WO2002076483A2 - Preparation bacteriophage - Google Patents

Preparation bacteriophage Download PDF

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Publication number
WO2002076483A2
WO2002076483A2 PCT/EP2002/003464 EP0203464W WO02076483A2 WO 2002076483 A2 WO2002076483 A2 WO 2002076483A2 EP 0203464 W EP0203464 W EP 0203464W WO 02076483 A2 WO02076483 A2 WO 02076483A2
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WIPO (PCT)
Prior art keywords
bacteriophages
composition according
bacterial
medicament
composition
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Ceased
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PCT/EP2002/003464
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German (de)
English (en)
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WO2002076483A3 (fr
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Nodar A. Danelia
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Individual
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Priority to AU2002304792A priority Critical patent/AU2002304792A1/en
Publication of WO2002076483A2 publication Critical patent/WO2002076483A2/fr
Publication of WO2002076483A3 publication Critical patent/WO2002076483A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • 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
    • A61K35/76—Viruses; Subviral particles; Bacteriophages
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • the present invention relates to a composition comprising bacteriophages and endotoxins and a medicament which contains such a composition and the use of this medicament for combating bacterial diseases and / or inflammation.
  • the composition according to the invention can also be used as a cleaning agent and / or disinfectant.
  • antibiotics for example carbohydrate antibiotics, macrocyclic lactones, cienones, amino acid antibiotics, peptide antibiotics, N-containing heterocyclic antibiotics, O-containing heterocyclic antibiotics, alicyclic antibiotics and aromatic antibiotics.
  • Multi-resistant bacteria in hospitals represent a particularly big problem, with the occurrence of resistant or multi-resistant bacteria being observed particularly often here, and infections with such bacteria, if they cannot be treated immediately, further weaken the patient.
  • DE 1 98 28 596 A1 describes a medicament for the treatment of bacterial diseases which contains polyvalent bacteriophages as an active ingredient.
  • Polyvalent bacteriophages are able to lyse different strains of bacteria, regardless of whether these bacteria are resistant to antibiotics or multi-resistant. In this way, an effective control of resistant bacterial strains is possible.
  • WO 98/51 31 8 describes pharmaceutical compositions which comprise a self-replicating agent against a heterologous pathogenic organism, for example bacteriophages which are specifically directed against a certain heterologous pathogenic organism.
  • EP 0 41 4 304 describes aqueous antibacterial compositions for controlling unwanted bacteria which contain a nonionic surface-active agent, a neutral salt and bacteriophages.
  • An object of the invention was to provide new compositions which, in particular, have an improved action in the treatment of pathogenic organisms.
  • Bacteriophages are viruses which infect bacteria and in particular viruses which specifically infect bacteria, ie do not infect the host, for example a mammal and in particular a human being. Infection of bacteria or other pathogenic microorganisms by virulent phages leads to the lytic cycle and thus ultimately to the lysis and destruction of the bacteria.
  • the lytic cycle begins with the adsorption of the phage to the bacterial cell.
  • the phage or its nucleic acids penetrate the host bacterium and cause its synthetic machinery to synthesize phage-specific proteins and nucleic acids.
  • Phage-specific proteins are, for example, early proteins, such as regulator proteins and catalytic proteins, and late proteins, such as capsid proteins and lysozyme. After the assembly of new phages (virions) from proteins and nucleic acids, the bacterial cell wall is dissolved with the help of the lysozyme (lysis) and the new phages are released. In addition to the lytic cycle, phage infection via the lysogenic pathway is also possible.
  • Endotoxins are bacterial toxins which, in contrast to exotoxins, are not excreted by living bacteria, but are only released by autolysis. Examples of endotoxins are the heat-stable lipopolysaccharide (LPS) fraction of the cell membrane anchored in the outer membrane of gram-negative bacteria.
  • LPS heat-stable lipopolysaccharide
  • Lipopolysaccharides consist of lipid A, the core polysaccharide, and an O-specific chain, lipid A being responsible for the toxic effects of lipopolysaccharides.
  • Endotoxins can be found in all Enterobacteriaceae, e.g. Salmonella (typhoid), Shigella (Ruhr) and many other gram-negative germs.
  • protein toxins of Gram-negative bacteria located in the cytoplasm are also referred to as endotoxins, such as, for example, toxins from Vibrio cholerae (cholera toxin), the bacteriocins (eg Colicine) or the gamma-endotoxins formed by Bacillus thuringiensis, which are polypeptide crystals.
  • interleukin-1 and kachectin tumor necrosis factor
  • endotoxins have so far been undesirable in pharmaceutical compositions, such as for controlling bacteria. Since it was assumed that endotoxins are rather harmful and at least unimportant for the success of a cure, only endotoxin-free preparations have so far been considered for use.
  • the composition according to the invention preferably has at least 10 5 , in particular at least 10 6 , more preferably at least 10 7 and preferably up to 10 10 , more preferably up to 10 9 and most preferably up to 10 8 bacteriophages per ml total volume of the composition. It is also possible to provide concentrate compositions which have a higher proportion of bacteriophages, for example up to 10 20 bacteriophages per ml total volume. Furthermore, it can be advantageous for some applications to use compositions which have a lower bacteriophage content, for example at least 10, at least 100 or at least 1,000 bacteriophages per ml of total volume.
  • compositions according to the invention furthermore preferably contain at least 0.05 ng, in particular at least 5 ng and more preferably at least 10 ng endotoxin per ml total volume of the composition.
  • the endotoxin content can be of any size, but is preferably up to 100,000 ng, more preferably up to 10,000 ng and most preferably up to 1000 ng per ml total volume of the composition.
  • the endotoxin content can be detected in a sample, for example, using the Limulus amoebocyte lysate test.
  • composition according to the invention can contain specific monovalent phages which are able to infect and lyse only a specific type of bacteria.
  • the composition according to the invention is preferably active against several bacteria at the same time, for example by containing several different monovalent bacteriophages and / or containing one or more polyvalent bacteriophages. Polyvalent bacteriophages are able to infect and lyse different types of bacteria.
  • Bacteriophages are preferred which can infect or lyse one or more of the following types of bacteria: Enterobacteriaceae, e.g. the representatives Proteus, in particular P. vulgaris, Salmonealla, Yersinia, in particular Y. pestis, Enterocolitica (Enterocolitiden), Vibrio, Enterobacter, Escherichia, in particular E.coli, Micorococcaceae, Staphylococci, in particular S. aureus, S. epidermidis and others.
  • Enterobacteriaceae e.g. the representatives Proteus, in particular P. vulgaris, Salmonealla, Yersinia, in particular Y. pestis, Enterocolitica (Enterocolitiden), Vibrio, Enterobacter, Escherichia, in particular E.coli, Micorococcaceae, Staphylococci, in particular S. aureus, S. epidermidis and others.
  • phages which can be used according to the invention are lysteriaphages, in particular Listeriaphagen A51 1, B054, Klebsiellaphagen, in particular Klebsiellaphagen K1 1, Klebsieila pneumonia bacteriophages, staphylococcus phages, in particular staphylococcus phages from group II, yeast LA virus, ScVL1, KVLa virus, ScVL1 Killer virus, Chlamydiaphagen such as Chp 1 (Storey et al., Gen. Virol. 70 (1,989), 1321-1327), Bacillus phages such as phi 20 (Inal et al., Curr. Microbiol.
  • phages are used which are able to infect and possibly lyse one of the following hosts: Listeriae, Klebsiellae, streptococci, staphylococci, pneumococci, Moraxellae, Legionellae, Vibrio, Edwardsiellae, Yersiniae, Escherichiae, Haemophilus influenza, Proteus , Salmonaellae, Chlamydiae, Aeromonas salmonicida, Renibacterium salmoninarum, Candida albicans, Leishmania, Anthrax, Trichomonas vaginalis, Giardia lamblia, Cryptosporidium parvum, Plasmodium falciparum, Entamoeba histolytica, Trypocystos carambiosiiensei, Trenseocanis cariniii.
  • Examples of special bacteria from these classes are Listeriae monocytogenesor, Klebsielle (K.) ozaenae, K. rhinoscleromatis scleromatis, K. pneumoniae, Staphylococcus aureus, Yersinia ruckeri, Renibacterium salmoninaram, Vibrio anguillarum, Vibrio chonicida, Vibrio chonicae, Vibrio , Vibrio viscosus, Edwardsieila ictalari but also mushrooms, such as Candida, for example Yeast Candida albicans, Candida guillermondii, Candida krusei, Candida parapsilosis, Candida pseudotropicalis, Candida pulcerrima, Candida stellatoidea, Candida tropicalis, Syringospora albicans, dermatophyte fungi, Trichophyton rubrum, T.
  • Listeriae monocytogenesor Klebsielle (K.) ozaenae, K
  • schoenleini T. mentagureumytes . verrucosum, T.interdigitalis, Empidermophtyton floccosum, Microsporum audouini, M. canis, M. gypseum, Mycophyta, Mycota, Eumycetes, Mycetes, Archi-, Phyco-, Asco- and Basidiomycetes, Adelomycetes, Deuteromycetes, saprophothores, saprophytophoree Emmonsia species or protozoa, such as Leishmania, and also chlamydia, such as Chlamydia pneumoniae, Chlamydia trachomatis and Chlamydia psittaci, Moraxella catarrhalis and Salmonella enteritides.
  • chlamydia such as Chlamydia pneumoniae, Chlamydia trachomatis and Chlamydia psittaci,
  • composition according to the invention can contain bacteriophages of the virulent type and / or the lysogenic type.
  • a composition is particularly preferred which contains bacteriophages, for example as a mixture or as multivalent bacteriophages, which are capable of infecting and lysing at least staphylococcus, streptococcus, E. coli, Pseudomonas and Proteus.
  • Bacteriophages which are active against Klebsiella, Enterococcus and / or Acinetobacter bacteria are also preferred.
  • compositions which is also referred to as IntestiPhag, includes salmonelosephages, staphylococcus phages,
  • Coli-Proteus comprises a mixture of
  • E.coliphagen and Proteusphagen are e.g. used for entercolitis or colpitis.
  • Further preferred compositions in human medicine include phages against streptococci, staphylococci, Escherichia coli,
  • Staphylococci Streptococci, Escherichia coli, Pseudomonas aeruginosa and Proteus or against Staphylococci and Escherichia coli or against
  • Proteus and Escherichia coli or against Pseudomonas au are particularly suitable for use in human medicine.
  • intestiphag for use in veterinary medicine, intestiphag,
  • wild-type bacteriophages are preferably used according to the invention.
  • bacteriophages and in particular the composition according to the invention are also effective against fungi and in particular against fungal attack if the phages are selected appropriately.
  • the composition according to the invention can contain other ingredients, in particular a carrier or solvent, such as water or a salt solution, in particular a physiological saline solution.
  • a carrier or solvent such as water or a salt solution, in particular a physiological saline solution.
  • further active ingredients to the composition in order to achieve a further improvement in effectiveness for certain applications or formulation auxiliaries to achieve a consistency and / or quality suitable for a proposed application.
  • the composition according to the invention is particularly suitable as a medicament.
  • the invention therefore furthermore comprises a medicament which comprises a composition according to the invention containing bacteriophages and endotoxin.
  • the medicament is particularly intended for the treatment of vertebrates such as birds, fish and mammals, preferably for the treatment of humans. It can therefore be used both in human medicine and in veterinary medicine.
  • the medicament according to the invention or the pharmaceutical composition according to the invention a positive effect on the overall healing process of many bacterial or inflammatory diseases can be achieved, even if bacteria or other pathogenic microorganisms are involved which are compared to conventional ones Antibiotics have developed resistance or multi-resistance.
  • the medicament according to the invention can be successfully used for the treatment of fungal attack and / or fungal diseases.
  • the medicament according to the invention can be used both as an outpatient and as an inpatient in hospitals, it being particularly advantageous in the latter case in particular because of the multi-resistant bacteria in hospitals.
  • the drug is suitable for use in intensive care and transplantation medicine as well as for symptomatic treatments.
  • bacteriophages in particular of the virulent type, use the infected bacterial cell to produce a large number of other effective bacteriophages, the bacteria can be effectively combated by further penetration of the released bacteriophages into other bacterial cells and lysis thereof, thereby enhancing the desired bacterial control is achieved in the presence of bacteria to be controlled.
  • the medicament according to the invention is suitable both for treatment and for the prophylaxis of bacterial diseases or inflammation or fungal diseases, in particular on account of the very low associated side effects. Due to the mechanism of action, which involves a multiplication of the active bacteriophages only when an infection of the host with a corresponding bacterium or fungus occurs, it is possible to administer prophylactically small amounts of bacteriophages and endotoxins which do not damage the host organism, but which do occur when bacteria or fungi to be combated can be multiplied in a short time. In acute infections, the administration of high doses of bacteriophages is possible because these selectively lyse the pathogenic microorganism without harming the host organism, for example a mammal.
  • the medicament according to the invention can be formulated for various applications, for example for topical, intravenous, intestinal, oral, rectal, intramuscular, subcutaneous or intraperitoneal use.
  • the medicament according to the invention is preferably formulated for external use, for example as a rinse, irrigation, bandage or tamponing, or for topical use, for example for use under the skin, for use in an inner cavity or for intramuscular use.
  • Both applications against fungal and / or infectious diseases are external applications, for example as an ointment, gel or solution, and oral applications, for example incorporated into a toothpaste or as a solution for gargling.
  • drugs for topical use preferably contain at least 10 ng endotoxin
  • drugs intended for intravenous administration preferably contain 0.05 ng to 0.1 ng endotoxin.
  • the type of formulation can also be adapted to the intended type of application.
  • the medicament according to the invention can be formulated, for example, as a solution, as a spray, as a rinsing liquid, as an injection, as a dragee, capsule, etc., depending on the carrier substances, both solid, liquid and gel-like formulations are possible.
  • the treatment of a patient with the medicament according to the invention is generally carried out over a period of about 3 to 7 days, with a noticeable effect being recognizable after 24 hours in most cases.
  • the dose depends on the type of disease and application, but usually comprises one or more, for example up to three times, administration of the drug per day.
  • topical Applications can be applied, for example, to compresses impregnated with the medicament according to the invention. In the case of large wounds, continuous dropwise application can also be advantageous.
  • the medicament according to the invention optionally contains pharmaceutically suitable auxiliaries and / or carriers. It preferably contains water, a saline solution, in particular a saline solution or a soda solution.
  • a physiological saline solution for example a phosphate-buffered physiological saline solution with a pH of 7 to 7.8, preferably of 7.3 to 7.5, is particularly preferably used as the carrier.
  • the medicament according to the invention preferably has a local antibacterial effect and can be used for wound cleaning of pus.
  • the medicament according to the invention can contain further active substances, each of which can be adapted to the disease to be treated and the form of use.
  • the medicament according to the invention can additionally have conventional antibiotics, immunrepressants or / and cytostatics.
  • the medicament according to the invention is particularly suitable for the treatment and / or prophylaxis of bacterial and / or inflammatory diseases, such as erysipelas, nasal-upper lip furuncles, otitis externa, perichondritis of the auricles, otitis media, mastoiditis, septal abscess, sinusitis acuta purulenta, nosocomial sinusitis, orbital Complications of sinusitis, rhinogenic brain abscess, floor of the mouth, tonsilitis, peritonsillar abscess, endocarditis prophylaxis in ENT surgery, pharyngitis, epiglotis, rhynopharyngitis, laryngitis, tracheitis, bacterial ENT infections, anthrax, diabetic foot ulcers, epidermophytiasis Decubitus, burns, chronic wounds, osteomyelitis, skin diseases, chronic dermatitis, especially of the hands and feet
  • the phages diffusing into the blood and urine and excreted in the urine, so that urological and nephrological diseases can be successfully treated.
  • infectious diseases preference is given to external applications, for example in the form of an ointment, a gel or a solution, or oral applications, for example in the form of a toothpaste or for gargling.
  • the medicament according to the invention is particularly preferably used for the treatment of diabetic ulcers, in particular diabetic foot.
  • solutions for example as a spray or in the form of soaked compresses, are preferably applied to the infected areas.
  • An amount of about 20 to 40 ml of composition containing at least 10 5 bacteriophages per ml and at least 5 ng endotoxin is usually sufficient for this type of application.
  • Pneumonia caused by pneumococci, meningitis and intestinal diseases are also preferred.
  • Sepsis can also be successfully treated by intravenous administration of the medicament according to the invention.
  • Fungal diseases that can be controlled include e.g. chronic dermatitis, especially on the hands and feet, epidermophytia, such as microsporum, trichophyton or epidermophyton, tinea capitis, T. corporis, T. pedis, T. unguium (onychomycosis), candidiasis, tinea versicolor, mycoses (e.g.
  • histoplasmosis coccidioidomycosis
  • Tinea cruris candidiasis, endo- or systemic mycoses, mycosis, endogenous mycosis, exogenous mycosis, blasto-, coccidioido-, chromomycosis, histoplasmosis, nocardiosis, sporotrichosis, dermatomycosis, pneumo-, entermycoses, chromo-, madura-, keloid- blasto- , Phyco-, blasto-, coccidioidomycosis, South American blastomycosis, pheomycotic cyst, rhinosporidiosis, sporotrichosis, adiaspiromycosis, cladosporiosis, histoplasmosis.
  • Medicament can be started and completed with antibiotics, treatment with antibiotics can be started and, if antibiotic resistance is formed or is established, can be completed with the medicament according to the invention or the treatment can be carried out simultaneously with the medicament and antibiotics according to the invention; no known side effects; Harmlessness to the host; - there is no age limit.
  • the medicament according to the invention can be used with great success for treatment, prophylaxis and / or sanitation.
  • the medicament according to the invention provides successful protection against infection by bacteriophages, a reduced risk of postoperative wound infections, an avoidance of infection-related longer periods of stay, low costs in short-term use, no side effects and no elicitation of allergy with a broad coverage of pathogens, for example coverage of the commonly occurring basic strains.
  • the composition according to the invention can also be used in other areas in which combating bacteria or pathogenic microorganisms is desired.
  • the invention therefore also includes the use of the composition according to the invention as a cleaning or / and disinfectant. It has been found that a composition which contains bacteriophages and endotoxins can also be used for disinfecting rooms, surfaces and / or devices, in particular for disinfecting in hospitals and / or pharmaceutical practices. When used as a cleaning agent and / or disinfectant, the advantage of bacteriophages over conventional antibiotics, namely the possibility of combating antibiotic-resistant microorganisms, has a particularly good effect.
  • the composition preferably contains only water, a sodium chloride or sodium carbonate solution, in particular a physiological sodium chloride solution.
  • compositions according to the invention can be obtained by combining a bacteriophage preparation which is obtained in a conventional manner as described in the prior art (e.g. in DE 1 98 28 569 A1) and a composition containing endotoxin.
  • a composition which already contains bacteriophages and endotoxins is preferably formed immediately during production.
  • bacterial strains which are also to be combated later, are infected with the corresponding phages and kept under conditions in which a complete lysis of the bacterial strains is achieved.
  • filtration of Phagolysate is carried out under conditions in which the bacteriophages and endotoxins remain in the recovered fraction, while undesirable components and bacteria residues are separated.
  • Such separation can be done, for example, by filtration with a filter with a pore diameter of at least 0.3 ⁇ m, more preferably at least 0.4 ⁇ m and up to 3 ⁇ m, more preferably up to 2 ⁇ m and particularly preferably up to 1.5 ⁇ m, for example with a 0.45 ⁇ m or a 1.2 ⁇ m pore filter through which the desired components can penetrate bacteriophages and endotoxins.
  • a combination preparation produced in this way can be used directly without further purification or isolation of the bacteriophages.
  • Phage breeds and bacterial strains were used as raw materials for the preparation.
  • the bacterial strains or phages are checked morphologically, serologically and biochemically once a quarter.
  • Bacterial strains or phages that do not match morphologically, serologically or biochemically are discarded.
  • the bacterial strains or phages are stored in a dry environment or on appropriate liquid or solid nutrient media.
  • the phages can be separated (extracted) from the environment (waste water, water reservoir) and from inflammable exudate, pus or faeces.
  • the phagoras must contain virulent phages that can completely lyse the corresponding bacterial strains.
  • Mother phages are obtained in a nutrient medium as in Example 1 and the corresponding bacterial strains are mixed together, the aim being a complete lysis of the bacterial strains. Complete lysis is determined experimentally. The incubation of the culture is e.g. at 37 ° C for 1 6 to 1 8 hours, during which time total lysis is achieved. Only bacterial strains without phages serve as controls. The cultures without complete lysis are discarded. The desired constituents, in particular phages and endotoxins, are then removed by removing unwanted constituents of the phagolysates, e.g. obtained by filtration through a filter with a pore diameter of 0.45 ⁇ m. The preparation can be filled and used directly without further cleaning steps, the preparation preferably being filled into ampoules. If desired, the manufactured preparations can be checked.
  • Each batch of preparations is checked and quantified and certified for physical properties, sterility, toxicity, biological activity, in particular bacteriophage and endotoxin content as well as exotoxin content.
  • the preparation prepared according to Example 2 is used locally in the form of the application and as a rinse.
  • the rinsing is carried out several times a day, advantageously after thorough cleaning of the wound area with 3 to 5% sodium hydrogen carbonate.
  • the application of the mucous membrane is advantageously carried out using the liquid preparation prepared according to Example 2 and 0.5% novocaine solution (for example 1 ml 0.5% novocaine + 3 ml preparation according to the invention).
  • the application is carried out every day until the pathological focus is liquidated, the duration of each treatment being 5 to 10 minutes.
  • the wound treated with 3 to 5% sodium hydrogen carbonate is watered with 3 to 5 ml of the preparation prepared according to Example 2, depending on the extent of the damaged tissue, and a drainage with tampons is left in the wound, which are soaked with the combination preparation according to the invention , Watering the wound and inserting the tampons into the wound is repeated for 3 to 6 days.
  • the preparation prepared according to Example 2 can be used successfully in the form of a spray. Irrigation of a pus wound with a spray has the advantage over tampons that no additional dressing is required and that parts of the wound that cannot be reached with a tampon are also treated with the spray.
  • the preparation prepared according to Example 2 can be punctured into the inner cavity of the pus after the pus has been aspirated be filled in.
  • the quantity of preparation introduced is advantageously somewhat less than the quantity of pus sucked out.
  • inhalation with the preparation prepared according to Example 2 is successfully used, atomization being carried out using a conventional inhaler.
  • the preparation is placed in an inhalation glass and the electric heater is heated to a temperature of 36 to 38 ° C.
  • the duration of the inhalation is usually 5 to 10 minutes, 5 ml of the preparation according to the invention being used.
  • a course of treatment typically involves 10 inhalations, with about 3 inhalations per day.

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Abstract

La présente invention concerne une composition contenant des bactériophages et des endotoxines, ainsi qu'un médicament contenant une telle composition et l'utilisation de ce médicament pour lutter contre des maladies bactériennes, des attaques par des champignons et/ou des inflammations. La composition selon l'invention peut également être utilisée comme agent de nettoyage et/ou désinfectant.
PCT/EP2002/003464 2001-03-28 2002-03-27 Preparation bacteriophage Ceased WO2002076483A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002304792A AU2002304792A1 (en) 2001-03-28 2002-03-27 Bacteriophage preparation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE10115310.4 2001-03-28
DE10115310A DE10115310A1 (de) 2001-03-28 2001-03-28 Bakteriophagen-Präparation

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WO2002076483A2 true WO2002076483A2 (fr) 2002-10-03
WO2002076483A3 WO2002076483A3 (fr) 2003-05-01

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012036580A3 (fr) * 2010-09-17 2012-11-01 Tecnifar-Indústria Técnica Farmacêutica, S.A. Phage antibactérien, peptides phagiques et leurs procédés d'utilisation
RU2616257C1 (ru) * 2015-11-05 2017-04-13 Общество с ограниченной ответственностью "Фармактивы Капитал" Биологический способ селективной дезинфекции с использованием бактериофагов

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EP3443970A3 (fr) * 2010-09-17 2019-05-15 Tecnifar-Indústria Técnica Farmacêutica, S.A. Phage antibactérien, peptides phagiques et leurs procédés d'utilisation
CN103732235A (zh) * 2010-09-17 2014-04-16 药物技术业制药技术股份有限公司 抗菌噬菌体、噬菌体肽及其使用方法
US9222077B2 (en) 2010-09-17 2015-12-29 Tecnifar—Industria Tecnica Farmaceutica, S.A. Antibacterial phage, phage peptides and methods of use thereof
US9399049B2 (en) 2010-09-17 2016-07-26 Technophage, Investigacao E Desenvolvimento Em Biotecnologia, Sa Antibacterial phage, phage peptides and methods of use thereof
RU2614114C2 (ru) * 2010-09-17 2017-03-22 Текнифар-Индустриа Текника Фармасьютика, С.А Бактериофаги, фаговые пептиды и способы их применения
US9737579B2 (en) 2010-09-17 2017-08-22 Technophage, Investigacao E Desenvolvimento Em Biotecnologia, Sa Antibacterial phage, phage peptides and methods of use thereof
EP3443970A2 (fr) 2010-09-17 2019-02-20 Tecnifar-Indústria Técnica Farmacêutica, S.A. Phage antibactérien, peptides phagiques et leurs procédés d'utilisation
WO2012036580A3 (fr) * 2010-09-17 2012-11-01 Tecnifar-Indústria Técnica Farmacêutica, S.A. Phage antibactérien, peptides phagiques et leurs procédés d'utilisation
RU2725726C2 (ru) * 2010-09-17 2020-07-03 Текнифар-Индустриа Текника Фармасьютика, С.А. Бактериофаги, фаговые пептиды и способы их применения
EP3789031A1 (fr) 2010-09-17 2021-03-10 Tecnifar-Indústria Técnica Farmacêutica, S.A. Phage antibactérien, peptides phagiques et leurs procédés d'utilisation
EP4332217A2 (fr) 2010-09-17 2024-03-06 Technophage, Investigação e Desenvolvimento em Biotecnologia, SA Phage antibactérien, peptides de phage et leurs procédés d'utilisation
RU2616257C1 (ru) * 2015-11-05 2017-04-13 Общество с ограниченной ответственностью "Фармактивы Капитал" Биологический способ селективной дезинфекции с использованием бактериофагов
RU2616257C9 (ru) * 2015-11-05 2017-07-24 Общество с ограниченной ответственностью "Фармактивы Капитал" Биологический способ селективной дезинфекции с использованием бактериофагов

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