SE511648C2 - Streptococcus preparations for the treatment of ear inflammation - Google Patents

Streptococcus preparations for the treatment of ear inflammation

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Publication number
SE511648C2
SE511648C2 SE9801337A SE9801337A SE511648C2 SE 511648 C2 SE511648 C2 SE 511648C2 SE 9801337 A SE9801337 A SE 9801337A SE 9801337 A SE9801337 A SE 9801337A SE 511648 C2 SE511648 C2 SE 511648C2
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Sweden
Prior art keywords
streptococcus
ncimb
otitis
pharmaceutical preparation
strains
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SE9801337A
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Swedish (sv)
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SE9801337D0 (en
SE9801337L (en
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Haakansson Eva Grahn
Kristian Roos
Stig Holm
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Bacterum Ab
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Application filed by Bacterum Ab filed Critical Bacterum Ab
Priority to SE9801337A priority Critical patent/SE511648C2/en
Publication of SE9801337D0 publication Critical patent/SE9801337D0/en
Priority to PL99343547A priority patent/PL343547A1/en
Priority to CA002325805A priority patent/CA2325805A1/en
Priority to EP99925517A priority patent/EP1071437A1/en
Priority to AU41777/99A priority patent/AU4177799A/en
Priority to JP2000544336A priority patent/JP2002512196A/en
Priority to PCT/SE1999/000608 priority patent/WO1999053932A1/en
Priority to IL13895899A priority patent/IL138958A0/en
Priority to IDW20002358A priority patent/ID26655A/en
Publication of SE9801337L publication Critical patent/SE9801337L/en
Publication of SE511648C2 publication Critical patent/SE511648C2/en
Priority to NO20005141A priority patent/NO20005141L/en
Priority to IS5661A priority patent/IS5661A/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/16—Otologicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Molecular Biology (AREA)
  • Epidemiology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A pharmaceutical preparation for prophylaxis and/or treatment of acute otitis media (inflammation of the ear) and middle otitis (inflammation of the middle ear) is described, comprising at least one of the microorganism strains Streptococcus sanguis under Accession No. NCIMB 40104, Streptococcus sanguis under Accession No. NCIMB 40873, Streptococcus oralis under Accession No. NCIMB 40875, Streptococcus oralis under Accession No. NCIMB 40876 and Streptococcus mitis under Accession No. NCIMB 40874 and, optionally, other alpha streptococcus strains having essentially the same capacity of inhibiting Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catharralis, in a pharmaceutically acceptable medium, in which the microorganism strains retain their viability.

Description

'10 15 20 25 30 35 511 648 2 med antibiotika i sig är olämplig p g a risken för ut- veckling av resistens. '10 15 20 25 30 35 511 648 2 with antibiotics per se is inappropriate due to the risk of developing resistance.

På senare år har i många länder, t ex Spanien och Frankrike, främst pneumokocker ökat sin motståndskraft mot penicillin och andra vanliga ”öronantibiotika”, vilket kan komma att innebära att vi står utan antibakte- riella medel inför dessa sjukdomar. Redan idag läggs barn in för intravenös antibiotikabehandling. Detta innebär stor risk för barnet, och stora kostnader för samhället är involverade. Denna situation hotar också att drabba Sverige, då vi med stor sannolikhet kommer att importera dessa bakteriestammar från utlandet. Detta har redan skett i vissa länder, t ex på Island. Världen över for- skas det intensivt för att hitta en lösning på detta problem. Man är helt överens om att vi måste minska vår antibiotikakonsumtion i syfte att reducera dessa resi- stenta bakteriers benägenhet att sprida sig och överleva.In recent years, in many countries, such as Spain and France, pneumococci have mainly increased their resistance to penicillin and other common “ear antibiotics”, which may mean that we are without antibacterial agents for these diseases. Already today, children are admitted for intravenous antibiotic treatment. This involves great risk for the child, and great costs to society are involved. This situation also threatens to affect Sweden, as we will in all probability import these bacterial strains from abroad. This has already happened in some countries, such as Iceland. The world is intensively researching to find a solution to this problem. It is fully agreed that we must reduce our consumption of antibiotics in order to reduce the tendency of these resistant bacteria to spread and survive.

Allvarliga komplikationer till öroninflammation är idag sällsynta i vårt land. Otosalpingit, även benämnt mellanöreinflammation, dvs inflammation i örontrumpeten (vätska i mellanörat) är däremot en mycket vanlig följd efter en öroninflammation. Denna läker ofta av sig själv, men fordrar i många fall en operativ åtgärd. Plaströrs- behandling av barn med mellanöreinflammation är det van- ligaste ingreppet på våra öronmottagningar, och kräver nästan alltid narkos. Dessa barn måste kontrolleras noga både före och efter ingreppet. Efterkontrollerna varar som regel i flera år. Ett mindre antal av dessa barn får, trots adekvat behandling, kvarstående besvär med s k kronisk otit (otitis media chronica). Denna kan senare kräva omfattande kirurgiska, hörselförbättrande ingrepp och/eller hörselhjälpmedel. Även om öroninflammation i vårt land är en tämligen banal åkomma, krävs p g a den stora mängden patienter stora medicinska resurser och även stora kostnader för samhället i form av produktionsbortfall hos föräldrar i samband med sjukdom och läkarbesök. 10 15 20 25 30 35 511 648 3 Hos icke otitbenägna barn domineras nasofarynxfloran av alfa-streptokocker, medan dessa finns i liten mängd eller saknas hos otitbenägna barn. Mycket talar i dagens läge för att det i nasofarynx finns en naturlig homeostas mellan den normala icke-patogena floran och de poten- tiellt otitinducerande bakterierna (se Fujimori, I. et al: The nasopharyngeal bacterial flora in children with otitis media with effusion. Eur. Arch. Otorhinolaryngol. 1996; 253:260-263; och Bernstein, J.M. et al: Bacterial interference in nasopharyngeal bacterial flora of otitis- prone and non-otitis prone children. Acta oto-rhino- iaryngoi. belg. 1994,- 48=1-9). i Sammanfattning av uppfinningen Ändamålet med föreliggande uppfinning är att undan- röja de problem som är förknippade med de olika typerna av otit.Serious complications of otitis media are rare today in our country. Otosalpingitis, also called otitis media, ie inflammation of the eardrum (fluid in the middle ear) is a very common consequence after an otitis media. This often heals on its own, but in many cases requires an operative measure. Plastic tube treatment of children with otitis media is the most common procedure at our ear clinics, and almost always requires anesthesia. These children must be carefully monitored both before and after the procedure. The follow-up inspections usually last for several years. A small number of these children get, despite adequate treatment, persistent problems with so-called chronic otitis (otitis media chronica). This may later require extensive surgical, hearing-enhancing procedures and / or hearing aids. Although ear inflammation in our country is a rather banal disease, due to the large number of patients, large medical resources and also large costs to society in the form of loss of production in parents are required in connection with illness and doctor visits. 10 15 20 25 30 35 511 648 3 In non-otitis-prone children, the nasopharyngeal flora is dominated by alpha-streptococci, while these are present in small amounts or absent in otitis-prone children. There is much to suggest today that in the nasopharynx there is a natural homeostasis between the normal non-pathogenic flora and the potentially otitis-inducing bacteria (see Fujimori, I. et al: The nasopharyngeal bacterial flora in children with otitis media with effusion. Eur Arch. Otorhinolaryngol. 1996; 253: 260-263; och Bernstein, JM et al: Bacterial interference in nasopharyngeal bacterial flora of otitis- prone and non-otitis prone children. Acta oto-rhino- iaryngoi. Belg. 1994, - 48 = 1-9). SUMMARY OF THE INVENTION The object of the present invention is to eliminate the problems associated with the various types of otitis.

Detta ändamål uppnås med hjälp av ett farmaceutiskt preparat av inledningsvis nämnt slag, vilket har de i det efterföljande patentkravet 1 angivna särdragen. Föredrag- na utföringsformer av det farmaceutiska preparatet anges i de underordnade kraven.This object is achieved by means of a pharmaceutical preparation of the kind mentioned in the introduction, which has the features stated in the following claim 1. Preferred embodiments of the pharmaceutical composition are set out in the dependent claims.

Bland mer än 300 olika alfa-streptokocker som isole- rats från tubarmynningen och adenoiden (lymfatisk vävnad i nässvalgrummet) hos friska barn har fem alfa-strepto- kockstammar selekterats fram som har särskilt god till- växthämmande effekt pà otit-patogener samt god adhere- rande förmåga till adenoidepitel. Fyra av dessa stammar har deponerats den 19 mars 1997 på National Collection of Industrial and Marine Bacteria Ltd (NCIMB), 23 st. Machar Drive, Aberdeen, AB2 1RY, Storbritannien, nämligen Streptococcus sanguis med depositionsbeteckningen NCIMB 40873, Streptococcus mitis med depositionsbeteckningen NCIMB 40874, Streptococcus oralis med depositions- beteckningen NCIMB 40875 och Streptococcus oralis med depositionsbeteckningen NCIMB 40876, medan en stam, Streptococcus sanguis med depositionsbeteckningen NCIMB 40104, deponerades den 3 februari 1989. Dessa stammar är ¿M lO 15 20 25 30 35 511 648 4 typade enligt API 20 Strep test, BioMerieux, Frankrike.Among more than 300 different alpha-streptococci isolated from the tubular orifice and adenoid (lymphatic tissue in the nasal cavity) in healthy children, five alpha-streptococcal strains have been selected that have a particularly good growth inhibitory effect on otitis pathogens and good adherence. ability of adenoid epithelium. Four of these strains were deposited on March 19, 1997 at the National Collection of Industrial and Marine Bacteria Ltd (NCIMB), 23 pcs. Machar Drive, Aberdeen, AB2 1RY, United Kingdom, namely Streptococcus sanguis with the deposit designation NCIMB 40873, Streptococcus mitis with the deposit designation NCIMB 40874, Streptococcus oralis with the deposition designation NCIMB 40875 and Streptococcus oral with the depositionBIMCIM 40104, was deposited on February 3, 1989. These strains are ¿M lO 15 20 25 30 35 511 648 4 typed according to API 20 Strep test, BioMerieux, France.

Typningsresultatet anges i tabell 3.The typing result is given in Table 3.

De fem ovannämnda mikroorganismstammarna kan före- komma individuellt eller i kombination av två eller flera i det farmaceutiska preparatet. Streptococcus oralis- stammen med depositionsbeteckningen NCIMB 40876 har visat sig vara mest verksam mot de angivna otit-patogenerna.The five microorganism strains mentioned above may be present individually or in combination of two or more in the pharmaceutical preparation. The Streptococcus oralis strain with the deposit designation NCIMB 40876 has been shown to be most effective against the indicated otitis pathogens.

Eventuellt kan en eller flera andra streptokockstammar med väsentligen samma förmåga att inhibera dessa otit- patogener också ingå i det farmaceutiska preparatet.Optionally, one or more other streptococcal strains having substantially the same ability to inhibit these otitis pathogens may also be included in the pharmaceutical composition.

Det farmaceutiskt acceptabla medium som stammarna förvaras i utgörs företrädesvis av skummjölk, NaCl eller något annat medium i vilket bakterierna bibehåller sin viabilitet. Var och en av mikroorganismstammarna i preparatet är närvarande i mediet i en koncentration av 104-1011 cfu/ml, företrädesvis 105-1010 cfu/ml, och helst 107-109 cfu/ml (cfu = kolonibildande enheter). De selek- terade alfa-streptokockerna odlas först i TY-medium, tvättas i NaCl och spädes upp till en koncentration av 109-1010 cfu/ml. Suspensionen fryses sedan till -20°C eller frystorkas. Administrering till patient sker lämpligtvis med en sprayflaska, med hjälp av vilken det då upptinade eller upplösta preparatet kan administreras nasalt. Företrädesvis sker administrering 2 ggr/dag.The pharmaceutically acceptable medium in which the strains are stored is preferably skim milk, NaCl or any other medium in which the bacteria retain their viability. Each of the microorganism strains in the preparation is present in the medium at a concentration of 104-1011 cfu / ml, preferably 105-1010 cfu / ml, and most preferably 107-109 cfu / ml (cfu = colony forming units). The selected alpha-streptococci are first grown in TY medium, washed in NaCl and diluted to a concentration of 109-1010 cfu / ml. The suspension is then frozen to -20 ° C or lyophilized. Administration to the patient is suitably by means of a spray bottle, by means of which the then thawed or dissolved preparation can be administered nasally. Preferably, administration takes place twice a day.

Det farmaceutiska preparatet enligt föreliggande uppfinning kan vara formulerat som en spraysuspension för nasal administrering, ett frystorkat pulver, en sug- tablett, en frystorkad tablett eller gurgelvatten.The pharmaceutical composition of the present invention may be formulated as a spray suspension for nasal administration, a lyophilized powder, a lozenge, a lyophilized tablet or gargle.

Försök a) Ett försök utfördes för bestämning av vilka alfa- streptokocker som dominerar floran på adenoiden och vid tubarmynningen hos friska barn. Provtagningen gjordes under narkos med en steril provtagningspinne med ett sterilt plaströr (Mülly suction catheter) för att prov- tagningen skulle kunna ske på rätt ställe och inte ge kontaminering. 10 15 20 25 30 35 511 648 5 Alfa-streptokocker isolerades hos 10 friska barn och typades enligt API 20 Strep test, BioMerieux, Frankrike.Experiments a) An experiment was performed to determine which alpha-streptococci dominate the flora on the adenoid and at the tubular mouth of healthy children. The sampling was performed under anesthesia with a sterile sampling stick with a sterile plastic tube (Mülly suction catheter) so that the sampling could take place in the right place and not cause contamination. 511 648 Alpha-streptococci were isolated in 10 healthy children and typed according to API 20 Strep test, BioMerieux, France.

De dominerande alfa-hemolytiska streptokockerna (AHS) tillhörde stammarna Streptococcus sanguis, oralis, mitis, salivarius och intermedius (se figur l). b) Ett försök utfördes för att testa de isolerade alfa~streptokockernas hämmande förmåga mot 25 st olika otit-patogener, såsom Streptococcus pneumoniae, Hemo- philus influenzae och Moraxella catharralis. Detta försök utvärderades med hjälp av en modifierad agarövergjut- ningsteknik. Resultatet visar att av alfa-streptokocker isolerade från friska barn har en bra hämmande effekt mot otit-patogener och att alfa-streptokocker isolerade från tubarmynningen hade bättre hämmande effekt än de som isolerats från adenoiden (se figur 2 och tabell 1). c) En studie utfördes för att visa att man på nytt kan finna tidigare administrerade alfa-streptokocker i nasofarynx och vid tubarmynningen. Två av de utvalda alfa-streptokockerna gjordes resistenta mot ett anti- biotika, nämligen erytromycin. Dessa bakterier sprayades i nasofarynx på tre friska frivilliga personer. Odlings- proven odlades på blodagarplattor med erytromycin för att särskilja tillförda alfa-streptokocker från försöks- personens egna alfa-streptokocker. Erytromycinresistenta alfa-streptokocker påträffades i nasofarynx under spray- behandling och upp till 24 h efter avslutad behandling (se tabell 2). d) Pilotförsök har också utförts på en 4-årig pojke med upprepade otiter (åtta otiter under ett år). Pojken tilldelades alfa-streptokocker efter penicillinbehand- ling. Han sprayades i näsan under 10 dagar och detta upp- repades en gång efter ytterligare en vecka. Inga nya otiter uppstod under uppföljningstiden pà 5 månader (december-april), då denna patient normalt borde ha haft flera upprepade otiter.The predominant alpha-hemolytic streptococci (AHS) belonged to the strains Streptococcus sanguis, oralis, mitis, salivarius and intermedius (see Figure 1). b) An experiment was performed to test the inhibitory ability of the isolated alpha-streptococci against 25 different otitis pathogens, such as Streptococcus pneumoniae, Hemophilus influenzae and Moraxella catharralis. This experiment was evaluated using a modified agar casting technique. The results show that alpha-streptococci isolated from healthy children have a good inhibitory effect against otitis pathogens and that alpha-streptococci isolated from the tubular mouth had a better inhibitory effect than those isolated from the adenoid (see Figure 2 and Table 1). c) A study was performed to show that previously administered alpha-streptococci can be rediscovered in the nasopharynx and at the tube orifice. Two of the selected alpha-streptococci were made resistant to an antibiotic, namely erythromycin. These bacteria were sprayed into the nasopharynx of three healthy volunteers. The culture samples were grown on blood agar plates with erythromycin to distinguish added alpha-streptococci added from the subject's own alpha-streptococci. Erythromycin-resistant alpha-streptococci were found in the nasopharynx during spray treatment and up to 24 hours after the end of treatment (see Table 2). d) Pilot trials have also been performed on a 4-year-old boy with recurrent otitis (eight otitis in one year). The boy was assigned alpha-streptococci after penicillin treatment. He was sprayed in the nose for 10 days and this was repeated once after another week. No new otitis occurred during the follow-up period of 5 months (December-April), as this patient should normally have had several repeated otitis.

M kni-v 511 648 6 TABELL 1 Genomsnittlig inhiberande aktivitet av AHS från ~ varje barn AHS från AHS från tubarmyn- adenoid Patient Ålder (år) ningen vävnad F.H. 3 88 72 D.B. 3,2 66 75 C.O-H 3,5 67 41 D.A 4 98 59 L.B-P. 4,5 88 84 C.L 5 83 75 E.B 5,8 100 96 J.O 6,9 66 65 C.H 9,1 78 26 L.H. 9,7 97 52 Medelvärde 5,5 83 64,5 TABELL 2 Prov 24 h efter Prov före Prov under avslutad Patient behandling behandling behandling Nr 1 Ingen växt I.E.R.A. I.E.R.A.M kni-v 511 648 6 TABLE 1 Mean Inhibitory Activity of AHS from ~ Each Child AHS from AHS from Tubar Mouth Adenoid Patient Age (s) Tissue F.H. 3 88 72 D.B. 3.2 66 75 C.O-H 3.5 67 41 D.A 4 98 59 L.B-P. 4.5 88 84 C.L 5 83 75 E.B 5.8 100 96 J.O 6.9 66 65 C.H 9.1 78 26 L.H. 9.7 97 52 Mean 5.5 83 64.5 TABLE 2 Samples 24 hours after Samples before Samples during completed Patient treatment treatment treatment No. 1 No plant I.E.R.A. I.E.R.A.

Nr 2 Ingen växt I.E.R.A. Ingen växt Nr 3 Ingen växt I.E.R.A. I.E.R.A.No. 2 No plant I.E.R.A. No plant No. 3 No plant I.E.R.A. I.E.R.A.

I.E.R.A. = isolerade erytromycinresistenta alfa- streptokocker 7 TABELL 3 511 648 RESULTAT VID TYPNING AV STREPTOCOCCUSSTAMMAR S. S. S. S. S. sanguis sanguis oralis mitis oralis NCIMB NCIMB NCIMB NCIMB NCIMB 40104 40872 40876 40873 40875 Test a89a a3 a4 a5 a6 VP - - - - - HIP - - - - - ESC - - - - - PYRA - - - - - uGAL + + + - + ßGUR - - - - - BGAL - + i - - - PAL + + + - - LAP + + + ADH + + - - - RIB - - - + - ARA - - - - - MAN - - - - - SOR - - - - - LAC + - + + + TRE (+) + - - - INU - - - - - RAF + + + - + AMD + - - - + GLYG - - - - - hemolys - - - - - alla har a-hemolys (grön hemolys) HI.E.R.A. = isolated erythromycin-resistant alpha-streptococci 7 TABLE 3 511 648 RESULTS WHEN TYPE OF STREPTOCOCCUS STEMS SSSSS sanguis sanguis oralis mitis oralis NCIMB NCIMB NCIMB NCIMB NCIMB 40104 40872 40876 40873 a8 - a - - a - Test a ESC - - - - - PYRA - - - - - uGAL + + + - + ßGUR - - - - - BGAL - + i - - - PAL + + + - - LAP + + + ADH + + - - - RIB - - - + - ARA - - - - - MAN - - - - - SOR - - - - - LAC + - + + + TRE (+) + - - - INU - - - - - RAF + + + - + AMD + - - - + GLYG - - - - - hemolysis - - - - - everyone has a-hemolysis (green hemolysis) H

Claims (6)

' rr 'iir-l 10 15 20 25 30 35 511 648 PATENTKRAV'rr' iir-l 10 15 20 25 30 35 511 648 PATENT REQUIREMENTS 1. Farmaceutiskt preparat för profylax mot och/eller behandling av akut media otit (öroninflammation) och otosalpingit (mellanöreinflammation), k ä n n e - t e c k n a t av att det inbegriper minst en av mikro- organismstammarna Streptococcus sanguis med depositions- beteckningen NCIMB 40104, Streptococcus sanguis med depo- sitionsbeteckningen NCIMB 40873, Streptococcus oralis med depositionsbeteckningen NCIMB 40875, Streptococcus oralis med depositionsbeteckningen NCIMB'40876 och Streptococcus mitis med depositionsbeteckningen NCIMB 40874 samt even- tuellt andra alfa-streptokockstammar med väsentligen- samma förmåga att inhibera Hemophilus influenzae, Strep- tococcus pneumoniae och Moraxella catharralis, i ett farmaceutiskt acceptabelt medium i vilket mikroorganism- stammarna bibehåller sin viabilitet.Pharmaceutical preparation for the prophylaxis and / or treatment of acute media otitis (otitis media) and otosalpingitis (otitis media), characterized in that it comprises at least one of the micro-organism strains Streptococcus sanguis with the deposit designation NCIMB 40104, sang Streptococcus with the deposition designation NCIMB 40873, Streptococcus oralis with the deposition designation NCIMB 40875, Streptococcus oralis with the deposition designation NCIMB'40876 and Streptococcus mitis with the deposition designation NCIMB 40874 and possibly other alpha-pneumonia and Moraxella catharralis, in a pharmaceutically acceptable medium in which the microorganism strains retain their viability. 2. Farmaceutiskt preparat enligt kravet 1, k ä n - n e t e c k n a t av att det innehåller endast Strepto- coccus oralis-stammen med depositionsbeteckningen NCIMB 40876.Pharmaceutical preparation according to Claim 1, characterized in that it contains only the Streptococcus oralis strain with the deposit designation NCIMB 40876. 3. Farmaceutiskt preparat enligt kraven 1 och 2, k ä n n e t e c k n a t av att mikroorganismstammarna isolerats från tubarmynningen och/eller adenoiden, före- trädesvis tubarmynningen, hos friska barn.Pharmaceutical preparation according to Claims 1 and 2, characterized in that the microorganism strains have been isolated from the tubular orifice and / or the adenoid, preferably the tubular orifice, in healthy children. 4. Farmaceutiskt preparat enligt kraven 1-3, k ä n n e t e c k n a t av att varje mikroorganismstam i preparatet är närvarande i en koncentration av 104-1011 cfu/ml, företrädesvis 1o5-1o10 efu/ml, helst es 107-109 cfu/ml, baserat på det farmaceutiskt acceptabla mediet.Pharmaceutical preparation according to claims 1-3, characterized in that each microorganism strain in the preparation is present in a concentration of 104-1011 cfu / ml, preferably 10-11010 efu / ml, preferably es 107-109 cfu / ml, on the pharmaceutically acceptable medium. 5. Farmaceutiskt preparat enligt kraven 1-4, k ä n n e t e c k n a t av att det föreligger i form av en spraysuspension för nasal administrering, ett frys- torkat pulver, en sugtablett, en frystorkad tablett eller gurgelvatten. 511 648 9Pharmaceutical composition according to claims 1-4, characterized in that it is in the form of a spray suspension for nasal administration, a freeze-dried powder, a lozenge, a freeze-dried tablet or gargle. 511 648 9 6. Farmaceutiskt preparat enligt något av de före-I gående kraven, k ä n n e t e c k n à t av att det farmaceutiskt acceptabla mediet är skummjölk eller NaCl.Pharmaceutical composition according to any one of the preceding claims, characterized in that the pharmaceutically acceptable medium is skimmed milk or NaCl.
SE9801337A 1998-04-17 1998-04-17 Streptococcus preparations for the treatment of ear inflammation SE511648C2 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
SE9801337A SE511648C2 (en) 1998-04-17 1998-04-17 Streptococcus preparations for the treatment of ear inflammation
IDW20002358A ID26655A (en) 1998-04-17 1999-04-16 MAKING STREPTOKOKUS
AU41777/99A AU4177799A (en) 1998-04-17 1999-04-16 Streptococcus preparation
CA002325805A CA2325805A1 (en) 1998-04-17 1999-04-16 Streptococcus preparation
EP99925517A EP1071437A1 (en) 1998-04-17 1999-04-16 Streptococcus preparation
PL99343547A PL343547A1 (en) 1998-04-17 1999-04-16 Streptococcus preparation
JP2000544336A JP2002512196A (en) 1998-04-17 1999-04-16 Streptococcus preparation
PCT/SE1999/000608 WO1999053932A1 (en) 1998-04-17 1999-04-16 Streptococcus preparation
IL13895899A IL138958A0 (en) 1998-04-17 1999-04-16 Streptococcus preparation
NO20005141A NO20005141L (en) 1998-04-17 2000-10-13 streptococcal Preparation
IS5661A IS5661A (en) 1998-04-17 2000-10-13 A mixture containing streptococci

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US20060258596A1 (en) * 2003-02-14 2006-11-16 Walsh Timothy R Antimicrobial agents
WO2010056198A1 (en) 2008-11-17 2010-05-20 Essum Ab Pharmaceutical preparation comprising a combination of streptococcus strains and lactobacillus strains
FR2999601B1 (en) 2012-12-17 2015-01-30 Urgo Lab METHOD FOR PREVENTING AND / OR TREATING INFECTIONS, COLONIZATIONS OR DISEASES ASSOCIATED WITH STAPHYLOCOCCUS AUREUS, PSEUDOMONAS AERUGINOSA, STREPTOCOCCUS PYOGENES, ENTEROCOCCUS FAECIUM, ENTEROBACTER CLOACAE, PROTEUS MIRABILIS AND / OR BACTEROIDES FRAGILIS
LT3015109T (en) * 2014-10-28 2019-12-27 D.M.G. Italia Srl Biological barrier with simethicone for the use in the treatment of naso-pharyngo-tubal infections

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CA2325805A1 (en) 1999-10-28
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NO20005141L (en) 2000-12-14
NO20005141D0 (en) 2000-10-13
WO1999053932A1 (en) 1999-10-28
IL138958A0 (en) 2001-11-25
SE9801337L (en) 1999-10-18
EP1071437A1 (en) 2001-01-31
ID26655A (en) 2001-01-25
PL343547A1 (en) 2001-08-27
IS5661A (en) 2000-10-13

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