000g；

Preparation method：Vaseline 750g and recipe quantity paraffin, hexadecanol are taken respectively, that lanolin is mixed in stainless steel is small In bucket, being heated to 60~70 DEG C makes to melt, and then sequentially adds Etimicin Sulfate, the fluocinolone acetonide vinegar of the recipe quantity of 100 mesh sieves Acid esters, stir and evenly mix, then add albolene to stir and evenly mix to full dose, dispense, seal by the specification of 20g/ branch, pack.

The preparation (specification 20g/ branch) of the Etimicin Sulfate fluorometholone ointment of embodiment 75

Prescription：Etimicin Sulfate 5g, fluorometholone 1g, paraffin 50g, hexadecanol 60g, lanolin 50g, albolene add to 1000g；

Preparation method：Paraffin, hexadecanol, the wool of sterilized vaseline 750g and sterilized recipe quantity are taken respectively Fat is mixed in stainless steel keg, and being heated to 60~70 DEG C makes to melt, added the recipe quantity of 100 mesh sieves Etimicin Sulfate, Fluorometholone, stir and evenly mix, then add albolene to stir and evenly mix to full dose, dispense, seal by the specification of 20g/ branch, pack.

The preparation (specification 5g/ branch) of the Etimicin Sulfate Loteprednol ophthalmic ointment of embodiment 76

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, Loteprednol 5g, taurine 3g, paraffin 50g, hexadecanol 60g, lanolin 50g, albolene add to 1000g；

Preparation method：Sterilized vaseline 760g and sterilized recipe quantity paraffin, hexadecanol, sheep will be taken respectively Hair fat is mixed in stainless steel keg, and being heated to 60~70 DEG C makes to melt, and then sequentially adds the sulfuric acid of the recipe quantity of 100 mesh sieves Etimicin, Loteprednol, are stirred and evenly mixed, then add albolene to be stirred and evenly mixed, the specification propped up by 5g/ dispenses, close to full dose Envelope, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate brufen ointment of embodiment 77

Prescription：Etimicin Sulfate 5g, brufen 50g, paraffin 50g, alginic acid 1 hydrate 30g, glycine 50g, L- essence Propylhomoserin 43g, hexadecanol 60g, lanolin 50g, albolene add to 1000g；

Preparation method：The paraffin of vaseline 600g and recipe quantity, hexadecanol, lanolin are mixed in stainless steel keg, Heating, being heated to 60~70 DEG C makes to melt, then sequentially added 100 mesh sieves recipe quantity be pre-mixed uniform sulfuric acid according to for Meter Xing, brufen, the hydrate of alginic acid 1, glycine, L-arginine mix powder, stir and evenly mix, and are dispensed by the specification of 20g/ branch, close Envelope, packaging.

The preparation (specification 10g/ branch) of the Etimicin Sulfate (S)-ibuprofen ointment of embodiment 78

Prescription：Etimicin Sulfate 5g, brufen 25g, paraffin 50g, hexadecanol 60g, lanolin 50g, albolene add To 1000g；

Preparation method：The paraffin of vaseline 750g and recipe quantity, hexadecanol, lanolin are mixed in stainless steel keg, Being heated to 60~70 DEG C makes to melt, and then sequentially added Etimicin Sulfate, the (S)-ibuprofen of the recipe quantity of 100 mesh sieves, and stirred Mixing is mixed, dispenses, seals by the specification of 10g/ branch, packaging.

The preparation (specification 20g/ branch) of the Etimicin Sulfate Ibuprofen Piconol ointment of embodiment 79

Prescription：Etimicin Sulfate 5g, Ibuprofen Piconol 50g, alginic acid 20g, glycine 30g, beeswax 50g, hexadecanol 60g, octadecyl alcolol 20g, lanolin 50g, albolene add to 1000g；

Preparation method：The paraffin of vaseline 600g and recipe quantity, hexadecanol, octadecyl alcolol, lanolin are mixed in stainless steel In keg, being heated to 60~70 DEG C makes to melt, and then sequentially adds Etimicin Sulfate, the Pi Kaobu of the recipe quantity of 100 mesh sieves Ibuprofen, alginic acid, glycine, are stirred and evenly mixed, packing.

The preparation (specification 10g/ branch) of the Etimicin Sulfate dextrorotation Ketorolac Tromethamine ointment of embodiment 80

Prescription：Etimicin Sulfate 5g, dextrorotation Ketorolac Tromethamine 12.5g, alginic acid 20g, glycine 30g, beeswax 50g, hexadecanol 60g, octadecyl alcolol 20g, lanolin 50g, albolene add to 1000g；

Preparation method：The paraffin of vaseline 600g and recipe quantity, hexadecanol, octadecyl alcolol, lanolin are mixed in stainless steel In keg, being heated to 60~70 DEG C makes to melt, and then sequentially adds Etimicin Sulfate, the dextrorotation ketone of the recipe quantity of 100 mesh sieves Lip river acid tromethamine, alginic acid, glycine, are stirred and evenly mixed, and are dispensed, are sealed by the specification of 10g/ branch, packaging.

The preparation (specification 10g/ branch) of the Etimicin Sulfate S- Etodolac ointment of embodiment 81

Prescription：Etimicin Sulfate 5g, S- Etodolac 25g, alginic acid 20g, glycine 30g, beeswax 50g, hexadecanol 60g, octadecyl alcolol 20g, lanolin 50g, albolene add to 1000g；

Preparation method：The paraffin of vaseline 600g and recipe quantity, hexadecanol, octadecyl alcolol, lanolin are mixed in stainless steel In keg, being heated to 60~70 DEG C makes to melt, and then sequentially adds the Etimicin Sulfate of the recipe quantity of 100 mesh sieves, S- is relied on Acid, alginic acid, glycine are spent, is stirred and evenly mixed, dispenses, seals by the specification of 10g/ branch, packaging.

The preparation (specification 10g/ branch) of the Etimicin Sulfate Diclofenac Potassium ointment of embodiment 82

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, Diclofenac Potassium 25g, paraffin 50g, hexadecanol 60g, sheep Hair fat 50g, vaseline add to 1000g；

Preparation method：Vaseline 720g and recipe quantity paraffin, hexadecanol are taken respectively, that lanolin is mixed in stainless steel is small In bucket, heating makes fusing, then sequentially adds Etimicin Sulfate, the Diclofenac Potassium of the recipe quantity of 100 mesh sieves, stirs Mix, then add vaseline to stir and evenly mix, dispensed by the specification of 10g/ branch, sealing, packaging to full dose.

The preparation (specification 10g/ branch) of the Etimicin Sulfate pranoprofen ointment of embodiment 83

Prescription：Etimicin Sulfate (in terms of Etimicin) 5g, pranoprofen 5g, lysine 4g, paraffin 50g, hexadecanol 60g, lanolin 50g, yellow petroleum jelly add to 1000g；

Preparation method：Yellow petroleum jelly 750g and recipe quantity paraffin, hexadecanol, lanolin is taken to be mixed in stainless steel respectively In keg, heating makes fusing, then sequentially adds the Etimicin Sulfate, pranoprofen, bad ammonia of the recipe quantity of 100 mesh sieves Acid, stir and evenly mix, add yellow petroleum jelly to stir and evenly mix to full dose, dispense, seal by the specification of 10g/ branch, pack.

The preparation (prescription 1000) of the sulfated compound Etimicin ocular inserts of embodiment 84

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, betamethasone sodium phosphate 0.5g, PVAC polyvinylalcohol (05- 88) 12g, glycerine 2.0g, 1M citric acid solution and appropriate sodium citrate solution, water for injection add to 50ml；

Preparation method：First by PVA (05-88), the appropriate water for injection of glycerine, fully water-bath is allowed to completely molten after expansion Solve, 200 mesh screens, add Etimicin Sulfate, the betamethasone sodium phosphate of recipe quantity, stirring and dissolving, with appropriate 1M lemons successively Lemon acid solution and sodium citrate solution adjust pH value to 6.8, add appropriate water for injection to be mixed to ormal weight.Stand, treat that bubble removes Film, 50 DEG C of dryings, demoulding afterwards are use up, 0.5 × 1.0cm diaphragm (every containing about Etimicin 3mg) is divided into, under uviol lamp 15min sterilizings are irradiated, are packed.

The preparation (prescription 1000) of the sulfated compound Etimicin film of embodiment 85

Prescription：Etimicin Sulfate (in terms of Etimicin) 1g, betamethasone sodium phosphate 100mg, tetracaine hydrochloride 4g, gather Vinyl alcohol (17-88) 4g, sodium carboxymethylcellulose 2.0g, glycerine 2.5g, Sucralose 0.05g, with 1M citric acid solutions and lemon Lemon acid sodium solution is appropriate, and water for injection adds to 100g.

Preparation method：First polyvinyl alcohol, sodium carboxymethylcellulose are soaked with appropriate water for injection respectively, fully after expansion Water-bath is allowed to be completely dissolved, and mixes the two, standby；Etimicin Sulfate, tetracaine hydrochloride, betamethasone sodium phosphate is taken to be dissolved in In 30ml waters for injection, Sucralose, glycerine stirring and dissolving are added, then by this decoction and above-mentioned standby polyvinyl alcohol, carboxylic first Base sodium cellulosate rubber cement liquid is well mixed, and is adjusted pH value to 6.8 with appropriate 1M citric acid solutions and sodium citrate solution, is added appropriate Water for injection mixes to ormal weight.Stand, the film after bubble eliminates, 50 DEG C of dryings, demoulding, be divided into 0.5 × 1.0cm's Diaphragm (every containing about Etimicin 1mg), 15min sterilizings are irradiated under uviol lamp, are packed.

Preparation (the prescription of the Etimicin betamethasone sticking tablet of embodiment 86：1000)

Preparation technology：

The Etimicin Sulfate for weighing recipe quantity is dissolved with 6ml waters for injection, will after betamethasone is dissolved with 6ml ethanol Two solution were sequentially added into the dextrin of the recipe quantity of 100 mesh sieves, were pelletized after fully mixing through 40 mesh sieves, and 50~55 After DEG C drying 2h, through 40 mesh sieve whole grains, add the mesh sieve of mistake 100 of recipe quantity carbopol 934, magnesium stearate fully mix after, With diameter 6mm flat punch tablettings, pressure about 6-8kg；Acrylic acid II resins alcohol 95 ml is dissolved, adds phthalic acid two Monooctyl ester, titanium dioxide, uranidin grinding are uniform, with Membrane jetter even application in plain piece surface, after drying, form the guarantor of tablet Sheath.

Preparation (the prescription of the Etimicin beclomethasone plastics of embodiment 87：1000ml)

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, BD 0.25g, pulullan polysaccharide 20g, POLYPROPYLENE GLYCOL 15g, ethylene glycol 80g, glycerine 20g, azone 5g, water for injection 400g, ethanol add to 1000ml.

Preparation technology：The pulullan polysaccharide and POLYPROPYLENE GLYCOL for weighing recipe quantity respectively are added in water for injection, are soaked and are added Heat, it is set fully to dissolve；Take the BD of recipe quantity to be dissolved in the ethylene glycol of recipe quantity respectively, glycerine, azone and In 100ml ethanol, two solution are well mixed, then, add ethanol to dispense in 30ml medicinal bottles to full dose, seal and produce.

Preparation (the prescription of the Etimicin betamethasone sticking tablet of embodiment 88：1000)

Medicated layer particle：

Protective layer particle：

Preparation process：

Medicated layer particle recipe：By in the Etimicin Sulfate 4ml waters for injection of recipe quantity, the betamethasone of recipe quantity is molten In 10% polyvinylpyrrolidone ethanol solution；After hydroxypropyl methyl cellulose, Acritamer 940 separately are crossed into 80 mesh sieves, with The dextrin mixing of 80 mesh is crossed, adds the above-mentioned polyvinylpyrrolidonesolution solution system dissolved with Etimicin Sulfate solution and betamethasone Softwood, stir, wet grain is made after crossing 40 mesh sieves, by wet grain in about 50 DEG C of dry dry granulars, separately added the tristearin of 80 mesh Sour magnesium is standby after mixing.

Protective layer pellet preparation method：Ethyl cellulose is dissolved in ethanol, 3% solution for standby is made.Ethyl cellulose, kermes It is red mixed with titanium dioxide after, add above-mentioned ethyl cellulose solution softwood processed in right amount, softwood is crossed into 40 mesh sieves is made wet grain, will It is wet 50-60 DEG C drying after, add magnesium stearate mix after it is standby；With diameter 6mm flat punch tablettings, pressure about 6-8kg will be upper State two kinds of pellets and be pressed into double-layer tablets on a bi-layer tablet press, produce.

The preparation of the sodium eye drops of 89 sulfated compound Etimicin ophthalmic solution of embodiment four

Prescription：Etimicin Sulfate (in terms of Etimicin) 3g, ophthalmic solution four sodium 30g, trehalose 5g, boric acid 0.5g, Cys 1g, 1B 3g, sodium pantothenate 1g, the 0.01g of polyquaternium -1, appropriate sodium chloride, 1M L-ASPARTIC ACIDs are molten Appropriate liquid, 1M sodium hydroxide solutions are appropriate, and water for injection adds to 1000ml

Industrial applicibility etc. and its explanation etc.：

The present invention is described in detail above by embodiment and embodiment, it will nevertheless be understood that these are said Bright that any restrictions are not formed to the scope of the present invention, person skilled substantially can be in the spirit without departing from the present invention and guarantor In the case of protecting scope, technical solutions and their implementation methods of the present invention can be carried out with a variety of modifications, improvement and replacement and group Close, to realize the technology of the present invention, these are because falling within the scope of protection of the present invention.In particular, it will be understood that The change of many details is possible, and all similar replacements and change are apparent for a person skilled in the art , they are considered as being included in the spirit, scope and content of the present invention, and the present invention is not limited to above-described embodiment.

Claims

1. the aminoglycoside medicaments composition being locally administered, Etimicin Sulfate or Etimicin containing effective dose or its It is any one or more of in pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound, its Described in composition also have anti-inflammatory effective dose steroid with non-steroidal antiinflammatory drugs or with anti-dry eye drugs Any one or more of, remaining is pharmaceutically acceptable carrier, wherein, steroid removes dexamethasone or dexamethasone acetate or ground Outside Sai meter Song sodium phosphate pharmaceutical salts.

2. the aminoglycoside medicaments composition being locally administered of claim 1, it is characterised in that：Per 1000ml or 1000g or 1000cm²Eye-drops preparations or ear use nose use or oral preparations in the Etimicin Sulfate containing effective dose or according to for rice It is any in star or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. Or it is a variety of, wherein the composition also steroid of the effective dose containing anti-inflammatory or with non-steroidal antiinflammatory drugs or with anti-xerophthalmia It is any one or more of in medicine；Remaining is pharmaceutically acceptable carrier；The pharmaceutical composition of the present invention is on pharmaceutical preparation Can be eye drops, gel for eye use, ophthalmic ointment, ocular inserts, ophthalmically acceptable dripping pill, external-use gel, ointment, emulsifiable paste, plastics, film Agent, auristilla, oral cavity adhesion tablet, buccal tablets.

3. the aminoglycoside medicaments composition being locally administered of claim 1,2, it is characterised in that：Per 1000ml or 1000g Or 1000cm²Said composition preparation in containing Etimicin Sulfate or Etimicin or its pharmaceutically acceptable salt or its Different crystallizations or amorphous article or its solvate or its inclusion compound or they in it is any one or more of, in terms of Etimicin Weight or ratio of weight and number be 0.010-1.0wt% or 0.01~10g, the steroid of the effective dose containing anti-inflammatory or with non-steroid Antiinflammatory drugs are calculated as 0.01-5.0wt% with weight or ratio of weight and number any one or more of in anti-dry eye drugs； Remaining is pharmaceutically acceptable carrier.

4. the aminoglycoside medicaments composition being locally administered according to claims 1 to 3, it is characterised in that：The medicine Composition contains Etimicin Sulfate or Etimicin or its pharmaceutically acceptable salt or its different crystallization or amorphous article Or its solvate or its inclusion compound or any one or more of concentration or weight are 0.10-0.8wt% in them, or often 1000ml or 1000g or 1000cm²Preparation in contain Etimicin or its pharmaceutically acceptable salt or its different crystallization Its solvate or its inclusion compound or they in it is any one or more of, with the weight of Etimicin be calculated as 1.0~8.0g or The unit of 1,000,000 units~8,000,000 is calculated as with Etimicin potency, wherein the steroid of the composition also effective dose containing anti-inflammatory Class or with non-steroidal antiinflammatory drugs or with it is any one or more of in anti-dry eye drugs；Remaining is pharmaceutically acceptable load Body.

Pharmaceutically acceptable carrier includes water, pharmaceutically acceptable thickener, pH adjusting agent and or pharmaceutically acceptable Preservative or bacteriostatic agent, antioxidant, stabilizer, isotonic regulator, sorbefacient, solubilizer, excipient, diluent, guarantor Humectant or they in it is any one or more of.

5. the aminoglycoside medicaments composition being locally administered according to claims 1 to 4, it is characterised in that：Often 1000ml or 1000g or 1000cm²Preparation in contain Etimicin or its pharmaceutically acceptable salt or its different crystallization Its solvate or its inclusion compound or they in it is any one or more of, 0.01~10g, steroid are calculated as with the weight of Etimicin Class or with non-steroidal antiinflammatory drugs or with any one or more of 0.01~50g in anti-dry eye drugs, remaining is pharmaceutically may be used The carrier of receiving.

6. the aminoglycoside medicaments composition being locally administered according to claims 1 to 5, it is characterised in that：Often 1000ml or 1000g or 1000cm²Preparation in contain Etimicin or its pharmaceutically acceptable salt or its different crystallization Its solvate or its inclusion compound or they in it is any one or more of, 3.0g is calculated as with the weight of Etimicin, steroid or With non-steroidal antiinflammatory drugs or with any one or more of 1.0g in anti-dry eye drugs, remaining is pharmaceutically acceptable load Body.

7. the aminoglycoside medicaments composition being locally administered according to claims 1 to 5, it is characterised in that：Often 1000ml or 1000g or 1000cm²Preparation in contain Etimicin or its pharmaceutically acceptable salt or its different crystallization Its solvate or its inclusion compound or they in it is any one or more of, 5.0g is calculated as with the weight of Etimicin, steroid or With non-steroidal antiinflammatory drugs or with any one or more of 1.0g in anti-dry eye drugs, remaining is pharmaceutically acceptable load Body.

8. the aminoglycoside medicaments composition being locally administered of claim 1,2, it is characterised in that：Per 1000ml or 1000g Or 1000cm²Eye-drops preparations or ear use nose use or oral preparations in the Etimicin Sulfate containing effective dose or according to for Any one in rice star or its pharmaceutically acceptable salt or different crystal forms or amorphous article or its solvate or its inclusion compound etc. Kind or it is a variety of, wherein the composition also steroid of the effective dose containing anti-inflammatory or with non-steroidal antiinflammatory drugs or with anti-dry eyes It is any one or more of in disease drug；Wherein described the composition also local anaesthetics containing effective dose, including but not limited to hydrochloric acid Totokaine, procaine, chloroprocanine, lidocaine, oxybuprocaine, phenmethylol, menthol, Etidocaine, Bupivacaine, Dyclonine, benzocainum, Ropivacaine or its pharmaceutical salts or its inclusion compound etc., its weight of material ratio can be whole weight of formulation 5~50% (w/w)；Remaining is pharmaceutically acceptable carrier.

9. the aminoglycoside medicaments composition being locally administered according to claim 1,2, it is characterised in that：Per 1000ml Or 1000g or 1000cm²Preparation in containing Etimicin or its pharmaceutically acceptable salt or its different crystallization or its is molten Agent compound or its inclusion compound or they in it is any one or more of, 0.5~50g is calculated as with the weight of Etimicin, steroid or and Non-steroidal antiinflammatory drugs or with anti-0.010~5g of dry eye drugs, remaining is pharmaceutically acceptable carrier.

10. the compound amino glycoside pharmaceutical composition being locally administered according to claims 1 to 5, it is characterised in that：Often 1000ml or 1000g or 1000cm²External preparation for skin or oral preparations in containing Etimicin Sulfate or Etimicin or its Pharmaceutically acceptable salt or its different crystallization or amorphous article or its solvate or its inclusion compound or they in any one Kind or it is a variety of, 0.25~10g is calculated as with the weight or parts by weight of Etimicin, the steroid containing anti-inflammatory effective dose or with it is non- Steroidal antiinflammatory drugs are calculated as 0.01-1.0wt% with the weight of anti-dry eye drugs or parts by weight；Wherein described composition is also Local anaesthetics containing effective dose, including but not limited to tetracaine hydrochloride, procaine, chloroprocanine, lidocaine, Ao Bu Cacaine, phenmethylol, menthol, Etidocaine, Bupivacaine, dyclonine, benzocainum, Ropivacaine or its pharmaceutical salts or its Inclusion compound etc., its weight is than that can be 5~50% (w/w) that whole weight of formulation or parts by weight are calculated as；Remaining is pharmaceutically may be used The carrier of receiving.

11. the aminoglycoside medicaments composition being locally administered according to claims 1 to 5, it is characterised in that：Often 1000ml or 1000g or 1000cm²Preparation in contain Etimicin or its pharmaceutically acceptable salt or its different crystallization Its solvate or its inclusion compound or they in it is any one or more of, 0.01~10g is calculated as with the weight of Etimicin, profit Any one or more of 0.1~5g in Mei Suolong, fluorometholone, fluorometholone acetate, momestasone furoate, Mometasone, remaining is medicine Acceptable carrier on.

12. the aminoglycoside medicaments composition being locally administered according to claims 1 to 5, it is characterised in that：Often 1000ml or 1000g or 1000cm²Preparation in contain Etimicin or its pharmaceutically acceptable salt or its different crystallization Its solvate or its inclusion compound or they in it is any one or more of, 0.01~10g, vinegar are calculated as with the weight of Etimicin Sour prednisolone, prednisolone, prednisolone disodium hydrogen phosphate, prednisone acetate, metacortandracin, cortisone, hydrocortisone acetate, Butyric acid hydrocortisone, hydrocortisone buteprate, hydrocortisone valerate, hydrocortisone, Rimexolone, chlorine are for bold and vigorous Any one or more of 0.1~10g in promise, Lotepredenol etabonate, desonide, remaining is pharmaceutically acceptable carrier.

13. the compound amino glycoside pharmaceutical composition being locally administered according to claim 1~12, it is characterised in that：

In its pharmaceutically acceptable carrier, it is selected from but is not limited only to water, glycerine, D- or L- or the amino acid of racemization or its salt, Such as D- or L- or DL-Lys, Lysine Acetate, cysteine, methionine, arginine or acetic arginine or L-aminobutanedioic acid Or Monosodium L-aspartate, glutamic acid, glycine, taurine, alanine, valine, leucine, isoleucine, serine, Soviet Union's ammonia Acid, cysteine, cystine, methionine, asparagine, glutamine, 5- oxylysines, histidine, phenylalanine, junket ammonia Acid, tryptophan, 3- hydroxy-prolines, 4- hydroxy-prolines, proline, homocysteine, homocystine, homoserine, bird ammonia Acid, citrulling, creatine, 3- alanine, theanine, 2-amino-butyric acid, 4-Aminobutanoicacid, 2- amino-2-methyls propionic acid, 2- first Base -3- alanines, 2,6- diaminopimelic acids, 2- amino-3-phenyl butyrics, phenylglycine, canavanine, secondary sword bean ammonia Acid, 4- hydroxyarginines, 4- hydroxyls ornithine, homoarginine, 4- hydroxyhomoarginines, beta-lysine, 2,4-diamino-butanoic, 2,3- diaminopropionic acids, 2- methyl serines etc. or unit or polybasic carboxylic acid or its pharmaceutical salts, gallic acid, gallic acid third It is ester, progallin A, gallate, malic acid, butanedioic acid, ascorbic acid, L-AA, sodium ascorbate, different anti- Bad hematic acid, sodium isoascorbate, nicotinic acid, niacinamide, pantothenic acid, sodium pantothenate, calcium pantothenate, vitamin B1, vitamin B2, vitamin E, Beta carotene, Pyridoxamine Hydrochloride, glutathione, allantoin, citric acid or sodium citrate or lactic acid, sodium lactate, lactobionic acid, Sodium lactonic, gluconic acid, sodium gluconate or trehalose, urea, thiocarbamide or maltitol, sorbierite, mannitol, lactose Alcohol, xylitol, antierythrite, Hyaluronic Acid or sodium hyaluronate or its hydrate or their pharmaceutically acceptable salt or theirs is different One or more in structure body etc., sorbierite include D- D-sorbites, anhydrous sorbierite or the water thing of sorbierite half or 1 water sorbierite Or the one or more in sorbitol instant etc., it is above-mentioned to include its isomers；Concentration range used in these compounds can With 0.000~5.0%；

Pharmaceutically acceptable pH adjusting agent is selected from but is not limited only to pharmaceutically acceptable inorganic acid or organic acid or its is medicinal The lewis acid or alkali of salt, inorganic base or organic base or its pharmaceutical salts or broad sense, can be hydrochloric acid, sulfuric acid or its medicine With salt, boric acid or its pharmaceutical salts, borax, phosphoric acid or its pharmaceutical salts, acetic acid or its pharmaceutical salts, such as sodium acetate, lactic acid and lactic acid Pharmaceutical salts, citric acid or its pharmaceutical salts, tartaric acid or citric acid or its pharmaceutical salts, disodium hydrogen phosphate, sodium dihydrogen phosphate, di(2-ethylhexyl)phosphate Hydrogen potassium, ascorbic acid, sodium ascorbate, arabo-ascorbic acid, sodium isoascorbate, sodium hydroxide, potassium hydroxide, sodium carbonate, carbon Sour hydrogen sodium, trihydroxy aminomethane, diethanol amine, monoethanolamine, diisopropanolamine (DIPA), 2- amino -2- (methylol) 1,3-PD Amine, N- methyl glucoses amine and their salt, multi-hydroxy carboxy acid and pharmaceutical salts, as glucuronic acid, gluconic acid, lactobionic acid, In malic acid, threonic acid, glucoheptonic acid, amino acid or their pharmaceutically acceptable salt or its hydrate or its isomers It is one or several kinds of；

Pharmaceutically acceptable antioxidant and stabilizer are selected from but are not limited only to sulfurous acid and its salt, bisulfites, burnt sulfurous Hydrochlorate, dithionite, TGA and its pharmaceutical salts, thiolactic acid and its pharmaceutical salts, thio-2 acid and salt, monohydroxy Or multi-hydroxy carboxy acid and pharmaceutical salts, tartaric acid, sorbic acid or its pharmaceutical salts, nitrate, acetic acid pharmaceutical salts, citrate, EDTA And edta salt including EDETATE SODIUM, the sodium of EDTA tetra-, Ca-EDTA sodium salt (including sodium ethylene diamine tetracetate calcium or ethylenediamine tetrem The sour hydrate of sodium calcium 2, the hydrate of sodium ethylene diamine tetracetate calcium 4), N- bis- (2- ethoxys) glycine, maltitol, xylose Alcohol, sorbierite, mannitol, vitamin E, beta carotene, Pyridoxamine Hydrochloride, taurine, amino acid or they pharmaceutically can connect One or several kinds in its hydrate of the salt received or its isomers etc.；

Pharmaceutically acceptable chelating agent be selected from but be not limited only to EDTA and edta salt including EDETATE SODIUM, the sodium of EDTA tetra-, according to ground Sour calcium disodium (including sodium ethylene diamine tetracetate calcium or the hydrate of sodium ethylene diamine tetracetate calcium 2, sodium ethylene diamine tetracetate calcium 4 are hydrated Thing), one in (2- ethoxys) glycine of N- bis- or its hydrate of their pharmaceutically acceptable salt or its isomers etc. Kind is several；

Pharmaceutically acceptable preservative or bacteriostatic agent, selected from organic acid bacteriostatic agent, oxybenzene esters compound or nipalgin Esters, methyl hydroxybenzoate, propylparaben, phenmethylol, benzyl carbinol, phenoxetol, anesin, quaternary ammonium derive Thing, Domiphen bromide, benzalkonium chloride, benzalkonium bromide, hexadecyl ammonium methyl, cetylpyridinium chloride, Benzethonium, polyquaternary amine Salt, polyquaternium -1, organic Mercury derivatives, thiomersalate, thimerosal, phenylmercuric acetate and phenylmercuric nitrate, pharmacy In upper acceptable phenol compound, o-phenyl phenol, chloreresol, chlorohexidene etc. or their pharmaceutically acceptable salt etc. One or more.Generally, concentration range used in these compounds is 0.0005-5.0%, and this prevents depending on selected Rotten agent or bacteriostatic agent；Polyquaternium -1 is more preferably used to be used as anti-microbial preservative；Typically with 0.001%-1.0wt%'s Concentration uses these preservatives；

Pharmaceutically acceptable isotonic regulator, pharmaceutically acceptable isotonic regulator are selected from but are not limited only to sodium chloride, chlorine Change potassium, calcium chloride, sodium bromide, sodium phosphate, sodium sulphate, sodium nitrate, glucose, boric acid, borax, glycerine, propane diols, poly- second two Alcohol, PEG-400, PEG300, PEG-200, glucose, fructose, maltitol, xylitol, sorbierite, mannitol, inverted sugar, Its hydrate of dextran, sodium lactate or sodium lactonic, gluconic acid or sodium gluconate or one kind or several in its isomers Kind；

Pharmaceutically acceptable carrier also includes solubilizer, and solubilizer is selected from but is not limited only to polyethylene glycol oxide list oleic acid sorbierite Acid anhydride ester, Tween-80, VE succinic acid macrogol ester (vitamin E TPGS), glycerine-polyethylene glycol epoxide stearate, PEG-32 glyceryl palmitostearates, lauryl sodium sulfate, Sorbitan monolaurate, polyethylene glycol, polyethylene glycol 400-6000, HS15, polyvinylpyrrolidone, polyvinyl alcohol, amino acid or its pharmaceutical salts, medicine Learn acceptable alcohols, pharmaceutically acceptable polyalcohol, poloxamer, poloxamer188, azone, laurocapram, cyclodextrin It is or cyclodextrin pharmaceutically acceptable derivates, amide-type or urea and derivative, inorganic acid or inorganic acid salt, pharmaceutically acceptable Organic acid or acylate, pharmaceutically acceptable carbohydrate or sugar lime, pharmaceutically acceptable amine etc. or theirs is chiral different One or more in structure body etc. or their pharmaceutically acceptable salt；

Pharmaceutically acceptable carrier --- thickener or stabilizer or matrix, it is selected from but is not limited only to water-soluble polymer and oozes Saturating accelerator and the composition of their mixture composition；The water-soluble polymeric that can be used in the pharmaceutical composition of the present invention Thing includes but is not limited to natural and synthesis polymer, polysaccharide, poly- aminoglycoside, cellulose derivative, guar gum, xanthan Glue, glucan, carboxyl vinyl polymer, Sodium Polyacrylate, hyaluronidase, hyaluronic acid, Sodium Hyaluronate, chondroitin sulfate Element, locust bean gum, poloxamer, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, gellan gum, Pulan polysaccharide, marine alga It is acid, methylcellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, poly- Derivative of vinyl alcohol or dextrin and dextrin etc. and their mixture；Thickener more preferably poloxamer, chondroitin sulfate, first Base cellulose, hydroxypropyl methyl cellulose, gellan gum, hydroxyethyl cellulose, polyvinylpyrrolidone, polyethylene glycol, thoroughly Bright matter acid or Sodium Hyaluronate, trehalose etc., the more excellent concentration with 0.02%-1wt% uses in eye drops；

The excipient of pharmaceutically acceptable carrier --- gel or the filler of the matrix of film or adhesion tablet are selected from but not only It is limited to the polymerization of chitosan, poly- (hydroxyethyl meth acrylate), poly- (NVP), polyvinyl alcohol, acrylic acid Thing, carbomer, polyvinyl alcohol, IR, hydroxypropyl methylcellulose, hydroxypropylcellulose, gelatin, Propiram Polysaccharide, modified starch, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone (PVP), carboxymethyl cellulose One or more in plain sodium (CMC-Na), chitosan, gelatin, starch, dextrin, wherein carbomer series include carbomer 934, One or more in carbomer940, Acritamer 940, Carbopol 941, CARBOPOL 974P.

14. claim 1-12 local medical composite for eye, it is characterised in that：Contain effective agent in medical composite for eye The antixerophthalmic polyethylene glycol of amount, trehalose, hyaluronic acid, Sodium Hyaluronate, chitosan, overstate ground phosphorus Suo Si sodium, Lifitegrast, polysaccharide, glucan, chondroitin sulfate, poloxamer, polyvinyl alcohol, polyvinylpyrrolidone, Methyl cellulose One or more in element, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, sodium carboxymethylcellulose, cellulose derivative.

15. the purposes of claim 1~12, wherein the composition is used to prepare the external ear for treating or preventing people or mammal Application in the topical drug of scorching and tympanitis illness, the ear of ear or nasa surgery operation patient or nose.

16. the purposes of claim 1~12, wherein the composition is used to prepare the conjunctiva for treating or preventing people or mammal Inflammation, angular blepharitis, keratitis, dacryocystitis, sty, trachoma, sterileization treatment, scheroma or the dry eyes of ophthalmology peri-operation period The application on local eye medicinal on disease or dry eye syndrome or cataract.

17. the purposes of claim 1~12, wherein the composition is used to prepare the sensitivity for treating or preventing people or mammal Skin soft-tissue infection's property disease caused by bacterium, such as epifolliculitis, furuncle, impetigo, trauma infection contamination and eczema infection；Convergence is burnt Wound, scald, the topical skin medicaments application on the pernio surface of a wound.

18. the purposes of claim 1~12, wherein the composition is used to prepare the sensitivity for treating or preventing people or mammal Application on the medicine of canker sore caused by bacterium.