DK173326B1

DK173326B1 - Focal ophthalmic preparation which comprises a combination of tobramycin and steroids

Info

Publication number: DK173326B1
Application number: DK198905619A
Authority: DK
Inventors: Gerald D Cagle; Thomas O Mcdonald; Allan L Rosenthal
Original assignee: Alcon Lab Inc
Priority date: 1988-03-09
Filing date: 1989-11-09
Publication date: 2000-07-24
Also published as: DK561989D0; DE365613T1; DK561989A

Description

DK 173326 B1DK 173326 B1

Den foreliggende opfindelse angår et præparat til ophthalmisk brug Indeholdende antibiotika i kombination med ant1 inflammatoriske steroider til brug ved behandling for ophthalmiske infektioner med ledsagende inflammation.The present invention relates to a composition for ophthalmic use Containing antibiotics in combination with anti-inflammatory steroids for use in the treatment of ophthalmic infections with accompanying inflammation.

55

Inden for den ophthalmiske teknik kendes præparater med antibiotika eller steroider. Der er imidlertid bekymringer og udtrykt tilbageholdenhed inden for den ophthalmiske verden med hensyn til sikkerheden og effektiviteten hos sådanne kendte 10 kombinationer. Der findes desuden et lange følt behov for et effektivt og sikkert fokalt ophthalmisk farmaceutisk praparat med et kraftigt steroid og et bredspektret antibiotikum, som, når det indgives til øjet, når ejer er indikation for bakterieinfektion eller som et profylaktisk middel efter ophthalmisk 15 trauma og beskadigelse, ikke som et muligt udtryk for den ste-roide bestanddel vil inhibere aktiviteten hos antibiotiket eller på skadelig måde indvirke i den normale sårheling, men derimod samtidig vil modvirke inflammation.In the ophthalmic technique, preparations with antibiotics or steroids are known. However, there are concerns and expressed restraint within the ophthalmic world regarding the safety and efficacy of such known combinations. There is also a long felt need for an effective and safe focal ophthalmic pharmaceutical preparation with a powerful steroid and a broad spectrum antibiotic which, when administered to the eye when the owner is indicative of bacterial infection or as a prophylactic agent after ophthalmic trauma and injury , not as a possible expression of the steroid component will inhibit the activity of the antibiotic or adversely affect normal wound healing, but at the same time will counteract inflammation.

2020

Ifølge den foreliggende opfindelse har det vist sig, at det bredspektrerede aminoglycosi-dantibiotikum tobramycin i kombination med dexamethason, der er et kraftigt steroid, opfylder disse kriterier.According to the present invention, it has been found that the broad-spectrum aminoglycoside antibiotic tobramycin in combination with dexamethasone, which is a potent steroid, meets these criteria.

2525

Den foreliggende opfindelse anviser fokale ophthalmiske præparater, der i kombination omfatter aminoglycosidantibiotiket tobramycin med det kraftige steroid, dexamethason.The present invention provides focal ophthalmic compositions which in combination comprise the aminoglycoside antibiotic tobramycin with the potent steroid, dexamethasone.

30 Den foreliggende opfindelse anviser fokale ophthalmiske præparater, der omfatter blandinger af det bredspektrede aminoglycosid-antibiotikum tobramycin i kombination med dexamethason. Mængden af tobramycin og dexamethason vil omfatte en terapeutisk effektiv mængde af hvert stof i kombination med en passende farmaceutisk acceptabel 3 s ophthalmisk vehikel. Fortrinsvis vil forholdet mellem tobramycin og dexamethason ligge DK 173326 B1 2 i området fra henholdsvis 0,1 til 1,0 op til 10,0 til 1,0. Fortrinsvis vil blandingen indeholde en vægtmængde tobramycin, der er ca. tre gange vægtmængden af steroidet.The present invention provides focal ophthalmic compositions comprising mixtures of the broad-spectrum aminoglycoside antibiotic tobramycin in combination with dexamethasone. The amount of tobramycin and dexamethasone will comprise a therapeutically effective amount of each substance in combination with a suitable pharmaceutically acceptable 3 s ophthalmic vehicle. Preferably, the ratio of tobramycin to dexamethasone will range from 0.1 to 1.0 up to 10.0 to 1.0, respectively. Preferably, the mixture will contain a weight amount of tobramycin which is approx. three times the weight amount of the steroid.

Tobramycin er et vandopløseligt aninoglycosidantibiotikum, der 5 er kendt kemisk som 0-3-anHno-3-desoxy-a-D-g1ucopyranosy 1 - (1 -* 4}-0-[2,6-diaminO“2,3,6-tridesoxy-o-D-ribo-hexapyranosy1 -(1 -* 6)]-2-desoxy-L~streptam1n. Tobramycin er rapporteret som forbindelse 9318 i the Merck Index, 10. udgave, 1983.Tobramycin is a water-soluble aninoglycoside antibiotic known chemically as 0-3-anHno-3-deoxy-α-D-glycopyranosyl 1- (1 - * 4} - 0 - [2,6-diamineO 2,3,6-tridesoxy -oD-ribo-hexapyranosyl [1- (6)] - 2-deoxy-L-streptamine Tobramycin is reported as compound 9318 in the Merck Index, 10th edition, 1983.

10 Dexamethason er en syntetisk analog til cortisol og har en kraftig antiinflammatorisk effekt. Det har en molekylvagt på 392,4 og dets kemiske navn er 9-fluor-110,17,21-trihydroxy-16a-methylpregna-l,4-dien-3,20-dion. Dexamethanson er beskrevet som forbindelse 2906 i the Merck Index, 10. udgave, 1983.10 Dexamethasone is a synthetic analogue of cortisol and has a powerful anti-inflammatory effect. It has a molecular weight of 392.4 and its chemical name is 9-fluoro-110,17,21-trihydroxy-16a-methylpregna-1,4-diene-3,20-dione. Dexamethansone is described as compound 2906 in the Merck Index, 10th edition, 1983.

1515

Præparaterne ifølge opfindelsen omfatter blandinger af tobramycin og dexamethason i de angivne mængder. Præparaterne vil også indeholde andre ingredienser, der konven- 20 tionelt anvendes i ophthalmiske præparater, såsom antimikrobielle konserveringsmidler, co-opløsningsmidler, viskositetsregulerende midler og lignende.The compositions of the invention comprise mixtures of tobramycin and dexamethasone in the amounts indicated. The compositions will also contain other ingredients conventionally used in ophthalmic compositions such as antimicrobial preservatives, co-solvents, viscosity regulators and the like.

Præparaterne ifølge opfindelsen indgives fokalt til mennesker og dyr. Dosisområdet er 25 0,001 til 5,0 mg pr. øje, hvor de nævnte tal for massen repræsenterer summen af de to bestanddele, dexamethason og tobramycin. Præparaterne ifølge opfindelsen kan indgives som opløsninger, suspensioner eller emulsioner (dispersioner) i en egnet ophthalmisk vehikel.The compositions of the invention are administered focally to humans and animals. The dose range is 0.001 to 5.0 mg per dose. eye, wherein said figures for the mass represent the sum of the two constituents, dexamethasone and tobramycin. The compositions of the invention may be administered as solutions, suspensions or emulsions (dispersions) in a suitable ophthalmic vehicle.

3030

Ved udformning af præparater til fokal indgift formuleres blandingerne af antibiotikum og dexamethason fortrinsvis som 0,01 til 2,0 vægt% opløsninger i vand ved en pH-værdi på 4,5 til 9,0 (talværdierne angår den kombinerede tilstedeværelse af tobramycin og 35 dexamethason). Selv om den nøjagtige behandling overlades til lægens skøn, anbefales DK 173326 B1 3 det, at den resulterende opløsning påføres forkalt ved at anbringe en dråbe i hvert øje hos mennesket eller dyret to gange om dagen.In designing focal administration formulations, the mixtures of antibiotic and dexamethasone are preferably formulated as 0.01 to 2.0% by weight solutions in water at a pH of 4.5 to 9.0 (the numerical values relate to the combined presence of tobramycin and 35 dexamethasone). Although the exact treatment is left at the discretion of the physician, it is recommended that the resulting solution be applied coldly by applying a drop to each eye of the human or animal twice a day.

Anti mikrobielt konserveringsmiddel 5 Ophthalmiske produkter emballeres typisk 1 multidosisform. Konserveringsmidler behøves derfor for at forhindre mikrobiel forurening under anvendelsen. Velegnede konserveringsmidler indbefatter: benzalkoniumchlorid, thimerosal, chlorbutanol, methyl paraben, propylparaben, phenylethylalkohol, edetat-di-2o natrium, sorbinsyre, onaner H eller andre midler, som er kendt for fagfolk. Typisk anvendes sådanne konserveringsmidler 1 en koncentration fra 0,001 til 1,0 vagt* 1 formuleringen.Anti-microbial preservative 5 Ophthalmic products are typically packaged in 1 multi-dose form. Preservatives are therefore needed to prevent microbial contamination during use. Suitable preservatives include: benzalkonium chloride, thimerosal, chlorobutanol, methyl paraben, propylparaben, phenylethyl alcohol, edetate-di-2-sodium, sorbic acid, masturbation H or other agents known to those skilled in the art. Typically, such preservatives 1 are used in a concentration of 0.001 to 1.0 weight * 1 formulation.

Co-opløsningsmidler 15Co-solvents 15

Opløseligheden af bestanddelene 1 praparaterne Ifølge opfindelsen kan forøges med et overfladeaktivt middel eller et andet passende co-opløsningsmiddel 1 præparatet. Sådanne co-op-løsnlngsmldler indbefatter polysorbat 20, 60 og 60, Pluronlc 20 F-66, F-64 og P-103, cyklodextrin og andre midler, som er kendt for fagfolk. Typisk anvendes sådanne co-opløsningsmidler 1 en koncentration fra 0,01 til 2 vagt* af formuleringen.The solubility of the constituents 1 of the compositions of the invention may be increased by a surfactant or other suitable co-solvent 1 of the composition. Such co-op solvents include polysorbate 20, 60 and 60, Pluronlc 20 F-66, F-64 and P-103, cyclodextrin and other agents known to those skilled in the art. Typically, such co-solvents 1 are used at a concentration of 0.01 to 2 wt * of the formulation.

Viskositetsmid ler 25Viscosity agent 25

Viskositetsstigning over viskositeten for simple vandige opløsninger kan vare ønskelig for at forøge ocular absorption af den aktive forbindelse, for at sanke variabiliteten ved dis-penserlng af formuleringen, for at nedsatte fysisk adskillelse 30 af bestanddelene 1 en suspension eller emulsion af formuleringen og/eller for ellers at forbedre den ophthalmiske formulering. Sådanne viskositetsdannende midler indbefatter f.eks.Viscosity increase over the viscosity of simple aqueous solutions may be desirable to increase ocular absorption of the active compound, to decrease the variability in dispensing the formulation, to reduce physical separation of the constituents of a suspension or emulsion of the formulation and / or otherwise to improve the ophthalmic formulation. Such viscosity forming agents include, e.g.

' 35 DK 173326 B1 4 polyvinylalkohol, polyvi nyl pyrrol idon, methylcellulose, hydro-xypropy1 methyl cel lul ose, hydroxyethylcellulose, carboxymethy1 -cellulose, hydroxypropylcellulose eller andre midler, der er kendt for fagfolk. Sådanne midler anvendes typisk i en koncen-5 tration fra 0,01 til 2 vagt*.Polyvinyl alcohol, polyvinyl pyrrolidone, methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose or other agents known to those skilled in the art. Such agents are typically used in a concentration of 0.01 to 2 watch *.

, Kombinationen af tobramycin og dexamethason ifølge opfindelsen giver et fokalt middel, der drager fordel af den bredspektrede aktivitet hos tobramy-10 cin over for oculare patogener indbefattet nogle stammer, der er resistente over for andre antibiotika, fordi det har et lavt potentiale for udvikling af resistens og lavere forekomst af overfølsomhedsreaktioner sammenlignet med andre antibiotika, såsom neomycin, som ofte har varet anvendt i kombination 15 med steroider.The combination of tobramycin and dexamethasone according to the invention provides a focal agent that benefits from the broad spectrum activity of tobramycin against ocular pathogens including some strains resistant to other antibiotics because it has a low potential for development of resistance and lower incidence of hypersensitivity reactions compared to other antibiotics, such as neomycin, which have often been used in combination with steroids.

I det kombinerede farmaceutiske praparat ifølge opfindelsen har det vist sig, at tobramycin forbliver et højeffektivt antibiotisk middel mod følsomme stammer af mikroorganismer, så-20 som stafylokokker Indbefattet S. aureus og S. epidermis, indbefattet penicillinresistente stammer såvel som streptokokker Indbefattet nogle gruppe A-arter og nogle Streptococcus pneumoniae. Det farmaceutiske kombinationspraparat har vist sig at vare effektiv ved behandling af de fleste eksterne oculare 1n-25 fektioner forårsaget af bakterier.In the combined pharmaceutical composition of the invention, it has been found that tobramycin remains a highly effective antibiotic against susceptible strains of microorganisms, such as staphylococci including S. aureus and S. epidermis, including penicillin resistant strains as well as streptococci. species and some Streptococcus pneumoniae. The pharmaceutical combination composition has been found to be effective in treating most external ocular 1n-25 infections caused by bacteria.

Praparaterne Ifølge opfindelsen er beregnet til behandling af patienter (dvs. "varter"), som udviser symptomerne forbundet med ophthalmiske infektioner og ledsagende inflammation såvel 30 som til behandling af inflammation hos patienter, der kan vare foruddlsponeret for udvikling af en ophthalmisk infektion, enten som et resultat af en immunundertrykkende effekt som tilskrives den steroide bestanddel 1 praparatet eller som resultatet af en tilstand (f.eks. skade), der ikke er forbundet 35 med steroidbehandlingen. Symptomerne, som er ledsaget med disse tilstande, er velkendte for ophthalmologer (dvs. lager med speciale 1 behandling af øjensygdomme) såvel som andre lager DK 173326 B1 5 og klinikere, som har ekspertise inden for behandlingen af ophthalmiske infektioner og inflammation.The compositions of the invention are intended for the treatment of patients (i.e., "hosts") who exhibit the symptoms associated with ophthalmic infections and accompanying inflammation, as well as for the treatment of inflammation in patients who may be predisposed to developing an ophthalmic infection, either as a result of an immunosuppressive effect attributed to the steroid component 1 of the preparation or as the result of a condition (e.g., damage) not associated with the steroid treatment. The symptoms associated with these conditions are well known to ophthalmologists (ie, specialist in the treatment of eye diseases) as well as other stockists and clinicians who have expertise in the treatment of ophthalmic infections and inflammation.

Der har lange varet et behov på det ophthalmiske område for en 5 forbedret, effektiv og sikker kombination af et antibiotikum og et antiinflammatorisk steroid. For at vare både effektiv og sikker må den ene bestanddel ikke kunne indvirke med eller andre virkningen hos den anden bestanddel. F.eks. må steroid-bestanddelen vare 1 stand til at bekampe inflammation uden at 10 Indvirke med virkningen hos antibiotiket. Den foreliggende opfindelse er baseret på den opdagelse, at en sarlig kombination af tobramycin og dexamethason tilfredsstiller disse kriterier.There has long been a need in the ophthalmic field for an improved, effective and safe combination of an antibiotic and an anti-inflammatory steroid. In order to be both effective and safe, one component must not be able to interfere with or affect the other component. Eg. the steroid component must be able to fight inflammation without interfering with the action of the antibiotic. The present invention is based on the finding that a particular combination of tobramycin and dexamethasone meets these criteria.

15 Toksikologien hos det farmaceutiske kombinationspraparat ifølge opfindelsen har vist sig at have en sikkerhedsmargen, der er lige så god eller bedre end den, der findes hos andre kombinationer af antibiotikum og steroid. Desuden er det ved kliniske effektivitetsundersøgelser vist, at det farmaceutiske 20 kombinationspraparat er sikkert og effektivt, når det anvendes forud for og efter ocularkirurgi.The toxicology of the pharmaceutical combination composition of the invention has been found to have a safety margin as good or better than that found in other combinations of antibiotic and steroid. In addition, clinical efficacy studies have shown that the pharmaceutical combination is safe and effective when used before and after ocular surgery.

Som navnt oven for er praparatet ifølge opfindelsen sarligt velegnet til brug som ophthalmiske praparater, der skal påfø-25 res fokalt, fortrinsvis ved Indgivelse af dråber i øjet efter den kliniske indikation. Det foretrukne praparat omfatter et præparat, der indeholder 0,3 vægt% tobramycin og 0,1 vægt% dexamethason. Blandingerne dannes ved konventionel sammenblanding af de nødvendige mængder af hvert af 3 de aktive materialer i kombination med de øvrige komponenter, som ønskes inkluderet i præparatet.As mentioned above, the composition according to the invention is particularly suitable for use as ophthalmic preparations to be applied focally, preferably by administration of drops in the eye according to the clinical indication. The preferred composition comprises a composition containing 0.3% by weight tobramycin and 0.1% by weight dexamethasone. The mixtures are formed by conventional mixing of the required amounts of each of the 3 active materials in combination with the other components desired to be included in the composition.

De efterfølgende eksempler er reprasentative farmaceutiske praparater ifølge opfindelsen til fokalt brug, når der er 1n-35 dikatlon mod inflammation og infektion. Dele er vagtdele med mindre andet er angivet. Eksemplerne anviser foretrukne formuleringer .The following examples are representative pharmaceutical preparations of the invention for focal use when there is 1n-35 dicatlon for inflammation and infection. Parts are guard parts unless otherwise stated. The examples show preferred formulations.

DK 173326 B1 6DK 173326 B1 6

Eksempel IExample I

dexamethason, 1,0 mg + 5* overskud 0,10% + 5% overskuddexamethasone, 1.0 mg + 5 * excess 0.10% + 5% excess

mikroniseret USPmicronized USP

5 tobramycin USP 3,0 mg + 5% overskud 0,30% + 5% overskud benzalkon iumchlo-ridopløsni ng (10%) NF 0,001 ml+10% overskud 0,10% + 10% overskudi di natriumedetat, USP 0,1 mg 0,10% natriumchlorld, USP 3,0 mg 0,3 % 1Q natriumsulfat, USP 12,0 mg 1,2 % tyloxapol, USP 0,5 mg 0,05% hydroxyethyl- cellulose 2,5 mg 0,25% svovlsyre og/eller natriumhydroxid, NF qs til pH-indsti 1 Ung til 5,5 ± 0,5 renset vand, USP qs til 1 ml qs til 100% 15 1 Koncentrationen af benzalkoniumchlorid NF er mkvivalent med 0,01% (+ 10% overskud).5 tobramycin USP 3.0 mg + 5% excess 0.30% + 5% excess benzalkonium chloride solution (10%) NF 0.001 ml + 10% excess 0.10% + 10% excess di sodium edetate, USP 0.1 0.10% sodium chloride, USP 3.0 mg 0.3% 1Q sodium sulfate, USP 12.0 mg 1.2% tyloxapol, USP 0.5 mg 0.05% hydroxyethyl cellulose 2.5 mg 0.25% sulfuric acid and / or sodium hydroxide, NF qs to pH 1 Young to 5.5 ± 0.5 purified water, USP qs to 1 ml qs to 100% 15 1 The concentration of benzalkonium chloride NF is equivalent to 0.01% (+ 10 % surplus).

Eksempel IIExample II

20 dexamethason, mikroniseret, USP 0,1% + 2% overskud 1 mg + 2% overskud tobramycin, mikroniseret, USP 0,3% + 7% overskud 3 mg + 7% overskud ; chlorbutanol, vandfrit, NF 0,5% + 25% overskud 5 mg + 25% overskud 25 mineralolie, USP 5% 50 mg hvid vaseline, USP qs 100% qs 1 g 30 35 7 DK 173326 B120 dexamethasone, micronized, USP 0.1% + 2% excess 1 mg + 2% excess tobramycin, micronized, USP 0.3% + 7% excess 3 mg + 7% excess; chlorobutanol, anhydrous, NF 0.5% + 25% excess 5 mg + 25% excess 25 mineral oil, USP 5% 50 mg white vaseline, USP qs 100% qs 1 g 30 35 7 DK 173326 B1

Eksempel IIIExample III

VV

Klinisk effekt 5 En kontrolleret multicenterundersøgelser gennemførtes med tre undersøgere for at fastslå sikkerheden og effektiviteten hos det ophthalmiske præparat ifølge opfindelsen i forhold til "Maxitrol"·, der er en ophthalmisk suspension, ved forhindring af infektion efter operation, og til bekæmpelse af inflamma-10 tion efter operation efter en kataraktkirurgi. Den ophthalmiske suspension ifølge opfindelsen var formuleringen ifølge eksempel 1, som indeholdt 0,3 vægtt tobramycin og 0,1 vægtt de-xamethason. "Maxitrol"· er en i handelen tilgængeligt mulitdo-siskombinationspræparat af antiinficerende steroid i steril 15 suspension til fokal indgift. Den aktive ingrediens er dexa-methason i mængder på 0,1 vægtt. Oe øvrige aktive ingredienser er neomyclnsulfat og polymyxinsulfat. "Maxitrol"· indiceres for inflammatoriske oculartilstande, der reagerer på steroid, hvor der er indikation for et cortikoidsteroid, og hvor der er 2o bakteriel infektion eller er en risiko for at der sker bakteriel ocularinfektion. Se Physician's Desk Reference for Oph-thamology, 12. udgave, 1984, side 72. Disse undersøgelser var dobbeltbli ndundersøge Iser og blev fordelt tilfældigt. Efter den trykte tilmeldelsesundersøgelse fik hver patient givet en 25 kodet behandling og Instrueret om at dosere 1 dråbe hver fjerde time derhjemme i tre dage forud for den kirurgiske behandling. Undersøgelser efter den kirurgiske behandling blev udført på dagene nr. 1, 4, 7, 14 og 21. Doseringen var som følger: 2 dråber hver 2. time, når patienten er vågen i 2 dage 30 begyndende den første gang, der skiftes øjenforbinding dagen efter det kirurgiske Indgreb; 1 dråbe 4 gange om dagen i de efterfølgende 7 dage; 1 dråbe dagligt 1 de næste 10 dage.Clinical efficacy 5 A controlled multicenter study was performed with three investigators to determine the safety and efficacy of the ophthalmic preparation of the invention in relation to "Maxitrol", which is an ophthalmic suspension, in preventing infection after surgery, and in controlling inflammation. after surgery after a cataract surgery. The ophthalmic suspension of the invention was the formulation of Example 1 which contained 0.3 weight tobramycin and 0.1 weight dexamethasone. "Maxitrol" is a commercially available multi-dose combination of anti-infecting steroid in sterile suspension for focal administration. The active ingredient is dexamethasone in 0.1 weight amounts. Other active ingredients are neomycline sulfate and polymyxin sulfate. "Maxitrol" is indicated for inflammatory ocular conditions that respond to steroid, where there is indication of a corticoid steroid and where there is 2o bacterial infection or there is a risk of bacterial ocular infection. See Physician's Desk Reference for Ophthamology, 12th Edition, 1984, page 72. These studies were double-blinded and randomized. Following the printed enrollment study, each patient was given a coded treatment and instructed to dose 1 drop every four hours at home for three days prior to the surgical treatment. Studies after the surgical treatment were performed on days 1, 4, 7, 14 and 21. The dosage was as follows: 2 drops every 2 hours when the patient is awake for 2 days 30 beginning the first time the eye connection is changed day after the surgical procedure; 1 drop 4 times a day for the next 7 days; 1 drop daily 1 for the next 10 days.

Af de 73 patienter, der blev vurderet for effektiviteten, mod-’ 35 tog 36 patienter præparatet ifølge eksempel I, og 37 fik ind givet "Maxitrol"·. De to behandlingsgrupper afvej ikke fra hinanden i de demografiske egenskaber, indledningsvise tegn ogOf the 73 patients evaluated for efficacy, 35 patients received the preparation of Example I and 37 were given "Maxitrol". The two treatment groups did not differ in demographic characteristics, initial signs, and

Claims

2. The invention is now described with reference to certain preferred embodiments. However, it will be understood that variations thereof will be apparent to those skilled in the art and that the invention is not to be construed as limited thereto.

Patent Claim I. Antibiotic / anti-inflammatory ophthalmic pharmaceutical preparation for focal administration to the eye, characterized in that it comprises a therapeutically effective amount of a mixture of tobramycin and the steroid dexamethasone and a suitably pharmaceutically acceptable ophthalmic vehicle. 'in DK 173326 B1

An antibiotic / anti-inflammatory ophthalmic pharmaceutical composition according to claim 1, characterized in that the ratio of tobramycin to steroid is in the range of 0.1: 1.0 to 10.0: 1.0.

Composition according to claim 1, characterized in that it is in the form of an aqueous solution, suspension or emulsion containing 0.01 to 2.0% by weight of the mixture at a pH of 4.5 to 8.0.

Composition according to claim 3, characterized in that it contains approx. 0.3% by weight tobramycin and approx. 0.1 wt% dexamethasone.

Composition according to claim 1, characterized in that it further contains one or more preservatives, co-solvents and / or viscosity-building agents.

Use of a therapeutically effective amount of a mixture of tobramycin and steroidal dexamethasone to produce a combined antibiotic and anti-inflammatory 2nd ophthalmic preparation for the eye for the treatment of inflammation and / or bacterial infection and / or as a prophylactic agent after ophthalmic trauma or lesion.

Use according to claim 6, characterized in that the ratio of tobramycin to steroid is in the range of 0.1: 1.0 to 10.0: 1.0.

Use according to claim 6, characterized in that it is in the form of an aqueous solution, suspension or emulsion containing 0.01 to 2.0% by weight of the combined mixture of tobramycin and steroid at a pH of 4.5 to 8.0.

Use according to claim 8, wherein the composition contains 0.3% by weight tobramycin and 0.1% by weight steroid. DK 173326 B1

Composition according to claim 1, characterized in that it is a suspension containing dexamethasone, 5. tobramycin, benzalkonium chloride, disodium edetate, sodium chloride, sodium sulfate, tyloxapol, hydroxyethyl cellulose, pH regulating agent (sulfuric acid and / or sodium hydroxide and / or sulfuric acid). ), as well as 15 - water.

Composition according to claim 1, characterized in that it is an ointment containing dexamethasone, 20. tobramycin, chlorobutanol, mineral oil and white vaseline. 25 30 3 5 Λ