CS212234B2 - Method of making the immunotherapeutical means against the infection decease uf urine and digesting ways - Google Patents
Method of making the immunotherapeutical means against the infection decease uf urine and digesting ways Download PDFInfo
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- CS212234B2 CS212234B2 CS805266A CS526680A CS212234B2 CS 212234 B2 CS212234 B2 CS 212234B2 CS 805266 A CS805266 A CS 805266A CS 526680 A CS526680 A CS 526680A CS 212234 B2 CS212234 B2 CS 212234B2
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- lysate
- sodium
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- escherichia coli
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- 238000004519 manufacturing process Methods 0.000 title claims description 5
- 208000015181 infectious disease Diseases 0.000 title description 2
- 210000002700 urine Anatomy 0.000 title 1
- 239000006166 lysate Substances 0.000 claims abstract description 31
- 241000588724 Escherichia coli Species 0.000 claims abstract description 7
- 208000035404 Autolysis Diseases 0.000 claims abstract description 6
- 206010057248 Cell death Diseases 0.000 claims abstract description 6
- 230000028043 self proteolysis Effects 0.000 claims abstract description 6
- 230000009089 cytolysis Effects 0.000 claims abstract description 5
- 208000035473 Communicable disease Diseases 0.000 claims abstract description 4
- 239000001963 growth medium Substances 0.000 claims abstract description 4
- 230000002485 urinary effect Effects 0.000 claims abstract description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 claims abstract description 3
- 210000001635 urinary tract Anatomy 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 12
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- 239000002609 medium Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 claims description 4
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 4
- 239000000284 extract Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 235000013372 meat Nutrition 0.000 claims description 4
- 239000011780 sodium chloride Substances 0.000 claims description 4
- 239000007787 solid Substances 0.000 claims description 4
- 235000015097 nutrients Nutrition 0.000 claims description 3
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 claims description 2
- 229920001817 Agar Polymers 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 241000206672 Gelidium Species 0.000 claims description 2
- 235000010419 agar Nutrition 0.000 claims description 2
- 229940041514 candida albicans extract Drugs 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts 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
- 239000001540 sodium lactate Substances 0.000 claims description 2
- 229940005581 sodium lactate Drugs 0.000 claims description 2
- 235000011088 sodium lactate Nutrition 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
- 239000012138 yeast extract Substances 0.000 claims description 2
- 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 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims 1
- 238000000855 fermentation Methods 0.000 claims 1
- 230000004151 fermentation Effects 0.000 claims 1
- 239000008103 glucose Substances 0.000 claims 1
- 238000009630 liquid culture Methods 0.000 claims 1
- 229910052708 sodium Inorganic materials 0.000 claims 1
- 239000011734 sodium Substances 0.000 claims 1
- 235000021419 vinegar Nutrition 0.000 claims 1
- 239000000052 vinegar Substances 0.000 claims 1
- 230000001580 bacterial effect Effects 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract 2
- 241000699670 Mus sp. Species 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 4
- 235000008504 concentrate Nutrition 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- 206010057249 Phagocytosis Diseases 0.000 description 3
- 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
- 229910052799 carbon Inorganic materials 0.000 description 3
- 230000008782 phagocytosis Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 238000002649 immunization Methods 0.000 description 2
- 230000003053 immunization Effects 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000011287 therapeutic dose Methods 0.000 description 2
- 239000004251 Ammonium lactate Substances 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 206010061126 Escherichia infection Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 206010064921 Urinary tract inflammation Diseases 0.000 description 1
- 229940059265 ammonium lactate Drugs 0.000 description 1
- 235000019286 ammonium lactate Nutrition 0.000 description 1
- RZOBLYBZQXQGFY-HSHFZTNMSA-N azanium;(2r)-2-hydroxypropanoate Chemical compound [NH4+].C[C@@H](O)C([O-])=O RZOBLYBZQXQGFY-HSHFZTNMSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007665 chronic toxicity Effects 0.000 description 1
- 231100000160 chronic toxicity Toxicity 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 208000020612 escherichia coli infection Diseases 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000005462 in vivo assay Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 210000001865 kupffer cell Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000000865 mononuclear phagocyte system Anatomy 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000004627 transmission electron microscopy Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
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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
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/02—Bacterial antigens
- A61K39/025—Enterobacteriales, e.g. Enterobacter
- A61K39/0258—Escherichia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
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- 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
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Reproductive Health (AREA)
- Urology & Nephrology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Endocrinology (AREA)
- Molecular Biology (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)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Vynález se týká způsobu výroby imunobioterapeutického prostředku proti infekčnímu onemocnění močových a zažívacích cest·The invention relates to a method for the production of an immunobiotherapeutic agent against infectious diseases of the urinary and digestive tract.
Předmětem vynálezu je způsob výroby imunobioterapeutického prostředku proti infekčnímu onemocnění močových a zářívacích cest, obsahujícího jakožto účinnou látku bakteriální lyzát z alespoň jednoho z nesledujících kmenů Escherichia coli:SUMMARY OF THE INVENTION The present invention provides a method for the manufacture of an immunobiotherapeutic agent against infectious diseases of the urinary and radiant tract comprising as active ingredient a bacterial lysate from at least one of the following strains of Escherichia coli:
NCTC 8603, NCTC 8621, NCTC 8622, NCTC 8623, NCTC 9026, NCTC 9111, NCTC 9119, NCTC 9707, NCTC 9708, 1-081, 1-082, 1-083, 1-084, 1-085, 1-086, 1-087, 1-088 a 1-089, jehož podstata spočívá v tom, že se uvedené kmeny Escherichia coli inkubují v pevném nebo kapalném Živném prostředí, načež se podrobí lyži nebo/a autolýze a takto získané lyzáty se izolují.NCTC 8603, NCTC 8621, NCTC 8623, NCTC 9026, NCTC 9111, NCTC 9119, NCTC 9707, NCTC 9708, 1-081, 1-082, 1-083, 1-084, 1-085, 1-086 , 1-087, 1-088 and 1-089, characterized in that said Escherichia coli strains are incubated in a solid or liquid medium, subjected to lysis and / or autolysis, and the lysates thus obtained are isolated.
Při způsobu podle vynálezu může být uvedená účinná látka tvořena směsí lyzátů ze všech uvedených kmenů Escherichia coli·In the process according to the invention, said active ingredient may consist of a mixture of lysates from all said Escherichia coli strains.
Předmětem vynálezu je rovněž Živné prostředí pro provádění jehož podstata spočívá v tom, že na jeden litr vody obsahuje*.The invention also relates to a medium for the production of which it contains * per liter of water.
způsobu podle vynálezu,of the method according to the invention,
přičemž se uvedená obsahy jednotlivých složek mohou pohybovat v rozmezí ± 5 %.said contents of each component being within ± 5%.
Živné prostředí podle vynálezu s výhodou ještě na jeden litr vody obsahuje za účelem ztužení 2 g želatiny a 24 g agar-agaru·The medium according to the invention preferably contains, for one liter of water, 2 g of gelatin and 24 g of agar-agar for solidification.
Kapalné prostředí pro porvádění způsobu podle vynálezu autolýzou 8 výhodou obsahuje na jeden litr vody:The liquid medium for carrying out the process according to the invention by autolysis 8 preferably contains per liter of water:
g gg g
8 masového extraktu chloridu sodného a sekundárního fosforečnanu sodného, přičemž se uvedené obsahy jednotlivých složek mohou pohybovat v rozmezí í 5 %·8 meat extract of sodium chloride and secondary sodium phosphate, the contents of which may be in the range of í 5% ·
Kmeny Eschericia coli NCTC jsou katalogizovány ve sbírce National Collection of Type Cultures, London a jsou přístupné veřejnosti, zatímco bakteriální kmeny s označením I byly uloženy autory tohoto vynálezu 7. března 1979 ve sbírce Collection natlonale de cultures de micro-organismes, Institut Pasteur, Paříž.Eschericia coli NCTC strains are cataloged in the National Collection of Type Cultures, London and are open to the public, whereas bacterial strains designated I were deposited by the inventors on March 7, 1979 in the Collection of Cultures of Micro-organisms, Institut Pasteur, Paris. .
Bakteriální kultury se připraví obvyklými bakterologickými technikami za podmínek, které jsou nejpříznivější pro množení zárodků.Bacterial cultures are prepared by conventional bacterological techniques under the conditions most favorable to germ propagation.
Zpracování kultur za účelem získání lyzátů se s výhodou provádí v prostředí, nárokovaném v bodech 4 nebo 5 předmětu vynálezu a to ve fermentoru například při teplotě 35 až 37 °C po dobu 8 až 14 hodin nebo v Rouxových láhvích například při teplotě 33 až 37 °C po dobu 24 až 48 hodin. V případě, že je žádoucí použít pevného živného prostředí, potom může být s výhodou použito živného prostředí nárokovaného v bodě 5 předmětu vynálezu.The cultivation of the cultures to obtain the lysates is preferably carried out in an environment as claimed in points 4 or 5 of the invention, in a fermenter, for example at 35 to 37 ° C for 8 to 14 hours, or in Roux bottles, for example at 33 to 37 ° C for 24 to 48 hours. If it is desired to use a solid culture medium, then the culture medium claimed in clause 5 of the invention may be advantageously used.
Nárůsty kultur se izolují obvyklými metodami. V každé z takto získaných bakteriálních suspenzí se vyhodnotí nárůst, načež se suspenze podrobí progresivní alkalické lyži (pH 9 až 10) při teplotě 20 až 40 °C hydroxidem sodným hydroxidem draselným primárním aminem, sekundárním aminem nebo terciárním aminem. Lyže se provádí po dobu jednoho až pěti dnů pod mikroskopickou kontrolou.Growth cultures are isolated by conventional methods. In each of the thus obtained bacterial suspensions, growth is evaluated, then the suspension is subjected to a progressive alkaline lysis (pH 9-10) at 20 to 40 ° C with sodium hydroxide, potassium hydroxide, a primary amine, a secondary amine or a tertiary amine. The lysis is performed for one to five days under microscopic control.
Objem lyzátu z každého bakteriálního kmene, vstupující do finálního koncentrátu, se vypočete v závislosti na zjištěných výsledcích nárůstu.The volume of lysate from each bacterial strain entering the final concentrate is calculated based on the observed growth results.
Zpracování kultur za účelem získání lyzátů autolýzou se s výhodou provádí v prostředí, nárokovaném v bodě 6 předmětu vynálezu. Naočkované kultury se inkubují po dobu 3 měsíců při teplotě 37 °C. Zfiltrovaný supernatant tvoří bakteriální lyzát kultury.The treatment of the cultures to obtain lysates by autolysis is preferably carried out in the environment claimed in clause 6 of the present invention. The inoculated cultures are incubated for 3 months at 37 ° C. The filtered supernatant forms a bacterial lysate of the culture.
Lyzáty jednotlivých bakteriálních kmenů, získané v pevném nebo/a kapalném živném prostředí, se potom smísí ve vhodném poměru к získání imunobioterapeutického prostředku podle bodu 1 předmětu vynálezu. Celkové množství buněk použitých bakteriálních kmenů se v denní dávce pro dospělého pacienta pohybuje v rozmezí 1 až 5 miliard.The lysates of the individual bacterial strains obtained in the solid and / or liquid nutrient medium are then mixed in a suitable ratio to obtain the immunobiotherapeutic agent of item 1 of the invention. The total number of cells of the bacterial strains used ranges from 1 to 5 billion per day for an adult patient.
Směs lyzátů tvoří nativní koncentrát, který se vyčiří zcentrifugováním a filtrací. Vyčiřený koncentrát se potom sterilizuje membránovou filtrací a takto slouží jako koncentrát bakteriálních lyzátů pro přípravu rozličných galenických formulací.The lysate mixture forms a native concentrate which is clarified by centrifugation and filtration. The clarified concentrate is then sterilized by membrane filtration and thus serves as a concentrate of bacterial lysates for the preparation of various galenic formulations.
Imunobioterapeutický prostředek podle vynálezu se s výhodou aplikuje perorální cestou ve formě komprimátů, kapslí, želatinových tobolek nebo granulí, které obsahují uvedený lyzát v lyofilizované formě, nebo ve formě pitných roztoků v jednodávkových ampulích, sirupů nebo kapek, obsahujících lyzát podle vynálezu. Prostředek může být rovněž aplikován parenterálně nebo také rektálně formou čípků.The immunobiotherapeutic agent of the invention is preferably administered by the oral route in the form of compresses, capsules, gelatin capsules or granules containing said lysate in lyophilized form, or in the form of drinking solutions in single-dose ampoules, syrups or drops containing the lysate of the invention. The composition may also be administered parenterally or also rectally by suppository.
Denní dávka pro dospělého jedince, která se s výhodou bere najednou, obsahuje lyzát v množství 1 až 50 miliard buněčných ekvivalentů. Dětská dávka činí polovidu dávky dospělého.The daily dosage for an adult, preferably taken at once, comprises lysate in an amount of 1 to 50 billion cell equivalents. The children's dose is half the adult dose.
Farmakologické testyPharmacological tests
Byla provedena experimentální studie imunizace u myší druhu Belb/c po perorální stimulaci lyzátem podle bodů 1 a 2 předmětu vynálezu. Tato studie zahrnuje imunizaci humorálních i buněčnou mediací, a to jak specifickou tak i nespecifickou.An experimental immunization study was performed in Belb / c mice following oral lysate stimulation according to items 1 and 2 of the subject invention. This study includes both humoral and cell mediated immunization, both specific and non-specific.
Stanovení ochranného účinkuDetermination of protective effect
Myším bylo po dobu 5 dnů perorálně podáváno 150 mg/kg lyzátu. Přitom bylo zjištěno,Mice were treated orally with 150 mg / kg of lysate for 5 days. It was found that
2122*34 že uvedený lyzát stimuluje statisticky významný ochranný účinek proti infekci Escherichia coli, infikovanou intraperitoneálně 10 až 30 dní po započetí aplikace lyzátu nebo proti infekci Salmonella typhimurium, infikované parenterálně 30 dní po započetí aplikace lyzátu.2122 * 34 that said lysate stimulates a statistically significant protective effect against Escherichia coli infection infected intraperitoneally 10 to 30 days after the start of the lysate application or against infection by Salmonella typhimurium, infected parenterally 30 days after the start of the lysate application.
Plaque forming Cells - testPlaque forming Cells - test
Tato technika umožňuje prokázat zvýšení počtu slezinných buněk v závislosti na čase u myší, kterým bylo podáváno po dobu 5 dní perorálně 150 mg/kg lyzátu. Test byl proveden 14 dní po započetí aplikace lyzátu.This technique makes it possible to demonstrate an increase in spleen cell counts over time in mice administered orally with 150 mg / kg lysate for 5 days. The test was performed 14 days after the start of lysate application.
Test stanovení fagocytózy in vivo s koloidním uhlíkemIn vivo assay for colloidal carbon phagocytosis
Koloidní uhlík, injikovaný myši, je z cévního systému eliminován Kupfferovými buňkami. Kinetika eliminace koloidního uhlíku je tedy ukazatelem účinnosti retikuloendoteliálního systému. Myším bylo po dobu 5 dní podáváno perorálně 150 mg/kg lyzátu. Test byl proveden 10 až 30 dní po započetí aplikace lyzátu. Přitom bylo zjištěno, že účinkem lyzátu došlo ke statisticky významnému zvýšení stupně fagocytózy.Colloid carbon injected into mice is eliminated from the vascular system by Kupffer cells. Thus, the kinetics of colloidal carbon elimination is an indicator of the effectiveness of the reticuloendothelial system. Mice were treated orally with 150 mg / kg of lysate for 5 days. The test was performed 10 to 30 days after the start of lysate application. It was found that the effect of the lysate resulted in a statistically significant increase in the degree of phagocytosis.
Studium účinnosti makrofágůStudy of macrophage efficacy
Myším bylo po dobu 5 dní podáváno perorálně 150 mg/kg lyzátu. Po 10 až 30 dnech od začátku aplikace lyzátu byly izolovány intraperitoneální makrofágy. Studie adhesní kapacity a stupně fagocytózy těchto makrofágů prokázala, že použitý lyzát vykazuje imunostimulační účinek. Rovněž byl prokázán charakteristický pokles enzymatické aktivity těchto feákrofágů, který je pravděpodobně zapříčiněn vyčerpáním těchto příliš exponovaných buněk. Tuto hypotézu potvrdilo i pozorování transmisním elektronovým mikroskopem; aktivované makrofágy vykazovaly silnou vakuolizaci.Mice were treated orally with 150 mg / kg of lysate for 5 days. Intraperitoneal macrophages were isolated 10-30 days after the start of lysate administration. A study of the adhesion capacity and the degree of phagocytosis of these macrophages showed that the lysate used had an immunostimulatory effect. A characteristic decrease in the enzymatic activity of these phophrophages, which is probably caused by depletion of these overexposed cells, has also been demonstrated. This hypothesis was also confirmed by transmission electron microscopy; activated macrophages showed strong vacuolization.
Studium chronické toxicityStudy of chronic toxicity
Lyzát podle vynálezu byl po dobu 13 týdnů podáván v dávkách, které u krys představovaly 100 a 1 OOOnásobek humánní terapeutické dávky a u psů představovaly 20 až 200násobek humánní terapeutické dávky. Během této aplikace nebylo u pokusných zvířat zjištěno žádné zhoršení funkcí ani stavu orgánů.The lysate of the invention was administered for 13 weeks at doses which were 100 and 1000 times the human therapeutic dose in rats and 20 to 200 times the human therapeutic dose in dogs. During this application, no deterioration in organ function or condition was observed in the test animals.
Klinické testy nemocným, trpícím chronickým zánětem močových cest, byla po dobu 6 až 12 měsíců 10 až 15 dní v měsíci podávána jedna dávka lyzátu dennš. Ve 14 případech bylo dosaženo totální eliminace recidiv a ve 3 případech došlo к méně částým recidivám.Clinical trials of patients suffering from chronic urinary tract inflammation were administered a single dose of lysate daily for 6 to 12 months 10 to 15 days per month. In 14 cases total relapse elimination was achieved and in 3 cases less frequent relapses occurred.
Claims (5)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH692479A CH639852A5 (en) | 1979-07-26 | 1979-07-26 | MEDICINE AGAINST INFECTIOUS DISEASES OF THE URINARY AND DIGESTIVE PATHWAYS. |
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| Publication Number | Publication Date |
|---|---|
| CS212234B2 true CS212234B2 (en) | 1982-03-26 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS805266A CS212234B2 (en) | 1979-07-26 | 1980-07-25 | Method of making the immunotherapeutical means against the infection decease uf urine and digesting ways |
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| Country | Link |
|---|---|
| JP (1) | JPS5622733A (en) |
| AR (1) | AR222887A1 (en) |
| BE (1) | BE884456A (en) |
| CH (1) | CH639852A5 (en) |
| CS (1) | CS212234B2 (en) |
| DD (1) | DD153192A5 (en) |
| DE (1) | DE3019448A1 (en) |
| ES (1) | ES491920A0 (en) |
| FR (1) | FR2462164A1 (en) |
| GB (1) | GB2054374B (en) |
| HU (1) | HU181725B (en) |
| IT (1) | IT1143025B (en) |
| PL (1) | PL127520B1 (en) |
| PT (1) | PT71612A (en) |
| RO (1) | RO80054A (en) |
| YU (1) | YU42532B (en) |
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| FR2550707B1 (en) * | 1983-08-17 | 1986-02-28 | Lipha | IMMUNOMODULATOR OF BIOLOGICAL MEDICINE AND PROCESS FOR PREPARING THE SAME |
| US4740585A (en) * | 1984-07-30 | 1988-04-26 | The Board Of Trustees Of The Leland Stanford Junior University | Synthetic vaccine against urinary infections |
| EP1641488B1 (en) | 2003-06-23 | 2011-03-30 | Biotech Tools S.A. | Epitope composition for enteric administration prepared by hydrolysis of antigenic structures with chymotrypsin |
| AU2008222863B2 (en) | 2007-03-05 | 2012-11-08 | Om Pharma | Bacterial extract for digestive or urinary tract disorders and process for its preparation |
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| GB1336015A (en) * | 1970-06-03 | 1973-11-07 | Unilever Ltd | Rearing pigs |
| BE789864A (en) * | 1971-10-14 | 1973-04-09 | Unilever Nv | CALF BREEDING |
| US3911109A (en) * | 1971-10-14 | 1975-10-07 | Lever Brothers Ltd | Rearing calves |
| JPS5219927B2 (en) * | 1972-06-08 | 1977-05-31 | ||
| GB1462384A (en) * | 1973-04-12 | 1977-01-26 | Unilever Ltd | Rearing of lambs |
| GB1560934A (en) * | 1975-05-07 | 1980-02-13 | Unilever Ltd | Methods for the resistance of non-human mammals to gastro-intestinal disorders |
| US4141970A (en) * | 1975-05-07 | 1979-02-27 | Internationale Octrooimaatschappij "Octropa" B.V. | Method for enhancing the resistance of new born mammalian young to gastro-intestinal infections |
| US4136167A (en) * | 1975-06-12 | 1979-01-23 | Internationale Octrooi Maatschappij "Octropa" B.V. | Process for reducing the incidence of neonatal diarrhoea in pigs |
| GB1581776A (en) * | 1976-08-18 | 1980-12-17 | Smith Kline Rit | Vaccines against oedema disease of piglets |
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1979
- 1979-07-26 CH CH692479A patent/CH639852A5/en not_active IP Right Cessation
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1980
- 1980-05-21 DE DE19803019448 patent/DE3019448A1/en active Granted
- 1980-05-28 ES ES491920A patent/ES491920A0/en active Granted
- 1980-06-06 FR FR8012677A patent/FR2462164A1/en active Granted
- 1980-07-10 HU HU801726A patent/HU181725B/en unknown
- 1980-07-14 DD DD222593A patent/DD153192A5/en not_active IP Right Cessation
- 1980-07-22 RO RO80101780A patent/RO80054A/en unknown
- 1980-07-24 PL PL1980225853A patent/PL127520B1/en unknown
- 1980-07-24 BE BE0/201514A patent/BE884456A/en not_active IP Right Cessation
- 1980-07-24 IT IT49314/80A patent/IT1143025B/en active
- 1980-07-25 PT PT71612A patent/PT71612A/en unknown
- 1980-07-25 JP JP10231580A patent/JPS5622733A/en active Granted
- 1980-07-25 CS CS805266A patent/CS212234B2/en unknown
- 1980-07-25 YU YU1896/80A patent/YU42532B/en unknown
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- 1980-07-25 GB GB8024420A patent/GB2054374B/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| ES8104402A1 (en) | 1981-04-01 |
| FR2462164B1 (en) | 1983-08-05 |
| PL127520B1 (en) | 1983-11-30 |
| GB2054374A (en) | 1981-02-18 |
| PT71612A (en) | 1980-08-01 |
| DE3019448A1 (en) | 1981-02-12 |
| YU42532B (en) | 1988-10-31 |
| JPS5622733A (en) | 1981-03-03 |
| IT8049314A0 (en) | 1980-07-24 |
| YU189680A (en) | 1983-06-30 |
| FR2462164A1 (en) | 1981-02-13 |
| HU181725B (en) | 1983-11-28 |
| DD153192A5 (en) | 1981-12-30 |
| BE884456A (en) | 1980-11-17 |
| ES491920A0 (en) | 1981-04-01 |
| IT1143025B (en) | 1986-10-22 |
| AR222887A1 (en) | 1981-06-30 |
| JPH0255407B2 (en) | 1990-11-27 |
| GB2054374B (en) | 1983-06-22 |
| RO80054A (en) | 1982-10-26 |
| CH639852A5 (en) | 1983-12-15 |
| DE3019448C2 (en) | 1987-07-30 |
| PL225853A1 (en) | 1981-05-08 |
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