US20080175865A1 - Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias - Google Patents
Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias Download PDFInfo
- Publication number
- US20080175865A1 US20080175865A1 US12/077,780 US7778008A US2008175865A1 US 20080175865 A1 US20080175865 A1 US 20080175865A1 US 7778008 A US7778008 A US 7778008A US 2008175865 A1 US2008175865 A1 US 2008175865A1
- Authority
- US
- United States
- Prior art keywords
- lactobacillus
- prostate
- vaccine
- lactobacillus strains
- inflammation
- 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.)
- Abandoned
Links
- 241000186660 Lactobacillus Species 0.000 title claims abstract description 42
- 229960005486 vaccine Drugs 0.000 title claims abstract description 22
- 210000002307 prostate Anatomy 0.000 title claims abstract description 18
- 206010061218 Inflammation Diseases 0.000 title claims abstract description 16
- 230000004054 inflammatory process Effects 0.000 title claims abstract description 16
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 title claims abstract description 11
- 229940039696 lactobacillus Drugs 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 6
- 206010020718 hyperplasia Diseases 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- 230000001580 bacterial effect Effects 0.000 claims description 3
- 241000186840 Lactobacillus fermentum Species 0.000 claims 2
- 241000186605 Lactobacillus paracasei Species 0.000 claims 2
- 240000006024 Lactobacillus plantarum Species 0.000 claims 2
- 235000013965 Lactobacillus plantarum Nutrition 0.000 claims 2
- 229940012969 lactobacillus fermentum Drugs 0.000 claims 2
- 229940072205 lactobacillus plantarum Drugs 0.000 claims 2
- 238000002360 preparation method Methods 0.000 abstract description 3
- 239000000969 carrier Substances 0.000 abstract description 2
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 2
- 238000011282 treatment Methods 0.000 description 8
- 230000017074 necrotic cell death Effects 0.000 description 7
- 210000001215 vagina Anatomy 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000003308 immunostimulating effect Effects 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 230000001717 pathogenic effect Effects 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 238000002255 vaccination Methods 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 208000005107 Premature Birth Diseases 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000000254 damaging effect Effects 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 239000008223 sterile water Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 244000199866 Lactobacillus casei Species 0.000 description 2
- 235000013958 Lactobacillus casei Nutrition 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 229940017800 lactobacillus casei Drugs 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 230000001338 necrotic effect Effects 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000003053 toxin Substances 0.000 description 2
- 231100000765 toxin Toxicity 0.000 description 2
- 108700012359 toxins Proteins 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 208000004926 Bacterial Vaginosis Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 231100000699 Bacterial toxin Toxicity 0.000 description 1
- 229910005390 FeSO4-7H2O Inorganic materials 0.000 description 1
- 229910005444 FeSO4—7H2O Inorganic materials 0.000 description 1
- 206010061977 Genital infection female Diseases 0.000 description 1
- 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 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 241000186610 Lactobacillus sp. Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229910017621 MgSO4-7H2O Inorganic materials 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241001632427 Radiola Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 241000224526 Trichomonas Species 0.000 description 1
- 208000005448 Trichomonas Infections Diseases 0.000 description 1
- 241000224527 Trichomonas vaginalis Species 0.000 description 1
- 206010044620 Trichomoniasis Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000000688 bacterial toxin Substances 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 210000002443 helper t lymphocyte Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 230000000644 propagated effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- YWYZEGXAUVWDED-UHFFFAOYSA-N triammonium citrate Chemical compound [NH4+].[NH4+].[NH4+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O YWYZEGXAUVWDED-UHFFFAOYSA-N 0.000 description 1
- 239000001393 triammonium citrate Substances 0.000 description 1
- 235000011046 triammonium citrate Nutrition 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Classifications
-
- 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
- A61K39/09—Lactobacillales, e.g. aerococcus, enterococcus, lactobacillus, lactococcus, streptococcus
-
- 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
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- 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
-
- 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
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- 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
-
- 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
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- 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
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/52—Bacterial cells; Fungal cells; Protozoal cells
- A61K2039/521—Bacterial cells; Fungal cells; Protozoal cells inactivated (killed)
-
- 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
- A61K2039/55—Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
- A61K2039/552—Veterinary vaccine
-
- 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
- A61K38/00—Medicinal preparations containing peptides
-
- 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
-
- 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
- A61K39/39—Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
Definitions
- the present invention relates to a vaccine comprising Lactobacillus strains useful in treating prostate inflammation and benign prostate hyperplasias (stages I and II).
- K. ⁇ jhelyi has found that necrosis can be induced also by Lactobacillus strains cultivated from vagina. Based on his observation, it can be stated that the body of the bacterium contains a toxin which is responsible for damaging the epithelia [ ⁇ jhelyi K. et al.: Role of Lactobacillus in urogenital inflammations and their treatment with vaccination, Symposium cum participations internationalis de Biocenosi Vaginae, Smolenie, 1983]. Certain strains, injected intradermally to the back of rabbits, cause necrosis of smaller or larger areas, while others cause necrosis only in higher concentration or do not cause necrosis at all. K.
- rabbits can be immunized by vaccination against the necrotic effect.
- He vaccinated rabbits intramuscularly with vaccine produced from certain Lactobacillus strains.
- Trichomonas vaginalis contributes to the rise in vaginal pH by consuming lactic acid produced by Lactobacillus strains in the vagina, thereby promoting the over-proliferation of Lactobacillus strains. Consequently toxin is present in higher concentration which, by damaging the mucous membrane, causes cell necrosis.
- Lactobacillus strains because of their receptor inhibiting and antibiotic activity as well as pH-modifying effect, are antagonistic to pyogenic microorganisms [Reddy et al.: Natural antibiotic activity of Lactobacillus, Dairy Prod. J 18:15-22 (1983); Salminen et al.: Lactic acid bacteria in the gut in normal and disordered states, Dig. Dis., 10:227-238 (1992)].
- Lactobacillus strains can bind directly to T-lymphocytes since both the T-helper and T-killer cells have specific receptors for Lactobacillus strains. Furthermore, Lactobacillus strains promote the gamma-interferon production of the lymphocytes and the cytotoxic activity of the natural killer cells [De Simone C., et al.: Enhancement of immune response of murine Peyer's pothes by a diet supplemented with yoghurt, J. Immunopharmacol., 1:87-95 (1987)].
- Lactobacillus strains aspecifically increase the production of IgM and IgG [Blocksma et al.: Adjuvant activity of lactobacilli, different effects of viable and killed bacteria, Clin. Exp. Immunol., 37:367-373]. Additionally, under experimental conditions, Lactobacillus strains show antitumour and macrophage-activating activity [Kato I. et al.,: Antitumor activity of Lactobacillus casei in mice, Gann, 72:517-523 (1983); Oda M. et al.: Antitumor polysaccharide from Lactobacillus sp., Agric Biol. Chem., 47:1623-1627 (1983)].
- Lactobacillus strains used parenterally administered Lactobacillus strains for aspecific immunostimulation and observed that the Lactobacillus strains used, in contrast to other aspecific immunostimulation (e.g. by BCG, endotoxins etc.), show protective effect against certain bacterial toxins. This applies especially to toxic Lactobacillus strains.
- the inventors of the present invention have, however, found that conditions in the prostate are favorable to the proliferation of Lactobacillus strains and that pathogenic lactobacilli can often be cultivated from patients suffering from chronic prostate inflammation and/or prostate hyperplasia. On this basis, therapeutic utilization of vaccines comprising Lactobacillus strains for treating such patients has been achieved.
- the invention relates to vaccines for treating prostate inflammations and benign prostate hyperplasias (stages I and II) comprising Lactobacillus strains in inactivated form and carriers and/or excipients commonly used in vaccine preparations.
- the invention relates to the use of Lactobacillus strains for producing vaccines capable of treating prostate inflammation and benign prostate hyperplasias (stages I and II).
- the invention relates to the use of Lactobacillus strains for treating patients suffering from prostate inflammation and benign prostate hyperplasias (stages I and II).
- the invention relates to a method of treating patients suffering from prostate inflammation and benign prostate hyperplasias (stages I and II) comprising administering an effective dose of a strain-suspension of Lactobacillus strains intramuscularly to a patient in need of such treatment.
- the strain-suspension of Lactobacillus strains comprises a mixed population of the said strains in inactivated form.
- the lactobacilli used in the vaccine of the invention are Lactobacillus strains used in the above-said vaccines Gynevac®, Gyantren® and Solco Trichovac® that previously have been cultivated from women suffering from gynecologic inflammations of bacterial origin.
- the single cultivated strains can be use per se or in the form of a blend of the strains.
- the vaccine of the invention can be produced by methods commonly used for preparing vaccines.
- the cultivated strains are stored in lyophilized form, then, before use, they are propagated by culturing in Man-Rogosa-Sharpe medium at 45° C.
- composition of the said medium and the preparation method are set forth below.
- the obtained solution is adjusted to 3000 ml by the addition of sterile water, filtered on G4 filter, bottles in smaller volumes and sterilized at 121° C.
- composition of the above-said salt solution is as follows: 28.75 g of MgSO 4 -7H 2 O, 6 g of MnSO 4 -2H 2 O and 1.7 of FeSO 4 -7H 2 O dissolved in 250 ml of sterile water.
- the protein content of the vaccine (suspension) of the invention is at least 0.08 mg/ml, and may be up to 1 mg/ml or more, preferably from about 0.08 to about 0.32 mg/ml, more preferably about 0.16 mg/ml.
- the dosage of the vaccine of the invention and the frequency of the administration depend on the conditions of the patient and the severity of the symptoms to be treated. The precise dose and frequency of administration should be specified by the practicing physician. During treatment, it is advantageous if the vaccine is administered intramuscularly in a volume of 1 ml, once a week for five weeks.
Abstract
The invention relates to vaccines for treating prostate inflammation and benign prostate hyperplasias (stages I and II) comprising Lactobacillus strains in an inactivated form and carriers and/or excipients commonly used in vaccine preparations.
Description
- The present invention relates to a vaccine comprising Lactobacillus strains useful in treating prostate inflammation and benign prostate hyperplasias (stages I and II).
- The pathogenecity of certain Lactobacillus strains has been reported in 1938 [F. Marshall: Der Döderleinische Bacillus vaginalis als Endokarditiserreger, Zentr. Bact. Parasit. Kde. I. Abt. Orig., 141:153-159 (1938); E. Biocca és A. Sepilli: Human infections caused by lactobacilli, J. Inf. Dis., 81:112-115 (1947); W. Sims: A pathogenic Lactobacillus, J. Path. Bact, 87:99-105 (1964); B. Rosan and B. F. Hammond: Toxicity of Lactobacillus casei, J. Dent. Res., 44:783-787 (1965); M. E. Sharpe, L. R. Hill and S. P. Lapage: Pathogenic lactobacilli, J. Med. Microbiol., 6, 281-286 (1973).
- G. Wied reported in 1952 [Zbl. Bact., 160:413 (1952)] that certain Lactobacillus strains show mucous membrane damaging activity. Rosan and Hammond [1965, ibid.] reported that, with Lactobacillus strains strongly pathogenic to mice, intradermal inoculation of bacteria both in living and in thermally inactivated states causes necrosis on the back of rabbits.
- K. Újhelyi has found that necrosis can be induced also by Lactobacillus strains cultivated from vagina. Based on his observation, it can be stated that the body of the bacterium contains a toxin which is responsible for damaging the epithelia [Újhelyi K. et al.: Role of Lactobacillus in urogenital inflammations and their treatment with vaccination, Symposium cum participations internationalis de Biocenosi Vaginae, Smolenie, 1983]. Certain strains, injected intradermally to the back of rabbits, cause necrosis of smaller or larger areas, while others cause necrosis only in higher concentration or do not cause necrosis at all. K. Újhelyi has found that rabbits can be immunized by vaccination against the necrotic effect. He vaccinated rabbits intramuscularly with vaccine produced from certain Lactobacillus strains. Six weeks later, he intradermally administered cell-suspensions prepared from strains that have been shown previously to be necrotic, and observed that necrosis was not caused or was only caused in a lesser degree than in the case of non-vaccinated rabbits.
- Furthermore, K. Újhelyi has found that Trichomonas vaginalis contributes to the rise in vaginal pH by consuming lactic acid produced by Lactobacillus strains in the vagina, thereby promoting the over-proliferation of Lactobacillus strains. Consequently toxin is present in higher concentration which, by damaging the mucous membrane, causes cell necrosis.
- Furthermore, it is known that Lactobacillus strains, because of their receptor inhibiting and antibiotic activity as well as pH-modifying effect, are antagonistic to pyogenic microorganisms [Reddy et al.: Natural antibiotic activity of Lactobacillus, Dairy Prod. J 18:15-22 (1983); Salminen et al.: Lactic acid bacteria in the gut in normal and disordered states, Dig. Dis., 10:227-238 (1992)].
- Recently, it has been shown that Lactobacillus strains can bind directly to T-lymphocytes since both the T-helper and T-killer cells have specific receptors for Lactobacillus strains. Furthermore, Lactobacillus strains promote the gamma-interferon production of the lymphocytes and the cytotoxic activity of the natural killer cells [De Simone C., et al.: Enhancement of immune response of murine Peyer's pothes by a diet supplemented with yoghurt, J. Immunopharmacol., 1:87-95 (1987)]. It has been shown that Lactobacillus strains aspecifically increase the production of IgM and IgG [Blocksma et al.: Adjuvant activity of lactobacilli, different effects of viable and killed bacteria, Clin. Exp. Immunol., 37:367-373]. Additionally, under experimental conditions, Lactobacillus strains show antitumour and macrophage-activating activity [Kato I. et al.,: Antitumor activity of Lactobacillus casei in mice, Gann, 72:517-523 (1983); Oda M. et al.: Antitumor polysaccharide from Lactobacillus sp., Agric Biol. Chem., 47:1623-1627 (1983)]. H. Rüttgers has found that immunostimulation by Lactobacillus strains causes a significant long-lasting rise in secretory immunoglobulin level in the vagina [Bacterial vaginitis: Protection against infection and secretory immunoglobulin levels in the vagina after immunization therapy with Gynatren, Gynecol. Obstet. Invest., 26:240-249 (1988)].
- Újhelyi et al. [1983, ibid.] used parenterally administered Lactobacillus strains for aspecific immunostimulation and observed that the Lactobacillus strains used, in contrast to other aspecific immunostimulation (e.g. by BCG, endotoxins etc.), show protective effect against certain bacterial toxins. This applies especially to toxic Lactobacillus strains.
- In trials carried out with vaccines (Gynevac®, Gynatren®, Solco Trichovac®) made of strains cultured by Újhelyi it has been demonstrated that immunostimulation by Lactobacillus strains, in contrast to other therapeutic treatments, restores the biological balance of the vagina, normalizes the pH, decreases the number of pathogenic bacteria, and contributes to the propagation of Döderlein-flora (a mixed population of Lactobacillus strains capable of being cultivated from vaginal specimens). It is an accepted fact that inflammatory diseases of the vagina caused by bacterial and Trichomonas infections can be cured in this way more successfully than by other therapy and that such inflammatory conditions are a major cause of premature births. Therefore, the frequency of premature births can also be decreased by such therapy [see e.g. in Genitalinfektion der Frau (SolcoTrichovac/Gynatren), Geburtsch. u. Frauenheilk, 44:311 (1984); E. Lázár, Gy. Varga, I. Institoris and K. Újhelyi: Investigating the factors, especially vaccination with lactobacilli, influencing the premature births, in Kazincbarcika (in Hungarian), Magyar Nöorvosok Lapja (Journal of Hungarian Gynaecologists), 51:353-356 (1986); E. Lázár, Gy. Varga, I. Institoris and K. Újhelyi: Decreasing the ratio of neonates with small weight by lactobact vaccination of pregnant women (in Hungarian), Orvosi Hetilap (Physicians Weekly), 37:2263-2268 (1981), Rüttgers, 1988, ibid., K. Újhelyi, Gy. Philipp, Gy. Plank and V. Sági: The Trichomonas syndrome I (in Hungarian), Magyar Nöorvosok Lapja (Journal of Hungarian Gynaecologists), 36:433-442 (1973); Sharon et al., New England Journal, Dec. 28, 1995.].
- More than 50% of men aged 50 or more suffer from prostate hyperplasia and/or prostate inflammation. In spite of numerous known and utilized therapies, treatment is often unsuccessful. Taking into consideration the known and generally accepted pathogenesis, it could not be supposed that such diseases can be healed with vaccines comprising Lactobacillus strains successfully.
- The inventors of the present invention have, however, found that conditions in the prostate are favorable to the proliferation of Lactobacillus strains and that pathogenic lactobacilli can often be cultivated from patients suffering from chronic prostate inflammation and/or prostate hyperplasia. On this basis, therapeutic utilization of vaccines comprising Lactobacillus strains for treating such patients has been achieved.
- The invention relates to vaccines for treating prostate inflammations and benign prostate hyperplasias (stages I and II) comprising Lactobacillus strains in inactivated form and carriers and/or excipients commonly used in vaccine preparations.
- In another aspect, the invention relates to the use of Lactobacillus strains for producing vaccines capable of treating prostate inflammation and benign prostate hyperplasias (stages I and II).
- In a further aspect, the invention relates to the use of Lactobacillus strains for treating patients suffering from prostate inflammation and benign prostate hyperplasias (stages I and II).
- Furthermore, the invention relates to a method of treating patients suffering from prostate inflammation and benign prostate hyperplasias (stages I and II) comprising administering an effective dose of a strain-suspension of Lactobacillus strains intramuscularly to a patient in need of such treatment.
- In an embodiment of the method of the invention, the strain-suspension of Lactobacillus strains comprises a mixed population of the said strains in inactivated form.
- The lactobacilli used in the vaccine of the invention are Lactobacillus strains used in the above-said vaccines Gynevac®, Gyantren® and Solco Trichovac® that previously have been cultivated from women suffering from gynecologic inflammations of bacterial origin. The single cultivated strains can be use per se or in the form of a blend of the strains.
- The vaccine of the invention can be produced by methods commonly used for preparing vaccines. Advantageously, the cultivated strains are stored in lyophilized form, then, before use, they are propagated by culturing in Man-Rogosa-Sharpe medium at 45° C.
- The composition of the said medium and the preparation method are set forth below.
- To 2300 ml of sterile water the following components are added sequentially, after dissolving the previously added component:
-
Bactotripton (Raenal) 30 g Lablemko (Reanal) 30 g K2HPO4 6 g triammonium citrate 6 g sodium acetate 15 g glucose 30 g lactose 30 g maltose 9 g yeast extract (Reanal) 15 g Tween 80 3 ml Salt solution (composition see below) 15 ml - The obtained solution is adjusted to 3000 ml by the addition of sterile water, filtered on G4 filter, bottles in smaller volumes and sterilized at 121° C.
- The composition of the above-said salt solution is as follows: 28.75 g of MgSO4-7H2O, 6 g of MnSO4-2H2O and 1.7 of FeSO4-7H2O dissolved in 250 ml of sterile water.
- After culturing, the cells are harvested by centrifuging and are suspended in physiological saline solution and treated with formaldehyde. The inactivated cells are harvested and resuspended in physiological saline solution. The level of dilution is adjusted on the basis of the protein content of the suspension. The protein content of the vaccine (suspension) of the invention is at least 0.08 mg/ml, and may be up to 1 mg/ml or more, preferably from about 0.08 to about 0.32 mg/ml, more preferably about 0.16 mg/ml.
- The dosage of the vaccine of the invention and the frequency of the administration depend on the conditions of the patient and the severity of the symptoms to be treated. The precise dose and frequency of administration should be specified by the practicing physician. During treatment, it is advantageous if the vaccine is administered intramuscularly in a volume of 1 ml, once a week for five weeks.
- The following example is given for the purpose of illustration of the invention without the intention of limiting of the scope claimed.
- Investigations were carried out with the vaccine of the invention by administering same to patients with a diagnosis of prostate inflammation and/or prostate hyperplasias (stages I and II). The patients were administered intramuscularly 1 ml of a vaccine comprising Lactobacillus strains of the invention once weekly for 5 weeks, without any other medical treatment. The results of the control examination carried out after this cure are summarized in the following Tables.
- Number of the treated patients: 127
Diagnosis: prostate hyperplasia stages I and II -
Condition of the Time elapsed after the treatment patients 4 to 8 weeks 2 to 4 months 6 months Healed 52 (40.94%) Worsening of the 60% of 94 Improved 47 (37.0%) condition was not examined patients Unchanged 28 (22.0%) observed in any of were symptom- Worsened 0 the patients. free.
Number of the treated patients: 168
Diagnosis: prostate inflammation -
Condition of the Time elapsed after the treatment patients 4 to 8 weeks 2 to 4 months 6 months Healed 76 (45.23%) Worsening of the 70% of 79 Improved 61 (36.31%) condition was not examined patients Unchanged 31 (18.45%) observed in any of were symptom- Worsened 0 the patients. free. - As can be seen in the above Tables, a significant ratio of the patients were healed or their conditions improved essentially.
Claims (4)
1. A process for treating a patient suffering from prostate inflammation, benign prostate hyperplasia stage I, or benign prostate hyperplasia stage II, said process comprising vaccinating the patient with a vaccine, said vaccine containing an effective amount of a mixture of Lactobacillus plantarum, Lactobacillus paracasei and Lactobacillus fermentum in its inactivated form.
2. A method of treating a patient suffering from prostate inflammation, benign prostate hyperplasia stage I, or benign prostate hyperplasia stage II, said method comprising vaccinating said patient intramuscularly with an effective dose of a suspension of a mixture of Lactobacillus plantarum, Lactobacillus paracasei and Lactobacillus fermentum in its inactivated form.
3. The method of claim 2 , wherein the patient is suffering from a benign hyperplasia stage I or II.
4. The method of claim 2 , wherein said Lactobacillus strains previously have been cultivated from women suffering from gynecologic inflammations of bacterial origin.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/077,780 US20080175865A1 (en) | 1999-11-25 | 2008-03-21 | Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
| US13/049,344 US9056073B2 (en) | 1999-11-25 | 2011-03-16 | Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
| US14/735,637 US20160051657A1 (en) | 1999-11-25 | 2015-06-10 | Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
| US15/891,620 US20180161414A1 (en) | 1999-11-25 | 2018-02-08 | Vaccine comprising lactobacillus strains for treating prostate inflammation and benign prostate hyperplasias |
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU9904408A HU227086B1 (en) | 1999-11-25 | 1999-11-25 | Lactobacillus vaccine for treating prostata inflammatory and benign prostata hyperplasia |
| HUP9904408 | 1999-11-25 | ||
| PCT/HU2000/000122 WO2001037862A2 (en) | 1999-11-25 | 2000-11-23 | A vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
| US13082302A | 2002-09-16 | 2002-09-16 | |
| US12/077,780 US20080175865A1 (en) | 1999-11-25 | 2008-03-21 | Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
Related Parent Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/HU2000/000122 Continuation WO2001037862A2 (en) | 1999-11-25 | 2000-11-23 | A vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
| US13082302A Continuation | 1999-11-25 | 2002-09-16 | |
| US10130823 Continuation | 2002-09-16 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US13/049,344 Continuation US9056073B2 (en) | 1999-11-25 | 2011-03-16 | Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US20080175865A1 true US20080175865A1 (en) | 2008-07-24 |
Family
ID=90014600
Family Applications (4)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US12/077,780 Abandoned US20080175865A1 (en) | 1999-11-25 | 2008-03-21 | Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
| US13/049,344 Expired - Fee Related US9056073B2 (en) | 1999-11-25 | 2011-03-16 | Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
| US14/735,637 Abandoned US20160051657A1 (en) | 1999-11-25 | 2015-06-10 | Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
| US15/891,620 Abandoned US20180161414A1 (en) | 1999-11-25 | 2018-02-08 | Vaccine comprising lactobacillus strains for treating prostate inflammation and benign prostate hyperplasias |
Family Applications After (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US13/049,344 Expired - Fee Related US9056073B2 (en) | 1999-11-25 | 2011-03-16 | Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
| US14/735,637 Abandoned US20160051657A1 (en) | 1999-11-25 | 2015-06-10 | Vaccine comprising lactobacilli for treating prostate inflammation and benign prostate hyperplasias |
| US15/891,620 Abandoned US20180161414A1 (en) | 1999-11-25 | 2018-02-08 | Vaccine comprising lactobacillus strains for treating prostate inflammation and benign prostate hyperplasias |
Country Status (20)
| Country | Link |
|---|---|
| US (4) | US20080175865A1 (en) |
| EP (1) | EP1272216B1 (en) |
| AT (1) | ATE470452T1 (en) |
| AU (1) | AU779214B2 (en) |
| CA (1) | CA2394843C (en) |
| CZ (1) | CZ302662B6 (en) |
| DE (1) | DE60044539D1 (en) |
| DK (1) | DK1272216T3 (en) |
| EA (1) | EA005198B1 (en) |
| ES (1) | ES2348591T3 (en) |
| HU (1) | HU227086B1 (en) |
| IL (2) | IL149779A0 (en) |
| PL (1) | PL201804B1 (en) |
| PT (1) | PT1272216E (en) |
| RO (1) | RO122760B1 (en) |
| RS (1) | RS51201B (en) |
| SI (1) | SI20960B (en) |
| SK (1) | SK288132B6 (en) |
| UA (1) | UA78673C2 (en) |
| WO (1) | WO2001037862A2 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1723965A1 (en) | 2005-05-18 | 2006-11-22 | Stallergenes Sa | Compositions for antigen-specific induction of immuno-tolerance via oral immunization |
| US9732131B2 (en) | 2006-02-27 | 2017-08-15 | Calviri, Inc. | Identification and use of novopeptides for the treatment of cancer |
| US20110027348A1 (en) | 2007-08-27 | 2011-02-03 | Janos Feher | Composition and method inhibiting inflammation |
| WO2018223094A1 (en) | 2017-06-02 | 2018-12-06 | Arizona Board Of Regents On Behalf Of Arizona State University | A method to create personalized canine cancer vaccines |
| US20200209241A1 (en) | 2017-09-15 | 2020-07-02 | Arizona Board Of Regents On Behalf Of Arizona State University | Methods of classifying response to immunotherapy for cancer |
| EP4038222A4 (en) | 2019-10-02 | 2023-10-18 | Arizona Board of Regents on behalf of Arizona State University | Methods and compositions for identifying neoantigens for use in treating and preventing cancer |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CH639280A5 (en) * | 1977-12-23 | 1983-11-15 | Solco Basel Ag | METHOD FOR PRODUCING A VACCINE AGAINST TRICHOMONAS SYNDROME. |
| DE19522472C2 (en) * | 1995-06-21 | 1998-07-02 | Eugen Baumgaertner | Manufacturing process of a fermentation product for the treatment of prostate disorders |
| DK2241616T3 (en) * | 1997-08-21 | 2013-02-18 | New Zealand Dairy Board | Immune-enhancing lactic acid bacteria |
| IT1298918B1 (en) * | 1998-02-20 | 2000-02-07 | Mendes Srl | USE OF ARGININE DEIMINASE BACTERIA TO INDUCE APOPTOSIS AND / OR REDUCE AN INFLAMMATORY REACTION AND PHARMACEUTICAL COMPOSITIONS |
| IT1306716B1 (en) * | 1999-06-21 | 2001-10-02 | Mendes S U R L | ASSOCIATION OF LACTIC BACTERIA AND ITS USE FOR THE PREVENTION AND / OR THERAPEUTIC TREATMENT OF INFECTIONS AND INFLAMMATORY STATES. |
-
1999
- 1999-11-25 HU HU9904408A patent/HU227086B1/en unknown
-
2000
- 2000-11-23 PT PT00981507T patent/PT1272216E/en unknown
- 2000-11-23 EA EA200200602A patent/EA005198B1/en not_active IP Right Cessation
- 2000-11-23 WO PCT/HU2000/000122 patent/WO2001037862A2/en active IP Right Grant
- 2000-11-23 AT AT00981507T patent/ATE470452T1/en active
- 2000-11-23 CZ CZ20021771A patent/CZ302662B6/en not_active IP Right Cessation
- 2000-11-23 CA CA2394843A patent/CA2394843C/en not_active Expired - Fee Related
- 2000-11-23 AU AU18741/01A patent/AU779214B2/en not_active Ceased
- 2000-11-23 SI SI200020063A patent/SI20960B/en active Search and Examination
- 2000-11-23 IL IL14977900A patent/IL149779A0/en unknown
- 2000-11-23 PL PL355886A patent/PL201804B1/en unknown
- 2000-11-23 DE DE60044539T patent/DE60044539D1/en not_active Expired - Lifetime
- 2000-11-23 RO ROA200200663A patent/RO122760B1/en unknown
- 2000-11-23 SK SK738-2002A patent/SK288132B6/en not_active IP Right Cessation
- 2000-11-23 UA UA2002064624A patent/UA78673C2/en unknown
- 2000-11-23 DK DK00981507.7T patent/DK1272216T3/en active
- 2000-11-23 ES ES00981507T patent/ES2348591T3/en not_active Expired - Lifetime
- 2000-11-23 RS YUP-374/02A patent/RS51201B/en unknown
- 2000-11-23 EP EP00981507A patent/EP1272216B1/en not_active Expired - Lifetime
-
2002
- 2002-05-21 IL IL149779A patent/IL149779A/en not_active IP Right Cessation
-
2008
- 2008-03-21 US US12/077,780 patent/US20080175865A1/en not_active Abandoned
-
2011
- 2011-03-16 US US13/049,344 patent/US9056073B2/en not_active Expired - Fee Related
-
2015
- 2015-06-10 US US14/735,637 patent/US20160051657A1/en not_active Abandoned
-
2018
- 2018-02-08 US US15/891,620 patent/US20180161414A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20180161414A1 (en) | Vaccine comprising lactobacillus strains for treating prostate inflammation and benign prostate hyperplasias | |
| CN1602199B (en) | Gram positive bacteria preparations for the treatment of diseases comprising an immune dysregulation | |
| AU691797B2 (en) | Immunotherapeutic composition | |
| RU2526910C2 (en) | Preventive anti-tuberculosis vaccine | |
| CN103157108B (en) | Immune modulator composition and pharmaceutical composition thereof and application | |
| JP3178720B2 (en) | Pasteurella multocida toxoid vaccine | |
| US20220370588A1 (en) | Application of pseudomonas aeruginosa vaccine in treating infection associated with burn or scald injury | |
| US20090162324A1 (en) | Use of Whole Cell Actinomycetales Bacteria to Treat Stress-Induced Pulmonary Haemorrhage | |
| RU2815387C1 (en) | Corynebacterium pseudotuberculosis bacteria strain, intended for producing mono- or polyvalent immunogenic compositions, aimed at specific prevention of caseous lymphadenitis (pseudotuberculosis) of small cattle | |
| CN114805554B (en) | Refined egg yolk antibody injection for resisting streptococcus suis and haemophilus parasuis and preparation method thereof | |
| Sprott et al. | Trichomonal vaginitis refractory to treatment: case report. | |
| KR970001710B1 (en) | Pseudomonas infection preventing agent and the method of preparation thereof | |
| CN113832068A (en) | Streptococcus strain and vaccine for preventing and treating swine streptococcosis | |
| RU2330681C1 (en) | Polyvalent corpuscular antigen for production of medical and preventive biological products for brucellosis | |
| Bizzini et al. | Experimental and Clinical Results | |
| KR20160133087A (en) | Anticancer Vaccine Adjuvant Comprising Inactivated Bacillus Subtilis Spore As Active Ingredient |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| STCB | Information on status: application discontinuation |
Free format text: EXPRESSLY ABANDONED -- DURING EXAMINATION |