DE2917730A1 - IMMUNOBIOTHERAPEUTIC MEDICINAL PREPARATION AND METHOD FOR ITS MANUFACTURING - Google Patents
IMMUNOBIOTHERAPEUTIC MEDICINAL PREPARATION AND METHOD FOR ITS MANUFACTURINGInfo
- Publication number
- DE2917730A1 DE2917730A1 DE19792917730 DE2917730A DE2917730A1 DE 2917730 A1 DE2917730 A1 DE 2917730A1 DE 19792917730 DE19792917730 DE 19792917730 DE 2917730 A DE2917730 A DE 2917730A DE 2917730 A1 DE2917730 A1 DE 2917730A1
- Authority
- DE
- Germany
- Prior art keywords
- nctc
- medicinal preparation
- strains
- lysate
- sodium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims description 16
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 238000000034 method Methods 0.000 title claims description 3
- 239000006166 lysate Substances 0.000 claims description 13
- 230000001580 bacterial effect Effects 0.000 claims description 7
- 208000015181 infectious disease Diseases 0.000 claims description 6
- 241000588653 Neisseria Species 0.000 claims description 5
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 4
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 210000002345 respiratory system Anatomy 0.000 claims description 4
- 241000606768 Haemophilus influenzae Species 0.000 claims description 3
- 241000588747 Klebsiella pneumoniae Species 0.000 claims description 3
- 229940041514 candida albicans extract Drugs 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 3
- 239000012138 yeast extract Substances 0.000 claims description 3
- 241000588744 Klebsiella pneumoniae subsp. ozaenae Species 0.000 claims description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 2
- 241000191967 Staphylococcus aureus Species 0.000 claims description 2
- 241000193998 Streptococcus pneumoniae Species 0.000 claims description 2
- 241000193996 Streptococcus pyogenes Species 0.000 claims description 2
- 241001312524 Streptococcus viridans Species 0.000 claims description 2
- 235000013372 meat Nutrition 0.000 claims description 2
- 235000001968 nicotinic acid Nutrition 0.000 claims description 2
- 229960003512 nicotinic acid Drugs 0.000 claims description 2
- 239000011664 nicotinic acid Substances 0.000 claims description 2
- 239000001632 sodium acetate Substances 0.000 claims description 2
- 235000017281 sodium acetate Nutrition 0.000 claims description 2
- 239000011780 sodium chloride Substances 0.000 claims description 2
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 claims description 2
- 235000019157 thiamine Nutrition 0.000 claims description 2
- 239000011721 thiamine Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 2
- 239000004251 Ammonium lactate Substances 0.000 claims 1
- 239000008156 Ringer's lactate solution Substances 0.000 claims 1
- 229940059265 ammonium lactate Drugs 0.000 claims 1
- 235000019286 ammonium lactate Nutrition 0.000 claims 1
- RZOBLYBZQXQGFY-HSHFZTNMSA-N azanium;(2r)-2-hydroxypropanoate Chemical compound [NH4+].C[C@@H](O)C([O-])=O RZOBLYBZQXQGFY-HSHFZTNMSA-N 0.000 claims 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 239000000243 solution Substances 0.000 claims 1
- 108060003951 Immunoglobulin Proteins 0.000 description 6
- 244000052616 bacterial pathogen Species 0.000 description 6
- 102000018358 immunoglobulin Human genes 0.000 description 6
- 229940072221 immunoglobulins Drugs 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000009089 cytolysis Effects 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 206010006458 Bronchitis chronic Diseases 0.000 description 2
- 241000588748 Klebsiella Species 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- 208000007451 chronic bronchitis Diseases 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 230000028327 secretion Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 201000009890 sinusitis Diseases 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 201000008197 Laryngitis Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 102000004160 Phosphoric Monoester Hydrolases Human genes 0.000 description 1
- 108090000608 Phosphoric Monoester Hydrolases Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 description 1
- 241000295644 Staphylococcaceae Species 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229910052785 arsenic Inorganic materials 0.000 description 1
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 238000003306 harvesting Methods 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000009630 liquid culture Methods 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000003024 peritoneal macrophage Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
Classifications
-
- 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
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
- C12N1/20—Bacteria; Culture media therefor
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Mycology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Wood Science & Technology (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Biomedical Technology (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- General Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Description
ELISABETH JUNG dr. phil.. cipl. cmem JÜRGEN SCHIRDEWAHN dr rer.nat. dipl-phyc GERHARD SCH MITT-NILSO N dr.-ing. GERHARD B. HAGEN drphil. -ELISABETH JUNG dr. phil .. cipl. cmem JÜRGEN SCHIRDEWAHN dr rer.nat. dipl-phyc GERHARD SCH MITT-NILSO N dr.-ing. GERHARD B. HAGEN drphil. -
8000 MÜNCHEN 4o2 9 1 7 7 ^ Π P.O. BOX 401468 'OU8000 MUNICH 4o2 9 1 7 7 ^ Π P.O. BOX 401468 'OU
CLEMENSSTRASSE 30 TELEFON: (089) 3450 67 TELEGRAMM/CABLE: INVENT MÖNCHEN TELEX: 5-29 686CLEMENSSTRASSE 30 TELEPHONE: (089) 3450 67 TELEGRAM / CABLE: INVENT MÖNCHEN TELEX: 5-29 686
2. Mai 1979May 2nd 1979
Q 089 C (J/MK/or)
Case 23Q 089 C (J / MK / or)
Case 23
LABORATOIRES OM SOCIETE ANONYME
Meyrin, SchweizLABORATOIRES OM SOCIETE ANONYME
Meyrin, Switzerland
Immunobiotherapeutisches ArEneipräparat und Verfahren zu seiner HerstellungImmunobiotherapeutic preparation and procedure too its manufacture
beanspruchte Priorität:claimed priority:
26. Mai 1978 - Schv/eiz - Nr. 5805/78May 26, 1978 - Schv / eiz - No. 5805/78
Die Erfindung betrifft ein immunobiotherapeutisches Arsneipräparat gegen Infektionen der Atemvege, das dadurch gekennzeichnet ist, dass es als Wirkstoff ein Bakterienlysat mindestens eines der folgenden Stämme enthält:The invention relates to an immunobiotherapeutic arsenic preparation against infections of the respiratory tract, which is characterized is that it contains a bacterial lysate of at least one of the following strains as an active ingredient:
909848/0578909848/0578
Staphylococcus aureusStaphylococcus aureus
Streptococcus viridans Neisseria catarrhalis Hemophilus influenzae Serotyp b Diplococcus pneumoniae Serotypen 1, 2, 3 und 47 Klebsiella pneumoniae Klebsiella ozaenae Streptococcus pyogenes Serogruppe A Neisseria catarrhalisStreptococcus viridans Neisseria catarrhalis Hemophilus influenzae serotype b Diplococcus pneumoniae serotypes 1, 2, 3 and 47 Klebsiella pneumoniae Klebsiella ozaenae Streptococcus pyogenes serogroup A Neisseria catarrhalis
1-049, 1-050, 1-051, 1-052, 1-053, 1-0541-049, 1-050, 1-051, 1-052, 1-053, 1-054
1-046, 1-047, I-04ö 1-0451-046, 1-047, I-04ö 1-045
NCTC 8467 NCTC 7465,7466,797b, 10319NCTC 8467 NCTC 7465,7466,797b, 10319
NCTC 204, 5056 NCTC 5050 NCTC 8191 NCTC 3622,3625NCTC 204, 5056 NCTC 5050 NCTC 8191 NCTC 3622,3625
Das erfindungsgemässe Arzneipräparat enthält vorzugsweise das Lysat aller angegebenen Stämme.The medicinal preparation according to the invention preferably contains the lysate of all indicated strains.
Die NCTC-Stämme sind bei der "National Collection of Cultures" London, hinterlegt, die I-Stämme wurden am 14. März 1978 bei der "Collection nationale de culture Ue microorganismes, Institut Pasteur", Paris, hinterlegt.The NCTC strains are on the National Collection of Cultures "London, deposited the I-strains on March 14th In 1978 deposited with the "Collection nationale de culture Ue microorganismes, Institut Pasteur", Paris.
Die Erfindung betrifft ferner ein Verfahren zur Herstellung des immunobiotherapeutischen Arzneipräparats, das dadurch gekennzeichnet ist, dass man jeden der angegebenen Stämme in einem Grundmedium kultiviert, das je Liter Wasser 22,5 g Fleischextrakt, 7,5 g Hefeextrakt, 2,5 g Natriumchlorid, 0,5 g Natriumacetat, 2,0 g Natriuinmonohydrogenphosphat, 2,0 ml einer 70gewichtsprozentigen Natriunilactatlösung, 2,O ml einer 50gewichtsprozentigen AruiTioniumlactatlösung, 3,0 mg Aneurin, r. The invention also relates to a method for producing the immunobiotherapeutic medicinal preparation, which is characterized in that each of the specified strains is cultivated in a basic medium containing 22.5 g of meat extract, 7.5 g of yeast extract, 2.5 g of sodium chloride, per liter of water. 0.5 g of sodium acetate, 2.0 g Natriuinmonohydrogenphosphat, 2.0 ml of a 70gewichtsprozentigen Natriunilactatlösung, 2, O ml of a 50gewichtsprozentigen AruiTioniumlactatlösung, 3.0 mg aneurine, r.
909848/0578909848/0578
3,0 mg Nicotinsäure und 3,0 g Glukose enthält, wobei üiese Werte um - 5 % schwanken können.Contains 3.0 mg nicotinic acid and 3.0 g glucose, whereby üiese Values can fluctuate by - 5%.
Das Kulturmedium wird entweder im Autoklaven oaer durch Filtrieren sterilisiert.The culture medium is either in the autoclave or by Filter sterilized.
Die Bakterienkulturen werden in an sich bekannter WeiseThe bacterial cultures are produced in a manner known per se
durchgeführt, .
bei Bedingungen / die am besten der Vermehrung üer Keimecarried out, .
under conditions / which are best for the multiplication of germs
angepasst sind:adapted are:
Der Stamm Hemophilus influenzae wird vorzugsweise im Fermentor bebrütet, wobei dem Grundmeuiurn 2 % eines Bäckerhefeextrakts und 0,5 % eines Extrakts "Fildes" zugegeben wird.The Hemophilus influenzae strain is preferably fermented in the fermentor incubated, 2% of a baker's yeast extract and 0.5% of an extract "Fildes" being added to the base material.
Die Bebrütung erfolgt bei einem pH-Wert von 7,0 und einer Temperatur von 37 C unter Belüftung und Bewegung währena 8 bis 14 Stunden.Incubation takes place at a pH of 7.0 and a temperature of 37 C with ventilation and agitation for a long time 8 to 14 hours.
Die Kultur der Pneumokokken erfolgt vorzugsweise im Fermentor, wobei dem Grundmedium 0,3 % Glukose und 0,5 % Pferaeserum zugesetzt werden. Auch hier wird bei einem j)H-Wert von 7,0 und einer Temperatur von 37°C unter Belüftung und Bewegung während 8 bis Ϊ4 Stunden bebrütet.The pneumococci are preferably cultivated in the fermentor, with 0.3% glucose and 0.5% horse serum as the basic medium can be added. Here, too, a j) H value of 7.0 incubated at a temperature of 37 ° C with aeration and agitation for 8 to Ϊ4 hours.
Auch die Streptokokken werden vorzugsweise im Fermentor unter den oben angegebenen Bedingungen kultiviert. Dem Grunumeuium weraen 0,3 % Glukose zugesetzt.The streptococci are also preferably cultivated in the fermentor under the conditions specified above. The Grunumeuium 0.3% glucose was added.
909848/0578909848/0578
Die Klebsiella-Stäirane werden vorzugsweise auf festem Medium in Roux-Plaschen bei 37 C während 48 Stunden bebrütet. Dem Grundmedium werden 0,2 % Gelatine und 2,4 % Agar zugesetzt.The Klebsiella starirans are preferably on solid medium incubated in Roux Plaschen at 37 C for 48 hours. To the 0.2% gelatin and 2.4% agar are added to the basic medium.
Auch die Staphylokokken und die Neisseria-Stämme werden vorzugsweise auf festem Medium unter den für die Klebsiella-Stämme angegebenen Bedingungen kultiviert.The Staphylococci and the Neisseria strains are also preferably used on solid medium among those for the Klebsiella strains cultivated conditions specified.
Am Ende der Inkubationszeit wird in den flüssigen Kulturen die Zellzahl für jeden Stamm entweaer durch Trübungsmessungen oder mikroskopisch bestimmt. Die Kulturen werden abzentrifugiert, in physiologischer Lösung suspendiert, erneut gezählt una dann einer alkalischen Lyse ( pH 9 bis 10) bei einer TemperaturAt the end of the incubation period, the number of cells in the liquid cultures for each strain is determined by measuring the turbidity or determined microscopically. The cultures are centrifuged off, suspended in physiological solution, counted again and then an alkaline lysis (pH 9 to 10) at one temperature
ο z.ü.ο z.ü.
von 20 bis 40 C unterworfen. Als Lysemittel werden/Natriumhydroxid, Kaliumhydroxid, primäre, sekundäre und tertiäre Amine verwendet. Die Lyse erfolgt während 1 bis 5 Tage unter mikroskopischer Kontrolle.subjected to from 20 to 40 C. The lysing agent used is / sodium hydroxide, Potassium hydroxide, primary, secondary and tertiary amines are used. Lysis takes place for 1 to 5 days microscopic control.
Die festen Kulturen werden in an sich bekannter Weise abgeerntet. Die Zellzahl wird für jeden Stamm bestimmt, die Suspensionen werden dann wie oben beschrieben einer alkalischen Lyse unterworfen.The solid cultures are harvested in a manner known per se. The cell number is determined for each strain that Suspensions are then subjected to alkaline lysis as described above.
Das Lysatvolumen jedes Bakterienstammes wird anhanu der Zellzahlen bestimmt. Zur Herstellung des erfindungsgemässen Arzneipräparats werden diese Lysate in entsprechenden Mengen vermischt. Die Keimzahlen der verwendeten Stänüne können innerhalb gewisser Grenzen schwanken, die Tagesdosis für einenThe lysate volume of each bacterial strain is determined based on the number of cells certainly. To produce the medicinal preparation according to the invention, these lysates are mixed in appropriate amounts. The germ counts of the Stänüne used can be within certain limits fluctuate, the daily dose for one
etwa . /^. ·approximately . / ^. ·
Erwachsenen beträgt/1 bis 50 Milliarden Keime.Adults is / 1 to 50 billion germs.
909848/0578909848/0578
Die Herstellung des erfindungsgemässen Wirkstoffes kann man wie folgt zusammenfassen:The preparation of the active ingredient according to the invention can be summarized as follows:
Beimpfen der BakterienstämmeInoculating the bacterial strains
Inkubation/ Ernten der Keime, Konzentration, Suspension Bestimmung der ZellzahlenIncubation / harvesting of the germs, concentration, suspension Determination of the number of cells
Lyse, Vermischen der Lysate zu einem Konzentrat, Zentrifugieren und Filtrieren dieses Konzentrat Sterilisieren durch Filtrieren.Lyse, mix the lysates into a concentrate, centrifuge and filter this concentrate Sterilize by filtering.
Das erfindungsgemässe Arzneipräparat wird vorzugsweise oral verabreicht in Form von Tabletten, Kapseln oder Granulat, die das Lysat in lyophilisierter Form enthalten, oder als Trinkampullen in Einzeldosen, als Sirup oder Tropfen. Man kann das erfindungsgemässe. Arzneipräparat aber auch in Form von Aerosolen oder Tropfen über die Nase einführen oaer parenteral verabreichen.The medicinal preparation according to the invention is preferably used orally administered in the form of tablets, capsules or granules containing the lysate in lyophilized form, or as drinking ampoules in single doses, as syrup or drops. You can the invention. Medicinal preparation but also in Introduce the form of aerosols or drops through the nose or administer parenterally.
Die Tagesdosis für einen Erwachsenen wird vorzugsweise auf einmal genommen und enthält eine Gesamtmenge an Lysat ent-The daily dose for an adult is preferably taken all at once and contains a total amount of lysate
etwa · .
sprechend/1 bis 50 Milliarden Keime.approximately · .
speaking / 1 to 50 billion germs.
Die Dosis für Kinder entspricht der halben Erwachsenendosis.The dose for children is half the adult dose.
909848/0578909848/0578
Pharmakologische VersuchePharmacological experiments
Ein lyophilisiertes Bakterienlysat, das auf eine Dosis vonA lyophilized bacterial lysate that is based on a dose of
in Anspruch 1 aufgeführtenlisted in claim 1
6 Milliarden Keime jedes/Stammes titriert worden ist, wira oral Balb/c-Mäusen in einem Fünftel der menschlichen Dosis während 10 Tagen verabreicht (Gruppen von je 24 Mäusen). 5 bis 10 Tage nach Ende der Verabreichung werden die Mäuse infiziert. Bei einer intraperitonealen Infektion mit Klebsiella pneumoniae 5 Tage nach Ende der Behandlung erhält6 billion germs of each / strain has been titrated, wira oral Balb / c mice at one-fifth the human dose administered over 10 days (groups of 24 mice each). 5 to 10 days after the end of the administration, the mice become infected. In the event of an intraperitoneal infection with Klebsiella pneumoniae, receive 5 days after the end of treatment
bei Infizierung/ man eine statistisch signifikante Schutzwirkung. Sogar/ 20 Tage nach der Behandlung kann man noch eine Verzögerung der Sterblichkeit beobachten. Das immunobiotherapeutische Lysat verursacht auch eine nicht spezifische Stimulierung der Abwehrmechanismen, die sich in einer Verzögerung der Sterblichkeit bei Tieren, die durch Aerosol mit Grippevirus infiziert worden sind? bemerkbar macht*a statistically significant protective effect in the event of infection. A delay in mortality can even be observed / 20 days after treatment. The immunobiotherapeutic lysate also causes a non-specific stimulation of the defense mechanisms, which results in a delay in mortality in animals infected with the flu virus by aerosol ? makes noticeable *
Bei den mit erfindungsgemässem Arzneipräparat behandelten und dann mit Klebsiella pneumoniae infizierten Mäusen wuraen die peritonealen Macrophagen biochemisch und morphologisch untersucht. 5 und 25 Tage nach Ende der Behandlung ist die Zahl und das Volumen der Zellen deutlich erhöht. Auch axe Phosphatase una die ß-Galectosidase sind im Vergleich zu Kontrollen erhöht.In the case of those treated with the medicinal preparation according to the invention and then mice infected with Klebsiella pneumoniae, the peritoneal macrophages became biochemically and morphologically examined. 5 and 25 days after the end of the treatment, the number and volume of cells are markedly increased. Also ax Phosphatase and ß-galectosidase are compared to Controls increased.
Der oralen Verabreichung des Lysats an die Maus folgt eine Erhöhung uer Inuaunglobuline A in der Spülflüssigkeit der Atemwege, die durch die Fällungsreaktion mit dem entsprechenden,Oral administration of the lysate to the mouse is followed by one Increase in the inuaoglobulins A in the rinsing liquid Respiratory tract, which is caused by the precipitation reaction with the corresponding,
909848/0578909848/0578
auf 1/16 verdünnten Antiserüm nachweisbar ist.is detectable on 1/16 diluted antiserum.
Wegen der geringen Menge der Immunglobuline A im Sekret unu in Anbetracht der beträchtlichen Erhöhung dieser Immunglobuline unter dem Einfluss des Lysats kann man vermuten, dass die Erhöhung der Gesamtimmunglobuline fast ausschliesslich auf der Erhöhung der Immunglobuline A beruht.Because of the small amount of immunoglobulins A in the secretion unu In view of the considerable increase in these immunoglobulins under the influence of the lysate, it can be assumed that the The increase in total immunoglobulins is based almost exclusively on the increase in immunoglobulins A.
Klinische Versuche ■Clinical trials ■
12 gesunden Versuchspersonen wird während 10 Tagen täglich eine Kapsel des erfindungsgemässen Arzneipräparats, die den. Wirkstoff entsprechend 6 Milliarden Keime jedes Stammes enthält, verabreicht. Die während 3 und mehr Monaten verfolgten Versuche zeigen eine statistisch signifikante Erhöhung der Menge.an Sekret-Immunglobuline A im Speichel und der Immunglobuline A im Serum. Dieses Ergebnis entspricht der aktuellen Vorstellung über die Mechanismen der Immunantwort.12 healthy test persons daily for 10 days a capsule of the medicinal preparation according to the invention, which the. Active ingredient corresponding to 6 billion germs of each strain is administered. Those persecuted for 3 months and more Experiments show a statistically significant increase in the amount of secretion immunoglobulins A in saliva and the Immunoglobulins A in serum. This result corresponds to the current idea about the mechanisms of the immune response.
Die oben beschriebene Kapsel des erfindungsgemässen Arzneiwurde/
präparats / von 7 Ärzten bei der chronischen BronchitisThe above-described capsule of the medicament according to the invention was /
preparation / by 7 doctors for chronic bronchitis
und bei Infektionen des Hals-Nasen-Ohrenbereichs, z.B. der Sinusitis, eingesetzt und die heilende sowie prophylaktischeand for infections of the ear, nose and throat area, e.g. sinusitis, and both curative and prophylactic
/wurue Wirkung abgeschätzt. Das Arzneipräparat / im allgemeinen während 10 Tagen jedes Monats während mehrerer Monate, im allgemeinen während der Wintermonate, verabreicht. Die Ergebnisse sind in der Tabelle zusammengefasst. / wu rue impact estimated. The medicinal preparation / generally administered for 10 days each month for several months, generally during the winter months. The results are summarized in the table.
909848/0578909848/0578
Das erfindungsgemässe Arzneipräparat wird vor allem bei akuter und chronischer Bronchitis, Angina, Mandelentzündungen, Kehlkopfentzündungen, RachenentZündungen, Rhinitis, Sinusitis, Otitis, bei Infektionen, die gegenüber der üblichen Antibiotikum-Therapie resistent sind, sowie bei bakteriellen Komplikationen bei Virusinfektionen des Atemsystems, insbesondere bei Kindern und altern Personen, empfohlen.The medicinal preparation according to the invention is mainly used in acute and chronic bronchitis, angina, tonsillitis, laryngitis, pharyngitis, rhinitis, sinusitis, Otitis, in infections that are resistant to the usual antibiotic therapy, as well as in bacterial ones Complications from viral infections of the respiratory system, especially in children and the elderly, are recommended.
9098A8/Q5789098A8 / Q578
Claims (3)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH580578A CH633188A5 (en) | 1978-05-26 | 1978-05-26 | MEDICINE FOR INFECTIOUS DISEASES OF THE RESPIRATORY TRACT. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2917730A1 true DE2917730A1 (en) | 1979-11-29 |
| DE2917730C2 DE2917730C2 (en) | 1986-04-03 |
Family
ID=4299594
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE2917730A Expired DE2917730C2 (en) | 1978-05-26 | 1979-05-02 | Immunobiotherapeutic medicinal preparation for infections of the respiratory tract and process for its manufacture |
Country Status (15)
| Country | Link |
|---|---|
| JP (1) | JPS54154509A (en) |
| BE (1) | BE876164A (en) |
| CH (1) | CH633188A5 (en) |
| CS (1) | CS222673B2 (en) |
| DD (1) | DD143729A5 (en) |
| DE (1) | DE2917730C2 (en) |
| ES (1) | ES480448A1 (en) |
| FR (1) | FR2426470A1 (en) |
| GB (1) | GB2021415B (en) |
| HU (1) | HU180005B (en) |
| IT (1) | IT1116213B (en) |
| PL (1) | PL126416B1 (en) |
| PT (1) | PT69674A (en) |
| RO (1) | RO78451A (en) |
| YU (1) | YU41864B (en) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2550707B1 (en) * | 1983-08-17 | 1986-02-28 | Lipha | IMMUNOMODULATOR OF BIOLOGICAL MEDICINE AND PROCESS FOR PREPARING THE SAME |
| CH680045A5 (en) * | 1990-02-16 | 1992-06-15 | Om Lab Sa | |
| CH685498A5 (en) * | 1992-02-14 | 1995-07-31 | Om Lab Sa | macromolecules bacterial extract, process for its preparation and pharmaceutical composition containing this extract. |
| AU6838996A (en) * | 1996-05-27 | 1998-01-05 | Alexei Nikolaevich Parfenov | Use of streptococcus faecium strains and composition containing the same |
| SE511648C2 (en) * | 1998-04-17 | 1999-11-01 | Bacterum Ab | Streptococcus preparations for the treatment of ear inflammation |
| DK2114421T3 (en) | 2007-03-05 | 2018-04-23 | Om Pharma | BACTERIA EXTRACTS FOR RESPIRATORY DISORDERS AND PROCEDURES FOR PREPARING THEREOF |
| CN104922330A (en) * | 2015-07-15 | 2015-09-23 | 龚灿锋 | Traditional Chinese medicine for treating amygdalitis |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE543985A (en) * | ||||
| FR2892M (en) * | 1963-07-25 | 1964-11-02 | Inst Rech Scient | Substances with immunizing and desensitizing action. |
| FR6513M (en) * | 1967-07-12 | 1968-12-02 | ||
| FR7010M (en) * | 1967-11-10 | 1969-06-02 | ||
| FR7461M (en) * | 1968-06-19 | 1970-01-05 | ||
| NL174267B (en) * | 1969-05-20 | Roussel Uclaf | IMPROVEMENT OF THE PROCESS FOR THE PREPARATION OF A SOMATIC ANTIGEN ACCORDING TO DUTCH PATENT 169754 AND PROCESS FOR PREPARING A PHARMACEUTICAL PREPARATION. | |
| US3929994A (en) * | 1969-05-20 | 1975-12-30 | Roussel Uclaf | Anti-inflammatory glycoprotein compositions and method of use |
| BE795417A (en) * | 1972-02-15 | 1973-08-14 | Roussel Uclaf | NEW COMPOUNDS OF BACTERIAL ORIGIN AND PROCESS FOR OBTAINING |
| FR2253499B1 (en) * | 1973-12-10 | 1977-11-04 | Fabre Sa Pierre | |
| GB1518277A (en) * | 1974-09-06 | 1978-07-19 | Inst Rech Chem Et Biolog Appli | Antigenic composition |
| FR2307542A1 (en) * | 1975-04-14 | 1976-11-12 | Synthelabo | Immuno-stimulant preparations for human and veterinary use - contg. a mixture of inactivated and lysed bacterial cells |
| FR2315944A1 (en) * | 1975-07-04 | 1977-01-28 | Tournade Francois | Non specific immunitary stimulants - contg. separately protein and lipid extracts from human mucosa microorganisms |
-
1978
- 1978-05-26 CH CH580578A patent/CH633188A5/en not_active IP Right Cessation
-
1979
- 1979-05-02 DE DE2917730A patent/DE2917730C2/en not_active Expired
- 1979-05-10 BE BE0/195087A patent/BE876164A/en not_active IP Right Cessation
- 1979-05-10 ES ES480448A patent/ES480448A1/en not_active Expired
- 1979-05-17 CS CS793429A patent/CS222673B2/en unknown
- 1979-05-22 RO RO7997611A patent/RO78451A/en unknown
- 1979-05-23 DD DD79213101A patent/DD143729A5/en not_active IP Right Cessation
- 1979-05-23 FR FR7913157A patent/FR2426470A1/en active Granted
- 1979-05-24 IT IT49157/79A patent/IT1116213B/en active
- 1979-05-24 PL PL1979215824A patent/PL126416B1/en unknown
- 1979-05-25 PT PT69674A patent/PT69674A/en unknown
- 1979-05-25 GB GB7918310A patent/GB2021415B/en not_active Expired
- 1979-05-25 HU HU79LA957A patent/HU180005B/en unknown
- 1979-05-25 JP JP6411579A patent/JPS54154509A/en active Granted
- 1979-05-25 YU YU1236/79A patent/YU41864B/en unknown
Non-Patent Citations (1)
| Title |
|---|
| NICHTS-ERMITTELT * |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2426470A1 (en) | 1979-12-21 |
| CS222673B2 (en) | 1983-07-29 |
| JPS54154509A (en) | 1979-12-05 |
| YU41864B (en) | 1988-02-29 |
| GB2021415A (en) | 1979-12-05 |
| DD143729A5 (en) | 1980-09-10 |
| ES480448A1 (en) | 1979-12-16 |
| RO78451A (en) | 1982-02-26 |
| PL126416B1 (en) | 1983-08-31 |
| DE2917730C2 (en) | 1986-04-03 |
| YU123679A (en) | 1983-04-30 |
| CH633188A5 (en) | 1982-11-30 |
| FR2426470B1 (en) | 1983-08-05 |
| IT7949157A0 (en) | 1979-05-24 |
| IT1116213B (en) | 1986-02-10 |
| PL215824A1 (en) | 1980-02-11 |
| GB2021415B (en) | 1983-03-30 |
| BE876164A (en) | 1979-09-03 |
| HU180005B (en) | 1983-01-28 |
| PT69674A (en) | 1979-06-01 |
| JPS6337770B2 (en) | 1988-07-27 |
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Representative=s name: JUNG, E., DIPL.-CHEM. DR.PHIL. SCHIRDEWAHN, J., DI |
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