DK162812B - Eye gel composition comprising fusidic acid - Google Patents
Eye gel composition comprising fusidic acid Download PDFInfo
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- DK162812B DK162812B DK425886A DK425886A DK162812B DK 162812 B DK162812 B DK 162812B DK 425886 A DK425886 A DK 425886A DK 425886 A DK425886 A DK 425886A DK 162812 B DK162812 B DK 162812B
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- fusidic acid
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- 239000000203 mixture Substances 0.000 title claims description 33
- IECPWNUMDGFDKC-UHFFFAOYSA-N Fusicsaeure Natural products C12C(O)CC3C(=C(CCC=C(C)C)C(O)=O)C(OC(C)=O)CC3(C)C1(C)CCC1C2(C)CCC(O)C1C IECPWNUMDGFDKC-UHFFFAOYSA-N 0.000 title claims description 18
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical compound O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 title claims description 18
- 229960004675 fusidic acid Drugs 0.000 title claims description 17
- 229920000447 polyanionic polymer Polymers 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 6
- 239000003981 vehicle Substances 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- WLAMNBDJUVNPJU-UHFFFAOYSA-N 2-methylbutyric acid Chemical compound CCC(C)C(O)=O WLAMNBDJUVNPJU-UHFFFAOYSA-N 0.000 claims description 4
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 3
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 239000003755 preservative agent Substances 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 2
- 239000008135 aqueous vehicle Substances 0.000 claims description 2
- 239000000022 bacteriostatic agent Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 239000003381 stabilizer Substances 0.000 claims description 2
- 210000000720 eyelash Anatomy 0.000 claims 1
- 238000002360 preparation method Methods 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000011282 treatment Methods 0.000 description 6
- 239000000499 gel Substances 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 229920002125 Sokalan® Polymers 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 208000001860 Eye Infections Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 208000011323 eye infectious disease Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229940023490 ophthalmic product Drugs 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 239000012086 standard solution Substances 0.000 description 2
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 241000027294 Fusi Species 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000003732 agents acting on the eye Substances 0.000 description 1
- 229960005274 benzocaine Drugs 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 229960001416 pilocarpine Drugs 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
iin
DK 162812 BDK 162812 B
Den foreliggende opfindelse angår en øjengelsammensætning til human og veterinær brug omfattende et øjenlægemiddel og et vehikel baseret på en polyanionisk polymer.The present invention relates to an eye gel composition for human and veterinary use comprising an eye drug and a vehicle based on a polyanionic polymer.
Et af hovedproblemerne i forbindelse med topisk øjenterapi 5 er at opretholde en passende koncentration af øjenlægemidlet på det ønskede aktionssted i et længere tidsrum. Således kan kun et ringe rumfang af et præparat indeholdes i fornix inferior, og det påførte præparat har tendens til at blive fortyndet af tårerne og at blive bortledt gennem næsetårekanalen.One of the main problems associated with topical eye therapy 5 is to maintain an appropriate concentration of the ophthalmic drug at the desired site of action for a prolonged period of time. Thus, only a small volume of a composition can be contained in the fornix inferiorly, and the applied composition tends to be diluted by the tears and to be discharged through the nasal canal.
10 Det er velkendt, at virkningstiden for kationiske øjenlæge- midler kan forøges ved at inkorporere sådanne lægemidler i geler baseret på polyanioniske polymerer, jvf. tysk offentliggørelsesskrift nr. 29 02 863, R.D. Schoenwald et al.: Influence of high-vis-cosity vehicles on miotic effect of pilocarpine, Jour, of Pharm.10 It is well known that the duration of action of cationic ophthalmic drugs can be increased by incorporating such drugs into gels based on polyanionic polymers, cf. German Publication No. 29 02 863, R.D. Schoenwald et al .: Influence of high-vis-cosity vehicles on the meiotic effect of pilocarpine, Jour, or Pharm.
15 Sciences, bind 67, nr. 9, september 1978, 1280-1283, F. Bottari et al: Semisolid ophthalmic vehicles II: Evaluation in albino rabbits of aqueous gel-type vehicles containing lidocaine and benzocaine,15 Sciences, Volume 67, No. 9, September 1978, 1280-1283, F. Bottari et al: Semisolid ophthalmic vehicles II: Evaluation in albino rabbits of aqueous gel-type vehicles containing lidocaine and benzocaine,
Can. J. of Pharm. Sci., bind 14, nr. 2, 1979, 39-43, og Engelbert Graf et al.: Interaction of Carbopol® 934 with diphenhydramine and 20 dexchlorpheniramine, Acta Pharmaceutica Technologica, 29 (3), 1983, 209-215.Can. J. of Pharm. Sci., Vol. 14, No. 2, 1979, 39-43, and Engelbert Graf et al .: Interaction of Carbopol® 934 with diphenhydramine and dexchloropheniramine, Acta Pharmaceutica Technologica, 29 (3), 1983, 209-215.
Disse gel sammensætninger har en virkningstid, som er ca. dobbelt så stor som for et kendt øjenpræparat.These gel compositions have an operating time which is approx. twice the size of a known eye preparation.
Det har nu overraskende vist sig, at øjeninfektioner kan 25 bekæmpes særdeles effektivt med en sammensætning omfattende fusidin-syre suspenderet i en gel af den ovenfor nævnte art.It has now surprisingly been found that eye infections can be very effectively combated with a composition comprising fusidic acid suspended in a gel of the kind mentioned above.
Sammensætningen ifølge opfindelsen omfatter fra 0,1 til 4%, vægt/volumen, fusidinsyre suspenderet i en vandig vehikel indeholdende fra 0,2 til 2%, vægt/volumen, polyanionisk polymer.The composition of the invention comprises from 0.1 to 4%, w / v, fusidic acid suspended in an aqueous vehicle containing from 0.2 to 2%, w / v, polyanionic polymer.
30 Den overraskende effektivitet af sammensætningen ifølge opfindelsen kommer til udtryk ved, at virkningstiden er ca. 10 gange større end for et præparat baseret på fusidinsyre og et kendt geldannelsesmiddel, jvf. nedenstående eksempel.The surprising efficiency of the composition according to the invention is expressed in that the operating time is approx. 10 times greater than that of a composition based on fusidic acid and a known gelling agent, cf. the example below.
Den meget væsentlige forlængelse af virkningen af fusidin er 35 særlig overraskende, når henses til, at man hidtil har formodet, at den forlængede virkning af de kendte sammensætninger baserer sig på en vekselvirkning mellem et positivt ladet lægemiddel og den negativt ladede polymer. Det kunne således forventes, at et lægemiddel,, såsom fusidinsyre, som er negativt ladet ved øjets pH-værdi, d.v.s.The very substantial prolongation of the action of fusidine is particularly surprising, considering that it has hitherto been thought that the prolonged action of the known compositions is based on an interaction between a positively charged drug and the negatively charged polymer. Thus, it could be expected that a drug, such as fusidic acid, which is negatively charged at the pH of the eye, i.e.
DK 162812BDK 162812B
2 ca. 7,4, ikke ville være i stand til at vekselvirke med den polyani-oniske polymer og tilvejebringe en forlænget virkning.2 approx. 7.4, would not be able to interact with the polyanionic polymer and provide an extended effect.
Sammensætningen ifølge opfindelsen er særlig anvendelig til lokal behandling af øjeninfektioner. Medens kendte øjenpræparater, 5 såsom chloramphenicol øjendråber, skal påføres 5-6 gange om dagen eller endnu oftere, er det således tilstrækkeligt at påføre præparater baseret på sammensætningen ifølge opfindelsen 1-2 gange daglig.The composition of the invention is particularly useful for the local treatment of eye infections. Thus, while known eye preparations, such as chloramphenicol eye drops, should be applied 5-6 times a day or even more frequently, it is sufficient to apply compositions based on the composition of the invention 1-2 times daily.
Sammensætningen ifølge opfindelsen indeholder fortrinsvis 10 ca. 1%, vægt/volumen, fusi di nsyre i form af partikler med en partikelstørrelse, der ikke overstiger 10 μηι og fortrinsvis er mellem 2 og 5 øm.Preferably, the composition of the invention contains about 10%. 1%, w / v, fusi diacid in the form of particles having a particle size not exceeding 10 μηι and preferably between 2 and 5 s.
Den polyanioniske polymer er fortrinsvis. en carboxyvinyl-polymer med en molekylvægt på fra ca. 400.000 til ca. 6 mill. De 15 viskose opløsninger, som dannes under fremstillingen af polymersuspensionen, har en viskositet på fra 10 til ca. 20.000 cP ved 25°C målt ved hjælp af RVT Brookfield viskosimeter.The polyanionic polymer is preferably. a carboxyvinyl polymer having a molecular weight of from ca. 400,000 to approx. 6 mill. The 15 viscous solutions formed during the preparation of the polymer suspension have a viscosity of from 10 to approx. 20,000 cP at 25 ° C measured by RVT Brookfield viscometer.
Den polyanioniske polymer er fortrinsvis af den type, som forekommer i handelen under varebetegnelsen "Carbopol" (B.F. Good-20 rich Company). En særlig foretrukken polyanionisk polymer er "Carbopol 934". "Carbopol" polymererne slører ikke det normale syn, idet gel strukturen nedbrydes kort tid efter påføringen på øjet under indvirkning af ioner, som er indeholdt i tårevæsken.The polyanionic polymer is preferably of the type that is commercially available under the trade name "Carbopol" (B.F. Good-rich Company). A particularly preferred polyanionic polymer is "Carbopol 934". The "Carbopol" polymers do not blur the normal view as the gel structure degrades shortly after application to the eye under the action of ions contained in the tear fluid.
pH-værdien for sammensætningen ifølge opfindelsen er for-25 trinsvis fra 5,0 til 6,5 og særligt foretrukket omkring 5,8.The pH of the composition of the invention is preferably from 5.0 to 6.5 and particularly preferably about 5.8.
Indstillingen af pH-værdien udføres fortrinsvis med en farmaceutisk og fysiologisk acceptabel base, såsom natriumhydroxid.The pH adjustment is preferably carried out with a pharmaceutically and physiologically acceptable base such as sodium hydroxide.
Et præparat baseret på sammensætningen ifølge opfindelsen kan indeholde hjælpemidler, såsom konserveringsmidler, stabiliseringsmidler 30 og bakteriostatiske midler.A composition based on the composition of the invention may contain adjuvants such as preservatives, stabilizers 30 and bacteriostatic agents.
Præparater baseret på sammensætningen ifølge opfindelsen anvendes fortrinsvis i doser på fra 5 til 100 mg og særligt foretrukket fra 2 til 50 mg, når præparatet tilføres fornix inferior i et inficeret øje.Preferably, compositions based on the composition of the invention are used in doses of from 5 to 100 mg and particularly preferably from 2 to 50 mg when the composition is administered to the inferix inferiorly in an infected eye.
35 Behandlingsfrekvensen varierer afhængig af infektionsgrad.The frequency of treatment varies depending on the degree of infection.
Som ovenfor nævnt er det normalt tilstrækkeligt at foretage en påføring to gange om dagen.As mentioned above, it is usually sufficient to apply twice a day.
Opfindelsen skal herefter beskrives nærmere under henvisning til følgende eksempel:The invention will now be described in more detail with reference to the following example:
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33
• EKSEMPEL• EXAMPLE
Der fremstilledes et øjenpræparat med følgende sammensætning pr. ml: 5 Præparat A:An eye preparation was prepared having the following composition per day. ml: 5 Preparation A:
Fusidinsyre, mikroniseret, steril 10 mg "Carbopol 934" 5 mgFusidic acid, micronized, sterile 10 mg "Carbopol 934" 5 mg
Natriumhydroxid, 5N, q.s. til pH = 5-6,0 Mannitol 50 mg 10 Benzalkoniumchlorid 0,1 mgSodium hydroxide, 5N, q.s. to pH = 5-6.0 Mannitol 50 mg 10 Benzalkonium chloride 0.1 mg
Tetracemindinatrium 0,5 mgTetracemindium sodium 0.5 mg
Vand, sterilt, op til 1 mlWater, sterile, up to 1 ml
Benzalkoniumchlorid, tetracemindinatrium og mannitol opløses 15 i det sterile vand.Benzalkonium chloride, tetracemin disodium and mannitol are dissolved in the sterile water.
"Carbopol 934" suspenderes aseptisk i opløsningen og steriliseres ved autoklavering ved 120°C i 20 minutter. Suspensionen afkøles, og den sterile fusidinsyre suspenderes heri. Til slut neutraliseres suspensionen ved tilsætning af steril natriumhydrox-20 idopløsning."Carbopol 934" is aseptically suspended in the solution and sterilized by autoclaving at 120 ° C for 20 minutes. The suspension is cooled and the sterile fusidic acid is suspended therein. Finally, the suspension is neutralized by the addition of sterile sodium hydroxide solution.
Det således fremstillede præparat (i det følgende betegnet præparat A) sammenlignedes med et præparat af fusidinsyre suspenderet i et vehikel baseret på et kendt gel dannende middel og yderligere indeholdende konserveringsmidler, tonicitetsmidler og en puf-25 fer. Dette præparat (i det følgende betegnet præparat B) havde følgende sammensætning pr. ml:The preparation thus prepared (hereinafter referred to as Preparation A) was compared with a preparation of fusidic acid suspended in a vehicle based on a known gel-forming agent and further containing preservatives, tonicity agents and a buffer. This preparation (hereinafter referred to as Preparation B) had the following composition per day. ml:
Præparat BPreparation B
Fusidinsyre, mikroniseret, steril 10 mg 30 Hydroxyethylcel1ulose 4 mgFusidic acid, micronized, sterile 10 mg 30 Hydroxyethyl cellulose 4 mg
Methyl cellul ose 0,2 mgMethyl cellulose 0.2 mg
Natriumacetat 1 mgSodium acetate 1 mg
Iseddikesyre, q.s. til pH = 5-6,0Glacial acetic acid, q.s. to pH = 5-6.0
Natriumchlorid 9 mg 35 Phenethanol 2,5 mgSodium chloride 9 mg Phenethanol 2.5 mg
Vand, sterilt, op til 1 ml.Water, sterile, up to 1 ml.
De to præparater sammenlignedes på følgende måde:The two preparations were compared as follows:
Fem new zealandske hvide kaniner med en vægt på ca. 3 kg 4Five New Zealand white rabbits weighing approx. 3 kg 4
DK 162812BDK 162812B
anvendtes ved undersøgelserne. Kaninerne betegnedes nr. 1-5 og anbragtes i begrænsningskasser de første 6 timer af undersøgelsesperioden og ved 24 timers prøveudtagningen. Mellem den 6.. time og 24 timers prøveudtagningen var dyrene i separate rum og fik pelleti-5 seret foder og vand ad libitum.used in the studies. The rabbits were designated # 1-5 and placed in restriction boxes for the first 6 hours of the study period and at the 24 hour sampling. Between the 6th hour and 24 hour sampling, the animals were in separate compartments and fed pelletized feed and water ad libitum.
Prøver til mi krobiologi sk undersøgelse blev udtaget ved at anbringe 6,0 ml AA skiver (Whatman) i fornix inferior, ved at lukke øjenlågene i ca. 10 sekunder og ved at fjerne skiverne med pincet. Skiverne anbragtes derpå på overfladen af podede agar-skåle med en 10 diameter på 14 cm sammen med skiver, der var blevet forbehandlet med standardopløsninger i 10 sekunder.Samples for microbiology study were taken by placing 6.0 ml AA slices (Whatman) in the fornix inferior, by closing the eyelids for approx. 10 seconds and by removing the washers with tweezers. The slices were then placed on the surface of grafted agar dishes of 10 cm diameter along with slices which had been pretreated with standard solutions for 10 seconds.
Skålene inkuberedes i 16 til 18 timer ved optimal temperatur for den omhandlede prøveorganisme. Prøvernes . inhiberingszoner måltes, og der foretoges interpolation på standardkurven, som blev 15 fastlagt som den bedste responslinie på basis af inhiberingszonerne for standardopløsningerne.The dishes were incubated for 16 to 18 hours at optimum temperature for the subject organism. The samples. inhibition zones were measured and interpolation was performed on the standard curve, which was determined as the best response line based on the inhibition zones for the standard solutions.
Forud for hver undersøgelse undersøgtes tårevæsken for hver kanin for at konstatere, at der ikke var stoffer til stede, som er inhiberende for prøveorganismerne.Prior to each study, the tear fluid for each rabbit was examined to find that there were no substances present which are inhibitory to the test organisms.
20 En dråbe af hvert præparat indførtes i fornix inferior på det venstre øje af hver af de fem kaniner. Prøver blev udtaget 1, 2,4,6 og 24 timer efter behandlingen.A drop of each preparation was introduced into the fornix inferior on the left eye of each of the five rabbits. Samples were taken 1, 2,4,6 and 24 hours after treatment.
Der var en periode på mindst 72 timer mellem behandlinger med forskellige præparater.There was a period of at least 72 hours between treatments with different preparations.
25 De opnåede resultater er angivet i nedenstående tabel, som viser, at fusidinsyre er til stede i målelige koncentrationer 24 timer efter behandlingen.The results obtained are given in the table below which shows that fusidic acid is present at measurable concentrations 24 hours after treatment.
Koncentrationen af fusidinsyre i 24 timers prøverne er imidlertid ca. 10 gange større for præparat A end for præparat B.However, the concentration of fusidic acid in the 24 hour samples is approx. 10 times greater for Preparation A than for Preparation B.
30 3530 35
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55
TABELTABLE
/tg fusidinsyre pr. ml tårevæske Dyr nr. Timer efter behandling 0 1 2 4 6 24/ tg fusidic acid per ml tear fluid Animal No. Hours after treatment 0 1 2 4 6 24
Præparat A 1 - 45 45 25 20 6 2 32 20 6 5 4 3 - 113 24 20 4 5 4 - 32 28 40 22 4 5 57 18 6 15 4Preparation A 1 - 45 45 25 20 6 2 32 20 6 5 4 3 - 113 24 20 4 5 4 - 32 28 40 22 4 5 57 18 6 15 4
Præparat B 1 14 5 5 3 0,4 2 - 20 12 11 8 0,2 3 - 28 28 8 6 0,6 4 - 23 10 4 4 0,4 5 - 34 12 10 4 0,5 -: viser en værdi, som er lavere end påvisningsgrænsen på 0,02 øg fusidinsyre pr. ml.Preparation B 1 14 5 5 3 0.4 2 - 20 12 11 8 0.2 3 - 28 28 8 6 0.6 4 - 23 10 4 4 0.4 5 - 34 12 10 4 0.5 -: shows a value which is lower than the detection limit of 0.02 increase fusidic acid per day. ml.
Claims (6)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DK425886A DK162812C (en) | 1985-01-07 | 1986-09-05 | ANGELING COMPOSITION CONTAINING FUSIDIC ACID |
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8500310 | 1985-01-07 | ||
| GB858500310A GB8500310D0 (en) | 1985-01-07 | 1985-01-07 | Pharmaceutical preparation |
| PCT/DK1986/000002 WO1986003966A1 (en) | 1985-01-07 | 1986-01-07 | Ophthalmic gel composition and method of treating eye infections |
| DK8600002 | 1986-01-07 | ||
| DK425886A DK162812C (en) | 1985-01-07 | 1986-09-05 | ANGELING COMPOSITION CONTAINING FUSIDIC ACID |
| DK425886 | 1986-09-05 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| DK425886D0 DK425886D0 (en) | 1986-09-05 |
| DK425886A DK425886A (en) | 1986-09-05 |
| DK162812B true DK162812B (en) | 1991-12-16 |
| DK162812C DK162812C (en) | 1992-05-04 |
Family
ID=26067409
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK425886A DK162812C (en) | 1985-01-07 | 1986-09-05 | ANGELING COMPOSITION CONTAINING FUSIDIC ACID |
Country Status (1)
| Country | Link |
|---|---|
| DK (1) | DK162812C (en) |
-
1986
- 1986-09-05 DK DK425886A patent/DK162812C/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| DK425886D0 (en) | 1986-09-05 |
| DK162812C (en) | 1992-05-04 |
| DK425886A (en) | 1986-09-05 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUP | Patent expired |