CZ31738U1 - A universal product for increasing the overall defences of the organism, for the prevention, prophylaxis and treatment of urinary tract diseases and other diseases of the urogenital tract - Google Patents

Description

Technical field

The technical solution belongs to the field of pharmaceutical and immunobiological preparations, eventually to foodstuffs for special nutrition and food supplements, and it concerns the composition of a universal preparation serving to increase the general immunity of the organism, prevention, prophylaxis and treatment of urinary tract diseases and other diseases of the urogenital tract in human and veterinary medicine.

BACKGROUND OF THE INVENTION

Infections, especially recurrent urinary tract infections, represent a serious therapeutic problem. About half of the acute infections managed by antibiotic or chemotherapy treatment recur within one year after cure, see Sabra, R .: Vesicoureteral reflex, reflux nephiropathy and urinary infections (Prague, Maxdorf - Jessenius 1995). The cause of relapses may be an immunological defect in the resistance of the mucous membranes of the vulva, vagina and distal part of the urethra, which allows the intestinal microorganisms to adhere to the epithelium of the urogenital system, as discussed by Prát, V., Matoušovic, K., Horčičková, M. Hatala, M., Milotová, Z .: Prophylaxis of Recurrent Urinary Infections with the Polymicrobial Vaccine Solco-Urovac (Čas. Lék. Čes., 128, 1989, pp. 1106-1109).

Antibiotics and chemotherapeutics are mostly used to manage recurrent uroinfections. Their alternative is immunotherapy with auto-vaccines as described in the articles Koukalová, D., Hajek, V., Koďousek, R .: Development of a vaccine for the treatment of urinary tract inflammatory diseases (Bratisl. Lek Listy 1999, 100 (2): 92) -95), Koukalova, D., Krocova, Z., Vitek, P., Macela, A., Hajek, V .: Immunostimulatory Activity of the Vaccine in the Treatment of Recurrent Urinary Infections. I (Bratisl Lek Listy 1999, 100 (3): 129-134), Koukalova, D., Krockova, Z., Vitek, P., Macela, A., Hajek, V .: Immunostimulatory Activity of the Vaccine Ušed in the treatment of recurrent urinary infections II (Bratislava Lek Listy 1999b), 100 (4): 215217) or Koukalova, D., Reif, R., Hajek, V., Mucha, Z., Vesely, J., Viktorinova, M. , Lochman, I .: Urva col vaccine in immunomodation of recurrent urinary tract infections (Bratislava Lek Listy 1999c), 100 (5): 246-251. Another possibility is to use commercial preparations, for example referred to as Uro-Vaxom. All substances stimulating the human immune system are discussed in a summary article by J. Bystron “Allergy Year” (Allergy, Asthma, Bronchitis, Issue 4, Volume 20/2017, pp. 16-22).

The composition of the polybacterial vaccine is the subject of patent CZ 278 469, where the disadvantage of the described preparation is the professionally unjustifiable use of three Propionibacterium acnes strains, the use of a harmful inactivating agent formalin, a complicated system of using the preparation in a manner not entirely satisfying the modern and professionally justified application. use of the product, use only in human medicine, non-use of the most advanced molecular biological methods of identification and biotechnological methods of cultivation of bacterial strains and their purification, lysis, stabilization and lyophilization, omission of modern vehicles and additives including immunomodulatory additives , release and use of the standard formulation, particularly in terms of harmlessness and efficacy.

Vitamin C is one of the best researched substances and improves a variety of metabolic processes. Based on the approved health claims of the European Commission, it is clearly shown that vitamin C contributes to the normal production of collagen for normal blood vessel function, contributes to the production of collagen for normal bone function, contributes to the production of collagen for normal function

Cartilage, contributes to the formation of collagen for normal gum and tooth function, contributes to the production of collagen for normal skin function, contributes to normal energy metabolism, contributes to normal nervous system activity, contributes to normal mental activity, contributes to normal function The immune system contributes to maintaining the normal function of the immune system during and after intensive physical exercise, contributes to the protection of cells against oxidative stress, contributes to reducing fatigue and exhaustion, contributes to the regeneration of a reduced form of vitamin E and increases iron absorption. Many studies have shown that there is no difference in the usefulness of natural and synthetic vitamin C for the human body.

In order to benefit from the health effects of vitamin C, at least 15% of the vitamin C value should be at the recommended daily dose (DDD). 100% of the vitamin C is 80 mg for human, 15% is at least 12 mg vitamin C daily for the human.

The claim that vitamin C contributes to the normal functioning of the immune system and that it contributes to maintaining the normal function of the immune system during and after intense physical exercise is in accordance with the co-use of vitamin C and bacterial lysate preparations. The efficacy of bacterial lysates is mainly based on the stimulation of all components of the immune system and on the development of a specific cellular and humoral component of immunity. Concomitant administration of vitamin C and bacterial lysate preparations thus has a synergistic effect and results in better efficacy results than simply application of bacterial lysate preparations alone. In addition, the application of vitamin C has other beneficial effects, as clearly stated in the health claims of the European Commission on vitamin C.

CZ19010 discloses a composition intended to enhance immunity, for the prevention and treatment of urinary tract diseases.

The aim of the technical solution is to present a new universal preparation, which greatly reduces the shortcomings of previously used preparations for vaccine therapy and vaccinoprevention of urinary tract and urogenital tract diseases and abnormality of used preparations leading to non-standard effects related to harmlessness and efficacy of preparations. os (orally, orally), sublingually (under the tongue), on the skin, by injection or other means guaranteeing a solid non-specific and specific immunity to the disease and is in accordance with the latest scientific knowledge of the molecular basis of bacterial immunomodulators. harmless with the intended route of administration and administration.

The essence of the technical solution

The achieved goal largely fulfills the composition of a universal preparation designed to increase the general immunity of the organism, for prevention, prophylaxis and treatment of urinary tract diseases and other diseases of the urogenital tract, based on a combination of one or more lysates of production bacterial strains causing urinary tract diseases and other diseases urogenital tract and vitamin C content, which is based on the selection of specific strains of Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis, Escherichia coli, Proteus mirabilis, Propionibacterium acnes or strains of Enterococcus species, containing vitamin C.

The product contains strains of Klebsiella pneumoniae CCM 7589, Pseudomonas aeruginosa CCM 7590, Enterococcus faecalis CCM 7591, Escherichia coli CCM 7593,

Proteus mirabilis CCM 7592, Propionibacterium acnes CCM 7586, and preferably comprises a mixture of:

- 5 to 15% by weight of Klebsiella pneumoniae CCM 7589 strain

-2CZ 31738 Ul

- 5 to 15% by weight of the strain Pseudomonas aeruginosa CCM 7590

- 5 to 15% by weight of the strain Enterococcus faecalis CCM 7591

- 5 to 15% by weight of the strain Escherichia coli CCM 7593

- 5 to 15% by weight of the Proteus mirabilis strain CCM 7592

25 to 75% by weight of the Propionibacterium acnes strain CCM 7586.

It is also an object of the invention that the total bacterial dry matter content of all production strains in a single application rate ranges from 1 to 1000 mg, and that the active ingredient mixture is mixed with up to 100 times the amount of physiologically harmless vehicle.

Another principle of the solution is that the preparation contains vitamin C in an amount of at least 15% of the recommended daily dose for humans in one daily application dose of the preparation, which represents at least 12 mg of vitamin C daily for humans.

The physiologically acceptable vehicle is preferably selected from the group consisting of silica and / or lactose and / or potato starch and / or magnesium silicate and / or magnesium stearate and / or propyl galanate and / or sodium glutamate and / or indigo carmine and / or gelatin and / or xylitol and / or mannitol and / or erythritol and / or hydroxypropylmethylcellulose and / or microcrystalline cellulose and / or sodium carboxymethylcellulose and / or magnesium stearate and / or aluminum hydroxide and / or aluminum phosphate or other vehicle.

Finally, it is an object of the invention that the active ingredient / vehicle mixture is preferably supplemented with additives, wherein the additives are selected from the group of vitamins and / or minerals and / or trace elements and / or immunobiological additives and / or flavors and / or adhesins and / or disinfectants. substances and / or immunomodulatory substances based on glucans or immunoglucans or other additives.

The present formulation exhibits a new standard effect through a wide range of uses by acting to increase overall human immunity and to a wide range of the most commonly occurring urinary tract agents, but also to other infectious and non-infectious diseases of the urogenital tract. In addition, the composition is applicable in various solid or liquid forms or sprays, such as injections, capsules, capsules, lozenges, tablets, globules, chewing gums or syrups, teas, mouthwash, toothpaste or oral suspensions, dusting powders, ointments, as well as other unnamed methods of application, which also extends the possibilities of its practical use.

Examples of technical solutions

In the preparation of the preparation, the production bacterial strains are individually propagated in a suitably selected solid or liquid culture medium (for production bacterial strains Klebsiella pneumoniae, Enterococcus faecalis, Escherichia coli and Proteus mirabilis it is preferably soil with hydrolyzates of soy and casein) it is preferably 4% casein hydrolysate with yeast extract and in the production bacterial strain Propionibacterium acnes it is preferably Reinforced Clostridial soil), in an air or airless atmosphere, at previously experimentally tested temperatures ranging from 20 ° C to 40 ° C, after a suitably selected period of 16 to 75 hours. The propagated cultures are rinsed with sterile water for injection or decanting and disintegrated by multiple freezing and thawing and heat inactivated. The bacterial mass is obtained by the ultrafiltration method. After checking for microbiological integrity and identity, all the masses of the individual inactivated bacterial strains are homogenized, micronized and lyophilized. Multiplication of individual production

For large-scale production, bacterial strains U1 can be performed by static culture in flasks, or preferably by fermentation culture in a fermenter, until a maximum viable cell growth of 1 x 10 ⁸ / ml up to 1 x 10 ¹⁰ / ml is achieved.

The multiplication of individual strains of bacteria in large-scale production is carried out by industrial fermentation culture in industrial fermenters. In this fermentation culture, the culture medium preferably used for the production bacterial strains Klebsiella pneumoniae, Enterococcus faecalis, Escherichia coli and Proteus mirabilis is preferably soil with hydrolyzates of soy akasein, in the production bacterial strain Pseudomonas aeruginosa it is preferably 4% casein hydrolysate extract. the production bacterial strain Propionibacterium acnes is preferably Reinforced Clostridial. After the basic multiplication of the individual bacterial production strains on solid soils on petri dishes and liquid soils in a small-bottle shaker or fermenter, the grown bacterial strains are transferred to an industrial fermenter at an oxygen supply of 80 l / min (airborne Propionibacterium acnes). atmosphere), 50 rpm, 0.2 bar. The growth of the bacterial strains to the top lag phase in an industrial fermenter takes 16 to 19 hours at a cultivation temperature of 37 ° C for bacterial strains outside the bacterial strain Propionibacterium acnes, and for the bacterial strain Propionibacterium acnes for 40 to 48 hours.

Thereafter, the individual lyophilized lysates of each production bacterial strain are mixed with the vitamin C content and the appropriate vehicle so that the proportion of the individual strains in the finished product corresponds to the selected unit weight ratio and the vitamin C content is at least 15% of the recommended daily human dose. (at least 12 mg of vitamin C) and the total content in the final formulation was 1 to 1000 mg of active substance per dose. In the final phase, the final product is formulated into selected user forms, i.e., capsules, tablets, lozenges, chewing gums, or the like, or the liquid phase product is filled into vials.

The examples given do not limit the utility of this utility model.

Example 1

Composition of one tablet for oral administration:

- Klebsiella pneumoniae CCM 7589 production strain

- Pseudomonas aeruginosa CCM 7590 production strain

- Enterococcus faecalis production strain CCM 7591

- the production strain of Escherichia coli CCM 7593

- the production strain Próteus mirabilis CCM 7592

- Propionibacterium acnes production strain CCM 7586

- vitamin C

- vehicle (xylitol T, mannitol, hypromellose, croscarmellose sodium, magnesium stearate, erythritol, glucal, menthol flavor) mg bacterial lysate 1 mg bacterial lysate 1 mg bacterial lysate 1 mg bacterial lysate mg bacterial lysate mg

482 mg

-4GB 31738 U1

Example 2

Composition of a single dose for injection:

- Klebsiella pneumoniae CCM 7589 production strain 0.5 mg bacterial lysate - Pseudomonas aeruginosa CCM 7590 production strain 0.5 mg bacterial lysate - Enterococcus faecalis production strain CCM 7591 0.5 mg bacterial lysate - the production strain of Escherichia coli CCM 7593 0.5 mg bacterial lysate - the production strain Próteus mirabilis CCM 7592 0.5 mg bacterial lysate - Propionibacterium acnes production strain CCM 7586 0.5 mg bacterial lysate - vitamin C 12 mg - alumina 2.0 mg Al ³⁺ - water for injections ad 1 ml

Example 3 Composition of one capsule for oral administration: - Klebsiella pneumoniae CCM 7589 production strain 0.67 mg of bacterial lysate - Pseudomonas aeruginosa CCM 7590 production strain 0.67 mg of bacterial lysate - Enterococcus faecalis production strain CCM 7591 0.67 mg of bacterial lysate - the production strain of Escherichia coli CCM 7593 0.67 mg of bacterial lysate - the production strain Próteus mirabilis CCM 7592 0.67 mg of bacterial lysate - Propionibacterium acnes production strain CCM 7586 1.66 mg of bacterial lysate - vitamin C 12 mg

- vehicle (silica, lactose, potato starch) 182.99 mg

Industrial applicability

A special universal preparation of this composition is useful for increasing the body's immunity, immunotherapeutically, immunopreventively and immunoprophylactically, especially against urinary tract diseases and other diseases of the urogenital tract. It can be administered simultaneously with the use of pharmaceuticals, antibiotics or other preventive and therapeutic agents and vaccines, for children, men and women of all ages, in various dosage forms for injection, oral, topical and other administration.

Claims (10)

A universal preparation for enhancing the body's immunity and for the prevention, prophylaxis and treatment of urinary tract diseases and other diseases of the urogenital tract, characterized in that it contains as active ingredients in a single application dose: 1.0 to 1000 mg of a mixture of the production strain lysates in a weight ratio, based on the microbial dry matter, of 5 to 15 wt. % Klebsiella pneumoniae CCM 7589, 5 to 15 wt. % Pseudomonas aeruginosa CCM 7590, 5 to 15 wt. % of Enterococcus faecalis CCM 7591, 5 to 15 wt. % of Escherichia coli CCM 7593, 5 to 15 wt. % of Proteus mirabilis CCM 7592 and 25 to 75 wt. % strain Propionibacterium acnes CCM 7586; are related to the microbial dry matter and; - 12 to 1000 mg of vitamin C. Universal formulation according to claim 1, characterized in that the active ingredient mixture is mixed with up to 100 times the amount of physiologically acceptable vehicle. Universal formulation according to claim 1 or 2, characterized in that the physiologically harmless vehicle is selected from one or more of water and / or silica and / or lactose and / or potato starch and / or magnesium silicate and / or magnesium stearate and / or propyl gallanate and / or sodium glutamate and / or mannitol and / or indigo carmine and / or gelatin and / or microcrystalline cellulose and / or collagen hydrolyzed gelatin and / or xylitol and / or delta-mannitol and / or erythritol and / or hydroxypropylmethylcellulose and / or sodium carboxymethylcellulose and / or menthol flavor. The universal preparation according to claims 1 to 3, characterized in that it comprises at least one immunostimulating additive selected from the group of vitamins and / or biologically acceptable minerals and / or physiologically acceptable trace elements and / or immunobiological additives. Universal preparation according to claims 1 to 4, characterized in that the vitamin is vitamin A, group B vitamins, vitamin D, vitamin E, vitamin K and / or the mineral is calcium, phosphorus, magnesium and / or the trace element is zinc , iodine, copper, selenium and / or the immunobiological additive is selected from glucan, betaglucan, immunoglucan, positive antibodies, stem cells, bacterial immunomodulators, plant immunomodulators, colostrum, nucleotides, probiotics, enzyme preparations, homeopathics and other additives. Universal formulation according to claims 1 to 5, characterized in that the amount of vitamin C per dose is 12 to 500 mg. Universal formulation according to claims 1 to 6, characterized in that it is in the form of enteric capsules. Universal preparation according to claims 1 to 7, characterized in that it is in the form of mouthwash. Universal preparation according to claims 1 to 8, characterized in that it is in the form of tablets. Universal formulation according to claims 1 to 9, characterized in that it is in the form of an injection for intramuscular or subcutaneous administration. End of document