CZ31739U1 - A universal product for increasing the overall defences of the organism, for the prevention, prophylaxis and therapy of infectious and other diseases of viral, bacterial, mycotic and parasitic origin - Google Patents

Description

Technical field

The technical solution falls within the field of pharmaceutical and immunobiological products, eventually foodstuffs for special nutrition and food supplements, and concerns the composition and use of a universal product serving to increase the general immunity of the organism, for prevention, prophylaxis and therapy of infectious and other diseases in human and veterinary medicine.

BACKGROUND OF THE INVENTION

Activation of non-specific parts of the immune system based on the recognition of pathogenic patterns is a key element in the mechanism of action of bacterial immunomodulators, as described in Weigl E., Raska M., Bohac S.: Molecular Basis of Effect of Bacterial Immunomodulators (Allergy, 3, 2000) ). Currently, bacterial immunomodulators are used in some clinical indications as published in Bystroň J .: Bacterial immunomodulators in pediatric practice (Pediatrician, 3, 11-15, 1998), Vlčková I., Bystroň J .: Our experience with lyophilized vaccines in the treatment of recurrent infections in the ENT area (Otorinolaryngol (Prague) 44 (1), 43-46, 1995), Viktorinova M., Koukalova D .: Bacterial immunomodulators available for treating chronic dermatoses (Dermatolog. prax, 2007, 2 , 60-63), Bystroň J., Boháč S., Braunová J., Koukalová D .: Our Experience with Treatment of Relapsing Herpetic Infections by Combined Non-specific Immunostimulation (Cas. Lék. Čes., 131, 1992, no. 5, pp. 137-141) or Koukalova D., Koďousek R., Hajek V., Kolar M .: Experimental nonspecific immunostimulation by propionbacterium acnes vaccine (Acta Univ. Palacki. Olomouc., Fac. Med., Volume 133, 1992, pp. 19-23). All substances stimulating the human immune system are discussed in a summary article by J. Bystron “Allergology Year (Allergy, Asthma, Bronchitis, Issue 4, Volume 20/2017, pp. 16-22). In particular, a significant non-specific effect of these bacterial immunomodulators is evident when administered orally. The results of testing these bacterial immunomodulators have indicated a wide range of applications for a wide range of indications and infections. Since the 1970s, a number of preparations of significantly different antigenic composition have been introduced into validation or clinical practice with a different selection of production bacterial strains for formulation. The preparations differ in different indications for use, methods of culturing production strains, methods for obtaining and purifying bacterial lysates, methods of administration and schedules of administration of these preparations, and many other indicators when the common goal of all investigations is to obtain an optimal harmlessness and efficacy ratio.

The fact is that enormous rapid progress, especially in the field of molecular biological methods and the development of world knowledge with the subsequent immediate introduction of this new knowledge and information into applied research and practice, leads to research, development and introduction of new types of preparations, including bacterial immunomodulators into clinical practice. and for practical use.

The composition of a non-specific polybacterial vaccine for the prevention and treatment of bacterial, fungal and viral infections is the subject of patent CZ 275 210, where the disadvantage of the described preparation is the freedom to use two production bacterial strains Enterobacter amnigenus or Propionibacterium acnes. efficiency. Another disadvantage of the vaccine composition is the determination of the active substance, i.e. the individual bacterial lysates, by the bacterial cell count method. This method is very inaccurate and does not guarantee accurate determination of the active substance to the final form of the preparation, which can lead to non-standard use of the preparation in terms of harmlessness and efficacy. Further disadvantages are limited application forms of use of the preparation only for oral administration, not determined

The optimum scheme for the use of the preparation for optimum results in terms of safety and efficacy, the non-use of the most advanced pharmaceutical vehicles and additives to optimize the use of the preparation for the end user, is the use of a harmless and highly effective bacterial immunomodulator.

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 normal collagen production for normal blood vessel function, contributes to collagen production for normal bone function, contributes to collagen production for normal cartilage function, contributes to normal collagen production gums and teeth, contributes to collagen production for normal skin function, contributes to normal energy metabolism, contributes to normal nervous system activity, contributes to normal mental activity, contributes to normal immune system function, contributes to maintaining normal immune system function during intense physical and after, helps protect cells from oxidative stress, helps reduce 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.

Vitamin C contributes to the normal functioning of the immune system and contributes to maintaining the normal function of the immune system during and after intensive physical exercise, which 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 for 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 introduce a new universal preparation, which greatly reduces the shortcomings of previously used preparations and the abnormality of used preparations leading to non-standard effects concerning harmlessness and effectiveness of preparations while being applied by oral (oral, oral), sublingual ), on the skin, by injection or otherwise, to provide solid specific and non-specific immunity to a wide range of infectious and other diseases, and is consistent with the world's latest knowledge of the molecular basis of bacterial immunomodulators and specific and non-specific cellular and humoral immunity effective and harmless in the intended mode of administration and administration.

The essence of the technical solution

The objective and other advantages largely satisfy the composition of the universal preparation for increasing the general immunity of the organism, for the prevention, prophylaxis and therapy of infectious and other diseases of viral, bacterial, fungal or parasitic origin, including herpes infections, based on a combination of one or more Lysates of production bacterial strains containing vitamin C, characterized in that the specific strains Klebsiella pneumoniae, Staphylococcus aureus and Propionibacterium acnes, in particular the Klebsiella pneumoniae CCM strains are selected as active ingredients in combination

-2GB 31739 U1

7589, Staphylococcus aureus CCM 7587 and Propionibacterium acnes CCM 7586. An optional combination of said strains together with Enterococcus species, Serratia species, Staphylococcus species, Pseudomonas species, Streptococcus species, Proteus species, Haemophilus species and others with vitamin E is described. In a preferred embodiment, the mixture comprises:

5 to 45% by weight of Klebsiella pneumoniae CCM 7589 strains

- 5 to 45% by weight, strains of Staphylococcus aureus CCM 7587

10 to 90% by weight of the strain Propionibacterium acnes CCM 7586.

In a further preferred embodiment, the total bacterial dry matter content of all production strains in a single application rate is in the range of 0.1 to 1000 mg and that the active ingredient mixture is mixed with up to 100 times the amount of physiologically acceptable 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, ie 12 to 500 mg, in another for administration the amount of vitamin C in one application dose 12 to 200 mg.

The physiologically acceptable vehicle is 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 aluminum hydroxide and / or aluminum phosphate and / or modified starch and other vehicles used in the art.

Finally, it is an object of the invention that the active compound / vehicle mixture is 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 and / or glucan or beta glucan based immunomodulatory agents and / or specific monoclonal antibodies and / or stem cells and others.

The present formulation exhibits a new standard effect through a wide range of uses, by not only affecting a wide range of the most commonly occurring pathogens of infectious diseases of viral, bacterial, fungal, parasitic origin, including herpes infections, but also other unspecified diseases. The product increases the general immunity of the body to physical and mental strain and is also applicable in various solid, liquid or droplet forms such as injections, capsules, capsules, lozenges, tablets, globules, chewing gums or syrups, teas, mouthwash, dental paste or oral suspensions, dusting powders, ointments, sprays, as well as other unspecified routes of application, which also extends the possibilities for its practical application.

Examples of technical solutions

In the manufacture of the preparation, the production bacterial strains of Klebsiella pneumoniae CCM 7589, Staphylococcus aureus CCM 7587 and Propionibacterium acnes CCM 7586 are individually propagated in a suitably selected solid or liquid culture medium (for production bacterial strains Klebsiella pneumoniae and Staphylococcus aureus preferably casein and in the production bacterial strain Propionibacterium acnes it is preferably soil (Reinforced Clostridial), in an air or airless atmosphere, at previously experimentally verified temperatures, ranging from 20 ° C to 40 ° C, for 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. Bacterial flesh is obtained by using

Ultrafiltration methods. After checking for microbiological integrity and identity, all the mass of each inactivated bacterial strain is homogenized, micronized and lyophilized. The multiplication of individual bacterial strains can be carried out in large scale production 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, preferably the soil with hydrolyzates of soybean and casein is used as the culture medium for the production bacterial strains Klebsiella pneumoniae and Staphylococcus aureus, and for the production bacterial strain Propionibacterium acnes it is preferably the soil 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, 20 kPa. The growth of 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 Propionibacterium acnes bacterial strain and 40 to 48 hours for the Propionibacterium acnes bacterial strain.

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, ie 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 production strain CCM 7589 4 mg of bacterial lysate - a production strain of Staphylococcus aureus CCM 7587 4 mg of bacterial lysate - Propionibacterium acnes production strain CCM 7586 4 mg of bacterial lysate

-4GB 31739 U1

- vitamin C 12 mg - vehicle (xylitol T, mannitol, hypromellose, croscarmellose sodium, magnesium stearate, erythritol, glucal, menthol aroma) 476 mg

Example 2

Single dose composition for injection

- Klebsiella pneumoniae production strain CCM 7589 0.1 mg bacterial lysate - a production strain of Staphylococcus aureus CCM 7587 0.1 mg bacterial lysate - Propionibacterium acnes production strain CCM 7586 0.1 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 production strain CCM 7589 3 mg bacterial lysate - a production strain of Staphylococcus aureus CCM 7587 3 mg bacterial lysate - Propionibacterium acnes production strain CCM 7586 3 mg bacterial lysate

-5 CZ 31739 U1

- vitamin C 12 mg vehicle (silica, lactose, starch) potato) 2.0 mg Al ³⁺ - water for injections ad 179 mg

Industrial applicability

A special universal preparation of this composition is useful for increasing the general immunity of the organism, for prevention, prophylaxis and therapy of infectious and other diseases immunotherapeutically, immunopreventively and immunoprophylactically, especially against a wide range of the most common pathogens of viral, bacterial, fungal, parasitic and other diseases , including herpetic ones, including increasing the body's overall defense against physical or psychological strain. It can be administered simultaneously with the use of pharmaceuticals, antibiotics or other preventive and therapeutic substances and vaccines for children, men and women of all ages, or used in human or veterinary medicine in various dosage forms for injection, oral, topical and other administration.

PROTECTION REQUIREMENTS

Claims (9)

A universal preparation for increasing the general immunity of the organism, for the prevention, prophylaxis and therapy of infectious and other diseases of viral, bacterial, fungal or parasitic origin, including herpes infections, characterized in that it contains as active ingredients in a single application dose: - 0.5 to 1000 mg of a mixture of production strain lysates of composition 5 to 45% by weight of Klebsiella pneumoniae CCM 7589 strains - 5 to 45% by weight, strains of Staphylococcus aureus CCM 7587 - 10 to 90% by weight, strain Propionibacterium acnes CCM 7586, where% by weight are based on the microbial dry matter, and - 12 to 500 mg of vitamin C. Universal formulation according to claim 1, characterized in that the active ingredient mixture is mixed with up to 10 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 galanate 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 the menthol aroma. 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 physiologically acceptable minerals and / or physiologically acceptable trace elements and / or immunobiological additives and / or glucans or immunoglucans, and / or specific monoclonal antibodies and / or stem cells. Universal formulation according to claim 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 the group of glucan, betaglucan, immunoglucan, positive monoclonal antibodies, stem cells, bacterial immunomodulators, plant immunomodulators, colostrum, nucleotides, probiotics, enzyme preparations and homeopathics. Universal formulation according to claims 1 to 5, characterized in that the amount of vitamin C per application is 12 to 200 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 6, characterized in that it is in the form of mouthwash. Universal formulation according to claims 1 to 6, characterized in that it is in the form of tablets. End of document